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Protein

Cullin-5

Gene

CUL5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • signaling 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
  • cellular response to DNA damage stimulus Source: GO_Central
  • 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
  • post-translational protein modification Source: Reactome
  • ubiquitin-dependent protein catabolic process Source: InterPro
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionReceptor
Biological processHost-virus interaction, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-180585 Vif-mediated degradation of APOBEC3G
R-HSA-8863795 Downregulation of ERBB2 signaling
R-HSA-8951664 Neddylation
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

EuPathDBiHostDB:ENSG00000166266.13
HGNCiHGNC:2556 CUL5
MIMi601741 gene
neXtProtiNX_Q93034

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

DisGeNETi8065
OpenTargetsiENSG00000166266
PharmGKBiPA27052

Polymorphism and mutation databases

BioMutaiCUL5
DMDMi14917099

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001197971 – 780Cullin-5Add BLAST780

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 (ELOB and ELOC), 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 (ELOB and ELOC), RBX1 and ELOA. May also form complexes containing CUL5, Elongin BC (ELOB and ELOC), 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

Show more details

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113743, 449 interactors
CORUMiQ93034
DIPiDIP-43696N
IntActiQ93034, 51 interactors
MINTiQ93034
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
OMAiQEFAIVK
OrthoDBiEOG091G02MQ
PhylomeDBiQ93034
TreeFamiTF105874

Family and domain databases

Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR016157 Cullin_CS
IPR016158 Cullin_homology
IPR036317 Cullin_homology_sf
IPR001373 Cullin_N
IPR019559 Cullin_neddylation_domain
IPR016159 Cullin_repeat-like_dom_sf
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF00888 Cullin, 1 hit
PF10557 Cullin_Nedd8, 1 hit
SMARTiView protein in SMART
SM00182 CULLIN, 1 hit
SM00884 Cullin_Nedd8, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF74788 SSF74788, 1 hit
SSF75632 SSF75632, 1 hit
PROSITEiView protein in PROSITE
PS01256 CULLIN_1, 1 hit
PS50069 CULLIN_2, 1 hit

Sequencei

Sequence statusi: Complete.

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_003478.4
UniGeneiHs.440320

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiCUL5_HUMAN
AccessioniPrimary (citable) accession number: Q93034
Secondary accession number(s): A8K960, O14766, Q9BZC6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 23, 2007
Last modified: May 23, 2018
This is version 170 of the entry and version 4 of the sequence. See 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

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