SH3KBP1

SH3 domain-containing kinase-binding protein 1 (synonyms - CIN85[5], in rodents - Ruk[6]) is an adaptor protein that in humans is encoded by the SH3KBP1 gene.[7][8]

SH3KBP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2BZ8, 2K6D, 2K9G, 2O2O, 2YDL, 5ABS, 2N64
Identifiers
Aliases	SH3KBP1, CD2BP3, CIN85, GIG10, HSB-1, HSB1, MIG18, SH3 domain containing kinase binding protein 1, IMD61, AGMX2
External IDs	OMIM: 300374 MGI: 1889583 HomoloGene: 10971 GeneCards: SH3KBP1
Gene location (Human) Chr. X chromosome (human)[1] Band Xp22.12 Start 19,533,977 bp[1] End 19,887,600 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X|X F4 Start 159,627,272 bp[2] End 159,978,069 bp[2]
Gene ontology Molecular function • SH3 domain binding • GO:0001948 protein binding Cellular component • cytosol • membrane • intercellular junction • focal adhesion • cell membrane • endocytic vesicle • synapse • cell junction • neuron projection • cytoskeleton • cytoplasmic vesicle membrane • cytoplasmic vesicle • cytoplasm Biological process • negative regulation of epidermal growth factor receptor signaling pathway • endocytosis • cell-cell signaling • cytoskeleton organization • regulation of cell shape • cell migration • apoptotic process • membrane organization • axon guidance • actin filament organization Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	30011	58194
Ensembl	ENSG00000147010	ENSMUSG00000040990
UniProt	Q96B97 Q5JPT2	Q8R550
RefSeq (mRNA)	NM_001024666 NM_001184960 NM_031892 NM_001353890 NM_001353891 NM_001353892 NM_001353893 NM_001353894 NM_001353895 NM_001353897	NM_001135727 NM_001135728 NM_001290661 NM_001290664 NM_021389 NM_001374701
RefSeq (protein)	NP_001019837 NP_001171889 NP_114098 NP_001340819 NP_001340820 NP_001340821 NP_001340822 NP_001340823 NP_001340824 NP_001340826	NP_001129199 NP_001129200 NP_001277590 NP_001277593 NP_067364 NP_001361630
Location (UCSC)	Chr X: 19.53 – 19.89 Mb	Chr X: 159.63 – 159.98 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

CBL (MIM 165360) constitutively interacts with SH3 domain-containing proteins and, upon tyrosine phosphorylation, with SH2 domain-containing proteins. The SH3KBP1 gene encodes an 85-kD CBL-interacting protein that enhances tumor necrosis factor (MIM 191160)-mediated apoptotic cell death (Narita et al., 2001).[supplied by OMIM][9]

Interactions

SH3KBP1 has been shown to interact with B-cell linker,[10] Grb2,[11][12] SH3GLB2,[13][14] SH3GL3,[13] SH3GL2,[14] BCAR1,[10] Epidermal growth factor receptor,[14][15] CBLB,[15] Cbl gene,[10][12][13][14][15] SOS1,[10] CRK[10] and PAK2.[16]

References

1. GRCh38: Ensembl release 89: ENSG00000147010 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000040990 - 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. Database, GeneCards Human Gene. "SH3KBP1 Gene - GeneCards | SH3K1 Protein | SH3K1 Antibody". www.genecards.org. Retrieved 2017-12-28.
6. Gout I, Middleton G, Adu J, Ninkina NN, Drobot LB, Filonenko V, Matsuka G, Davies AM, Waterfield M, Buchman VL (August 2000). "Negative regulation of PI 3-kinase by Ruk, a novel adaptor protein". The EMBO Journal. 19 (15): 4015–25. doi:10.1093/emboj/19.15.4015. PMC 306608. PMID 10921882.
7. Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, et al. (September 1996). "Generation and analysis of 280,000 human expressed sequence tags". Genome Research. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549.
8. Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O (September 1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence" (PDF). Nature. 377 (6547 Suppl): 3–174. PMID 7566098.
9. "Entrez Gene: SH3KBP1 SH3-domain kinase binding protein 1".
10. Watanabe S, Take H, Takeda K, Yu ZX, Iwata N, Kajigaya S (November 2000). "Characterization of the CIN85 adaptor protein and identification of components involved in CIN85 complexes". Biochemical and Biophysical Research Communications. 278 (1): 167–74. doi:10.1006/bbrc.2000.3760. PMID 11071869.
11. Gout I, Middleton G, Adu J, Ninkina NN, Drobot LB, Filonenko V, Matsuka G, Davies AM, Waterfield M, Buchman VL (August 2000). "Negative regulation of PI 3-kinase by Ruk, a novel adaptor protein". The EMBO Journal. 19 (15): 4015–25. doi:10.1093/emboj/19.15.4015. PMC 306608. PMID 10921882.
12. Borinstein SC, Hyatt MA, Sykes VW, Straub RE, Lipkowitz S, Boulter J, Bogler O (December 2000). "SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins". Cellular Signalling. 12 (11–12): 769–79. doi:10.1016/S0898-6568(00)00129-7. PMID 11152963.
13. Petrelli A, Gilestro GF, Lanzardo S, Comoglio PM, Migone N, Giordano S (March 2002). "The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met". Nature. 416 (6877): 187–90. doi:10.1038/416187a. PMID 11894096.
14. Soubeyran P, Kowanetz K, Szymkiewicz I, Langdon WY, Dikic I (March 2002). "Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors". Nature. 416 (6877): 183–7. doi:10.1038/416183a. PMID 11894095.
15. Szymkiewicz I, Kowanetz K, Soubeyran P, Dinarina A, Lipkowitz S, Dikic I (October 2002). "CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases". The Journal of Biological Chemistry. 277 (42): 39666–72. doi:10.1074/jbc.M205535200. PMID 12177062.
16. Kurakin AV, Wu S, Bredesen DE (September 2003). "Atypical recognition consensus of CIN85/SETA/Ruk SH3 domains revealed by target-assisted iterative screening". The Journal of Biological Chemistry. 278 (36): 34102–9. doi:10.1074/jbc.M305264200. PMID 12829691.

Further reading

• Salvatore P, Hanash CR, Kido Y, Imai Y, Accili D (March 1998). "Identification of sirm, a novel insulin-regulated SH3 binding protein that associates with Grb-2 and FYN". The Journal of Biological Chemistry. 273 (12): 6989–97. doi:10.1074/jbc.273.12.6989. PMID 9507006.
• Li J, Nishizawa K, An W, Hussey RE, Lialios FE, Salgia R, Sunder-Plassmann R, Reinherz EL (December 1998). "A cdc15-like adaptor protein (CD2BP1) interacts with the CD2 cytoplasmic domain and regulates CD2-triggered adhesion". The EMBO Journal. 17 (24): 7320–36. doi:10.1093/emboj/17.24.7320. PMC 1171078. PMID 9857189.
• Take H, Watanabe S, Takeda K, Yu ZX, Iwata N, Kajigaya S (February 2000). "Cloning and characterization of a novel adaptor protein, CIN85, that interacts with c-Cbl". Biochemical and Biophysical Research Communications. 268 (2): 321–8. doi:10.1006/bbrc.2000.2147. PMID 10679202.
• Chen B, Borinstein SC, Gillis J, Sykes VW, Bogler O (June 2000). "The glioma-associated protein SETA interacts with AIP1/Alix and ALG-2 and modulates apoptosis in astrocytes". The Journal of Biological Chemistry. 275 (25): 19275–81. doi:10.1074/jbc.M908994199. PMID 10858458.
• Gout I, Middleton G, Adu J, Ninkina NN, Drobot LB, Filonenko V, Matsuka G, Davies AM, Waterfield M, Buchman VL (August 2000). "Negative regulation of PI 3-kinase by Ruk, a novel adaptor protein". The EMBO Journal. 19 (15): 4015–25. doi:10.1093/emboj/19.15.4015. PMC 306608. PMID 10921882.
• Watanabe S, Take H, Takeda K, Yu ZX, Iwata N, Kajigaya S (November 2000). "Characterization of the CIN85 adaptor protein and identification of components involved in CIN85 complexes". Biochemical and Biophysical Research Communications. 278 (1): 167–74. doi:10.1006/bbrc.2000.3760. PMID 11071869.
• Borinstein SC, Hyatt MA, Sykes VW, Straub RE, Lipkowitz S, Boulter J, Bogler O (December 2000). "SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins". Cellular Signalling. 12 (11–12): 769–79. doi:10.1016/S0898-6568(00)00129-7. PMID 11152963.
• Narita T, Amano F, Yoshizaki K, Nishimoto N, Nishimura T, Tajima T, Namiki H, Taniyama T (2001). "Assignment of SH3KBP1 to human chromosome band Xp22.1-->p21.3 by in situ hybridization". Cytogenetics and Cell Genetics. 93 (1–2): 133–4. doi:10.1159/000056966. PMID 11474197.
• Soubeyran P, Kowanetz K, Szymkiewicz I, Langdon WY, Dikic I (March 2002). "Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors". Nature. 416 (6877): 183–7. doi:10.1038/416183a. PMID 11894095.
• Petrelli A, Gilestro GF, Lanzardo S, Comoglio PM, Migone N, Giordano S (March 2002). "The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met". Nature. 416 (6877): 187–90. doi:10.1038/416187a. PMID 11894096.
• Scott MP, Zappacosta F, Kim EY, Annan RS, Miller WT (August 2002). "Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1". The Journal of Biological Chemistry. 277 (31): 28238–46. doi:10.1074/jbc.M202783200. PMID 12029088.
• Verdier F, Valovka T, Zhyvoloup A, Drobot LB, Buchman V, Waterfield M, Gout I (July 2002). "Ruk is ubiquitinated but not degraded by the proteasome". European Journal of Biochemistry. 269 (14): 3402–8. doi:10.1046/j.1432-1033.2002.03031.x. PMID 12135478.
• Szymkiewicz I, Kowanetz K, Soubeyran P, Dinarina A, Lipkowitz S, Dikic I (October 2002). "CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases". The Journal of Biological Chemistry. 277 (42): 39666–72. doi:10.1074/jbc.M205535200. PMID 12177062.
• Haglund K, Shimokawa N, Szymkiewicz I, Dikic I (September 2002). "Cbl-directed monoubiquitination of CIN85 is involved in regulation of ligand-induced degradation of EGF receptors". Proceedings of the National Academy of Sciences of the United States of America. 99 (19): 12191–6. doi:10.1073/pnas.192462299. PMC 129420. PMID 12218189.
• Buchman VL, Luke C, Borthwick EB, Gout I, Ninkina N (July 2002). "Organization of the mouse Ruk locus and expression of isoforms in mouse tissues". Gene. 295 (1): 13–17. doi:10.1016/S0378-1119(02)00821-1. PMID 12242006.
• Tibaldi EV, Reinherz EL (March 2003). "CD2BP3, CIN85 and the structurally related adaptor protein CMS bind to the same CD2 cytoplasmic segment, but elicit divergent functional activities". International Immunology. 15 (3): 313–29. doi:10.1093/intimm/dxg032. PMID 12618476.
• Hutchings NJ, Clarkson N, Chalkley R, Barclay AN, Brown MH (June 2003). "Linking the T cell surface protein CD2 to the actin-capping protein CAPZ via CMS and CIN85". The Journal of Biological Chemistry. 278 (25): 22396–403. doi:10.1074/jbc.M302540200. PMID 12690097.