GIT1

ARF GTPase-activating protein GIT1 is an enzyme that in humans is encoded by the GIT1 gene.[5][6][7]

GIT1
Identifiers
Aliases	GIT1, GIT ArfGAP 1
External IDs	OMIM: 608434 MGI: 1927140 HomoloGene: 32204 GeneCards: GIT1
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q11.2 Start 29,573,469 bp[1] End 29,594,054 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 B5 Start 77,493,562 bp[2] End 77,507,786 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0032403 macromolecular complex binding • GO:0001948 protein binding • metal ion binding • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity Cellular component • membrane • focal adhesion • cytoplasm • cytosol • calyx of Held Biological process • ephrin receptor signaling pathway • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • regulation of cytokinesis • regulation of G-protein coupled receptor protein signaling pathway • presynaptic modulation of chemical synaptic transmission • regulation of synaptic vesicle exocytosis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	28964	216963
Ensembl	ENSG00000108262	ENSMUSG00000011877
UniProt	Q9Y2X7	Q68FF6
RefSeq (mRNA)	NM_001085454 NM_014030	NM_001004144 NM_001374758
RefSeq (protein)	NP_001078923 NP_054749	NP_001004144 NP_001361687
Location (UCSC)	Chr 17: 29.57 – 29.59 Mb	Chr 11: 77.49 – 77.51 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

GIT1 contains an ARFGAP domain, Anykrin repeats, and a GRK-interacting domain. The Arf-GAP domain, which enables it to act as a GTPase activating protein (GAP) for the Arf family of GTPases, has been shown to be involved in phosphorylation and inhibition of the ADRB2. If synaptic localization of GIT1 is disturbed, then this is known to affect dendritic spine morphology and formation---this is thought to occur through the Rac1/PAK1/LIMK/CFL1 pathway.[8]

Interactions

GIT1 has been shown to interact with:

• ARHGEF7,[9][10]
• Beta adrenergic receptor kinase,[5][6]
• GIT2,[9]
• PCLO,[9]
• PLCG1,[11]
• PPFIA4[12][13]
• PTK2,[9][12][14] and
• liprin-alpha-1.[12][13]

References

1. GRCh38: Ensembl release 89: ENSG00000108262 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000011877 - 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. Premont RT, Claing A, Vitale N, Freeman JL, Pitcher JA, Patton WA, Moss J, Vaughan M, Lefkowitz RJ (December 1998). "beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein". Proc Natl Acad Sci U S A. 95 (24): 14082–14087. doi:10.1073/pnas.95.24.14082. PMC 24330. PMID 9826657.
6. Premont RT, Claing A, Vitale N, Perry SJ, Lefkowitz RJ (August 2000). "The GIT family of ADP-ribosylation factor GTPase-activating proteins. Functional diversity of GIT2 through alternative splicing". J Biol Chem. 275 (29): 22373–22380. doi:10.1074/jbc.275.29.22373. PMID 10896954.
7. "Entrez Gene: GIT1 G protein-coupled receptor kinase interactor 1".
8. Zhang H, Webb DJ, Asmussen H, Horwitz AF (2003). "Synapse formation is regulated by the signaling adaptor GIT1". J. Cell Biol. 161 (1): 131–142. doi:10.1083/jcb.200211002. PMC 2172873. PMID 12695502.
9. Kim S, Ko J, Shin H, Lee JR, Lim C, Han JH, Altrock WD, Garner CC, Gundelfinger ED, Premont RT, Kaang BK, Kim E (February 2003). "The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo". J. Biol. Chem. 278 (8): 6291–300. doi:10.1074/jbc.M212287200. PMID 12473661.
10. Bagrodia S, Bailey D, Lenard Z, Hart M, Guan JL, Premont RT, Taylor SJ, Cerione RA (August 1999). "A tyrosine-phosphorylated protein that binds to an important regulatory region on the cool family of p21-activated kinase-binding proteins". J. Biol. Chem. 274 (32): 22393–400. doi:10.1074/jbc.274.32.22393. PMID 10428811.
11. Haendeler J, Yin G, Hojo Y, Saito Y, Melaragno M, Yan C, Sharma VK, Heller M, Aebersold R, Berk BC (December 2003). "GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor". J. Biol. Chem. 278 (50): 49936–44. doi:10.1074/jbc.M307317200. PMID 14523024.
12. Ko J, Kim S, Valtschanoff JG, Shin H, Lee JR, Sheng M, Premont RT, Weinberg RJ, Kim E (March 2003). "Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting". J. Neurosci. 23 (5): 1667–77. doi:10.1523/JNEUROSCI.23-05-01667.2003. PMC 6741975. PMID 12629171.
13. Ko J, Na M, Kim S, Lee JR, Kim E (October 2003). "Interaction of the ERC family of RIM-binding proteins with the liprin-alpha family of multidomain proteins". J. Biol. Chem. 278 (43): 42377–85. doi:10.1074/jbc.M307561200. PMID 12923177.
14. Zhao ZS, Manser E, Loo TH, Lim L (September 2000). "Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly". Mol. Cell. Biol. 20 (17): 6354–63. doi:10.1128/mcb.20.17.6354-6363.2000. PMC 86110. PMID 10938112.

Further reading

• Hoefen RJ, Berk BC (2006). "The multifunctional GIT family of proteins". J. Cell Sci. 119 (Pt 8): 1469–1475. doi:10.1242/jcs.02925. PMID 16598076.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Zhao ZS, Manser E, Loo TH, Lim L (2000). "Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly". Mol. Cell. Biol. 20 (17): 6354–6363. doi:10.1128/MCB.20.17.6354-6363.2000. PMC 86110. PMID 10938112.
• Kawachi H, Fujikawa A, Maeda N, Noda M (2001). "Identification of GIT1/Cat-1 as a substrate molecule of protein tyrosine phosphatase zeta /beta by the yeast substrate-trapping system". Proc. Natl. Acad. Sci. U.S.A. 98 (12): 6593–6598. doi:10.1073/pnas.041608698. PMC 34398. PMID 11381105.
• Manabe R, Kovalenko M, Webb DJ, Horwitz AR (2002). "GIT1 functions in a motile, multi-molecular signaling complex that regulates protrusive activity and cell migration". J. Cell Sci. 115 (Pt 7): 1497–510. PMID 11896197.
• Nishiya N, Shirai T, Suzuki W, Nose K (2003). "Hic-5 interacts with GIT1 with a different binding mode from paxillin". J. Biochem. 132 (2): 279–89. doi:10.1093/oxfordjournals.jbchem.a003222. PMID 12153727.
• Kim S, Ko J, Shin H, Lee JR, Lim C, Han JH, Altrock WD, Garner CC, Gundelfinger ED, Premont RT, Kaang BK, Kim E (2003). "The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo". J. Biol. Chem. 278 (8): 6291–6300. doi:10.1074/jbc.M212287200. PMID 12473661.
• Shin H, Wyszynski M, Huh KH, Valtschanoff JG, Lee JR, Ko J, Streuli M, Weinberg RJ, Sheng M, Kim E (2003). "Association of the kinesin motor KIF1A with the multimodular protein liprin-alpha". J. Biol. Chem. 278 (13): 11393–11401. doi:10.1074/jbc.M211874200. PMID 12522103.
• Ko J, Kim S, Valtschanoff JG, Shin H, Lee JR, Sheng M, Premont RT, Weinberg RJ, Kim E (2003). "Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting". J. Neurosci. 23 (5): 1667–77. doi:10.1523/JNEUROSCI.23-05-01667.2003. PMID 12629171.
• Ko J, Na M, Kim S, Lee JR, Kim E (2004). "Interaction of the ERC family of RIM-binding proteins with the liprin-alpha family of multidomain proteins". J. Biol. Chem. 278 (43): 42377–42385. doi:10.1074/jbc.M307561200. PMID 12923177.
• Haendeler J, Yin G, Hojo Y, Saito Y, Melaragno M, Yan C, Sharma VK, Heller M, Aebersold R, Berk BC (2004). "GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor". J. Biol. Chem. 278 (50): 49936–49944. doi:10.1074/jbc.M307317200. PMID 14523024.
• van Nieuw Amerongen GP, Natarajan K, Yin G, Hoefen RJ, Osawa M, Haendeler J, Ridley AJ, Fujiwara K, van Hinsbergh VW, Berk BC (2004). "GIT1 mediates thrombin signaling in endothelial cells: role in turnover of RhoA-type focal adhesions". Circ. Res. 94 (8): 1041–1049. doi:10.1161/01.RES.0000125627.77235.0C. PMID 15016733.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–12135. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Goehler H, Lalowski M, Stelzl U, Waelter S, Stroedicke M, Worm U, Droege A, Lindenberg KS, Knoblich M, Haenig C, Herbst M, Suopanki J, Scherzinger E, Abraham C, Bauer B, Hasenbank R, Fritzsche A, Ludewig AH, Büssow K, Buessow K, Coleman SH, Gutekunst CA, Landwehrmeyer BG, Lehrach H, Wanker EE (2004). "A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease". Mol. Cell. 15 (6): 853–865. doi:10.1016/j.molcel.2004.09.016. PMID 15383276.

External links

• GIT1 Info with links in the Cell Migration Gateway