Reviewed, UniProtKB/Swiss-Prot Q93034 (CUL5_HUMAN)

Names and origin

Protein names

Recommended name:
    Cullin-5
      Short name=CUL-5
Alternative name(s):
    Vasopressin-activated calcium-mobilizing receptor
    VACM-1

Gene names

Name:	CUL5
Synonyms:	VACM1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	780 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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 poteosomal degradation of p53/TP53 stimulated by adenovirus E1B-55 kDa protein. May form a cell surface vasopressin receptor.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	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. 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. Interacts with RNF7/RBX2, LRRC41, SOCS3, SPSB1, SPSB2, SPSB4 and RAB40C. Interacts with ASB1, ASB2, ASB6, ASB7 and ASB12. Ref.5 Ref.9 Ref.10 Ref.11
Post-translational modification	Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex By similarity.
Sequence similarities	Belongs to the cullin family.

Ontologies

Keywords
Biological process	Host-virus interaction Ubl conjugation pathway
Molecular function	Receptor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	G1/S transition of mitotic cell cycle Traceable author statement. Source: ProtInc cell cycle arrest Traceable author statement. Source: ProtInc cell proliferation Ref.1 Traceable author statement. Source: ProtInc induction of apoptosis by intracellular signals Traceable author statement. Source: ProtInc interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell proliferation Traceable author statement. Source: ProtInc ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA cullin-RING ubiquitin ligase complex Inferred from electronic annotation. Source: InterPro cytosol Inferred from Experiment. Source: Reactome
Molecular function	calcium channel activity Traceable author statement. Source: ProtInc receptor activity Traceable author statement. Source: ProtInc ubiquitin protein ligase binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RBX1	P62877	1	EBI-1057139,EBI-398523

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 780	779	Cullin-5		PRO_0000119797
Amino acid modifications
	Modified residue	210	1	Phosphothreonine Ref.12
	Cross-link	724		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) By similarity
Experimental info
	Sequence conflict	9	1	N → D in AAB70253. Ref.2
	Sequence conflict	12	1	S → F in AAB70253. Ref.2
	Sequence conflict	16	1	E → G in AAB70253. Ref.2
	Sequence conflict	32 – 34	3	QES → RDF in AAB70253. Ref.2
	Sequence conflict	38	1	Q → R in AAB70253. Ref.2
	Sequence conflict	50 – 52	3	VCL → FCF in AAB70253. Ref.2
	Sequence conflict	68	1	D → DF in AAB70253. Ref.2
	Sequence conflict	224	1	Q → P in CAA57465. Ref.1
	Sequence conflict	648	1	L → F in CAA57465. Ref.1
	Sequence conflict	651	1	E → D in CAA57465. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q93034-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 57463CB4ED76E303	FASTA	780	90,955
	10 20 30 40 50 60 MATSNLLKNK GSLQFEDKWD FMRPIVLKLL RQESVTKQQW FDLFSDVHAV CLWDDKGPAK 70 80 90 100 110 120 IHQALKEDIL EFIKQAQARV LSHQDDTALL KAYIVEWRKF FTQCDILPKP FCQLEITLMG 130 140 150 160 170 180 KQGSNKKSNV EDSIVRKLML DTWNESIFSN IKNRLQDSAM KLVHAERLGE AFDSQLVIGV 190 200 210 220 230 240 RESYVNLCSN PEDKLQIYRD NFEKAYLDST ERFYRTQAPS YLQQNGVQNY MKYADAKLKE 250 260 270 280 290 300 EEKRALRYLE TRRECNSVEA LMECCVNALV TSFKETILAE CQGMIKRNET EKLHLMFSLM 310 320 330 340 350 360 DKVPNGIEPM LKDLEEHIIS AGLADMVAAA ETITTDSEKY VEQLLTLFNR FSKLVKEAFQ 370 380 390 400 410 420 DDPRFLTARD KAYKAVVNDA TIFKLELPLK QKGVGLKTQP ESKCPELLAN YCDMLLRKTP 430 440 450 460 470 480 LSKKLTSEEI EAKLKEVLLV LKYVQNKDVF MRYHKAHLTR RLILDISADS EIEENMVEWL 490 500 510 520 530 540 REVGMPADYV NKLARMFQDI KVSEDLNQAF KEMHKNNKLA LPADSVNIKI LNAGAWSRSS 550 560 570 580 590 600 EKVFVSLPTE LEDLIPEVEE FYKKNHSGRK LHWHHLMSNG IITFKNEVGQ YDLEVTTFQL 610 620 630 640 650 660 AVLFAWNQRP REKISFENLK LATELPDAEL RRTLWSLVAF PKLKRQVLLY EPQVNSPKDF 670 680 690 700 710 720 TEGTLFSVNQ EFSLIKNAKV QKRGKINLIG RLQLTTERMR EEENEGIVQL RILRTQEAII 730 740 750 760 770 780 QIMKMRKKIS NAQLQTELVE ILKNMFLPQK KMIKEQIEWL IEHKYIRRDE SDINTFIYMA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and analysis of expression of human VACM-1, a cullin gene family member located on chromosome 11q22-23." Byrd P.J., Stankovic T., McConville C.M., Smith A.D., Cooper P.R., Taylor A.M.R. Genome Res. 7:71-75(1997) [PubMed: 9037604] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Longo K.A., North W.G., Du J., Fay M.J. Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	Kanaya K., Kamitani T. Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[5]	"ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity." Ohta T., Michel J.J., Schottelius A.J., Xiong Y. Mol. Cell 3:535-541(1999) [PubMed: 10230407] [Abstract] Cited for: INTERACTION WITH RBX1 AND RNF7.
[6]	"Covalent modification of all members of human cullin family proteins by NEDD8." Hori T., Osaka F., Chiba T., Miyamoto C., Okabayashi K., Shimbara N., Kato S., Tanaka K. Oncogene 18:6829-6834(1999) [PubMed: 10597293] [Abstract] Cited for: NEDDYLATION.
[7]	"Muf1, a novel elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase." Kamura T., Burian D., Yan Q., Schmidt S.L., Lane W.S., Querido E., Branton P.E., Shilatifard A., Conaway R.C., Conaway J.W. J. Biol. Chem. 276:29748-29753(2001) [PubMed: 11384984] [Abstract] Cited for: IDENTIFICATION IN E3 UBIQUITIN-PROTEIN LIGASE COMPLEX WITH LRRC41, IDENTIFICATION IN A COMPLEX WITH TCEB3, IDENTIFICATION IN A COMPLEX WITH SOCS1, IDENTIFICATION IN A COMPLEX WITH WSB1.
[8]	"Analysis of the adenovirus E1B-55K-anchored proteome reveals its link to ubiquitination machinery." Harada J.N., Shevchenko A., Shevchenko A., Pallas D.C., Berk A.J. J. Virol. 76:9194-9206(2002) [PubMed: 12186903] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH HUMAN ADENOVIRUS 5 PROTEINS, NEDDYLATION.
[9]	"Phosphorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif-Cul5 complex that promotes APOBEC3G degradation." Mehle A., Goncalves J., Santa-Marta M., McPike M., Gabuzda D. Genes Dev. 18:2861-2866(2004) [PubMed: 15574592] [Abstract] Cited for: INTERACTION WITH HIV VIF.
[10]	"VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases." Kamura T., Maenaka K., Kotoshiba S., Matsumoto M., Kohda D., Conaway R.C., Conaway J.W., Nakayama K.I. Genes Dev. 18:3055-3065(2004) [PubMed: 15601820] [Abstract] Cited for: IDENTIFICATION IN THE ECS(LRRC41) COMPLEX, IDENTIFICATION IN THE ECS(SOCS3) COMPLEX, IDENTIFICATION IN THE ECS(SPSB1) COMPLEX, IDENTIFICATION IN THE ECS(SPSB2) COMPLEX, IDENTIFICATION IN THE ECS(SPSB4) COMPLEX, IDENTIFICATION IN THE ECS(RAB40C) COMPLEX, IDENTIFICATION IN THE ECS(WSB1) COMPLEX, MASS SPECTROMETRY, INTERACTION WITH LRRC41; SOCS3; SPSB1; SPSB2; SPSB4; WSB1 AND RAB40C.
[11]	"ASB proteins interact with cullin5 and Rbx2 to form E3 ubiquitin ligase complexes." Kohroki J., Nishiyama T., Nakamura T., Masuho Y. FEBS Lett. 579:6796-6802(2005) [PubMed: 16325183] [Abstract] Cited for: INTERACTION WITH ASB1; ASB2; ASB6; ASB7 AND ASB12.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-210, MASS SPECTROMETRY.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X81882 mRNA. Translation: CAA57465.1.
AF017061 mRNA. Translation: AAB70253.1.
AF327710 mRNA. Translation: AAK07472.1.
BC063306 mRNA. Translation: AAH63306.1.

IPI

IPI00216003.

RefSeq

NP_003469.2.

UniGene

Hs.440320
Hs.701122

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3DPL	X-ray	2.60	C	401-780	[»]
3DQV	X-ray	3.00	C/D	401-780	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q93034. 6 interactions.

PTM databases

PhosphoSite

Q93034.

Proteomic databases

PRIDE

Q93034.

Genome annotation databases

Ensembl

ENSG00000166266. Homo sapiens. [Contig view]

GeneID

8065.

KEGG

hsa:8065.

Organism-specific databases

GeneCards

GC11P107384.

H-InvDB

HIX0026128.

HGNC

HGNC:2556. CUL5.

HPA

CAB017787.
HPA002185.

MIM

601741. gene.

PharmGKB

PA27052.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q93034.

HOVERGEN

Q93034.

OMA

Q93034. KLMLDSW.

Enzyme and pathway databases

Reactome

REACT_6185. HIV Infection.

Gene expression databases

ArrayExpress

Q93034.

Bgee

Q93034.

CleanEx

HS_CUL5.

GermOnline

ENSG00000166266. Homo sapiens.

Family and domain databases

InterPro

IPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR011991. Wing_hlx_DNA_bd.
[Graphical view]

Gene3D

G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.

Pfam

PF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]

SMART

SM00182. CULLIN. 1 hit.
[Graphical view]

PROSITE

PS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

30655.

SOURCE

Search...

Entry information

Entry name

CUL5_HUMAN

Accession

Primary (citable) accession number: Q93034
Secondary accession number(s): O14766, Q9BZC6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 80 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)