CUL5

CUL5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3DPL, 3DQV, 4JGH, 4N9F
Identifiers
Aliases	CUL5 , VACM-1, VACM1, cullin 5, CUL-5
External IDs	OMIM: 601741; MGI: 1922967; HomoloGene: 2597; GeneCards: CUL5; OMA:CUL5 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11q22.3 Start 108,008,898 bp [1] End 108,107,761 bp [1]
Gene location (Mouse) Chr. Chromosome 9 (mouse) [2] Band 9|9 A5.3 Start 53,525,882 bp [2] End 53,581,314 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte glutes muscle of arm biceps brachii triceps brachii muscle deltoid muscle Skeletal muscle tissue of biceps brachii Skeletal muscle tissue of rectus abdominis thoracic diaphragm Epithelium of choroid plexus Top expressed in Rostral migratory stream morula tail of embryo zygote spermatid ascending aorta aortic valve spermatocyte muscle of thigh genital tubercle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding ubiquitin protein ligase binding ubiquitin protein ligase activity calcium channel activity ubiquitin-protein transferase activity signaling receptor activity Cellular component cullin-RING ubiquitin ligase complex cytosol Cul5-RING ubiquitin ligase complex Cul4-RING E3 ubiquitin ligase complex SCF ubiquitin ligase complex Biological process intrinsic apoptotic signaling pathway cell population proliferation ubiquitin-dependent protein catabolic process negative regulation of cell population proliferation protein ubiquitination viral process ERBB2 signaling pathway calcium ion transmembrane transport cellular response to DNA damage stimulus post-translational protein modification G1/S transition of mitotic cell cycle SCF-dependent proteasomal ubiquitin-dependent protein catabolic process proteasome-mediated ubiquitin-dependent protein catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8065 75717 Ensembl ENSG00000166266 ENSMUSG00000032030 UniProt Q93034 Q9D5V5 RefSeq (mRNA) NM_003478 NM_001161618 NM_027807 RefSeq (protein) NP_003469 NP_001155090 NP_082083 Location (UCSC) Chr 11: 108.01 – 108.11 Mb Chr 9: 53.53 – 53.58 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Cullin-5 is a protein that in humans is encoded by the CUL5 gene. ^{[5] [6] [7]}

Discovery

The mammalian gene product was originally discovered by expression cloning, due to the protein's ability to mobilize intracellular calcium in response to the peptide hormone arginine vasopressin. It was first titled VACM-1, for vasopressin-activated, calcium-mobilizing receptor. ^[8] Since then, VACM-1 has been shown to be homologous to the Cullin family of proteins, and was subsequently dubbed cul5.

Tissue distribution

Studies have shown that the cul5 protein is expressed at its highest levels in heart and skeletal tissue, and is specifically expressed in vascular endothelium and renal collecting tubules. ^[9]

Function

Cul5 inhibits cellular proliferation, potentially through its involvement in the SOCS/ BC-box/ eloBC/ cul5/ RING E3 ligase complex, which functions as part of the ubiquitin system for protein degradation. ^[10]

One study have shown that Cul5 plays a role in Reelin signaling cascade, participating in the DAB1 degradation and thus ensuring the negative feedback mechanism of Reelin signaling during corticogenesis. ^[11]

Interactions

CUL5 has been shown to interact with RBX1. ^{[12] [13]}

References

1. GRCh38: Ensembl release 89: ENSG00000166266 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000032030 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Kipreos ET, Lander LE, Wing JP, He WW, Hedgecock EM (Aug 1996). "cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family". Cell. 85 (6): 829–39. doi: 10.1016/S0092-8674(00)81267-2 . PMID   8681378. S2CID   15805562.
6. Byrd PJ, Stankovic T, McConville CM, Smith AD, Cooper PR, Taylor AM (May 1997). "Identification and analysis of expression of human VACM-1, a cullin gene family member located on chromosome 11q22-23". Genome Res. 7 (1): 71–5. doi: 10.1101/gr.7.1.71 . PMID   9037604.
7. "Entrez Gene: CUL5 cullin 5".
8. Burnatowska-Hledin MA, Spielman WS, Smith WL, et al. (1995). "Expression cloning of an AVP-activated, calcium-mobilizing receptor from rabbit kidney medulla". Am J Physiol. 268 (6): F1198–210. doi:10.1152/ajprenal.1995.268.6.F1198. PMID   7611460.
9. Burnatowska-Hledin M, Lazdins IB, Listenberger L, et al. (1999). "VACM-1 receptor is specifically expressed in rabbit vascular endothelium and renal collecting tubule". Am J Physiol. 276 (2 Pt 2): F199–209. doi:10.1152/ajprenal.1999.276.2.F199. PMID   9950950.
10. Petroski MD, Deshaies RJ (2005). "Function and regulation of cullin-RING E3 ligases" (PDF). Nature Reviews Molecular Cell Biology. 6 (1): 9–21. doi:10.1038/nrm1547. PMID   15688063. S2CID   24159190.
11. Feng L, Allen NS, Simo S, Cooper JA (November 2007). "Cullin 5 regulates Dab1 protein levels and neuron positioning during cortical development". Genes Dev. 21 (21): 2717–30. doi:10.1101/gad.1604207. PMC   2045127 . PMID   17974915.
12. Duda DM, Borg Laura A, Scott Daniel C, Hunt Harold W, Hammel Michal, Schulman Brenda A (Sep 2008). "Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation". Cell. 134 (6). United States: 995–1006. doi:10.1016/j.cell.2008.07.022. PMC   2628631 . PMID   18805092.
13. Ohta T, Michel J J, Schottelius A J, Xiong Y (Apr 1999). "ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity". Mol. Cell. 3 (4). UNITED STATES: 535–41. doi: 10.1016/S1097-2765(00)80482-7 . ISSN   1097-2765. PMID   10230407. S2CID   19371828.

External links

• Human CUL5 genome location and CUL5 gene details page in the UCSC Genome Browser .

Further reading

• Hillier LD, Lennon G, Becker M, et al. (1997). "Generation and analysis of 280,000 human expressed sequence tags". Genome Res. 6 (9): 807–28. doi: 10.1101/gr.6.9.807 . PMID   8889549.
• Stankovic T, Byrd PJ, Cooper PR, et al. (1997). "Construction of a transcription map around the gene for ataxia telangiectasia: identification of at least four novel genes". Genomics. 40 (2): 267–76. doi:10.1006/geno.1996.4595. PMID   9119394.
• North WG, Fay MJ, Longo KA, Du J (1998). "Expression of all known vasopressin receptor subtypes by small cell tumors implies a multifaceted role for this neuropeptide". Cancer Res. 58 (9): 1866–71. PMID   9581826.
• Burnatowska-Hledin M, Lazdins IB, Listenberger L, et al. (1999). "VACM-1 receptor is specifically expressed in rabbit vascular endothelium and renal collecting tubule". Am. J. Physiol. 276 (2 Pt 2): F199–209. doi:10.1152/ajprenal.1999.276.2.F199. PMID   9950950.
• Wada H, Yeh ET, Kamitani T (1999). "Identification of NEDD8-conjugation site in human cullin-2". Biochem. Biophys. Res. Commun. 257 (1): 100–5. doi:10.1006/bbrc.1999.0339. PMID   10092517.
• Ohta T, Michel JJ, Schottelius AJ, Xiong Y (1999). "ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity". Mol. Cell. 3 (4): 535–41. doi: 10.1016/S1097-2765(00)80482-7 . PMID   10230407. S2CID   19371828.
• Hori T, Osaka F, Chiba T, et al. (2000). "Covalent modification of all members of human cullin family proteins by NEDD8". Oncogene. 18 (48): 6829–34. doi: 10.1038/sj.onc.1203093 . PMID   10597293.
• Burnatowska-Hledin M, Zhao P, Capps B, et al. (2000). "VACM-1, a cullin gene family member, regulates cellular signaling". Am. J. Physiol., Cell Physiol. 279 (1): C266–73. doi:10.1152/ajpcell.2000.279.1.C266. PMID   10898738. S2CID   19845050.
• Kamura T, Burian D, Yan Q, et al. (2001). "Muf1, a novel Elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase". J. Biol. Chem. 276 (32): 29748–53. doi: 10.1074/jbc.M103093200 . PMID   11384984.
• Burnatowska-Hledin M, Zeneberg A, Roulo A, et al. (2001). "Expression of VACM-1 protein in cultured rat adrenal endothelial cells is linked to the cell cycle". Endothelium. 8 (1): 49–63. doi:10.3109/10623320109063157. PMID   11409851.
• Harada JN, Shevchenko A, Shevchenko A, et al. (2002). "Analysis of the Adenovirus E1B-55K-Anchored Proteome Reveals Its Link to Ubiquitination Machinery". J. Virol. 76 (18): 9194–206. doi:10.1128/JVI.76.18.9194-9206.2002. PMC   136464 . PMID   12186903.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Liu J, Furukawa M, Matsumoto T, Xiong Y (2003). "NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases". Mol. Cell. 10 (6): 1511–8. doi: 10.1016/S1097-2765(02)00783-9 . PMID   12504025. S2CID   28959307.
• Van Dort C, Zhao P, Parmelee K, et al. (2004). "VACM-1, a cul-5 gene, inhibits cellular growth by a mechanism that involves MAPK and p53 signaling pathways". Am. J. Physiol., Cell Physiol. 285 (6): C1386–96. doi:10.1152/ajpcell.00338.2002. PMID   12917106.
• Yu X, Yu Y, Liu B, et al. (2003). "Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex". Science. 302 (5647): 1056–60. Bibcode:2003Sci...302.1056Y. doi:10.1126/science.1089591. PMID   14564014. S2CID   29676466.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID   14702039.
• Burnatowska-Hledin MA, Kossoris JB, Van Dort CJ, et al. (2004). "T47D breast cancer cell growth is inhibited by expression of VACM-1, a cul-5 gene". Biochem. Biophys. Res. Commun. 319 (3): 817–25. doi:10.1016/j.bbrc.2004.05.057. PMID   15184056.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.