Reviewed,
UniProtKB/Swiss-Prot Q13618 (CUL3_HUMAN)
Last modified
November 3, 2009.
Version 95.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
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Names and origin
| Protein names | Recommended name: Cullin-3 Short name=CUL-3 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 768 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 BCR (BTB-CUL3-RBX1) 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 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 BCR complex depends on the BTB domain-containing protein as the susbstrate recognition component. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, H2AFY and DAXX, and probably GLI2 or GLI3. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. |
| Pathway | |
| Subunit structure | Forms neddylation-dependent homodimers. Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein acting as both, adapter to cullin and substrate recognition subunit. The BCR complex may be active as a heterodimeric complex, in which NEDD8, covalently attached to one CUL3 molecule, binds to the C-terminus of a second CUL3 molecule. Interacts with RBX1, RNF7, CYCE and TIP120A/CAND1. Part of the BCR(SPOP) containing SPOP. Part of the probable BCR(KLHL9-KLHL13) complex with BTB domain proteins KLHL9 and KLHL13. Part of the BCR(KBTBD10) complex containing KBTBD10. Part of the BCR(ENC1) complex containing ENC1. Part of a complex consisting of BMI1/PCGF4, CUL3 and SPOP. Part of a complex consisting of H2AFY, CUL3 and SPOP. Interacts with KLHL9, KLHL13, GAN, ZBTB16, KLHL21, KLHL3, KLHL15, KLHL20, C16orf44, GMCL1L, BTBD1. Part of a complex that contains CUL3, RBX1 and GAN. Ref.10 Ref.13 Ref.14 Ref.15 Ref.20 Ref.21 Ref.23 |
| Subcellular location | |
| Tissue specificity | Widely expressed. |
| Post-translational modification | Neddylated. Attachment of NEDD8 is required for the E3 ubiquitin-protein ligase activity of the BCR complex. Deneddylated via its interaction with the COP9 signalosome (CSN) complex. |
| Sequence similarities | Belongs to the cullin family. |
| Sequence caution | The sequence AAC28621.1 differs from that shown. Reason: Frameshift at position 452. The sequence AAC36682.1 differs from that shown. Reason: Frameshift at positions 159 and 179. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| CAND1 | Q86VP6 | 1 | EBI-456129,EBI-456077 | |
| CASP8 | Q14790 | 3 | EBI-456129,EBI-78060 | |
| TNFSF10 | P50591 | 2 | EBI-456129,EBI-495373 |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q13618-1) Also known as: Cul-3 Long; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q13618-2) The sequence of this isoform differs from the canonical sequence as follows: 1-24: Missing. | ||||||
| Isoform 3 (identifier: Q13618-3) Also known as: Cul-3 Short; The sequence of this isoform differs from the canonical sequence as follows: 23-88: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 768 | 768 | Cullin-3 | PRO_0000119793 | |||||
Amino acid modifications | |||||||||
| Modified residue | 58 | 1 | Phosphotyrosine Ref.18 | ||||||
| Modified residue | 450 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 737 | 1 | Phosphoserine Ref.16 | ||||||
| Cross-link | 712 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) By similarity | |||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 24 | 24 | Missing in isoform 2. | VSP_008824 | |||||
| Alternative sequence | 23 – 88 | 66 | Missing in isoform 3. | VSP_008825 | |||||
| Natural variant | 13 | 1 | D → H: dbSNP rs2969802. | VAR_017194 | |||||
| Natural variant | 184 | 1 | R → S: dbSNP rs17480168. | VAR_048839 | |||||
| Natural variant | 567 | 1 | V → I: dbSNP rs3738952. | VAR_017195 | |||||
Experimental info | |||||||||
| Sequence conflict | 13 | 1 | D → G in AAC36682. Ref.3 | ||||||
| Sequence conflict | 397 | 1 | K → T in AAQ01660. Ref.4 | ||||||
| Sequence conflict | 481 | 1 | N → T in AAQ01660. Ref.4 | ||||||
| Sequence conflict | 609 | 1 | E → G in AAH31844. Ref.7 | ||||||
| Sequence conflict | 666 | 1 | T → I in AAQ01660. Ref.4 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning and expression analysis of a novel salicylate suppressible gene, Hs-CUL-3, a member of cullin/Cdc53 family." Du M., Sansores-Garcia L., Zu Z., Wu K.K. J. Biol. Chem. 273:24289-24292(1998) [PubMed: 9733711] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [2] | "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed: 9734811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain. |
| [3] | "Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A." Michel J.J., Xiong Y. Cell Growth Differ. 9:435-449(1998) [PubMed: 9663463] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Colon carcinoma. |
| [4] | "Cloning and characterization of a new isoform of CUL3 gene in testis." Xu M., Huang X.Y., Yin L.L., Xu Z.Y., Lu L., Zhou Z.M., Sha J.H. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Testis. |
| [5] | "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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). |
| [6] | 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. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "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] (ISOFORM 1). Tissue: Ovary, Skin and Uterus. |
| [8] | "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 192-768. |
| [9] | Yu W., Sarginson J., Gibbs R.A. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 398-768. Tissue: Brain. |
| [10] | "Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells." Singer J.D., Gurian-West M., Clurman B., Roberts J.M. Genes Dev. 13:2375-2387(1999) [PubMed: 10500095] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORMS 1 AND 3), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CYCE, NEDDYLATION. |
| [11] | "In vitro ubiquitination of cyclin D1 by ROC1-CUL1 and ROC1-CUL3." Maeda I., Ohta T., Koizumi H., Fukuda M. FEBS Lett. 494:181-185(2001) [PubMed: 11311237] [Abstract] Cited for: FUNCTION. |
| [12] | "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. |
| [13] | "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. |
| [14] | "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. |
| [15] | "Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases." Furukawa M., He Y.J., Borchers C., Xiong Y. Nat. Cell Biol. 5:1001-1007(2003) [PubMed: 14528312] [Abstract] Cited for: INTERACTION WITH GAN; ZBTB16; KLHL9; KLHL13; KLHL211; KLHL3; KLHL15; KLHL20; C16ORF44; GMCL1L; BTBD1 AND SPOP. |
| [16] | "Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-737, MASS SPECTROMETRY. Tissue: Epithelium. |
| [17] | "Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway." Zhang D.D., Lo S.C., Sun Z., Habib G.M., Lieberman M.W., Hannink M. J. Biol. Chem. 280:30091-30099(2005) [PubMed: 15983046] [Abstract] Cited for: IDENTIFICATION IN THE BCR(KBTBD10) COMPLEX, IDENTIFICATION IN THE BCR(ENC1) COMPLEX, IDENTIFICATION IN A COMPLEX WITH RBX1 AND GAN. |
| [18] | "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-58, MASS SPECTROMETRY. |
| [19] | "Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase." Hernandez-Munoz I., Lund A.H., van der Stoop P., Boutsma E., Muijrers I., Verhoeven E., Nusinow D.A., Panning B., Marahrens Y., van Lohuizen M. Proc. Natl. Acad. Sci. U.S.A. 102:7635-7640(2005) [PubMed: 15897469] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH SPOP AND BMI1, IDENTIFICATION IN A COMPLEX WITH SPOP AND H2AFY, FUNCTION. |
| [20] | "BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase." Kwon J.E., La M., Oh K.H., Oh Y.M., Kim G.R., Seol J.H., Baek S.H., Chiba T., Tanaka K., Bang O.S., Joe C.O., Chung C.H. J. Biol. Chem. 281:12664-12672(2006) [PubMed: 16524876] [Abstract] Cited for: IDENTIFICATION IN THE BCR(SPOP) COMPLEX, INTERACTION WITH SPOP, FUNCTION IN UBIQUITINATION OF DAXX. |
| [21] | "A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells." Sumara I., Quadroni M., Frei C., Olma M.H., Sumara G., Ricci R., Peter M. Dev. Cell 12:887-900(2007) [PubMed: 17543862] [Abstract] Cited for: FUNCTION, INTERACTION WITH KLHL9 AND KLHL13. |
| [22] | "Characterization of cullin-based E3 ubiquitin ligases in intact mammalian cells -- evidence for cullin dimerization." Chew E.H., Poobalasingam T., Hawkey C.J., Hagen T. Cell. Signal. 19:1071-1080(2007) [PubMed: 17254749] [Abstract] Cited for: SELF-ASSOCIATION. |
| [23] | "The Cullin3 ubiquitin ligase functions as a Nedd8-bound heterodimer." Wimuttisuk W., Singer J.D. Mol. Biol. Cell 18:899-909(2007) [PubMed: 17192413] [Abstract] Cited for: BCR COMPLEX HOMODIMERIZATION. |
| [24] | 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 | |
|---|---|
| AF064087 mRNA. Translation: AAC36304.1. AB014517 mRNA. Translation: BAA31592.2. Different initiation. AF062537 mRNA. Translation: AAC36682.1. Frameshift. AY337761 mRNA. Translation: AAQ01660.1. AK291151 mRNA. Translation: BAF83840.1. CH471063 Genomic DNA. Translation: EAW70828.1. BC031844 mRNA. Translation: AAH31844.1. BC039598 mRNA. Translation: AAH39598.1. BC092409 mRNA. Translation: AAH92409.1. U58089 mRNA. Translation: AAC50546.1. AF052147 mRNA. Translation: AAC28621.1. Frameshift. | |
| IPI | IPI00014312. IPI00382458. IPI00382459. |
| RefSeq | NP_003581.1. |
| UniGene | Hs.372286 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q13618. 8 interactions. |
| STRING | Q13618. |
PTM databases | |
| PhosphoSite | Q13618. |
Proteomic databases | |
| PRIDE | Q13618. |
Genome annotation databases | |
| Ensembl | ENST00000264414; ENSP00000264414; ENSG00000036257; Homo sapiens. [Genome view] ENST00000344951; ENSP00000343601; ENSG00000036257; Homo sapiens. [Genome view] ENST00000409096; ENSP00000387200; ENSG00000036257; Homo sapiens. [Genome view] ENST00000409777; ENSP00000386525; ENSG00000036257; Homo sapiens. [Genome view] ENST00000432260; ENSP00000400361; ENSG00000036257; Homo sapiens. [Genome view] ENST00000436172; ENSP00000400935; ENSG00000036257; Homo sapiens. [Genome view] ENST00000451538; ENSP00000410575; ENSG00000036257; Homo sapiens. [Genome view] ENST00000454323; ENSP00000400558; ENSG00000036257; Homo sapiens. [Genome view] |
| GeneID | 8452. |
| KEGG | hsa:8452. |
| UCSC | uc002vny.1. human. uc010fwy.1. human. |
Organism-specific databases | |
| CTD | 8452. |
| GeneCards | GC02M225043. |
| H-InvDB | HIX0002888. |
| HGNC | HGNC:2553. CUL3. |
| HPA | CAB002678. |
| MIM | 603136. gene. |
| PharmGKB | PA27049. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | Q13618. |
| HOVERGEN | Q13618. |
| OMA | EREYLQR. |
Enzyme and pathway databases | |
| Pathway_Interaction_DB | aurora_b_pathway. Aurora B signaling. |
Gene expression databases | |
| ArrayExpress | Q13618. |
| Bgee | Q13618. |
| CleanEx | HS_CUL3. |
| Genevestigator | Q13618. |
| GermOnline | ENSG00000036257. 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 | 31630. |
| SOURCE | Search... |
Entry information
| Entry name | CUL3_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q13618 Secondary accession number(s): A8K536 Q9UET7 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 2 Human chromosome 2: 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


