Q93034 (CUL5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cullin-5
Short name=CUL-5

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

Gene names

Name:	CUL5
Synonyms:	VACM1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
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 Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1/S transition of mitotic cell cycle Traceable author statement PubMed 8681378. Source: ProtInc cell cycle arrest Traceable author statement PubMed 8681378. Source: ProtInc cell proliferation Traceable author statement Ref.1. Source: ProtInc cytosolic calcium ion homeostasis Inferred from electronic annotation. Source: Compara intrinsic apoptotic signaling pathway Traceable author statement PubMed 9581826. Source: ProtInc negative regulation of cell proliferation Traceable author statement PubMed 8681378. Source: ProtInc protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway response to osmotic stress Inferred from electronic annotation. Source: Compara ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro viral reproduction Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Cul5-RING ubiquitin ligase complex Inferred from direct assay PubMed 17636018. Source: UniProtKB cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	calcium channel activity Traceable author statement PubMed 9581826. Source: ProtInc receptor activity Traceable author statement PubMed 9581826. Source: ProtInc ubiquitin protein ligase binding Inferred from direct assay PubMed 17636018. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RBX1	P62877	3	EBI-1057139,EBI-398523
vif	P12504	5	EBI-1057139,EBI-779991	From a different organism.

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.14

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

Secondary structure

1

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780

Helix Strand Turn

Details...

Helix

405 – 416

12

Beta strand

417 – 419

3

Helix

420 – 423

4

Helix

427 – 438

12

Helix

439 – 443

5

Helix

447 – 463

17

Helix

470 – 482

13

Helix

487 – 513

27

Helix

523 – 525

3

Beta strand

526 – 532

7

Helix

533 – 536

4

Helix

549 – 552

4

Helix

555 – 563

9

Beta strand

566 – 573

8

Helix

575 – 577

3

Beta strand

579 – 585

7

Beta strand

590 – 596

7

Helix

597 – 603

7

Helix

604 – 606

3

Helix

616 – 623

8

Helix

627 – 638

12

Beta strand

647 – 652

6

Helix

657 – 659

3

Beta strand

665 – 668

4

Beta strand

674 – 687

14

Turn

690 – 693

4

Helix

697 – 723

27

Beta strand

726 – 729

4

Helix

731 – 741

11

Turn

742 – 745

4

Helix

750 – 762

13

Beta strand

765 – 769

5

Beta strand

772 – 778

7

Sequences

	Sequence		Length	Mass (Da)
	Q93034 [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] [Europe PMC] [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]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[7]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RBX1 AND RNF7.
[8]	"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] [Europe PMC] [Abstract] Cited for: NEDDYLATION.
[9]	"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] [Europe PMC] [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.
[10]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH HUMAN ADENOVIRUS 5 PROTEINS, NEDDYLATION.
[11]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIV VIF.
[12]	"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] [Europe PMC] [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.
[13]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ASB1; ASB2; ASB6; ASB7 AND ASB12.
[14]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-210, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00216003.

RefSeq

NP_003469.2. NM_003478.3.

UniGene

Hs.440320.
Hs.701122.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

Q93034.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-43696N.

IntAct

Q93034. 18 interactions.

MINT

MINT-1184052.

STRING

9606.ENSP00000299351.

PTM databases

PhosphoSite

Q93034.

Polymorphism databases

DMDM

14917099.

Proteomic databases

PaxDb

Q93034.

PRIDE

Q93034.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000393094; ENSP00000376808; ENSG00000166266.
ENST00000531427; ENSP00000435376; ENSG00000166266.

GeneID

8065.

KEGG

hsa:8065.

UCSC

uc001pjv.3. human.

Organism-specific databases

CTD

8065.

GeneCards

GC11P107913.

HGNC

HGNC:2556. CUL5.

HPA

CAB017787.
HPA002185.

MIM

601741. gene.

neXtProt

NX_Q93034.

PharmGKB

PA27052.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5647.

HOGENOM

HOG000007610.

HOVERGEN

HBG099672.

InParanoid

Q93034.

KO

K10612.

OMA

EVTTFQM.

OrthoDB

EOG46Q6RZ.

PhylomeDB

Q93034.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q93034.

Bgee

Q93034.

CleanEx

HS_CUL5.

Genevestigator

Q93034.

GermOnline

ENSG00000166266. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.10. 2 hits.

InterPro

IPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

Pfam

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

SMART

SM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]

SUPFAM

SSF75632. Cullin_homology. 1 hit.
SSF74788. Cullin_repeat-like. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

EvolutionaryTrace

Q93034.

GenomeRNAi

8065.

NextBio

30655.

SOURCE

Search...

Entry information

Entry name

CUL5_HUMAN

Accession

Primary (citable) accession number: Q93034
Secondary accession number(s): A8K960, O14766, Q9BZC6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 121 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.