a SCF-I2 ( M) DMSO 40 80 160 320 input · a, Schematic of fluorescence polarization (FP) assay used...
13
a c d input DMSO 8 40 80 320 - SCF-I2 (μM) 160 +160 μM SCF-I2 no compound Met4 Met4-(Ub) n 160 μM input DMSO 160 μM DMSO Ub GST- Ub 10 20 30 45 10 20 30 45 min SCF-I2 (μM) input DMSO 8 40 80 320 160 Sic1 Cdc4 bound input DMSO 40 80 320 160 Far1 anti-Far1 Cdc4 bound SCF-I2 (μM) anti-Sic1 pSic1 pSic1-(Ub) n b Fbox P + inhibitor + high polarization signal low polarization signal fluorescein Skp1 P fluorescein I Cdc4 Fbox Skp1 Cdc4 I WD40 WD40 Figure S1. Binding and inhibitory properties of SCF-I2 on Cdc4-substrate interactions. a, Schematic of fluorescence polarization (FP) assay used to monitor interactions between a fluorescein-labeled cyclin E-derived phosphopeptide (GLLpTPPQSG) and recombinant Skp1-Cdc4 complex. b, Inhibition of Sic1 (top panel) and Far1 (bottom panel) capture by Skp1-Cdc4 resin by the indicated concentrations of SCF-I2. c, Inhibition of SCFCdc4-mediated Sic1 ubiquitination by SCF-I2. Dose-response assays were carried out in the presence of the indicated concentrations of SCF-I2 at 30°C for 45 min (left panel). Time course assays were carried out in the presence or absence of 160 μM SCF-I2 at 30°C for the indicated times. d, Ubiquitination of Met4 by SCFMet30 is unaffected by SCF-I2. Complete ubiquitina- tion reactions were carried out as for SCFCdc4 with recombinant Met4 and SCFMet30 using either ubiquitin or GST-ubiquitin in the absence or presence of 160 μM SCF-I2. Nature Biotechnology: doi:10.1038/nbt.1646
Transcript of a SCF-I2 ( M) DMSO 40 80 160 320 input · a, Schematic of fluorescence polarization (FP) assay used...
a
c
d
inpu
t
DM
SO
8 40 80 320-
SCF-I2 (μM)
160
+160 μM SCF-I2 no compound
Met4
Met4-(Ub)n
160 μM
inpu
t
DM
SO
160 μM
DM
SO
Ub GST- Ub
10 20 30 45 10 20 30 45 min
SCF-I2 (μM)
inpu
t
DM
SO
8 40 80 320
160
Sic1
Cdc4 bound
inpu
t
DM
SO
40 80 320
160
Far1anti-Far1
Cdc4 bound
SCF-I2 (μM)
anti-Sic1
pSic1
pSic1-(Ub)n
b
Fbox
P+ inhibitor +
high polarization
signal
low polarization
signal
fluorescein
Skp1
Pfluorescein
I
Cdc4
Fbox
Skp1
Cdc4
IWD40
WD40
Figure S1. Binding and inhibitory properties of SCF-I2 on Cdc4-substrate interactions. a, Schematic of fluorescence polarization (FP) assay used to monitor interactions between a fluorescein-labeled cyclin E-derived phosphopeptide (GLLpTPPQSG) and recombinant Skp1-Cdc4 complex. b, Inhibition of Sic1 (top panel) and Far1 (bottom panel) capture by Skp1-Cdc4 resin by the indicated concentrations of SCF-I2. c, Inhibition of SCFCdc4-mediated Sic1 ubiquitination by SCF-I2. Dose-response assays were carried out in the presence of the indicated concentrations of SCF-I2 at 30°C for 45 min (left panel). Time course assays were carried out in the presence or absence of 160 μM SCF-I2 at 30°C for the indicated times. d, Ubiquitination of Met4 by SCFMet30 is unaffected by SCF-I2. Complete ubiquitina-tion reactions were carried out as for SCFCdc4 with recombinant Met4 and SCFMet30 using either ubiquitin or GST-ubiquitin in the absence or presence of 160 μM SCF-I2.
Nature Biotechnology: doi:10.1038/nbt.1646
Figure S2. Structure-based sequence alignments of the WD40 repeat domains of Cdc4 orthologs. Secondary structure elements are highlighted at the top of the alignment for each WD40 repeat motif (labeled on the left of each alignment). Red, blue and yellow background shading denote regions of each repeat that composes the four adjacent β-strands of each propeller blade (labeled on the right of each alignment). Yellow highlights indicate general conserved positions in WD40 repeats; green highlights indicate conserved positions in the CPD binding pocket; blue highlights indicate positions in the SCF-I2 binding pocket. The red highlight indicates the only position common to both CPD and SCF-I2 binding pockets (Leu634). Grey boxes denote sites and size of insertions. Red asterisk denotes sequence and position of an insertion between strands β 12 and β 13 that forms a non-canonical fifth β -strand in propeller blade 2. Cdc4 orthologs are indicated in red and paralogs in black.
380 390 400 410| | | |
S c C dc4 3 6 7 N P 4 Q R T T L R G H M T S V I T C L Q F E D - - N Y V I T G A D D K M I R V Y D S IS p P op1 3 9 1 H A 4 K R C S F P I H G V R L I T K L Q F D D - - D K I I V S T C S P R I N I Y D T KC e S E L 10 2 4 2 A N 3 G S A V L R G H E D H V I T C M Q I H D - - D V L V T G S D D N T L K V W C I DDm A G O 9 8 1 S R 3 K P K V L K G H D D H V I T C L Q F S G - - N R I V S G S D D N T L K V W S A VHs F bw7 3 6 7 R G 3 S P K V L K G H D D H V I T C L Q F C G - - N R I V S G S D D N T L K V W S A VC e L in23 2 0 7 R G 4 T R I N C Q S E N S K G V Y C L Q Y D D - - D K I V S G L R D N T I K I W D R KDm S limb 1 9 5 T G 4 R R I N C R S E N S K G V Y C L Q Y D D - - G K I V S G L R D N T I K I W D R THs βT rC P 1 2 5 2 C G 4 Q R I H C R S E T S K G V Y C L Q Y D D - - Q K I V S G L R D N T I K I W D K NS c Met30 2 9 0 K G 2 R I Q E F K G H M - D G V L T L Q F N Y - - R L L F T G S Y D S T I G I W D L F
420 430 440 450| | | |
S c C dc4 4 1 1 N K K F L L Q L S G H D - G G V W A L K Y A H - G G I L V S G S T D R T V R V W D I KS p P op1 4 3 5 T G V L I R S L E E H E - G D V W T F E Y V G - - D T L V T G S T D R T V R V W D L R
C e S E L 10 2 8 5 K G E V M Y T L V G H T - G G V W T S Q I S Q C G R Y I V S G S T D R T V K V W S T VDm A G O 1 0 2 4 N G K C L R T L V G H T - G G V W S S Q M S G - - N I I I S G S T D R T L K V W D M DHs F bw7 4 1 0 T G K C L R T L V G H T - G G V W S S Q M R D - - N I I I S G S T D R T L K V W N A EC e L in23 2 5 1 D Y S C S R I L S G H T - G S V L C L Q Y D N - - R V I I S G S S D A T V R V W D V EDm S limb 2 3 9 D L Q C V K T L M G H T - G S V L C L Q Y D D - - K V I I S G S S D S T V R V W D V NHs βT rC P 1 2 9 6 T L E C K R I L T G H T - G S V L C L Q Y D E - - R V I I T G S S D S T V R V W D V NS c Met30 3 3 1 T G K L I R R L S G H S - D G V K T L Y F D D - - R K L I T G S L D K T I R V W N Y I
460 470 480 490| | | |
S c C dc4 4 5 2 K G C C T H V F E G H N - S T V R C L D I V 2 K N 2 Y I V T G S R D N T L H V W K L PS p P op1 4 7 5 T G E C K Q V F Y G H T - S T I R C I K I V 27 - - P Y I I S S S R D C T I R L W S L 26C e S E L 10 3 2 7 D G S L L H T L Q G H T - S T V R C M A M A G - - S I L V T G S R D T T L R V W D V EDm A G O 1 0 6 4 S G A C V H T L Q G H T - S T V R C M H L H G - - S K V V S G S R D A T L R V W D I EHs F bw7 4 5 0 T G E C I H T L Y G H T - S T V R C M H L H E - - K R V V S G S R D A T L R V W D I EC e L in23 2 9 1 T G E C I K T L I H H C - E A V L H L R F A N - - G I M V T C S K D R S I A V W D M VDm S limb 2 7 9 T G E M V N T L I H H C - E A V L H L R F N N - - G M M V T C S K D R S I A V W D M THs bT rC P 1 3 3 6 T G E M L N T L I H H C - E A V L H L R F N N - - G M M V T C S K D R S I A V W D M AS c Met30 3 7 1 T G E C I S T Y R G H S - D S V L S V D S Y Q - - K V I V S G S A D K T V K V W H V E
520 530 540 550| | | |
S c C dc4 5 1 9 N P Y F V G V L R G H M - A S V R T V S G H G - - N I V V S G S Y D N T L I V W D V AS p P op1 5 6 6 N P F Y I R T L R G H T - D S V R E V A C L G - - D L I V S A S Y D G T L R V W K A SC e S E L 10 3 6 7 S G R H L A T L H G H H - A A V R C V Q F D G - - T T V V S G G Y D F T V K I W N A HDm A G O 1 1 0 4 Q G S C L H V L V G H L - A A V R C V Q Y D G - - K L I V S G A Y D Y M V K I W H P EHs F bw7 4 9 0 T G Q C L H V L M G H V - A A V R C V Q Y D G - - R R V V S G A Y D F M V K V W D P EC e L in23 3 3 1 S 4 T I R R V L V G H R - A A V N V V D F D D - - R Y I V S A S G D R T I K V W S M DDm S limb 3 1 9 S 4 T L R R V L V G H R - A A V N V V D F D E - - K Y I V S A S G D R T I K V W S T SHs βT rC P 1 3 7 6 S 4 T L R R V L V G H R - A A V N V V D F D D - - K Y I V S A S G D R T I K V W N T SS c Met30 4 1 1 S R T C - Y T L R G H T - E W V N C V K L H P K S F S C F S C S D D T T I R M W D I R
560 570 580 590 600| | | | |
S c C dc4 5 5 9 Q M K C L Y I L S G H T - D R I Y S T I Y D H E R K R C I S A S M D T T I R I W D L ES p P op1 6 0 6 T G V C L H V L R G H V - G R V Y S V T I N P S R Q Q C I S A G T D A K I R I W N L EC e S E L 10 4 0 7 T G R C I R T L T G H N - N R V Y S L L F E S E R S I V C S G S L D T S I R V W D F 3Dm A G O 1 1 4 4 R Q E C L H T L Q G H T - N R V Y S L Q F D G - - L H V V S G S L D T S I R V W D V EHs F bw7 5 3 0 T E T C L H T L Q G H T - N R V Y S L Q F D G - - I H V V S G S L D T S I R V W D V EC e L in23 3 7 4 T L E F V R T L A G H R - R G I A C L Q Y R G - - R L V V S G S S D N T I R L W D I HDm S limb 3 6 2 T C E F V R T L N G H K - R G I A C L Q Y R D - - R L V V S G S S D N S I R L W D I EHs bT rC P 1 4 1 9 T C E F V R T L N G H K - R G I A C L Q Y R D - - R L V V S G S S D N T I R L W D I ES c Met30 4 5 2 T N S C L K V F R G H V - G Q V Q K I I P L T I 48 T H L L S C G L D N T I K L W D V K
630 640 650 660| | | |
S c C dc4 6 0 1 N G E L M Y T L Q G H T - A L V G L L R L S D - - K F L V S A A A D G S I R G W D A NS p P op1 6 4 8 S G E L L Q T L H G H S - N L V S Q V T F N Q - - N I L V S A S A 3 T S L R V W D L NC e S E L 10 4 5 1 E G 2 C V A L L Q G H T - S L T S G M Q L R G - - N I L V S C N A D S H V R V W D I HDm A G O 1 1 8 4 T G N C K H T L M G H Q - S L T S G M E L R Q - - N I L V S G N A D S T V K V W D I THs F bw7 5 7 0 T G N C I H T L T G H Q - S L T S G M E L K D - - N I L V S G N A D S T V K I W D I KC e L in23 4 1 4 S G V C L R V L E G H E - E L V R C I R F D E - - K R I V S G A Y D G K I K V W D L 10Dm S limb 4 0 2 C G A C L R V L E G H E - E L V R C I R F D T - - K R I V S G A Y D G K I K V W D L 10Hs βT rC P 1 4 5 9 C G A C L R V L E G H E - E L V R C I R F D N - - K R I V S G A Y D G K I K V W D L 10S c Met30 5 4 1 T G K C I R T Q F G H V - E G V W D I A A D N - - F R I I S G S H D G S I K V W D L Q
670 680 690 700| | | |
S c C dc4 6 6 1 D Y S R K F S Y H - H T 2 S A I T T F Y V S D - - N I L V S G S - E N Q F N I Y N L RS p P op1 6 9 0 T G S C R D I L K - C P - L G H I F F Q H D E - - S K V V S G S - H S T L Q L W D I RC e S E L 10 4 9 2 E G T C V H M L S G H R - S A I T S L Q W F G R - N M V A T S S D D G T V K L W D I EDm A G O 1 2 2 4 T G Q C L Q T L 4 K H H - S A V T C L Q F N S - - R F V V T S S D D G T V K L W D V KHs F bw7 6 1 0 T G Q C L Q T L 4 K H Q - S A V T C L Q F N K - - N F V I T S S D D G T V K L W D L KC e L in23 4 6 3 S E I C L C S L V Q H T - G R V F R L Q F D D - - F Q I V S S S H D D T I L I W D F LDm S limb 4 5 1 N T L C L N T L V E H T - G R V F R L Q F D E - - F Q I V S S S H D D T I L I W D F LHs βT rC P 1 5 0 8 G T L C L R T L V E H S - G R V F R L Q F D E - - F Q I V S S S H D D T I L I W D F LS c Met30 5 8 1 S G K C M H T F 17 G D K V A P I A C V C I G D - - S E C F S G D E F G C V K M Y K F D
710 720 730 740| | | |
S c C dc4 7 0 1 S G K L V H 2 I L K - D A D Q I W S V N F K G - - K T L V A A V 4 Q S F L E I L D F SS p P op1 7 2 8 S G K L V R D L L T - D L D I I W Q V A Y N E - - N V C V A A V 4 R F W I E V L E F GC e S E L 10 5 3 3 R G A L I R D L V T L D 5 G C I W R L C S T S - - T M L A C A V 7 E T K V I L L D F DDm A G O 1 2 6 7 T G D F I R N L V A L D 5 G V V W R I R A N D - - T K L I C A V 7 E T K L M V L D F DHs F bw7 6 5 3 T G E F I R N L V T L E 5 G V V W R I R A S N - - T K L V C A V 7 E T K L L V L D F D
500 510| |
K E S S V P D H G E E H D Y P L V F H T P E E
520|
N P Y F V G V L R GN P F Y I R T L R GS G R H L A T L H GQ G S C L H V L V GT G Q C L H V L M GS 4 T I R R V L V GS 4 T L R R V L V GS 4 T L R R V L V GS R T C - Y T L R G
530 540 550| | |
H M - A S V R T V S G H G - - N I V V S G S Y D N T L I V W D V AH T - D S V R E V A C L G - - D L I V S A S Y D G T L R V W K A SH H - A A V R C V Q F D G - - T T V V S G G Y D F T V K I W N A HH L - A A V R C V Q Y D G - - K L I V S G A Y D Y M V K I W H P EH V - A A V R C V Q Y D G - - R R V V S G A Y D F M V K V W D P EH R - A A V N V V D F D D - - R Y I V S A S G D R T I K V W S M DH R - A A V N V V D F D E - - K Y I V S A S G D R T I K V W S T SH R - A A V N V V D F D D - - K Y I V S A S G D R T I K V W N T SH T - E W V N C V K L H P K S F S C F S C S D D T T I R M W D I R
470 480 490| | |
H N - S T V R C L D I V 2 K N 2 Y I V T G S R D N T L H V W K L PH T - S T I R C I K I V 27 - - P Y I I S S S R D C T I R L W S L 26H T - S T V R C M A M A G - - S I L V T G S R D T T L R V W D V EH T - S T V R C M H L H G - - S K V V S G S R D A T L R V W D I EH T - S T V R C M H L H E - - K R V V S G S R D A T L R V W D I EH C - E A V L H L R F A N - - G I M V T C S K D R S I A V W D M VH C - E A V L H L R F N N - - G M M V T C S K D R S I A V W D M TH C - E A V L H L R F N N - - G M M V T C S K D R S I A V W D M AH S - D S V L S V D S Y Q - - K V I V S G S A D K T V K V W H V E
460|
K G C C T H V F E G HT G E C K Q V F Y G HD G S L L H T L Q G HS G A C V H T L Q G HT G E C I H T L Y G HT G E C I K T L I H HT G E M V N T L I H HT G E M L N T L I H HT G E C I S T Y R G H
0 390 400 410| | |
M T S V I T C L Q F E D - - N Y V I T G A D D K M I R V Y D S IG V R L I T K L Q F D D - - D K I I V S T C S P R I N I Y D T KE D H V I T C M Q I H D - - D V L V T G S D D N T L K V W C I DD D H V I T C L Q F S G - - N R I V S G S D D N T L K V W S A VD D H V I T C L Q F C G - - N R I V S G S D D N T L K V W S A VN S K G V Y C L Q Y D D - - D K I V S G L R D N T I K I W D R KN S K G V Y C L Q Y D D - - G K I V S G L R D N T I K I W D R TT S K G V Y C L Q Y D D - - Q K I V S G L R D N T I K I W D K NM - D G V L T L Q F N Y - - R L L F T G S Y D S T I G I W D L F
380|
N P 4 Q R T T L R G HH A 4 K R C S F P I HA N 3 G S A V L R G HS R 3 K P K V L K G HR G 3 S P K V L K G HR G 4 T R I N C Q S ET G 4 R R I N C R S EC G 4 Q R I H C R S E TK G 2 R I Q E F K G H
0 640 650 660| | |
H T - A L V G L L R L S D - - K F L V S A A A D G S I R G W D A NH S - N L V S Q V T F N Q - - N I L V S A S A 3 T S L R V W D L NH T - S L T S G M Q L R G - - N I L V S C N A D S H V R V W D I HH Q - S L T S G M E L R Q - - N I L V S G N A D S T V K V W D I TH Q - S L T S G M E L K D - - N I L V S G N A D S T V K I W D I KH E - E L V R C I R F D E - - K R I V S G A Y D G K I K V W D L 10H E - E L V R C I R F D T - - K R I V S G A Y D G K I K V W D L 10H E - E L V R C I R F D N - - K R I V S G A Y D G K I K V W D L 10H V - E G V W D I A A D N - - F R I I S G S H D G S I K V W D L Q
720 730 740| | |
- D A D Q I W S V N F K G - - K T L V A A V 4 Q S F L E I L D F S- D L D I I W Q V A Y N E - - N V C V A A V 4 R F W I E V L E F GL D 5 G C I W R L C S T S - - T M L A C A V 7 E T K V I L L D F DL D 5 G V V W R I R A N D - - T K L I C A V 7 E T K L M V L D F DL E 5 G V V W R I R A S N - - T K L V C A V 7 E T K L L V L D F D
630|
N G E L M Y T L Q G HS G E L L Q T L H G HE G 2 C V A L L Q G HT G N C K H T L M G HT G N C I H T L T G HS G V C L R V L E G HC G A C L R V L E G HC G A C L R V L E G HT G K C I R T Q F G H
670 680 690 700| | | |
H T 2 S A I T T F Y V S D - - N I L V S G S - E N Q F N I Y N L RC P - L G H I F F Q H D E - - S K V V S G S - H S T L Q L W D I RH R - S A I T S L Q W F G R - N M V A T S S D D G T V K L W D I EH H - S A V T C L Q F N S - - R F V V T S S D D G T V K L W D V KH Q - S A V T C L Q F N K - - N F V I T S S D D G T V K L W D L KH T - G R V F R L Q F D D - - F Q I V S S S H D D T I L I W D F LH T - G R V F R L Q F D E - - F Q I V S S S H D D T I L I W D F LH S - G R V F R L Q F D E - - F Q I V S S S H D D T I L I W D F LD K V A P I A C V C I G D - - S E C F S G D E F G C V K M Y K F D
β2 β3 β4
β5 β6 β7 β8
β9 β10 β11 β12
β13 β14 β15 β16
β17 β18 β19 β20
β21 β22 β23 β24
β25 β26 β27 β28
β1
*
β29 β30 β31 β32
β9'
420|
N K K F L L Q L S G HT G V L I R S L E E H
K G E V M Y T L V G HN G K C L R T L V G HT G K C L R T L V G HD Y S C S R I L S G HD L Q C V K T L M G HT L E C K R I L T G HT G K L I R R L S G H
ββ5
430 440 450| | |
D - G G V W A L K Y A H - G G I L V S G S T D R T V R V W D I KE - G D V W T F E Y V G - - D T L V T G S T D R T V R V W D L R
T - G G V W T S Q I S Q C G R Y I V S G S T D R T V K V W S T VT - G G V W S S Q M S G - - N I I I S G S T D R T L K V W D M DT - G G V W S S Q M R D - - N I I I S G S T D R T L K V W N A ET - G S V L C L Q Y D N - - R V I I S G S S D A T V R V W D V ET - G S V L C L Q Y D D - - K V I I S G S S D S T V R V W D V NT - G S V L C L Q Y D E - - R V I I T G S S D S T V R V W D V NS - D G V K T L Y F D D - - R K L I T G S L D K T I R V W N Y I
ββ6 ββ7 ββ8
560|
Q M K C L Y I L S G HT G V C L H V L R G HT G R C I R T L T G HR Q E C L H T L Q G HT E T C L H T L Q G HT L E F V R T L A G HT C E F V R T L N G HT C E F V R T L N G HT N S C L K V F R G H
ββ17
0570 580 590 600| | | |
H T - D R I Y S T I Y D H E R K R C I S A S M D T T I R I W D L EH V - G R V Y S V T I N P S R Q Q C I S A G T D A K I R I W N L EH N - N R V Y S L L F E S E R S I V C S G S L D T S I R V W D F 3H T - N R V Y S L Q F D G - - L H V V S G S L D T S I R V W D V EH T - N R V Y S L Q F D G - - I H V V S G S L D T S I R V W D V EH R - R G I A C L Q Y R G - - R L V V S G S S D N T I R L W D I HH K - R G I A C L Q Y R D - - R L V V S G S S D N S I R L W D I EH K - R G I A C L Q Y R D - - R L V V S G S S D N T I R L W D I EH V - G Q V Q K I I P L T I 48 T H L L S C G L D N T I K L W D V K
ββ18 β19 β20
D Y S R K F S Y H -T G S C R D I L K -E G T C V H M L S GT G Q C L Q T L 4 KT G Q C L Q T L 4 KS E I C L C S L V QN T L C L N T L V EG T L C L R T L V ES G K C M H T F 17 G
β25
710|
S G K L V H 2 I L KS G K L V R D L L TR G A L I R D L V TT G D F I R N L V AT G E F I R N L V T
β29
*
WD repeat # 1
WD repeat # 5
WD repeat # 7
WD repeat # 8
WD repeat # 2
WD repeat # 3
WD repeat # 4
WD repeat # 6
Propeller Blade #8/Propeller Blade #1
Propeller Blade #1/Propeller Blade #2
Propeller Blade #2/Propeller Blade #3
Propeller Blade #3/Propeller Blade #4
Propeller Blade #4/Propeller Blade #5
Propeller Blade #5/Propeller Blade #6
Propeller Blade #6/Propeller Blade #7
Propeller Blade #7/Propeller Blade #8
Nature Biotechnology: doi:10.1038/nbt.1646
Vectoronly
Vectoronly
WT
Wt
R655A
R655A
R664A
R664A
5-FOA
Trp- Ura-
a
b
c
-7 -6 -5 -4 -30
25
50
75
100
125
150
175
log [inhibitor] (M)
mP
COOHC OOH
COOHCOOH
OMeOMe
B
B
OH
OH
OH
OH
OHOH
COOMeC OOMe
OO
P OHO
SCF-I2 IC50 = 2.7 ± 0.2 μM
BINOL IC50 = 53 ± 4 μM
SCF-I2 analog 1 IC50 = No detectable binding
SCF-I2 analog 4 IC50 > 1000 μM
SCF-I2 analog 3 IC50 > 350 μM
SCF-I2 analog 2 IC50 > 350 μM
Figure S3. Mutational analysis of residues that interact with SCF-I2. a, Arg655 and Arg644 are not essential for Cdc4 function. A cdc4::HIS3 <CDC4 URA3 CEN> plasmid shuffle strain was transformed with either empty vector or the indicated CDC4 alleles on a <TRP1 CEN> vector and incubated for 3 days on either 5-FOA containing medium to select against the wild type copy of CDC4 or, as a control, on Trp- Ura- medium to select for both wild type and mutant copies of CDC4. b, Activity of an analog series for SCF-I2. IC50 values were determined by standard FP inhibition assay against fluorescein labeled cyclin E peptide. c, FP competition binding curves for SCF-I2 and each analog. Colors are according to scheme in panel b.
Nature Biotechnology: doi:10.1038/nbt.1646
SCF-I2 Binding
Residue Matchesidentical similar
yCDC4 I R I W D L E N G E L M Y T L Q G H T A L V G L L R L - S - - - D K F L V S A A A D G S I R G W D A N D Y S - R K F S 10 0
FBXW7_HUMAN I R V W D V E T G N C I H T L T G H Q S L T S G M E L - K - - - D N I L V S G N A D S T V K I W D I K T G Q - K H Q S 7 2
FBW1B_HUMAN I R L W D I E C G A C L R V L E G H E E L R C I R F - D - - - N K R I V S G A Y D G K I K V W D L Q A A L - C L R T 7 2
FBW1A_HUMAN I R L W D I E C G A C L R V L E G H E E L V R C I R F - D - - - N K R I V S G A Y D G K I K V W D L V A A L - C L R T 7 2
PRP4_HUMAN C K V W D L R Q R R C V Y T I P A H Q N L V T G V K F - E P I H G N F L L T G A Y D N T A K I W T H P G W S - K V M G 6 4
BUB3_HUMAN L K M H D L - N T D Q E N L V G T H D A P I R C V E Y - C P E - V N V M V T G S W D Q T V K L W D P R T P C - K V Y T 4 4
STRN_HUMAN N N K D A L R T WN P K F T L R S H F D G I R A L A F - H P I - E P V L I T A S E D H T L K MW N L Q K T A - K S T S 5 3
TAF5L_HUMAN V R L W S A Q Q G N S V R L F T G H R G P V L S L A F - S P N - G K Y L A S A G E D Q R L K L W D L A S G T - R G H T 4 5
LIS1_HUMAN D P K E W I P R P P E K Y A L S G H R S P V T R V I F - H P V - F S V M V S A S E D A T I K V W D Y E T G D - K G H T 4 4
COPA_HUMAN I R V W N W Q S R T C V C V L T G H N H Y V M C A Q F - H P T - E D L V V S A S L D Q T V R V W D I S G L - - K N L S 6 3
HIRA_HUMAN V V I W N A 2 F P E I L A T L R G H S G L V K G L T W - D P V - G K Y I A S Q A D D R S L K V W R T L D W Q - K P F D 6 3
WDR5_HUMAN K P T P V K P N Y A L K F T L A G H T K A V S S V K F - S P N - G E W L A S S S A D K L I K I W G A Y D G K - K T I S 5 3
TBL3_HUMAN C L K V F E L Q T S A C Q I L H G H T D I V L A L D V - F R K - G W L F A S C A K D Q S V R I W R M N K A G - H T H S 8 0
STRN3_HUMAN N K D A F R K T WN P K Y T L R S H F D G V R A L A F - H P V - E P V L V T A S E D H T L K L W N L Q K T V - K S A S 5 3
TRAF7_HUMAN I K V W D T 2 T Y K C Q K T L E G H D G I V L A L C I - Q - - - G C K L Y S G S A D C T I I V W D I Q N L Q - K V N T 6 3
BRWD3_HUMAN P S S A Y Q H I K M H K R I L - G H L S S V Y C V A F - D R S - G R R I F T G S D D C L V K I W A T D D G R - R G H S 6 2
WDR88_HUMAN V K L W D P V 2 S V V R D F E H R P K A P V V E C S I - T G D - S S R V I A A S Y D K T V R A W D L E T G K - R Y D T 4 3
WDR86_HUMAN V V T L C Y P T Y R R G N R L G G H E S Y V T F C Q L - E - - - D E A A F T C S A D C T I R R W D V L T G Q - R G H T 6 2
WDR5B_HUMAN I I I W G A Y D G K Y E K T L Y G H N L E I S D V A W - S S D - S S R L V S A S D D K T L K L W D V R S G K - K G H S 6 3
CD20B_HUMAN Y H H D V R V A Q H H V G T L R - H K Q A V C A L K W - S P D - G R L L S S G C S D G L L T I W P H D P G A - K V I T 4 3
WDR49_HUMAN V R F W D I Y K K Q L L A E F L A H S G V G S I I M S - T D K M N R Y L T T G D L D G W L K I W N I E E Y C - K A P T 2 6
WDR69_HUMAN C W L W D T A S G E E L N T L E G H R N V V Y A I A F - N N P Y G D K I A T G S F D K T C K L W S V E T G K - R G H T 5 5
AHI1_HUMAN I I L Y E I P S G R F M R E L C G H L N I I Y D L S W - S K D - D H Y I L T S S S D G T A R I W K N E I N N - P H P S 8 1
WD51A_HUMAN L M V W H M K P Q S R A Y R F T G H K D A V T C V N F - S P S - G H L L A S G S R D K T V R I W V P N V K G - R A H T 6 3
WDR48_HUMAN T A L T A S N N T V T T S S L S G N K D S I Y S L A M - N Q L - G T I I V S G S T E K V L R V W D P R T C A - K G H T 4 3
TF3C2_HUMAN L S D G S L K L Y P F Q C F L - A H D Q A V R T L Q W - C K A N S H F L V S A G S D R K I K F W D L R R P Y - R F L S 5 2
PI3R4_HUMAN P P G W R P K - G L L V A H L H E H K S A V N R I R V - S D E - H S L F A T C S N D G T V K I W N S Q K M - - K T T T 4 4
KTNB1_HUMAN I R V W D L E A A K I L R T L M G H K A N I C S L D F - H P Y - G E F V A S G S Q D T N I K L W D I R R K G - R G H S 7 2
WDR6_HUMAN T A L A D N K P V A P D R R I S G H V G I I F S M S Y - L E S - K G L L A T A S E D R S V R I W K V G D L R - V Q N I 6 1
BRWD1_HUMAN P G T M Y Q H I K M H R R I L - G H L S A V Y C V A F - D R T - G H R I F T G S D D C L V K I W S T H N G R - R G H S 6 2
WSB2_HUMAN I K I W E V Q T G L L L L N L S G H Q D V V R D L S F - T P S G S L I L V S A S R D K T L R I W D L N K H G - Q V L S 7 2
WDR3_HUMAN L Q L Y D L A S G N L L E T I D A H D G A L W S M S L - S P D - Q R G F V T G G A D K S V K F W D F E L V K - K R L S 6 3
PLAP_HUMAN - M T S G A T R Y R L S C S L R G H E L D V R G L V C - P - - - P G A F V S V S R D R T T R L W A P D S - - - R S F T 6 2
STRAP_HUMAN M L R Q G D T G D W I G T F L - G H K G A V W G A T L - N K D - A T K A A T A A A D F T A K V W D A V S G D - I V K T 5 2
WSB1_HUMAN I K I W D V Y T G K L L L N L V D H T E V V R D L T F - A P D G S L I L V S A S R D K T L R V W D L K D D G - R G H Q 7 2
Figure S4. Sequence alignment of human WD40 repeat domain proteins that contain a potential SCF-I2 binding pocket. Aligned regions correspond to residues Ile594 to Ser667 of S. cerevisiae Cdc4, which encompasses the 10 residues that line the SCF-I2 binding pocket as illustrated in Figure 2C. The degree of pocket residue conservation is indicated at the right. Dark and light green denote strong or moderate matches respectively of hydrophobic binding pocket positions; dark and light blue denote perfect or close matches of basic binding pocket positions; red denotes a perfect match of an acidic binding pocket position; dark and light yellow denote a perfect or close match of a small side chain position; dark and light orange denote a perfect or close match of a polar small side chain position. For some proteins (colored purple in the first column), conservation of the first position (equivalent to Ile594 in ScCdc4) could not be evaluated because a landmark Trp residue (labeled by underline) of the WD40 repeat motif was not readily identified. These proteins either contain a cryptic WD40 repeat not discernable by sequence alignment or, alternatively, may derive the missing element (i.e., the equivalent to Ile594 in ScCdc4) from the last WD40 repeat in the circularly permuted structure.
Nature Biotechnology: doi:10.1038/nbt.1646
pSic1
50% in
put
DMSOGcn
4 pep
tide
SCF-I1
SCF-I2
SCF-I3
SCF-I4
SCF-I5
SCF-I6
SCF-I7
SCF-I8
SCF-I9
DMSO
Figure S5. Uncropped image of Sic1 ubiquitination assays shown in Figure 1b.
pSic1-(Ub)n
pSic1
Nature Biotechnology: doi:10.1038/nbt.1646
Table S1: Data collection and Refinement Statistics Data collection Space group P32; a=b= 108.3 Å, c= 165.6 Å
α=β=90º, γ=120º
Wavelength (Å) 0.9000 Resolution (Å) 2.6 Rsym (%) 5.8 (43.5) Total Reflections 1 056 243 Unique Reflections 66 846 Completeness (%) 99.8 (100) I/σ 24.3 (3.6) Refinement
Resolution range (Å) 93.66-2.6 Reflections 63268 Rfactor/Rfree (%) 21.1/26.6 RMS deviations Bonds (Å) 0.019 Angles (o) 1.968 Ramachandran Data Most favoured 86.5 % Additionally allowed 12.4 % Generously allowed 1.1 % Disallowed 0.1 %
Nature Biotechnology: doi:10.1038/nbt.1646
Table S2. Proteins that contain WD40 repeat domains in Saccharomyces cerevisiaeGene name ORF name Description Essential ProcessAIP1 YMR092C Actin cortical patch component, interacts with the actin depolymerizing factor cofilin N cytoskeletonAMA1 YGR225W Activator of meiotic anaphase promoting complex (APC/C) ubiquitin ligase N ubiquitin systemARC40 YBR234C Subunit of the ARP2/3 complex, required for cortical actin patches Y cytoskeletonASA1 YPR085C Subunit of the ASTRA chromatin remodeling complex (Rvb1, Rvb2, Tra1, Tti1, Tti2, Asa1) Y chromatin modificationASC1 YMR116C G-protein beta subunit and guanine nucleotide dissociation inhibitor for Gpa2 N signal transductionATG18 YFR021W Phosphoinositide binding protein required for vesicle formation in autophagy and the Cvt pathway N autophagyATG21 YPL100W Phosphoinositide binding protein required for vesicle formation in the Cvt pathway N autophagyBPH1 YCR032W Role in protein sorting, homologous to human Chediak-Higashi syndrome and murine Beige proteins N vesicle traffickingBUB3 YOR026W Kinetochore checkpoint protein, interacts with Mad1-Bub1, Cdc20, Mad2 and Mad3 N signal transductionCAC2 YML102W Component of the chromatin assembly complex, assembles newly synthesized histones onto replicated DNA N chromatin modificationCAF4 YKR036C Associated with the CCR4-NOT complex, interacts with Ssn2, Fis1, Mdv1 and Dnm1 N mRNA regulationCDC20 YGL116W Activator of anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase Y ubiquitin systemCDC4 YFL009W F-box protein required for G1/S and G2/M transition, substrates include Sic1, Far1, Gcn4 and Tec1 Y ubiquitin systemCDC40 YDR364C Pre-mRNA splicing factor, important for catalytic step II of pre-mRNA splicing N mRNA regulationCDC55 YGL190C Non-essential regulatory subunit B of protein phosphatase 2A N signal transductionCDH1 YGL003C Activator of anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase N ubiquitin systemCIA1 YDR267C Involved in assembly of cytosolic and nuclear iron-sulfur proteins Y complex assemblyCMR1 YDL156W Implicated in genome stability N unknownCOP1 YDL145C Subunit of COPI vesicle coatomer complex, transport of vesicles in the early secretory pathway Y vesicle traffickingCRN1 YLR429W Coronin, cortical actin cytoskeletal component that associates with the Arp2p/Arp3p complex N cytoskeletonCTF4 YPR135W Chromatin-associated protein, interacts with Pol1, and may link DNA synthesis to sister chromatid cohesion N DNA replication/repairDGR2 YKL121W Unknown function, deletion causes resistance to 2-deoxy-D-glucose and abnormally elongated buds N unknownDIP2 YLR129W Subunit of small subunit (SSU) processome, required for 18S rRNA biogenesis Y ribosome biogenesisDOA1 YKL213C Interacts with Cdc48, controls cellular ubiquitin concentration N ubiquitin systemDSE1 YER124C Daughter cell-specific protein, regulates cross-talk between the mating and filamentation pathways N unknownDUF1 YOL087C Unknown function, deletion causes sensitivity to phenanthroline, sanguinarine and nordihydroguaiaretic acid N unknownDUG2 YBR281C Peptidase subunit, associates with Dug1 and Dug3 to degrade glutathione N complex assemblyELP2 YGR200C Elongator subunit, histone acetyltransferase, required for modification of wobble nucleosides in tRNA N chromatin modificationENP2 YGR145W Subunit of 90S preribosome, interacts with Mpp10 and Bfr2 Y ribosome biogenesisERB1 YMR049C Subunit of 66S pre-ribosomal particle, interacts with Nop7 and Ytm1, maturation of 25S and 5.8S rRNA Y ribosome biogenesisGID7 YCL039W Unknown function, involved in proteasome-dependent catabolite inactivation of fructose-1,6-bisphosphatase N ubiquitin systemGLE2 YER107C Subunit of Nup82 subcomplex of the nuclear pore complex, required for polyadenylated RNA export N complex assemblyHAT2 YEL056W Subunit of Hat1-Hat2 histone acetyltransferase complex, required for binding to free histone H4 N chromatin modificationHIR1 YBL008W Subunit of HIR nucleosome assembly complex, regulation of histone gene transcription N chromatin modificationHIR2 YOR038C Subunit of HIR nucleosome assembly complex in histone gene transcription and heterochromatic gene silencing N chromatin modificationHSV2 YGR223C Phosphatidylinositol 3,5-bisphosphate-binding protein, role in micronucleophagy N autophagyIPI3 YNL182C Subunit of Rix1 complex (Rix1p, Ipi1p, Ipi3p), required for processing of ITS2 sequences from 35S pre-rRNA Y ribosome biogenesisJIP5 YPR169W Interacts with proteins involved in RNA processing, ribosome biogenesis, ubiquitination and demethylation Y unknownKOG1 YHR186C Subunit of TORC1 kinase complex, interacts with Tor1/2, Lst8 and Tco89, ortholog of mammalian Raptor Y signal transductionLST8 YNL006W Subunit of TORC1 and TORC2 complexes, interacts with Tor1/2, Kog1, Tco89 and Tor2, Avo1, Avo2, Tsc11, Bit61 Y signal transductionMAK11 YKL021C Involved in 60S ribosomal subunit biogenesis Y ribosome biogenesisMDV1 YJL112W Required for mitochondrial fission, interacts with Fis1 and Dnm1 Y organelle biogenesisMET30 YIL046W F-box protein that regulates Met4 transcription factor to control sulfur metabolism gene expression N ubiquitin systemMSI1 YBR195C Subunit of chromatin assembly factor I (CAF-1), similar to to human Rb binding proteins RbAp48 and RbAp46 N chromatin modificationMTC5 YDR128W Unknown function, deletion is synthetically sick with cdc13-1 N unknownNAN1 YPL126W Subunit of small subunit (SSU) processome, required for 18S rRNA biogenesis, U3 snoRNP protein Y ribosome biogenesisPAC1 YOR269W Involved in nuclear migration and dynein/dynactin pathway, targets dynein to microtubules N cytoskeletonPAC11 YDR488C Dynein intermediate chain, acts in the dynein pathway with Num1; deletion defective in nuclear migration N cytoskeletonPAN2 YGL094C Subunit of the Pan2-Pan3 poly(A)-ribonuclease complex, controls poly(A) tail length and postreplication repair N mRNA regulationPEP5 YMR231W Subunit of CORVET complex required for vacuole biogenesis N vesicle traffickingPEX7 YDR142C Peroxisomal receptor for peroxisomal matrix proteins; defects in human homolog cause lethal RCDP disease N organelle biogenesisPFS2 YNL317W Pre-mRNA cleavage and polyadenylation factor, essential for mRNA 3'-end formation Y mRNA regulationPRP4 YPR178W Spliceosome factor, component of the U4/U6-U5 snRNP complex Y mRNA regulationPRP46 YPL151C Spliceosome NTC complex subunit, stabilizes U6 snRNA in catalytic forms of the spliceosome Y mRNA regulationPTR3 YFR029W Component of the SPS plasma membrane amino acid sensor system, regulates amino acid permease genes Y signal transductionPWP1 YLR196W rRNA processing factor Y ribosome biogenesisPWP2 YCR057C 90S pre-ribosomal subunit, endonucleolytic cleavage of the 35 S rRNA precursor at A0, A1, and A2 sites Y ribosome biogenesisRAD28 YDR030C Involved in DNA repair, related to the human CSA protein implicated in transcription-coupled NER N DNA replication/repairRAV1 YJR033C RAVE complex subunit, interacts with Rav1, Rav2, Skp1, promotes assembly of the V-ATPase N complex assemblyRPN14 YGL004C Subunit of base subcomplex of the 19S proteasome regulatory particle, interacts with Rpt5 N ubiquitin systemRRB1 YMR131C Ribosome biogenesis factor, interacts with the ribosomal protein Rpl3 Y ribosome biogenesisRRP9 YPR137W Subunit of small subunit (SSU) processome, required for 18S rRNA biogenesis, U3 snoRNP protein Y ribosome biogenesisRRT13 YER066W Unknown function, deletion has decreased levels of rDNA transcription N ribosome biogenesisRRT2 YBR246W Unknown function, deletion has increased levels of rDNA transcription N ribosome biogenesisRSA4 YCR072C Ribosome biogenesis factor, required for intra-nuclear transport of pre-60S ribosomal subunits Y ribosome biogenesisRTC1 YOL138C Unknown function; may interact with ribosomes, null mutation suppresses cdc13-1 temperature sensitivity N ribosome biogenesis
Nature Biotechnology: doi:10.1038/nbt.1646
RTT10 YPL183C Regulator of Ty1 transposition N DNA replication/repairSEC12 YNR026C Guanine nucleotide exchange factor (GEF), vesicle budding from ER, activator of the GTPase Sar1 Y vesicle traffickingSEC13 YLR208W Subunit of Nup84 nuclear pore sub-complex and COPII complex in ER to Golgi vesicle transport Y vesicle traffickingSEC27 YGL137W Subunit of COPI coatomer, involved in ER-to-Golgi and Golgi-to-ER transport Y vesicle traffickingSEC31 YDL195W Subunit of COPII complex in ER to Golgi vesicle transport Y vesicle traffickingSED4 YCR067C ER membrane protein, positive regulator of Sar1, participates in vesicle formation, similar to Sec12 N vesicle traffickingSEH1 YGL100W Subunit of Nup84 nuclear pore sub-complex N complex assemblySIF2 YBR103W Subunit of the Set3C histone deacetylase complex N chromatin modificationSKI8 YGL213C Subunit of Ski complex, mediates 3'-5' RNA degradation by the cytoplasmic exosome N mRNA regulationSOF1 YLL011W Required for biogenesis of 40S (small) ribosomal subunit Y ribosome biogenesisSPT8 YLR055C Subunit of SAGA histone acetyltransferase complex N chromatin modificationSQT1 YIR012W Required for biogenesis of 60S ribosomal subunit Y ribosome biogenesisSRO7 YPR032W Subunit of CORVET complex required for trafficking of CPY sorting receptor, contains RING finger motif N vesicle traffickingSRO77 YBL106C Docking and fusion of post-Golgi vesicles with plasma membrane, homolog of Drosophila lgl tumor suppressor N vesicle traffickingSTE4 YOR212W G protein beta subunit of pheromone GPCR, forms a heterotrimer with Gpa1 and Ste18 in pheromone signaling N signal transductionSWD1 YAR003W Subunit of COMPASS (Set1C) complex, methylates histone H3 on lysine 4 N chromatin modificationSWD2 YKL018W Subunit of COMPASS (Set1C) complex, methylates histone H3 on lysine 4 Y chromatin modificationSWD3 YBR175W Subunit of COMPASS (Set1C) complex, methylates histone H3 on lysine 4 N chromatin modificationSWT21 YNL187W Involved in mRNA splicing, interacts genetically with Prp40 and Tgs1 N mRNA regulationTAF5 YBR198C Subunit of TFIID and SAGA complexes, RNA polymerase II transcription initiation and chromatin modification Y transcriptionTEX1 YNL253W Subunit of transcription mRNA export (TREX) complex N mRNA regulationTFC6 YDR362C Subunit of RNA polymerase III transcription initiation factor complex (TFIIIC) Y transcriptionTIF34 YMR146C Subunit of translation initiation factor 3 (eIF3) complex Y protein synthesisTRM82 YDR165W Subunit of tRNA methyltransferase complex, catalyzes 7-methylguanosine modification of tRNA N protein synthesisTUP1 YCR084C Repressor of transcription, interacts with Cyc8/Ssn6 N chromatin modificationUFO1 YML088W F-box protein that targets phosphorylated Ho endonuclease for degradation N ubiquitin systemUME1 YPL139C Repression of meiotic genes during vegetative growth, interacts with histone deacetylase Rpd3 N transcriptionUTP13 YLR222C Subunit of small subunit (SSU) processome, required for 18S rRNA biogenesis, U3 snoRNP protein Y ribosome biogenesisUTP15 YMR093W Subunit of small subunit (SSU) processome, required for 18S rRNA biogenesis, U3 snoRNP protein Y ribosome biogenesisUTP18 YJL069C Involved in maturation of pre-18S rRNA, U3 snoRNP protein Y ribosome biogenesisUTP21 YLR409C Subunit of 90S preribosome and small subunit (SSU) processome, required for 18S rRNA biogenesis Y ribosome biogenesisUTP4 YDR324C Subunit of 90S preribosome and small subunit (SSU) processome, required for 18S rRNA biogenesis Y ribosome biogenesisUTP5 YDR398W Subunit of small subunit (SSU) processome, required for 18S rRNA biogenesis Y ribosome biogenesisUTP7 YER082C Subunit of small subunit (SSU) processome, required for 18S rRNA biogenesis, U3 snoRNP protein Y ribosome biogenesisUTP9 YHR196W Subunit of small subunit (SSU) processome, required for 18S rRNA biogenesis, U3 snoRNP protein Y ribosome biogenesisVID27 YNL212W Unknown function, possibly involved in vacuolar protein degradation N vesicle traffickingVPS15 YBR097W Protein kinase involved in vacuolar protein sorting, recruits Vps34 to Golgi N vesicle traffickingVPS41 YDR080W Subunit of homotypic vacuole fusion and vacuole protein sorting (HOPS) complex N vesicle traffickingVPS8 YAL002W Subunit of CORVET complex required for trafficking of CPY sorting receptor, contains RING finger motif N vesicle traffickingWTM1 YOR230W Transcriptional modulator involved in regulation of meiosis, silencing, and expression of RNR genes N transcriptionWTM2 YOR229W Transcriptional modulator involved in regulation of meiosis, silencing, and expression of RNR genes N transcriptionYBL104c YBL104c Unknown function N unknownYGR054W YGR054W Eukaryotic initiation factor (eIF) 2A, associates with 40S subunits and 80 S ribosomes N protein synthesisYLR149C YLR149C Unknown function, overexpression causes cell cycle delay, deletion decreases PM electron transport N unknownYMR102C YMR102C Unknown function, deletion causes increased resistance to azoles N unknownYNL035C YNL035C Unknown function, localizes to the nucleus N unknownYPL247C YPL247C Unknown function, overexpression causes a cell cycle delay or arrest N unknownYTM1 YOR272W Subunit of 66S pre-ribosomal particles, required for maturation of the large ribosomal subunit Y ribosome biogenesis
Nature Biotechnology: doi:10.1038/nbt.1646
Tabl
e S3
. Pro
tein
s th
at c
onta
in W
D40
repe
at d
omai
ns in
Hom
o sa
pien
sG
ene
nam
e(s)
Acc
essi
onEn
try
nam
ePr
otei
n de
scrip
tion
AA
AS
(AD
RA
CA
LA, G
L003
)Q
9NR
G9
AA
AS
_HU
MA
NA
ladi
n (A
drac
alin
)A
AM
PQ
1368
5A
AM
P_H
UM
AN
Ang
io-a
ssoc
iate
d m
igra
tory
cel
l pro
tein
AH
I1Q
8N15
7A
HI1
_HU
MA
NJo
uber
in (A
bels
on h
elpe
r int
egra
tion
site
1 p
rote
in h
omol
og, A
HI-1
)A
MB
RA
1 (K
IAA
1736
)Q
9C0C
7A
MR
A1_
HU
MA
NA
ctiv
atin
g m
olec
ule
in B
EC
N1-
regu
late
d au
toph
agy
prot
ein
1A
PA
F1 (K
IAA
0413
)O
1472
7A
PA
F_H
UM
AN
Apo
ptot
ic p
rote
ase-
activ
atin
g fa
ctor
1 (A
paf-1
)A
RP
C1A
(SO
P2L
)Q
9274
7A
RC
1A_H
UM
AN
Act
in-r
elat
ed p
rote
in 2
/3 c
ompl
ex s
ubun
it 1A
(SO
P2-
like
prot
ein)
AR
PC
1B (A
RC
41)
O15
143
AR
C1B
_HU
MA
NA
ctin
-rel
ated
pro
tein
2/3
com
plex
sub
unit
1B (A
rp2/
3 co
mpl
ex 4
1 kD
a su
buni
t, p4
1-A
RC
)A
TG16
L1 (A
PG
16L,
UN
Q93
93/P
RO
3430
7)Q
676U
5A
16L1
_HU
MA
NA
utop
hagy
-rel
ated
pro
tein
16-
1 (A
PG
16-li
ke 1
)A
TG16
L2 (W
DR
80)
Q8N
AA
4A
16L2
_HU
MA
NA
utop
hagy
-rel
ated
pro
tein
16-
2 (A
PG
16-li
ke 2
, WD
repe
at-c
onta
inin
g pr
otei
n 80
)B
CA
S3
Q9H
6U6
BC
AS
3_H
UM
AN
Bre
ast c
arci
nom
a-am
plifi
ed s
eque
nce
3 (M
aab1
pro
tein
, GA
OB
1)B
OP
1 (K
IAA
0124
)Q
1413
7B
OP
1_H
UM
AN
Rib
osom
e bi
ogen
esis
pro
tein
BO
P1
(Blo
ck o
f pro
lifer
atio
n 1
prot
ein)
BR
WD
1 (C
21or
f107
, WD
R9)
Q9N
SI6
BR
WD
1_H
UM
AN
Bro
mod
omai
n an
d W
D re
peat
-con
tain
ing
prot
ein
1 (W
D re
peat
-con
tain
ing
prot
ein
9)B
RW
D2
(KIA
A13
51, W
DR
11, W
DR
15)
Q9B
ZH6
BR
WD
2_H
UM
AN
Bro
mod
omai
n an
d W
D re
peat
-con
tain
ing
prot
ein
2 (W
D re
peat
-con
tain
ing
prot
ein
11, W
D re
peat
-con
tain
ing
prot
ein
15)
BR
WD
3Q
6RI4
5B
RW
D3_
HU
MA
NB
rom
odom
ain
and
WD
repe
at-c
onta
inin
g pr
otei
n 3
BTR
C (B
TRC
P, F
BW
1A, F
BX
W1A
)Q
9Y29
7FB
W1A
_HU
MA
NF-
box/
WD
repe
at-c
onta
inin
g pr
otei
n 1A
(bet
a-Tr
CP
, E3R
SIk
appa
B, p
Ikap
paB
alph
a-E
3 re
cept
or s
ubun
it)B
UB
3O
4368
4B
UB
3_H
UM
AN
Mito
tic c
heck
poin
t pro
tein
BU
B3
CD
C20
Q12
834
CD
C20
_HU
MA
NC
ell d
ivis
ion
cycl
e pr
otei
n 20
hom
olog
(p55
CD
C)
CD
C20
B (G
6VTS
7651
9)Q
86Y
33C
D20
B_H
UM
AN
Cel
l div
isio
n cy
cle
prot
ein
20 h
omol
og B
CD
C40
(EH
B3,
PR
P17
, PR
PF1
7)O
6050
8P
RP
17_H
UM
AN
Pre
-mR
NA
-pro
cess
ing
fact
or 1
7 (h
PR
P17
, Cel
l div
isio
n cy
cle
40 h
omol
og, E
H-b
indi
ng p
rote
in 3
, Ehb
3)C
DR
T1 (C
17or
f1, C
17or
f1A
, HR
EP
)O
9517
0C
DR
T1_H
UM
AN
CM
T1A
dup
licat
ed re
gion
tran
scrip
t 1 p
rote
inC
HA
F1B
(CA
F1A
, CA
F1P
60, M
PH
OS
PH
7, M
PP
7)Q
1311
2C
AF1
B_H
UM
AN
Chr
omat
in a
ssem
bly
fact
or 1
sub
unit
B (C
AF-
1 su
buni
t B, C
hrom
atin
ass
embl
y fa
ctor
I p6
0 su
buni
t,CA
F-Ip
60, M
-pha
se p
hosp
hopr
otei
n 7)
CIA
O1
(WD
R39
)O
7607
1C
IAO
1_H
UM
AN
Pro
babl
e cy
toso
lic ir
on-s
ulfu
r pro
tein
ass
embl
y pr
otei
n C
IAO
1 (W
D re
peat
-con
tain
ing
prot
ein
39)
CIR
H1A
(KIA
A19
88)
Q96
9X6
CIR
1A_H
UM
AN
Cirh
inC
OP
AP
5362
1C
OP
A_H
UM
AN
Coa
tom
er s
ubun
it al
pha
(Alp
ha-c
oat p
rote
in, A
lpha
-CO
P, H
EP
-CO
P, H
EP
CO
P)
CO
PB
2P
3560
6C
OP
B2_
HU
MA
NC
oato
mer
sub
unit
beta
' (B
eta'
-coa
t pro
tein
, Bet
a'-C
OP
, p10
2)C
OR
O1A
(CO
RO
1)P
3114
6C
OR
1A_H
UM
AN
Cor
onin
-1A
(Cor
onin
-like
pro
tein
p57
, Clip
in-A
, Try
ptop
han
aspa
rtate
-con
tain
ing
coat
pro
tein
, TA
CO
)C
OR
O1B
Q9B
R76
CO
R1B
_HU
MA
NC
oron
in-1
B (C
oron
in-2
)C
OR
O1C
(CR
NN
4)Q
9ULV
4C
OR
1C_H
UM
AN
Cor
onin
-1C
(Cor
onin
-3, h
CR
NN
4)C
OR
O2A
(IR
10, W
DR
2)Q
9282
8C
OR
2A_H
UM
AN
Cor
onin
-2A
(WD
repe
at-c
onta
inin
g pr
otei
n 2,
IR10
)C
OR
O2B
(KIA
A09
25)
Q9U
Q03
CO
R2B
_HU
MA
NC
oron
in-2
B (C
oron
in-li
ke p
rote
in C
, Clip
in-C
, Pro
tein
FC
96)
CO
RO
6 (P
P10
09, P
P17
82, P
P18
81)
Q6Q
EF8
CO
RO
6_H
UM
AN
Cor
onin
-6C
OR
O7
P57
737
CO
RO
7_H
UM
AN
Cor
onin
-7 (C
rn7,
70
kDa
WD
repe
at tu
mor
reje
ctio
n an
tigen
hom
olog
)C
STF
1Q
0504
8C
STF
1_H
UM
AN
Cle
avag
e st
imul
atio
n fa
ctor
50
kDa
subu
nit (
CS
TF 5
0 kD
a su
buni
t, C
F-1
50 k
Da
subu
nit,
Cst
F-50
)D
DB
2Q
9246
6D
DB
2_H
UM
AN
DN
A d
amag
e-bi
ndin
g pr
otei
n 2
(DD
B p
48 s
ubun
it, D
DB
b, U
V-d
amag
ed D
NA
-bin
ding
pro
tein
2, U
V-D
DB
2)
DE
NN
D3
(KIA
A08
70)
A2R
US
2D
EN
D3_
HU
MA
ND
EN
N d
omai
n-co
ntai
ning
pro
tein
3D
MW
D (D
M9)
Q09
019
DM
WD
_HU
MA
ND
ystro
phia
myo
toni
ca W
D re
peat
-con
tain
ing
prot
ein
(DM
R-N
9 pr
otei
n, P
rote
in 5
9)D
MX
L1 (X
L1)
Q9Y
485
DM
XL1
_HU
MA
ND
mX
-like
pro
tein
1 (X
-like
1 p
rote
in)
DM
XL2
(KIA
A08
56)
Q8T
DJ6
DM
XL2
_HU
MA
ND
mX
-like
pro
tein
2 (R
abco
nnec
tin-3
)D
NA
I1Q
9UI4
6D
NA
I1_H
UM
AN
Dyn
ein
inte
rmed
iate
cha
in 1
, axo
nem
al (A
xone
mal
dyn
ein
inte
rmed
iate
cha
in 1
)D
NA
I2Q
9GZS
0D
NA
I2_H
UM
AN
Dyn
ein
inte
rmed
iate
cha
in 2
, axo
nem
al (A
xone
mal
dyn
ein
inte
rmed
iate
cha
in 2
)D
TL (C
DT2
, CD
W1,
DC
AF2
, L2D
TL, R
AM
P)
Q9N
ZJ0
DTL
_HU
MA
ND
entic
lele
ss p
rote
in h
omol
og (D
db1-
and
Cul
4-as
soci
ated
fact
or 2
, Ret
inoi
c ac
id-r
egul
ated
nuc
lear
mat
rix-a
ssoc
iate
d pr
otei
n)D
YN
C1I
1 (D
NC
I1, D
NC
IC1)
O14
576
DC
1I1_
HU
MA
NC
ytop
lasm
ic d
ynei
n 1
inte
rmed
iate
cha
in 1
(Dyn
ein
inte
rmed
iate
cha
in 1
, cyt
osol
ic, D
H IC
-1)
DY
NC
1I2
(DN
CI2
, DN
CIC
2)Q
1340
9D
C1I
2_H
UM
AN
Cyt
opla
smic
dyn
ein
1 in
term
edia
te c
hain
2 (D
ynei
n in
term
edia
te c
hain
2, c
ytos
olic
, DH
IC-2
)E
ED
O75
530
EE
D_H
UM
AN
Pol
ycom
b pr
otei
n E
ED
(hE
ED
, WD
pro
tein
ass
ocia
ting
with
inte
grin
cyt
opla
smic
tails
1, W
AIT
-1)
EIF
3I (E
IF3S
2, T
RIP
1)Q
1334
7E
IF3I
_HU
MA
NE
ukar
yotic
tran
slat
ion
initi
atio
n fa
ctor
3 s
ubun
it I (
eIF3
i, eI
F3 p
36, T
GF-
beta
rece
ptor
-inte
ract
ing
prot
ein
1, T
RIP
-1)
ELP
2 (S
TATI
P1)
Q6I
A86
ELP
2_H
UM
AN
Elo
ngat
or c
ompl
ex p
rote
in 2
(ELP
2, S
TAT3
-inte
ract
ing
prot
ein,
StIP
1, S
HIN
C-2
)E
ML1
(EM
AP
1, E
MA
PL,
EM
AP
L1)
O00
423
EM
AL1
_HU
MA
NE
chin
oder
m m
icro
tubu
le-a
ssoc
iate
d pr
otei
n-lik
e 1
(EM
AP
-1, H
uEM
AP
-1)
EM
L2 (E
MA
P2,
EM
AP
L2)
O95
834
EM
AL2
_HU
MA
NE
chin
oder
m m
icro
tubu
le-a
ssoc
iate
d pr
otei
n-lik
e 2
(EM
AP
-2, H
uEM
AP
-2)
EM
L3Q
32P
44E
MA
L3_H
UM
AN
Ech
inod
erm
mic
rotu
bule
-ass
ocia
ted
prot
ein-
like
3 (E
MA
P-3
)E
ML4
(C2o
rf2, E
MA
PL4
)Q
9HC
35E
MA
L4_H
UM
AN
Ech
inod
erm
mic
rotu
bule
-ass
ocia
ted
prot
ein-
like
4 (E
MA
P-4
, Res
trict
edly
ove
rexp
ress
ed p
rolif
erat
ion-
asso
ciat
ed p
rote
in, R
opp
120)
EM
L5Q
05B
V3
EM
AL5
_HU
MA
NE
chin
oder
m m
icro
tubu
le-a
ssoc
iate
d pr
otei
n-lik
e 5
(EM
AP
-5)
EM
L6 (E
ML5
L)Q
6ZM
W3
EM
AL6
_HU
MA
NE
chin
oder
m m
icro
tubu
le-a
ssoc
iate
d pr
otei
n-lik
e 6
(Ech
inod
erm
mic
rotu
bule
-ass
ocia
ted
prot
ein-
like
5-lik
e)
Nature Biotechnology: doi:10.1038/nbt.1646
ER
CC
8 (C
KN
1, C
SA
)Q
1321
6E
RC
C8_
HU
MA
ND
NA
exc
isio
n re
pair
prot
ein
ER
CC
-8 (C
ocka
yne
synd
rom
e W
D re
peat
pro
tein
CS
A)
FBX
W10
Q5X
X13
FBW
10_H
UM
AN
F-bo
x/W
D re
peat
-con
tain
ing
prot
ein
10FB
XW
11 (B
TRC
P2,
FB
W1B
, FB
XW
1B, K
IAA
0696
)Q
9UK
B1
FBW
1B_H
UM
AN
F-bo
x/W
D re
peat
-con
tain
ing
prot
ein
11 (F
-box
/WD
repe
at-c
onta
inin
g pr
otei
n 1B
, bet
a-Tr
CP
2, H
omol
ogou
s to
Slim
b pr
otei
n, H
OS
)FB
XW
2 (F
BW
2, F
WD
2)Q
9UK
T8FB
XW
2_H
UM
AN
F-bo
x/W
D re
peat
-con
tain
ing
prot
ein
2 (F
-box
and
WD
-40
dom
ain-
cont
aini
ng p
rote
in 2
, Pro
tein
MD
6)FB
XW
4 (F
BW
4, S
HFM
3)P
5777
5FB
XW
4_H
UM
AN
F-bo
x/W
D re
peat
-con
tain
ing
prot
ein
4 (F
-box
and
WD
-40
dom
ain-
cont
aini
ng p
rote
in 4
, Dac
tylin
)FB
XW
5 (F
BW
5, P
P39
71)
Q96
9U6
FBX
W5_
HU
MA
NF-
box/
WD
repe
at-c
onta
inin
g pr
otei
n 5
FBX
W7
(FB
W7,
FB
X30
, SE
L10)
Q96
9H0
FBX
W7_
HU
MA
NF-
box/
WD
repe
at-c
onta
inin
g pr
otei
n 7
(F-b
ox p
rote
in F
BX
30, h
Cdc
4, A
rchi
pela
go h
omol
og, h
Ago
, SE
L-10
)FB
XW
8 (F
BW
6, F
BW
8, F
BX
29, F
BX
O29
, FB
XW
6)Q
8N3Y
1FB
XW
8_H
UM
AN
F-bo
x/W
D re
peat
-con
tain
ing
prot
ein
8 (F
-box
onl
y pr
otei
n 29
)FB
XW
9 (F
BW
9)Q
5XU
X1
FBX
W9_
HU
MA
NF-
box/
WD
repe
at-c
onta
inin
g pr
otei
n 9
(F-b
ox a
nd W
D-4
0 do
mai
n-co
ntai
ning
pro
tein
9)
FZR
1 (C
DH
1, F
YR
, FZR
, KIA
A12
42)
Q9U
M11
FZR
_HU
MA
NFi
zzy-
rela
ted
prot
ein
hom
olog
(Fzr
, Cdh
1/H
ct1
hom
olog
, hC
DH
1, C
DC
20-li
ke p
rote
in 1
)G
EM
IN5
Q8T
EQ
6G
EM
I5_H
UM
AN
Gem
-ass
ocia
ted
prot
ein
5 (G
emin
5)G
ene
nam
e(s)
Acc
essi
onE
ntry
nam
eP
rote
in d
escr
iptio
nG
NB
1P
6287
3G
BB
1_H
UM
AN
Gua
nine
nuc
leot
ide-
bind
ing
prot
ein
G(I)
/G(S
)/G(T
) sub
unit
beta
-1 (T
rans
duci
n be
ta c
hain
1)
GN
B1L
(GY
2, K
IAA
1645
, WD
R14
, FK
SG
1)Q
9BY
B4
GN
B1L
_HU
MA
NG
uani
ne n
ucle
otid
e-bi
ndin
g pr
otei
n su
buni
t bet
a-lik
e pr
otei
n 1
(Pro
tein
WD
VC
F, W
D re
peat
-con
tain
ing
prot
ein
14, D
GC
RK
3)G
NB
2P
6287
9G
BB
2_H
UM
AN
Gua
nine
nuc
leot
ide-
bind
ing
prot
ein
G(I)
/G(S
)/G(T
) sub
unit
beta
-2 (T
rans
duci
n be
ta c
hain
2, G
pro
tein
sub
unit
beta
-2)
GN
B2L
1 (H
LC7,
PIG
21)
P63
244
GB
LP_H
UM
AN
Gua
nine
nuc
leot
ide-
bind
ing
prot
ein
subu
nit b
eta-
2-lik
e 1
(RA
CK
1, C
ell p
rolif
erat
ion-
indu
cing
gen
e 21
pro
tein
, HLC
-7)
GN
B3
P16
520
GB
B3_
HU
MA
NG
uani
ne n
ucle
otid
e-bi
ndin
g pr
otei
n G
(I)/G
(S)/G
(T) s
ubun
it be
ta-3
(Tra
nsdu
cin
beta
cha
in 3
)G
NB
4Q
9HA
V0
GB
B4_
HU
MA
NG
uani
ne n
ucle
otid
e-bi
ndin
g pr
otei
n su
buni
t bet
a-4
(Tra
nsdu
cin
beta
cha
in 4
)G
NB
5O
1477
5G
BB
5_H
UM
AN
Gua
nine
nuc
leot
ide-
bind
ing
prot
ein
subu
nit b
eta-
5 (T
rans
duci
n be
ta c
hain
5, G
beta
5)G
RW
D1
(GR
WD
, KIA
A19
42, W
DR
28)
Q9B
Q67
GR
WD
1_H
UM
AN
Glu
tam
ate-
rich
WD
repe
at-c
onta
inin
g pr
otei
n 1
GTF
3C2
(KIA
A00
11)
Q8W
UA
4TF
3C2_
HU
MA
NG
ener
al tr
ansc
riptio
n fa
ctor
3C
pol
ypep
tide
2 (T
rans
crip
tion
fact
or II
IC s
ubun
it be
ta, T
F3C
-bet
a, T
FIIIC
110)
HE
RC
1Q
1575
1H
ER
C1_
HU
MA
NP
roba
ble
E3
ubiq
uitin
-pro
tein
liga
se H
ER
C1
(HE
CT
dom
ain
and
RC
C1-
like
dom
ain-
cont
aini
ng p
rote
in 1
, p53
2, p
619)
HIR
A (D
GC
R1,
HIR
, TU
PLE
1)P
5419
8H
IRA
_HU
MA
NP
rote
in H
IRA
(TU
P1-
like
enha
ncer
of s
plit
prot
ein
1)IF
T122
(SP
G, W
DR
10, W
DR
140)
Q9H
BG
6IF
122_
HU
MA
NIn
trafla
gella
r tra
nspo
rt pr
otei
n 12
2 ho
mol
og (W
D re
peat
-con
tain
ing
prot
ein
10)
IFT1
40 (K
IAA
0590
, WD
TC2)
Q96
RY
7IF
140_
HU
MA
NIn
trafla
gella
r tra
nspo
rt pr
otei
n 14
0 ho
mol
og (W
D a
nd te
tratri
cope
ptid
e re
peat
s pr
otei
n 2)
IFT1
72 (K
IAA
1179
)Q
9UG
01IF
172_
HU
MA
NIn
trafla
gella
r tra
nspo
rt pr
otei
n 17
2 ho
mol
ogIF
T80
(KIA
A13
74, W
DR
56)
Q9P
2H3
IFT8
0_H
UM
AN
Intra
flage
llar t
rans
port
prot
ein
80 h
omol
og (W
D re
peat
-con
tain
ing
prot
ein
56)
IQW
D1
(MS
TP05
5)Q
58W
W2
IQW
D1_
HU
MA
NN
ucle
ar re
cept
or in
tera
ctio
n pr
otei
n (N
RIP
, IQ
mot
if an
d W
D re
peat
-con
tain
ing
prot
ein
1, A
ndro
gen
rece
ptor
com
plex
-ass
ocia
ted
prot
ein)
KA
TNB
1Q
9BV
A0
KTN
B1_
HU
MA
NK
atan
in p
80 W
D40
-con
tain
ing
subu
nit B
1 (K
atan
in p
80 s
ubun
it B
1, p
80 k
atan
in)
KIA
A18
75A
6NE
52K
1875
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
KIA
A18
75K
IF21
A (K
IAA
1708
, KIF
2)Q
7Z4S
6K
I21A
_HU
MA
NK
ines
in-li
ke p
rote
in K
IF21
A (K
ines
in-li
ke p
rote
in K
IF2,
Ren
al c
arci
nom
a an
tigen
NY
-RE
N-6
2)K
IF21
B (K
IAA
0449
)O
7503
7K
I21B
_HU
MA
NK
ines
in-li
ke p
rote
in K
IF21
BLL
GL1
(DLG
4, H
UG
L, H
UG
L1)
Q15
334
L2G
L1_H
UM
AN
Leth
al(2
) gia
nt la
rvae
pro
tein
hom
olog
1 (L
LGL,
Hum
an h
omol
og to
the
D-lg
l gen
e pr
otei
n, H
ugl-1
, DLG
4)LL
GL2
Q6P
1M3
L2G
L2_H
UM
AN
Leth
al(2
) gia
nt la
rvae
pro
tein
hom
olog
2 (H
GL)
LRB
A (B
GL,
CD
C4L
, LB
A)
P50
851
LRB
A_H
UM
AN
Lipo
poly
sacc
harid
e-re
spon
sive
and
bei
ge-li
ke a
ncho
r pro
tein
(CD
C4-
like
prot
ein,
Bei
ge-li
ke p
rote
in)
LRW
D1
Q9U
FC0
LRW
D1_
HU
MA
NLe
ucin
e-ric
h re
peat
and
WD
repe
at-c
onta
inin
g pr
otei
n 1
LYS
T (C
HS
, CH
S1)
Q99
698
LYS
T_H
UM
AN
Lyso
som
al-tr
affic
king
regu
lato
r (B
eige
hom
olog
)M
AP
KB
P1
(JN
KB
P1,
KIA
A05
96)
O60
336
MA
BP
1_H
UM
AN
Mito
gen-
activ
ated
pro
tein
kin
ase-
bind
ing
prot
ein
1 (J
NK
-bin
ding
pro
tein
1, J
NK
BP
1)M
ED
16 (D
RIP
92, T
HR
AP
5)Q
9Y2X
0M
ED
16_H
UM
AN
Med
iato
r of R
NA
pol
ymer
ase
II tra
nscr
iptio
n su
buni
t 16
(Tra
p95,
Vita
min
D3
rece
ptor
-inte
ract
ing
prot
ein
com
plex
com
pone
nt D
RIP
92)
MLS
T8 (G
BL,
LS
T8)
Q9B
VC
4LS
T8_H
UM
AN
Targ
et o
f rap
amyc
in c
ompl
ex s
ubun
it LS
T8 (T
OR
C s
ubun
it LS
T8, M
amm
alia
n le
thal
with
SE
C13
pro
tein
8, m
LST8
, Pro
tein
Gbe
taL,
Gab
le)
MO
RG
1Q
9BR
X9
MO
RG
1_H
UM
AN
Mito
gen-
activ
ated
pro
tein
kin
ase
orga
nize
r 1 (M
AP
K o
rgan
izer
1)
NB
EA
(BC
L8B
, KIA
A15
44,L
YS
T2)
Q8N
FP9
NB
EA
_HU
MA
NN
euro
beac
hin
(Lys
osom
al-tr
affic
king
regu
lato
r 2, P
rote
in B
CL8
B)
NB
EA
L1 (A
LS2C
R17
)Q
6ZS
30N
BE
L1_H
UM
AN
Neu
robe
achi
n-lik
e pr
otei
n 1
(Am
yotro
phic
late
ral s
cler
osis
2 c
hrom
osom
al re
gion
can
dida
te g
ene
17 p
rote
in)
NB
EA
L2 (K
IAA
0540
, UN
Q25
3/P
RO
290)
Q6Z
NJ1
NB
EL2
_HU
MA
NN
euro
beac
hin-
like
prot
ein
2N
ED
D1
Q8N
HV
4N
ED
D1_
HU
MA
NP
rote
in N
ED
D1
(Neu
ral p
recu
rsor
cel
l exp
ress
ed d
evel
opm
enta
lly d
own-
regu
late
d pr
otei
n 1,
NE
DD
-1)
NLE
1 (H
US
SY
-07)
Q9N
VX
2N
LE1_
HU
MA
NN
otch
less
pro
tein
hom
olog
1N
SM
AF
(FA
N)
Q92
636
FAN
_HU
MA
NP
rote
in F
AN
(Fac
tor a
ssoc
iate
d w
ith n
eutra
l sph
ingo
mye
linas
e ac
tivat
ion,
Fac
tor a
ssoc
iate
d w
ith N
-SM
ase
activ
atio
n)N
UP
37Q
8NFH
4N
UP
37_H
UM
AN
Nuc
leop
orin
Nup
37 (p
37, N
up10
7-16
0 su
bcom
plex
sub
unit
Nup
37)
NU
P43
Q8N
FH3
NU
P43
_HU
MA
NN
ucle
opor
in N
up43
(p42
, Nup
107-
160
subc
ompl
ex s
ubun
it N
up43
)N
WD
1Q
149M
9N
WD
1_H
UM
AN
NA
CH
T an
d W
D re
peat
dom
ain-
cont
aini
ng p
rote
in 1
PA
AF1
(WD
R71
)Q
9BR
P4
PA
AF1
_HU
MA
NP
rote
asom
al A
TPas
e-as
soci
ated
fact
or 1
(WD
repe
at-c
onta
inin
g pr
otei
n 71
, Pro
tein
G-1
6)P
AFA
H1B
1 (L
IS1,
MD
CR
, MD
S, P
AFA
HA
)P
4303
4LI
S1_
HU
MA
NP
late
let-a
ctiv
atin
g fa
ctor
ace
tylh
ydro
lase
IB s
ubun
it al
pha
(PA
F-A
H 4
5 kD
a su
buni
t, P
AFA
H a
lpha
, Lis
senc
epha
ly-1
pro
tein
, LIS
-1)
PA
K1I
P1
(PIP
1, W
DR
84)
Q9N
WT1
PK
1IP
_HU
MA
Np2
1-ac
tivat
ed p
rote
in k
inas
e-in
tera
ctin
g pr
otei
n 1
(PA
K1-
inte
ract
ing
prot
ein
1, h
PIP
1, W
D re
peat
-con
tain
ing
prot
ein
84)
PE
X7
(PTS
2R)
O00
628
PE
X7_
HU
MA
NP
erox
isom
al ta
rget
ing
sign
al 2
rece
ptor
(PTS
2 re
cept
or, P
erox
in-7
)P
HIP
(WD
R11
)Q
8WW
Q0
PH
IP_H
UM
AN
PH
-inte
ract
ing
prot
ein
(PH
IP, I
RS
-1 P
H d
omai
n-bi
ndin
g pr
otei
n, W
D re
peat
-con
tain
ing
prot
ein
11)
Nature Biotechnology: doi:10.1038/nbt.1646
PIK
3R4
Q99
570
PI3
R4_
HU
MA
NP
hosp
hoin
ositi
de 3
-kin
ase
regu
lato
ry s
ubun
it 4
(EC
2.7
.11.
1, P
I3-k
inas
e p1
50 s
ubun
it, P
hosp
hoin
ositi
de 3
-kin
ase
adap
tor p
rote
in)
PLA
A (P
LAP
)Q
9Y26
3P
LAP
_HU
MA
NP
hosp
holip
ase
A-2
-act
ivat
ing
prot
ein
(PLA
2P, P
LAP
)P
LRG
1O
4366
0P
LRG
1_H
UM
AN
Ple
iotro
pic
regu
lato
r 1P
PP
2R2A
P63
151
2AB
A_H
UM
AN
Ser
ine/
thre
onin
e-pr
otei
n ph
osph
atas
e 2A
55
kDa
regu
lato
ry s
ubun
it B
alp
ha is
ofor
m (P
P2A
sub
unit
B, P
R55
-alp
ha is
ofor
m)
PP
P2R
2BQ
0000
52A
BB
_HU
MA
NS
erin
e/th
reon
ine-
prot
ein
phos
phat
ase
2A 5
5 kD
a re
gula
tory
sub
unit
B b
eta
isof
orm
(PP
2A s
ubun
it B
bet
a is
ofor
m, P
R55
-bet
a is
ofor
m)
PP
P2R
2CQ
9Y2T
42A
BG
_HU
MA
NS
erin
e/th
reon
ine-
prot
ein
phos
phat
ase
2A 5
5 kD
a re
gula
tory
sub
unit
B g
amm
a is
ofor
m (R
2-ga
mm
a is
ofor
m, I
MY
PN
O1)
PP
P2R
2D (K
IAA
1541
)Q
66LE
62A
BD
_HU
MA
NS
erin
e/th
reon
ine-
prot
ein
phos
phat
ase
2A 5
5 kD
a re
gula
tory
sub
unit
B d
elta
isof
orm
(PP
2A s
ubun
it B
, PR
55-d
elta
isof
orm
)P
PW
D1
(KIA
A00
73)
Q96
BP
3P
PW
D1_
HU
MA
NP
eptid
ylpr
olyl
isom
eras
e do
mai
n an
d W
D re
peat
-con
tain
ing
prot
ein
1 (E
C 5
.2.1
.8)
PR
EB
(SE
C12
)Q
9HC
U5
PR
EB
_HU
MA
NP
rola
ctin
regu
lato
ry e
lem
ent-b
indi
ng p
rote
in (M
amm
alia
n gu
anin
e nu
cleo
tide
exch
ange
fact
or m
Sec
12)
PR
PF1
9 (N
MP
200,
PR
P19
, SN
EV
)Q
9UM
S4
PR
P19
_HU
MA
NP
re-m
RN
A-p
roce
ssin
g fa
ctor
19
(PR
P19
/PS
O4
hom
olog
, hP
so4,
Nuc
lear
mat
rix p
rote
in 2
00, S
enes
cenc
e ev
asio
n fa
ctor
)P
RP
F4 (P
RP
4)O
4317
2P
RP
4_H
UM
AN
U4/
U6
smal
l nuc
lear
ribo
nucl
eopr
otei
n P
rp4
(U4/
U6
snR
NP
60
kDa
prot
ein,
WD
spl
icin
g fa
ctor
Prp
4, h
Prp
4)P
WP
1Q
1361
0P
WP
1_H
UM
AN
Per
iodi
c try
ptop
han
prot
ein
1 ho
mol
og (K
erat
inoc
yte
prot
ein
IEF
SS
P 9
502)
PW
P2
(PW
P2H
)Q
1526
9P
WP
2_H
UM
AN
Per
iodi
c try
ptop
han
prot
ein
2 ho
mol
ogR
AE
1 (M
RN
P41
)P
7840
6R
AE
1L_H
UM
AN
mR
NA
exp
ort f
acto
r (m
RN
A-a
ssoc
iate
d pr
otei
n m
rnp
41, R
ae1
prot
ein
hom
olog
)R
BB
P4
(RB
AP
48)
Q09
028
RB
BP
4_H
UM
AN
His
tone
-bin
ding
pro
tein
RB
BP
4 (R
b-bi
ndin
g pr
otei
n 4,
Chr
omat
in a
ssem
bly
fact
or 1
sub
unit
C, N
ucle
osom
e-re
mod
elin
g fa
ctor
RB
AP
48)
RB
BP
5 (R
BQ
3)Q
1529
1R
BB
P5_
HU
MA
NR
etin
obla
stom
a-bi
ndin
g pr
otei
n 5
(RB
BP
-5, R
etin
obla
stom
a-bi
ndin
g pr
otei
n R
BQ
-3)
RB
BP
7 (R
BA
P46
)Q
1657
6R
BB
P7_
HU
MA
NH
isto
ne-b
indi
ng p
rote
in R
BB
P7
(Ret
inob
last
oma-
bind
ing
prot
ein
7, H
isto
ne a
cety
ltran
sfer
ase
type
B s
ubun
it 2,
RB
AP
46)
RFW
D2
(CO
P1,
RN
F200
)Q
8NH
Y2
RFW
D2_
HU
MA
NE
3 ub
iqui
tin-p
rote
in li
gase
RFW
D2
(Con
stitu
tive
phot
omor
phog
enes
is p
rote
in 1
hom
olog
, hC
OP
1, R
ING
fing
er p
rote
in 2
00)
RFW
D3
(RN
F201
)Q
6PC
D5
RFW
D3_
HU
MA
NR
ING
fing
er a
nd W
D re
peat
dom
ain-
cont
aini
ng p
rote
in 3
(RIN
G fi
nger
pro
tein
201
)R
PTO
R (K
IAA
1303
, RA
PTO
R)
Q8N
122
RP
TOR
_HU
MA
NR
egul
ator
y-as
soci
ated
pro
tein
of m
TOR
(Rap
tor,
P15
0 ta
rget
of r
apam
ycin
TO
R-s
caffo
ld p
rote
in)
RR
P9
(RN
U3I
P2,
U35
5K)
O43
818
U3I
P2_
HU
MA
NU
3 sm
all n
ucle
olar
RN
A-in
tera
ctin
g pr
otei
n 2
(U3
snoR
NP
-ass
ocia
ted
55 k
Da
prot
ein,
U3-
55K
, RR
P9
hom
olog
)S
CA
P (K
IAA
0199
, PS
EC
0227
)Q
1277
0S
CA
P_H
UM
AN
Ste
rol r
egul
ator
y el
emen
t-bin
ding
pro
tein
cle
avag
e-ac
tivat
ing
prot
ein
(SR
EB
P c
leav
age-
activ
atin
g pr
otei
n, S
CA
P)
SE
C13
(D3S
1231
E, S
EC
13L1
, SE
C13
R)
P55
735
SE
C13
_HU
MA
NP
rote
in S
EC
13 h
omol
og (S
EC
13-li
ke p
rote
in 1
)S
EC
31A
(KIA
A09
05, S
EC
31L1
, HS
PC
275,
HS
PC
334)
O94
979
SC
31A
_HU
MA
NP
rote
in tr
ansp
ort p
rote
in S
ec31
A (S
EC
31-r
elat
ed p
rote
in A
, SE
C31
-like
1, A
BP
125,
AB
P13
0, W
eb1-
like
prot
ein)
SE
C31
B (S
EC
31L2
)Q
9NQ
W1
SC
31B
_HU
MA
NP
rote
in tr
ansp
ort p
rote
in S
ec31
B (S
EC
31-r
elat
ed p
rote
in B
, SE
C31
B-1
, SE
C31
-like
2)
SE
H1L
(SE
C13
L, S
EH
1)Q
96E
E3
SE
H1_
HU
MA
NN
ucle
opor
in S
EH
1 (N
up10
7-16
0 su
bcom
plex
sub
unit
SE
H1,
SE
C13
-like
pro
tein
)S
HK
BP
1 (P
P20
3)Q
8TB
C3
SH
KB
1_H
UM
AN
SH
3KB
P1-
bind
ing
prot
ein
1S
MU
1Q
2TA
Y7
SM
U1_
HU
MA
NW
D40
repe
at-c
onta
inin
g pr
otei
n S
MU
1 (S
mu-
1 su
ppre
ssor
of m
ec-8
and
unc
-52
prot
ein
hom
olog
)S
NR
NP
40 (P
RP
8BP
, SFP
38, W
DR
57)
Q96
DI7
SN
R40
_HU
MA
NU
5 sm
all n
ucle
ar ri
bonu
cleo
prot
ein
40 k
Da
prot
ein
(38
kDa-
splic
ing
fact
or, W
D re
peat
-con
tain
ing
prot
ein
57, P
rp8-
bind
ing
prot
ein,
hP
RP
8BP
)S
PA
G16
(PF2
0)Q
8N0X
2S
PG
16_H
UM
AN
Spe
rm-a
ssoc
iate
d an
tigen
16
prot
ein
(Pf2
0 pr
otei
n ho
mol
og)
STR
AP
(MA
WD
, UN
RIP
)Q
9Y3F
4S
TRA
P_H
UM
AN
Ser
ine-
thre
onin
e ki
nase
rece
ptor
-ass
ocia
ted
prot
ein
(UN
R-in
tera
ctin
g pr
otei
n, W
D-4
0 re
peat
pro
tein
PT-
WD
, MA
P a
ctiv
ator
with
WD
repe
ats)
STR
NO
4381
5S
TRN
_HU
MA
NS
triat
inS
TRN
3 (G
S2N
A, S
G2N
A)
Q13
033
STR
N3_
HU
MA
NS
triat
in-3
(Cel
l-cyc
le a
utoa
ntig
en S
G2N
A, S
/G2
antig
en)
STR
N4
(ZIN
)Q
9NR
L3S
TRN
4_H
UM
AN
Stri
atin
-4 (Z
ined
in)
STX
BP
5 (L
LGL3
)Q
5T5C
0S
TXB
5_H
UM
AN
Syn
taxi
n-bi
ndin
g pr
otei
n 5
(Tom
osyn
-1, L
etha
l(2) g
iant
larv
ae p
rote
in h
omol
og 3
)S
TXB
P5L
(KIA
A10
06, L
LGL4
)Q
9Y2K
9S
TB5L
_HU
MA
NS
ynta
xin-
bind
ing
prot
ein
5-lik
e (T
omos
yn-2
, Let
hal(2
) gia
nt la
rvae
pro
tein
hom
olog
4)
TAF5
(TA
F2D
)Q
1554
2TA
F5_H
UM
AN
Tran
scrip
tion
initi
atio
n fa
ctor
TFI
ID s
ubun
it 5
(TA
F(II)
100,
TA
FII-1
00)
TAF5
L (P
AF6
5B)
O75
529
TAF5
L_H
UM
AN
TAF5
-like
RN
A p
olym
eras
e II
p300
/CB
P-a
ssoc
iate
d fa
ctor
-ass
ocia
ted
fact
or 6
5 kD
a su
buni
t 5L
(PC
AF-
asso
ciat
ed fa
ctor
65
beta
, PA
F65-
beta
)TB
L1X
(TB
L1)
O60
907
TBL1
X_H
UM
AN
F-bo
x-lik
e/W
D re
peat
-con
tain
ing
prot
ein
TBL1
X (T
rans
duci
n be
ta-li
ke p
rote
in 1
X, S
MA
P55
)TB
L1X
R1
(IRA
1, T
BLR
1)Q
9BZK
7TB
L1R
_HU
MA
NF-
box-
like/
WD
repe
at-c
onta
inin
g pr
otei
n TB
L1X
R1
(Nuc
lear
rece
ptor
cor
epre
ssor
/HD
AC
3 co
mpl
ex s
ubun
it TB
LR1,
TB
L1-r
elat
ed p
rote
in 1
)TB
L1Y
(TB
L1)
Q9B
Q87
TBL1
Y_H
UM
AN
F-bo
x-lik
e/W
D re
peat
-con
tain
ing
prot
ein
TBL1
Y (T
rans
duci
n-be
ta-li
ke p
rote
in 1
, Y-li
nked
)TB
L2 (W
BS
CR
13, U
NQ
563/
PR
O11
25)
Q9Y
4P3
TBL2
_HU
MA
NTr
ansd
ucin
bet
a-lik
e pr
otei
n 2
(WS
-bet
aTR
P, W
illia
ms-
Beu
ren
synd
rom
e ch
rom
osom
al re
gion
13
prot
ein)
TBL3
(SA
ZD)
Q12
788
TBL3
_HU
MA
NTr
ansd
ucin
bet
a-lik
e pr
otei
n 3
(WD
repe
at-c
onta
inin
g pr
otei
n S
AZD
)TE
P1
(TLP
1, T
P1)
Q99
973
TEP
1_H
UM
AN
Telo
mer
ase
prot
ein
com
pone
nt 1
(Tel
omer
ase-
asso
ciat
ed p
rote
in 1
, p24
0, p
80 te
lom
eras
e ho
mol
og)
THO
C3
Q96
J01
THO
C3_
HU
MA
NTH
O c
ompl
ex s
ubun
it 3
(Tho
3, T
EX
1 ho
mol
og, h
TRE
X45
)TH
OC
6 (W
DR
58, P
SE
C00
06)
Q86
W42
THO
C6_
HU
MA
NTH
O c
ompl
ex s
ubun
it 6
hom
olog
(WD
repe
at-c
onta
inin
g pr
otei
n 58
, Fun
ctio
nal s
plic
eoso
me-
asso
ciat
ed p
rote
in 3
5, fS
AP
35)
TLE
1Q
0472
4TL
E1_
HU
MA
NTr
ansd
ucin
-like
enh
ance
r pro
tein
1 (E
nhan
cer o
f spl
it gr
ouch
o-lik
e pr
otei
n 1,
ES
G1)
TLE
2Q
0472
5TL
E2_
HU
MA
NTr
ansd
ucin
-like
enh
ance
r pro
tein
2 (E
SG
2)TL
E3
(KIA
A15
47)
Q04
726
TLE
3_H
UM
AN
Tran
sduc
in-li
ke e
nhan
cer p
rote
in 3
(ES
G3)
TLE
4 (K
IAA
1261
)Q
0472
7TL
E4_
HU
MA
NTr
ansd
ucin
-like
enh
ance
r pro
tein
4TL
E6
Q9H
808
TLE
6_H
UM
AN
Tran
sduc
in-li
ke e
nhan
cer p
rote
in 6
TRA
F7 (R
FWD
1, R
NF1
19)
Q6Q
0C0
TRA
F7_H
UM
AN
E3
ubiq
uitin
-pro
tein
liga
se T
RA
F7 (T
NF
rece
ptor
-ass
ocia
ted
fact
or 7
, RIN
G fi
nger
pro
tein
119
)TS
SC
1Q
53H
C9
TSS
C1_
HU
MA
NP
rote
in T
SS
C1
(Tum
or-s
uppr
essi
ng s
ubch
rom
osom
al tr
ansf
erab
le fr
agm
ent c
andi
date
gen
e 1
prot
ein)
TULP
4 (K
IAA
1397
, TU
BL4
, TU
SP
)Q
9NR
J4TU
LP4_
HU
MA
NTu
bby-
rela
ted
prot
ein
4 (T
ubby
-like
pro
tein
4, T
ubby
sup
erfa
mily
pro
tein
)U
TP15
Q8T
ED
0U
TP15
_HU
MA
NU
3 sm
all n
ucle
olar
RN
A-a
ssoc
iate
d pr
otei
n 15
hom
olog
Nature Biotechnology: doi:10.1038/nbt.1646
WD
FY1
(KIA
A14
35, W
DF1
, ZFY
VE
17)
Q8I
WB
7W
DFY
1_H
UM
AN
WD
repe
at a
nd F
YV
E d
omai
n pr
otei
n 1
(Pho
spho
inos
itide
-bin
ding
pro
tein
1, F
EN
S-1
, Zin
c fin
ger F
YV
E d
omai
n-co
ntai
ning
pro
tein
17)
WD
FY2
(WD
F2, Z
FYV
E22
)Q
96P
53W
DFY
2_H
UM
AN
WD
repe
at a
nd F
YV
E d
omai
n pr
otei
n 2
(WD
40- a
nd F
YV
E d
omai
n-co
ntai
ning
pro
tein
2, Z
inc
finge
r FY
VE
dom
ain-
cont
aini
ng p
rote
in 2
2)W
DFY
3 (K
IAA
0993
)Q
8IZQ
1W
DFY
3_H
UM
AN
WD
repe
at a
nd F
YV
E d
omai
n-co
ntai
ning
pro
tein
3 (A
utop
hagy
-link
ed F
YV
E p
rote
in, A
lfy)
WD
FY4
(C10
orf6
4, K
IAA
1607
)Q
6ZS
81W
DFY
4_H
UM
AN
Pro
tein
WD
FY4
WD
HD
1 (A
ND
1)O
7571
7W
DH
D1_
HU
MA
NW
D re
peat
and
HM
G-b
ox D
NA
-bin
ding
pro
tein
1 (A
cidi
c nu
cleo
plas
mic
DN
A-b
indi
ng p
rote
in 1
, And
-1)
WD
R1
O75
083
WD
R1_
HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
1 (A
ctin
-inte
ract
ing
prot
ein
1, A
IP1,
NO
RI-1
)W
DR
12Q
9GZL
7W
DR
12_H
UM
AN
Rib
osom
e bi
ogen
esis
pro
tein
WD
R12
(WD
repe
at-c
onta
inin
g pr
otei
n 12
)W
DR
13Q
9H1Z
4W
DR
13_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 13
WD
R17
Q8I
ZU2
WD
R17
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
17W
DR
18Q
9BV
38W
DR
18_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 18
WD
R19
(KIA
A16
38)
Q8N
EZ3
WD
R19
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
19W
DR
20Q
8TB
Z3W
DR
20_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 20
(Pro
tein
DM
R)
WD
R21
A (W
DR
21)
Q8W
V16
WD
21A
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
21A
WD
R21
BQ
3SX
M0
WD
21B
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
21B
WD
R21
CQ
8NA
75W
D21
C_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 21
CW
DR
22 (B
CR
G2,
KIA
A18
24)
Q96
JK2
WD
R22
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
22 (B
reak
poin
t clu
ster
regi
on p
rote
in 2
, BC
RP
2)W
DR
23 (G
L014
, PR
O23
89)
Q8T
EB
1W
DR
23_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 23
WD
R24
(JFP
7)Q
96S
15W
DR
24_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 24
WD
R25
Q64
LD2
WD
R25
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
25W
DR
26 (C
DW
2, M
IP2,
PR
O08
52)
Q9H
7D7
WD
R26
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
26 (C
UL4
- and
DD
B1-
asso
ciat
ed W
DR
pro
tein
2, M
yoca
rdia
l isc
hem
ic p
reco
nditi
onin
g up
-reg
ulat
ed p
rote
in 2
)W
DR
27A
2RR
H5
WD
R27
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
27W
DR
3Q
9UN
X4
WD
R3_
HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
3W
DR
31Q
8NA
23W
DR
31_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 31
WD
R32
Q5Q
P82
WD
R32
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
32W
DR
33 (W
DC
146)
Q9C
0J8
WD
R33
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
33 (W
D re
peat
-con
tain
ing
prot
ein
WD
C14
6)W
DR
34Q
96E
X3
WD
R34
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
34W
DR
35 (K
IAA
1336
)Q
9P2L
0W
DR
35_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 35
WD
R36
Q8N
I36
WD
R36
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
36 (T
-cel
l act
ivat
ion
WD
repe
at-c
onta
inin
g pr
otei
n, T
A-W
DR
P)
WD
R37
(KIA
A09
82)
Q9Y
2I8
WD
R37
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
37W
DR
38Q
5JTN
6W
DR
38_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 38
WD
R4
P57
081
WD
R4_
HU
MA
NtR
NA
(gua
nine
-N(7
)-)-
met
hyltr
ansf
eras
e su
buni
t WD
R4
(WD
repe
at-c
onta
inin
g pr
otei
n 4)
WD
R40
A (K
IAA
1892
, TC
C52
)Q
5T6F
0W
D40
A_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 40
A (C
entro
som
e-re
late
d pr
otei
n TC
C52
, Tes
tis c
ance
r cen
troso
me-
rela
ted
prot
ein)
WD
R40
BQ
5VU
92W
D40
B_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 40
BW
DR
40C
Q5V
W00
WD
40C
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
40C
WD
R41
(MS
TP04
8)Q
9HA
D4
WD
R41
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
41W
DR
42A
(H32
6)Q
5TA
Q9
WD
42A
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
42A
WD
R42
BA
6NG
E4
WD
42B
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
42B
WD
R42
CP
0C7V
8W
D42
C_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 42
CW
DR
43 (K
IAA
0007
)Q
1506
1W
DR
43_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 43
WD
R44
Q5J
SH
3W
DR
44_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 44
(Rab
phili
n-11
)W
DR
45 (W
DR
X1,
WD
RX
I4, W
IPI4
, JM
5)Q
9Y48
4W
IPI4
_HU
MA
NW
D re
peat
dom
ain
phos
phoi
nosi
tide-
inte
ract
ing
prot
ein
4 (W
IPI-4
, WD
repe
at-c
onta
inin
g pr
otei
n 45
)W
DR
46 (B
ING
4, C
6orf1
1, F
P22
1)O
1521
3W
DR
46_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 46
(WD
repe
at-c
onta
inin
g pr
otei
n B
ING
4)W
DR
47 (K
IAA
0893
)O
9496
7W
DR
47_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 47
WD
R48
(KIA
A14
49, U
AF1
)Q
8TA
F3W
DR
48_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 48
(WD
repe
at e
ndos
omal
pro
tein
, US
P1-
asso
ciat
ed fa
ctor
1, p
80)
WD
R49
Q8I
V35
WD
R49
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
49W
DR
5 (B
IG3)
P61
964
WD
R5_
HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
5 (B
MP
2-in
duce
d 3-
kb g
ene
prot
ein)
WD
R51
AQ
8NB
T0W
D51
A_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 51
AW
DR
51B
Q8T
C44
WD
51B
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
51B
WD
R52
Q96
MT7
WD
R52
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
52W
DR
53Q
7Z5U
6W
DR
53_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 53
WD
R54
Q9H
977
WD
R54
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
54W
DR
55Q
9H6Y
2W
DR
55_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 55
WD
R59
(KIA
A19
23, F
P97
7)Q
6PJI
9W
DR
59_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 59
WD
R5B
Q86
VZ2
WD
R5B
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
5BW
DR
6Q
9NN
W5
WD
R6_
HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
6
Nature Biotechnology: doi:10.1038/nbt.1646
WD
R60
Q8W
VS
4W
DR
60_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 60
WD
R61
Q9G
ZS3
WD
R61
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
61 (M
eiot
ic re
com
bina
tion
RE
C14
pro
tein
hom
olog
)W
DR
62 (C
19or
f14)
O43
379
WD
R62
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
62W
DR
63Q
8IW
G1
WD
R63
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
63 (T
estis
dev
elop
men
t pro
tein
NY
D-S
P29
)W
DR
64B
1AN
S9
WD
R64
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
64W
DR
65Q
96M
R6
WD
R65
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
65W
DR
66Q
8TB
Y9
WD
R66
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
66W
DR
67Q
96D
N5
WD
R67
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
67W
DR
68 (H
AN
11)
P61
962
WD
R68
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
68 (W
D re
peat
-con
tain
ing
prot
ein
An1
1 ho
mol
og)
WD
R69
Q8N
136
WD
R69
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
69W
DR
7 (K
IAA
0541
, TR
AG
)Q
9Y4E
6W
DR
7_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 7
(TG
F-be
ta re
sist
ance
-ass
ocia
ted
prot
ein
TRA
G, R
abco
nnec
tin-3
bet
a)W
DR
70Q
9NW
82W
DR
70_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 70
WD
R72
Q3M
J13
WD
R72
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
72W
DR
73 (H
SP
C26
4)Q
6P4I
2W
DR
73_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 73
WD
R74
(NS
A1)
Q6R
FH5
WD
R74
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
74 (N
OP
sev
en-a
ssoc
iate
d pr
otei
n 1)
WD
R75
Q8I
WA
0W
DR
75_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 75
WD
R76
Q9H
967
WD
R76
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
76W
DR
77 (M
EP
50, H
KM
T106
9, N
bla1
0071
)Q
9BQ
A1
ME
P50
_HU
MA
NM
ethy
loso
me
prot
ein
50 (M
EP
-50,
WD
repe
at-c
onta
inin
g pr
otei
n 77
, And
roge
n re
cept
or c
ofac
tor p
44, p
44/M
ep50
)W
DR
78Q
5VTH
9W
DR
78_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 78
WD
R79
(TC
AB
1, W
RA
P53
)Q
9BU
R4
TCA
B1_
HU
MA
NTe
lom
eras
e C
ajal
bod
y pr
otei
n 1
(WD
repe
at-c
onta
inin
g pr
otei
n 79
, WD
40 re
peat
-con
tain
ing
prot
ein
enco
ding
RN
A a
ntis
ense
to p
53)
WD
R8
Q9P
2S5
WD
R8_
HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
8W
DR
81Q
562E
7W
DR
81_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 81
WD
R82
(WD
R82
A, U
NQ
9342
/PR
O34
047)
Q6U
XN
9W
DR
82_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 82
(Sw
d2)
WD
R85
(C9o
rf112
)Q
9BTV
6W
DR
85_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 85
WD
R86
Q86
TI4
WD
R86
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
86W
DR
87Q
6ZQ
Q6
WD
R87
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
87 (T
estis
dev
elop
men
t pro
tein
NY
D-S
P11
)W
DR
88 (P
QW
D)
Q6Z
MY
6W
DR
88_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 88
(PQ
Q re
peat
and
WD
repe
at-c
onta
inin
g pr
otei
n)W
DR
89 (C
14or
f150
, MS
TP05
0)Q
96FK
6W
DR
89_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 89
WD
R90
(C16
orf1
5, C
16or
f16,
C16
orf1
7, K
IAA
1924
)Q
96K
V7
WD
R90
_HU
MA
NW
D re
peat
-con
tain
ing
prot
ein
90W
DR
91 (H
SP
C04
9)A
4D1P
6W
DR
91_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 91
WD
R92
Q96
MX
6W
DR
92_H
UM
AN
WD
repe
at-c
onta
inin
g pr
otei
n 92
(WD
repe
at-c
onta
inin
g pr
otei
n M
onad
)W
DS
OF1
(HS
PC
064)
Q9N
V06
SO
F1_H
UM
AN
WD
repe
at a
nd S
OF
dom
ain-
cont
aini
ng p
rote
in 1
WD
SU
B1
(WD
SA
M1)
Q8N
9V3
WS
DU
1_H
UM
AN
WD
repe
at, S
AM
and
U-b
ox d
omai
n-co
ntai
ning
pro
tein
1W
DTC
1 (K
IAA
1037
)Q
8N5D
0W
DTC
1_H
UM
AN
WD
and
tetra
trico
pept
ide
repe
ats
prot
ein
1W
IPI1
(WIP
I49)
Q5M
NZ9
WIP
I1_H
UM
AN
WD
repe
at d
omai
n ph
osph
oino
sitid
e-in
tera
ctin
g pr
otei
n 1
(WIP
I-1, W
IPI 4
9 kD
a, A
tg18
pro
tein
hom
olog
)W
IPI2
(CG
I-50)
Q9Y
4P8
WIP
I2_H
UM
AN
WD
repe
at d
omai
n ph
osph
oino
sitid
e-in
tera
ctin
g pr
otei
n 2
(WIP
I-2, W
IPI4
9-lik
e pr
otei
n 2)
WS
B1
(SW
IP1)
Q9Y
6I7
WS
B1_
HU
MA
NW
D re
peat
and
SO
CS
box
-con
tain
ing
prot
ein
1 (W
SB
-1, S
OC
S b
ox-c
onta
inin
g W
D p
rote
in S
WiP
-1)
WS
B2
Q9N
YS
7W
SB
2_H
UM
AN
WD
repe
at a
nd S
OC
S b
ox-c
onta
inin
g pr
otei
n 2
(WS
B-2
, CS
box
-con
tain
ing
WD
pro
tein
)ZF
P10
6 (S
H3B
P3,
ZN
F474
)Q
9H2Y
7ZF
106_
HU
MA
NZi
nc fi
nger
pro
tein
106
hom
olog
(Zfp
-106
, Zin
c fin
ger p
rote
in 4
74)
Nature Biotechnology: doi:10.1038/nbt.1646
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