Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Cullin-5

Gene

CUL5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Core component of multiple SCF-like ECS (Elongin-Cullin 2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. ECS(SOCS1) seems to direct ubiquitination of JAK2. Seems to be involved in proteosomal degradation of p53/TP53 stimulated by adenovirus E1B-55 kDa protein. May form a cell surface vasopressin receptor.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

  • calcium channel activity Source: ProtInc
  • receptor activity Source: ProtInc
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: Reactome

GO - Biological processi

  • cell cycle arrest Source: ProtInc
  • cell proliferation Source: ProtInc
  • ERBB2 signaling pathway Source: Reactome
  • G1/S transition of mitotic cell cycle Source: ProtInc
  • intrinsic apoptotic signaling pathway Source: ProtInc
  • negative regulation of cell proliferation Source: ProtInc
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Host-virus interaction, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000166266-MONOMER.
ReactomeiR-HSA-180585. Vif-mediated degradation of APOBEC3G.
R-HSA-8863795. Downregulation of ERBB2 signaling.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SIGNORiQ93034.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Cullin-5
Short name:
CUL-5
Alternative name(s):
Vasopressin-activated calcium-mobilizing receptor 1
Short name:
VACM-1
Gene namesi
Name:CUL5
Synonyms:VACM1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:2556. CUL5.

Subcellular locationi

GO - Cellular componenti

  • Cul5-RING ubiquitin ligase complex Source: UniProtKB
  • cytosol Source: Reactome
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi8065.
OpenTargetsiENSG00000166266.
PharmGKBiPA27052.

Polymorphism and mutation databases

BioMutaiCUL5.
DMDMi14917099.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001197972 – 780Cullin-5Add BLAST779

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei34PhosphoserineCombined sources1
Modified residuei210PhosphothreonineCombined sources1
Cross-linki724Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)1 Publication

Post-translational modificationi

Neddylated; which enhances the ubiquitination activity of SCF and prevents binding of the inhibitor CAND1. Deneddylated via its interaction with the COP9 signalosome (CSN).4 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ93034.
MaxQBiQ93034.
PaxDbiQ93034.
PeptideAtlasiQ93034.
PRIDEiQ93034.

PTM databases

iPTMnetiQ93034.
PhosphoSitePlusiQ93034.

Expressioni

Gene expression databases

BgeeiENSG00000166266.
CleanExiHS_CUL5.
ExpressionAtlasiQ93034. baseline and differential.
GenevisibleiQ93034. HS.

Organism-specific databases

HPAiCAB017787.
HPA002185.

Interactioni

Subunit structurei

Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes formed of CUL5, Elongin BC (TCEB1 and TCEB2), RBX2 and a variable SOCS box domain-containing protein as substrate-specific recognition component. Component of the probable ECS(LRRC41) complex with the substrate recognition component LRRC41. Component of the probable ECS(SOCS1) complex with the substrate recognition component SOCS1. Component of the probable ECS(WSB1) complex with the substrate recognition subunit WSB1. Component of the probable ECS(SOCS3) complex with the substrate recognition component SOCS3. Component of the probable ECS(SPSB1) complex with the substrate recognition component SPSB1. Component of the probable ECS(SPSB2) complex with the substrate recognition component SPSB2. Component of the probable ECS(SPSB4) complex with the substrate recognition component SPSB4. Component of the probable ECS(RAB40C) complex with the substrate recognition subunit RAB40C. May also form complexes containing CUL5, elongin BC complex (TCEB1 and TCEB2), RBX1 and TCEB3. May also form complexes containing CUL5, Elongin BC (TCEB1 and TCEB2), RBX1 and VHL. Interacts with RNF7/RBX2, LRRC41, SOCS3, SPSB1, SPSB2, SPSB4 and RAB40C. Interacts with ASB1, ASB2, ASB6, ASB7 and ASB12. Interacts (when neddylated) with ARIH2; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655).7 Publications
(Microbial infection) The substrate recognition component can also be a viral protein such as HIV Vif, or human adenovirus 5 E1B large T-antigen and E4-orf6.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ARIH2O9537612EBI-1057139,EBI-711158
ASB2Q96Q274EBI-1057139,EBI-2880677
CCNDBP1O952733EBI-1057139,EBI-748961
GAMMAHV.ORF73O419742EBI-1057139,EBI-6933128From a different organism.
GOLGA2Q083793EBI-1057139,EBI-618309
RBX1P628773EBI-1057139,EBI-398523
RNF7Q9UBF66EBI-1057139,EBI-398632
vifP125045EBI-1057139,EBI-779991From a different organism.

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113743. 444 interactors.
DIPiDIP-43696N.
IntActiQ93034. 42 interactors.
MINTiMINT-1184052.
STRINGi9606.ENSP00000376808.

Structurei

Secondary structure

1780
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi15 – 30Combined sources16
Helixi37 – 53Combined sources17
Helixi57 – 81Combined sources25
Helixi86 – 103Combined sources18
Turni104 – 108Combined sources5
Helixi109 – 111Combined sources3
Helixi112 – 115Combined sources4
Helixi134 – 146Combined sources13
Helixi148 – 167Combined sources20
Helixi175 – 186Combined sources12
Helixi196 – 199Combined sources4
Helixi202 – 224Combined sources23
Helixi227 – 248Combined sources22
Beta strandi252 – 254Combined sources3
Helixi257 – 269Combined sources13
Helixi271 – 273Combined sources3
Helixi274 – 277Combined sources4
Helixi278 – 280Combined sources3
Helixi281 – 286Combined sources6
Helixi290 – 300Combined sources11
Turni304 – 306Combined sources3
Helixi310 – 333Combined sources24
Helixi337 – 357Combined sources21
Turni358 – 361Combined sources4
Helixi363 – 377Combined sources15
Helixi405 – 416Combined sources12
Beta strandi417 – 419Combined sources3
Helixi420 – 423Combined sources4
Helixi427 – 438Combined sources12
Helixi439 – 443Combined sources5
Helixi447 – 463Combined sources17
Helixi470 – 482Combined sources13
Helixi487 – 513Combined sources27
Helixi523 – 525Combined sources3
Beta strandi526 – 532Combined sources7
Helixi533 – 536Combined sources4
Helixi549 – 552Combined sources4
Helixi555 – 563Combined sources9
Beta strandi566 – 573Combined sources8
Helixi575 – 577Combined sources3
Beta strandi579 – 585Combined sources7
Beta strandi590 – 596Combined sources7
Helixi597 – 603Combined sources7
Helixi604 – 606Combined sources3
Helixi616 – 623Combined sources8
Helixi627 – 638Combined sources12
Beta strandi647 – 652Combined sources6
Helixi657 – 659Combined sources3
Beta strandi665 – 668Combined sources4
Beta strandi674 – 687Combined sources14
Turni690 – 693Combined sources4
Helixi697 – 723Combined sources27
Beta strandi726 – 729Combined sources4
Helixi731 – 741Combined sources11
Turni742 – 745Combined sources4
Helixi750 – 762Combined sources13
Beta strandi765 – 769Combined sources5
Beta strandi772 – 778Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3DPLX-ray2.60C401-780[»]
3DQVX-ray3.00C/D401-780[»]
4JGHX-ray3.00D10-386[»]
4N9FX-ray3.303/9/C/I/O/U/V/f/l/r/w/x12-321[»]
ProteinModelPortaliQ93034.
SMRiQ93034.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ93034.

Family & Domainsi

Sequence similaritiesi

Belongs to the cullin family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2285. Eukaryota.
COG5647. LUCA.
GeneTreeiENSGT00760000119212.
HOGENOMiHOG000007610.
HOVERGENiHBG099672.
InParanoidiQ93034.
KOiK10612.
OMAiNQEFAIV.
OrthoDBiEOG091G02MQ.
PhylomeDBiQ93034.
TreeFamiTF105874.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]
SMARTiSM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF74788. SSF74788. 1 hit.
SSF75632. SSF75632. 1 hit.
PROSITEiPS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q93034-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATSNLLKNK GSLQFEDKWD FMRPIVLKLL RQESVTKQQW FDLFSDVHAV
60 70 80 90 100
CLWDDKGPAK IHQALKEDIL EFIKQAQARV LSHQDDTALL KAYIVEWRKF
110 120 130 140 150
FTQCDILPKP FCQLEITLMG KQGSNKKSNV EDSIVRKLML DTWNESIFSN
160 170 180 190 200
IKNRLQDSAM KLVHAERLGE AFDSQLVIGV RESYVNLCSN PEDKLQIYRD
210 220 230 240 250
NFEKAYLDST ERFYRTQAPS YLQQNGVQNY MKYADAKLKE EEKRALRYLE
260 270 280 290 300
TRRECNSVEA LMECCVNALV TSFKETILAE CQGMIKRNET EKLHLMFSLM
310 320 330 340 350
DKVPNGIEPM LKDLEEHIIS AGLADMVAAA ETITTDSEKY VEQLLTLFNR
360 370 380 390 400
FSKLVKEAFQ DDPRFLTARD KAYKAVVNDA TIFKLELPLK QKGVGLKTQP
410 420 430 440 450
ESKCPELLAN YCDMLLRKTP LSKKLTSEEI EAKLKEVLLV LKYVQNKDVF
460 470 480 490 500
MRYHKAHLTR RLILDISADS EIEENMVEWL REVGMPADYV NKLARMFQDI
510 520 530 540 550
KVSEDLNQAF KEMHKNNKLA LPADSVNIKI LNAGAWSRSS EKVFVSLPTE
560 570 580 590 600
LEDLIPEVEE FYKKNHSGRK LHWHHLMSNG IITFKNEVGQ YDLEVTTFQL
610 620 630 640 650
AVLFAWNQRP REKISFENLK LATELPDAEL RRTLWSLVAF PKLKRQVLLY
660 670 680 690 700
EPQVNSPKDF TEGTLFSVNQ EFSLIKNAKV QKRGKINLIG RLQLTTERMR
710 720 730 740 750
EEENEGIVQL RILRTQEAII QIMKMRKKIS NAQLQTELVE ILKNMFLPQK
760 770 780
KMIKEQIEWL IEHKYIRRDE SDINTFIYMA
Length:780
Mass (Da):90,955
Last modified:January 23, 2007 - v4
Checksum:i57463CB4ED76E303
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9N → D in AAB70253 (Ref. 2) Curated1
Sequence conflicti12S → F in AAB70253 (Ref. 2) Curated1
Sequence conflicti16E → G in AAB70253 (Ref. 2) Curated1
Sequence conflicti32 – 34QES → RDF in AAB70253 (Ref. 2) Curated3
Sequence conflicti38Q → R in AAB70253 (Ref. 2) Curated1
Sequence conflicti50 – 52VCL → FCF in AAB70253 (Ref. 2) Curated3
Sequence conflicti68D → DF in AAB70253 (Ref. 2) Curated1
Sequence conflicti224Q → P in CAA57465 (PubMed:9037604).Curated1
Sequence conflicti648L → F in CAA57465 (PubMed:9037604).Curated1
Sequence conflicti651E → D in CAA57465 (PubMed:9037604).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X81882 mRNA. Translation: CAA57465.1.
AF017061 mRNA. Translation: AAB70253.1.
AF327710 mRNA. Translation: AAK07472.1.
AK292575 mRNA. Translation: BAF85264.1.
CH471065 Genomic DNA. Translation: EAW67102.1.
BC063306 mRNA. Translation: AAH63306.1.
CCDSiCCDS31668.1.
RefSeqiNP_003469.2. NM_003478.3.
UniGeneiHs.440320.

Genome annotation databases

EnsembliENST00000393094; ENSP00000376808; ENSG00000166266.
ENST00000531427; ENSP00000435376; ENSG00000166266.
GeneIDi8065.
KEGGihsa:8065.
UCSCiuc001pjv.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X81882 mRNA. Translation: CAA57465.1.
AF017061 mRNA. Translation: AAB70253.1.
AF327710 mRNA. Translation: AAK07472.1.
AK292575 mRNA. Translation: BAF85264.1.
CH471065 Genomic DNA. Translation: EAW67102.1.
BC063306 mRNA. Translation: AAH63306.1.
CCDSiCCDS31668.1.
RefSeqiNP_003469.2. NM_003478.3.
UniGeneiHs.440320.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3DPLX-ray2.60C401-780[»]
3DQVX-ray3.00C/D401-780[»]
4JGHX-ray3.00D10-386[»]
4N9FX-ray3.303/9/C/I/O/U/V/f/l/r/w/x12-321[»]
ProteinModelPortaliQ93034.
SMRiQ93034.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113743. 444 interactors.
DIPiDIP-43696N.
IntActiQ93034. 42 interactors.
MINTiMINT-1184052.
STRINGi9606.ENSP00000376808.

PTM databases

iPTMnetiQ93034.
PhosphoSitePlusiQ93034.

Polymorphism and mutation databases

BioMutaiCUL5.
DMDMi14917099.

Proteomic databases

EPDiQ93034.
MaxQBiQ93034.
PaxDbiQ93034.
PeptideAtlasiQ93034.
PRIDEiQ93034.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000393094; ENSP00000376808; ENSG00000166266.
ENST00000531427; ENSP00000435376; ENSG00000166266.
GeneIDi8065.
KEGGihsa:8065.
UCSCiuc001pjv.4. human.

Organism-specific databases

CTDi8065.
DisGeNETi8065.
GeneCardsiCUL5.
HGNCiHGNC:2556. CUL5.
HPAiCAB017787.
HPA002185.
MIMi601741. gene.
neXtProtiNX_Q93034.
OpenTargetsiENSG00000166266.
PharmGKBiPA27052.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2285. Eukaryota.
COG5647. LUCA.
GeneTreeiENSGT00760000119212.
HOGENOMiHOG000007610.
HOVERGENiHBG099672.
InParanoidiQ93034.
KOiK10612.
OMAiNQEFAIV.
OrthoDBiEOG091G02MQ.
PhylomeDBiQ93034.
TreeFamiTF105874.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000166266-MONOMER.
ReactomeiR-HSA-180585. Vif-mediated degradation of APOBEC3G.
R-HSA-8863795. Downregulation of ERBB2 signaling.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SIGNORiQ93034.

Miscellaneous databases

ChiTaRSiCUL5. human.
EvolutionaryTraceiQ93034.
GeneWikiiCUL5.
GenomeRNAii8065.
PROiQ93034.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166266.
CleanExiHS_CUL5.
ExpressionAtlasiQ93034. baseline and differential.
GenevisibleiQ93034. HS.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]
SMARTiSM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF74788. SSF74788. 1 hit.
SSF75632. SSF75632. 1 hit.
PROSITEiPS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCUL5_HUMAN
AccessioniPrimary (citable) accession number: Q93034
Secondary accession number(s): A8K960, O14766, Q9BZC6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 158 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.