Cullin-2 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot Q13617 (CUL2_HUMAN)

Last modified June 16, 2009. Version 81. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
Cullin-2
Short name=CUL-2

Gene names

Name:

CUL2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	745 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. May serve as a rigid scaffold in the complex and may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 By similarity. The functional specificity of the ECS complex depends on the substrate recognition component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF).
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 CUL2, Elongin BC (TCEB1 and TCEB2), RBX1 and a variable substrate-specific adapter. Component of the ECS(VHL) or CBC(VHL) complex containing VHL. Component of the ECS(MED8) complex with the probable substrate recognition component MED8 By similarity. Component of the ECS(PPIL5) complex with the probable substrate recognition component PPIL5. Component of a probable ECS E3 ubiquitin-protein ligase complex containing CUL2, RBX1, TCEB1, TCEB2 and FEM1B. Part of an E3 ubiquitin-protein ligase complex including ZYG11B, CUL2 and Elongin BC. Part of an E3 ubiquitin-protein ligase complex including ZYG11BL, CUL2 and Elongin BC.Interacts with RBX1, RNF7, FEM1B and TIP120A/CAND1. Interacts with COPS2, and MED8 By similarity. Interacts with human respiratory syncytial virus (HRSV) protein NS1.
Post-translational modification	CBC(VHL) complex formation seems to promote neddylation. Deneddylated via its interaction with the COP9 signalosome (CSN) complex By similarity.
Sequence similarities	Belongs to the cullin family.

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Ontologies

Keywords
Biological process	Host-virus interaction Ubl conjugation pathway
Coding sequence diversity	Polymorphism
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	G1/S transition of mitotic cell cycle Ref.5 Traceable author statement. Source: ProtInc cell cycle arrest Ref.5 Traceable author statement. Source: ProtInc induction of apoptosis by intracellular signals Ref.5 Traceable author statement. Source: ProtInc negative regulation of cell proliferation Ref.5 Traceable author statement. Source: ProtInc ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	cullin-RING ubiquitin ligase complex Inferred from electronic annotation. Source: InterPro
Molecular function	ubiquitin protein ligase binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
CAB39	Q9Y376	1	EBI-456179,EBI-306905
CAND1	Q86VP6	2	EBI-456179,EBI-456077
CMBL	Q96DG6	1	EBI-456179,EBI-1044268
DLG3	Q92796	1	EBI-456179,EBI-80440
fem-1	P17221	1	EBI-456179,EBI-1998155	From a different organism.
KCTD5	Q9NXV2	1	EBI-456179,EBI-1056857
P4HB	P07237	1	EBI-456179,EBI-395883
PFKFB3	Q16875	1	EBI-456179,EBI-764464
RNMTL1	Q9HC36	1	EBI-456179,EBI-1045440
STOM	P27105	1	EBI-456179,EBI-1211440
TFE3	P19532	1	EBI-456179,EBI-1048957
TIMM13	Q9Y5L4	1	EBI-456179,EBI-1057344
VHL	P40337	1	EBI-456179,EBI-301246
ZER1	Q7Z7L7	1	EBI-456179,EBI-1811449
ZYG11B	Q9C0D3	1	EBI-456179,EBI-1811414

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 745

745

Cullin-2

PRO_0000119790

Amino acid modifications

Modified residue

394

Phosphotyrosine By similarity

Modified residue

661

Phosphothreonine Ref.15

Cross-link

689

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) Ref.2 Ref.11

Natural variations

Natural variant

109

N → S: dbSNP rs1131503. Ref.2 Ref.1

VAR_011374

Experimental info

Mutagenesis

621

K → R: No effect on conjugation with NEDD8. Ref.2

Mutagenesis

689

K → R: Loss of conjugation with NEDD8. Ref.2

Mutagenesis

719

K → R: No effect on conjugation with NEDD8. Ref.2

Sequence conflict

95 – 98

SKGA → IRHE Ref.5

Sequence conflict

681

Q → H in AAC50545. Ref.5

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Sequences

Sequence

Length

Mass (Da)

Tools

Q13617-1 [UniParc].

Last modified August 14, 2001. Version 2.
Checksum: 30647248F671AB0E
Show »

FASTA

745

86,983

        10         20         30         40         50         60 
MSLKPRVVDF DETWNKLLTT IKAVVMLEYV ERATWNDRFS DIYALCVAYP EPLGERLYTE 

        70         80         90        100        110        120 
TKIFLENHVR HLHKRVLESE EQVLVMYHRY WEEYSKGADY MDCLYRYLNT QFIKKNKLTE 

       130        140        150        160        170        180 
ADLQYGYGGV DMNEPLMEIG ELALDMWRKL MVEPLQAILI RMLLREIKND RGGEDPNQKV 

       190        200        210        220        230        240 
IHGVINSFVH VEQYKKKFPL KFYQEIFESP FLTETGEYYK QEASNLLQES NCSQYMEKVL 

       250        260        270        280        290        300 
GRLKDEEIRC RKYLHPSSYT KVIHECQQRM VADHLQFLHA ECHNIIRQEK KNDMANMYVL 

       310        320        330        340        350        360 
LRAVSTGLPH MIQELQNHIH DEGLRATSNL TQENMPTLFV ESVLEVHGKF VQLINTVLNG 

       370        380        390        400        410        420 
DQHFMSALDK ALTSVVNYRE PKSVCKAPEL LAKYCDNLLK KSAKGMTENE VEDRLTSFIT 

       430        440        450        460        470        480 
VFKYIDDKDV FQKFYARMLA KRLIHGLSMS MDSEEAMINK LKQACGYEFT SKLHRMYTDM 

       490        500        510        520        530        540 
SVSADLNNKF NNFIKNQDTV IDLGISFQIY VLQAGAWPLT QAPSSTFAIP QELEKSVQMF 

       550        560        570        580        590        600 
ELFYSQHFSG RKLTWLHYLC TGEVKMNYLG KPYVAMVTTY QMAVLLAFNN SETVSYKELQ 

       610        620        630        640        650        660 
DSTQMNEKEL TKTIKSLLDV KMINHDSEKE DIDAESSFSL NMNFSSKRTK FKITTSMQKD 

       670        680        690        700        710        720 
TPQEMEQTRS AVDEDRKMYL QAAIVRIMKA RKVLRHNALI QEVISQSRAR FNPSISMIKK 

       730        740 
CIEVLIDKQY IERSQASADE YSYVA

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins." Pause A., Lee S., Worrel R., Chen D.Y.T., Burgess W.H., Linehan W.M., Klausner R.D. Proc. Natl. Acad. Sci. U.S.A. 94:2156-2161(1997) [PubMed: 9122164] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-109, IDENTIFICATION IN COMPLEX WITH VHL AND ELONGIN BC. Tissue: Kidney.
[2]	"Identification of NEDD8-conjugation site in human cullin-2." Wada H., Yeh E.T.H., Kamitani T. Biochem. Biophys. Res. Commun. 257:100-105(1999) [PubMed: 10092517] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-109, MUTAGENESIS OF LYS-621; LYS-689 AND LYS-719, NEDDYLATION AT LYS-689. Tissue: Brain.
[3]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: Brain and Skin.
[5]	"cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family." Kipreos E.T., Lander L.E., Wing J.P., He W.W., Hedgecock E.M. Cell 85:829-839(1996) [PubMed: 8681378] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 95-745.
[6]	"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.
[7]	"Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex." Kamura T., Sato S., Iwai K., Czyzyk-Krzeska M., Conaway R.C., Conaway J.W. Proc. Natl. Acad. Sci. U.S.A. 97:10430-10435(2000) [PubMed: 10973499] [Abstract] Cited for: IDENTIFICATION IN CBC(VHL) COMPLEX.
[8]	"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 COMPLEX WITH VHL; ELONGIN BC AND RBX1.
[9]	"Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase." Brower C.S., Sato S., Tomomori-Sato C., Kamura T., Pause A., Stearman R., Klausner R.D., Malik S., Lane W.S., Sorokina I., Roeder R.G., Conaway J.W., Conaway R.C. Proc. Natl. Acad. Sci. U.S.A. 99:10353-10358(2002) [PubMed: 12149480] [Abstract] Cited for: IDENTIFICATION IN E3 UBIQUITIN-PROTEIN LIGASE COMPLEX WITH MED8.
[10]	"TIP120A associates with cullins and modulates ubiquitin ligase activity." Min K.-W., Hwang J.-W., Lee J.-S., Park Y., Tamura T.-A., Yoon J.-B. J. Biol. Chem. 278:15905-15910(2003) [PubMed: 12609982] [Abstract] Cited for: INTERACTION WITH TIP120A.
[11]	"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.
[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: 15601820] [Abstract] Cited for: INTERACTION WITH PPIL5 AND FEM1B.
[13]	"The Caenorhabditis elegans cell-cycle regulator ZYG-11 defines a conserved family of CUL-2 complex components." Vasudevan S., Starostina N.G., Kipreos E.T. EMBO Rep. 8:279-286(2007) [PubMed: 17304241] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH TCEB1 AND ZYG11B, IDENTIFICATION IN COMPLEX WITH TCEB1; TCEB2 AND CUL2.
[14]	"Respiratory syncytial virus NS1 protein degrades STAT2 by using the Elongin-Cullin E3 ligase." Elliott J., Lynch O.T., Suessmuth Y., Qian P., Boyd C.R., Burrows J.F., Buick R., Stevenson N.J., Touzelet O., Gadina M., Power U.F., Johnston J.A. J. Virol. 81:3428-3436(2007) [PubMed: 17251292] [Abstract] Cited for: INTERACTION WITH HRSV VIRUS PROTEIN NS1.
[15]	"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-661, MASS SPECTROMETRY.
[16]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.

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Cross-references

Sequence databases
	U83410 mRNA. Translation: AAC51190.1. AF126404 mRNA. Translation: AAD23581.1. AL392046 Genomic DNA. Translation: CAI13163.1. BC009591 mRNA. Translation: AAH09591.1. BC110901 mRNA. Translation: AAI10902.1. U58088 mRNA. Translation: AAC50545.1.
IPI	IPI00014311.
RefSeq	NP_003582.2.
UniGene	Hs.82919
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13617. 27 interactions.
PTM databases
PhosphoSite	Q13617.
Proteomic databases
PRIDE	Q13617.
Genome annotation databases
Ensembl	ENSG00000108094. Homo sapiens. [Contig view]
GeneID	8453.
KEGG	hsa:8453.
Organism-specific databases
GeneCards	GC10M035338.
H-InvDB	HIX0008760.
HGNC	HGNC:2552. CUL2.
HPA	CAB002677.
MIM	603135. gene.
PharmGKB	PA27048.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q13617.
HOVERGEN	Q13617.
OMA	Q13617. MANMYTL.
Enzyme and pathway databases
Pathway_Interaction_DB	hif1apathway. Hypoxic and oxygen homeostasis regulation of HIF-1-alpha.
Gene expression databases
ArrayExpress	Q13617.
Bgee	Q13617.
CleanEx	HS_CUL2.
GermOnline	ENSG00000108094. 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. 2 hits.
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	31634.
SOURCE	Search...

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Entry information

Entry name

CUL2_HUMAN

Accession

Primary (citable) accession number: Q13617
Secondary accession number(s): O00200, Q5T2B6, Q9UNF9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	August 14, 2001
Last modified:	June 16, 2009
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents