CUL5

Last updated
CUL5
Protein CUL5 PDB 3DPL.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CUL5 , VACM-1, VACM1, cullin 5, CUL-5
External IDs OMIM: 601741 MGI: 1922967 HomoloGene: 2597 GeneCards: CUL5
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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]

Contents

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]

Related Research Articles

<span class="mw-page-title-main">CUL1</span> Protein-coding gene in humans

Cullin 1, also known as CUL1, is a human protein and gene from cullin family. This protein plays an important role in protein degradation and protein ubiquitination.

<span class="mw-page-title-main">NEDD8</span>

NEDD8 is a protein that in humans is encoded by the NEDD8 gene. This ubiquitin-like (UBL) protein becomes covalently conjugated to a limited number of cellular proteins, in a process called NEDDylation similar to ubiquitination. Human NEDD8 shares 60% amino acid sequence identity to ubiquitin. The primary known substrates of NEDD8 modification are the cullin subunits of cullin-based E3 ubiquitin ligases, which are active only when NEDDylated. Their NEDDylation is critical for the recruitment of E2 to the ligase complex, thus facilitating ubiquitin conjugation. NEDD8 modification has therefore been implicated in cell cycle progression and cytoskeletal regulation.

<span class="mw-page-title-main">NEDD4L</span> Protein-coding gene in the species Homo sapiens

Neural precursor cell expressed developmentally downregulated gene 4-like (NEDD4L) or NEDD4-2 is an enzyme of the NEDD4 family. In human the protein is encoded by the NEDD4L gene. In mouse the protein is commonly known as NEDD4-2 and the gene Nedd4-2.

<span class="mw-page-title-main">RBX1</span> Protein-coding gene in the species Homo sapiens

RING-box protein 1 is a protein that in humans is encoded by the RBX1 gene.

<span class="mw-page-title-main">CUL4A</span> Protein-coding gene in humans

Cullin-4A is a protein that in humans is encoded by the CUL4A gene. CUL4A belongs to the cullin family of ubiquitin ligase proteins and is highly homologous to the CUL4B protein. CUL4A regulates numerous key processes such as DNA repair, chromatin remodeling, spermatogenesis, haematopoiesis and the mitotic cell cycle. As a result, CUL4A has been implicated in several cancers and the pathogenesis of certain viruses including HIV. A component of a CUL4A complex, Cereblon, was discovered to be a major target of the teratogenic agent thalidomide.

<span class="mw-page-title-main">SCNN1G</span> Protein-coding gene in the species Homo sapiens

The SCNN1G gene encodes for the γ subunit of the epithelial sodium channel ENaC in vertebrates. ENaC is assembled as a heterotrimer composed of three homologous subunits α, β, and γ or δ, β, and γ. The other ENAC subunits are encoded by SCNN1A, SCNN1B, and SCNN1D.

<span class="mw-page-title-main">CUL2</span> Protein-coding gene in humans

Cullin-2 is a protein that in humans is encoded by the CUL2 gene.

<span class="mw-page-title-main">AMFR</span> Protein-coding gene in the species Homo sapiens

Autocrine motility factor receptor, isoform 2 is a protein that in humans is encoded by the AMFR gene.

<span class="mw-page-title-main">CUL4B</span> Protein-coding gene in humans

Cullin-4B is a protein that in humans is encoded by the CUL4B gene which is located on the X chromosome. CUL4B has high sequence similarity with CUL4A, with which it shares certain E3 ubiquitin ligase functions. CUL4B is largely expressed in the nucleus and regulates several key functions including: cell cycle progression, chromatin remodeling and neurological and placental development in mice. In humans, CUL4B has been implicated in X-linked intellectual disability and is frequently mutated in pancreatic adenocarcinomas and a small percentage of various lung cancers. Viruses such as HIV can also co-opt CUL4B-based complexes to promote viral pathogenesis. CUL4B complexes containing Cereblon are also targeted by the teratogenic drug thalidomide.

<span class="mw-page-title-main">CUL3</span> Protein-coding gene in humans

Cullin 3 is a protein that in humans is encoded by the CUL3 gene.

<span class="mw-page-title-main">RNF7</span> Protein-coding gene in the species Homo sapiens

RING-box protein 2 is a protein that in humans is encoded by the RNF7 gene.

<span class="mw-page-title-main">APPBP1</span> Protein-coding gene in the species Homo sapiens

NEDD8-activating enzyme E1 regulatory subunit is a protein that in humans is encoded by the NAE1 gene.

<span class="mw-page-title-main">UBE1C</span> Protein-coding gene in the species Homo sapiens

NEDD8-activating enzyme E1 catalytic subunit is a protein that in humans is encoded by the UBA3 gene.

<span class="mw-page-title-main">ANAPC2</span> Protein-coding gene in the species Homo sapiens

Anaphase-promoting complex subunit 2 is an enzyme that in humans is encoded by the ANAPC2 gene.

<span class="mw-page-title-main">CAND1</span> Protein-coding gene in humans

Cullin-associated NEDD8-dissociated protein 1 is a protein that in humans is encoded by the CAND1 gene.

<span class="mw-page-title-main">UBE2M</span> Protein-coding gene in the species Homo sapiens

NEDD8-conjugating enzyme Ubc12 is a protein that in humans is encoded by the UBE2M gene.

<span class="mw-page-title-main">SENP8</span> Protein-coding gene in the species Homo sapiens

Sentrin-specific protease 8 is an enzyme that in humans is encoded by the SENP8 gene.

<span class="mw-page-title-main">ANAPC11</span> Protein-coding gene in the species Homo sapiens

Anaphase-promoting complex subunit 11 is an enzyme that in humans is encoded by the ANAPC11 gene.

<span class="mw-page-title-main">KCNA10</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily A member 10 also known as Kv1.8 is a protein that in humans is encoded by the KCNA10 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit.

<span class="mw-page-title-main">Cullin</span> Hydrophobic scaffold protein

Cullins are a family of hydrophobic scaffold proteins which provide support for ubiquitin ligases (E3). All eukaryotes appear to have cullins. They combine with RING proteins to form Cullin-RING ubiquitin ligases (CRLs) that are highly diverse and play a role in myriad cellular processes, most notably protein degradation by ubiquitination.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000166266 - Ensembl, May 2017
  2. 1 2 3 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. United States. 134 (6): 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. UNITED STATES. 3 (4): 535–41. doi: 10.1016/S1097-2765(00)80482-7 . ISSN   1097-2765. PMID   10230407. S2CID   19371828.

Further reading