Reviewed,
UniProtKB/Swiss-Prot Q13617 (CUL2_HUMAN)
Last modified
June 16, 2009.
Version 81.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Cullin-2 Short name=CUL-2 | ||
| Gene names |
| ||
| 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 | 745 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
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 | |
| 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. |
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.5Traceable author statement. Source: ProtInc induction of apoptosis by intracellular signals Ref.5Traceable author statement. Source: ProtInc negative regulation of cell proliferation Ref.5Traceable author statement. Source: ProtInc ubiquitin-dependent protein catabolic processInferred 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... | |
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 |
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 | 1 | Phosphotyrosine By similarity | ||||||
| Modified residue | 661 | 1 | 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 | 1 | N → S: dbSNP rs1131503. Ref.2 Ref.1 | VAR_011374 | |||||
Experimental info | |||||||||
| Mutagenesis | 621 | 1 | K → R: No effect on conjugation with NEDD8. Ref.2 | ||||||
| Mutagenesis | 689 | 1 | K → R: Loss of conjugation with NEDD8. Ref.2 | ||||||
| Mutagenesis | 719 | 1 | K → R: No effect on conjugation with NEDD8. Ref.2 | ||||||
| Sequence conflict | 95 – 98 | 4 | SKGA → IRHE Ref.5 | ||||||
| Sequence conflict | 681 | 1 | Q → H in AAC50545. Ref.5 | ||||||
Sequences
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References
| « Hide '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. |
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... |
Entry information
| Entry name | CUL2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q13617 Secondary accession number(s): O00200, Q5T2B6, Q9UNF9 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
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 |

Clusters with


