GIT2

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a
Wikidata
View/Edit Human

ARF GTPase-activating protein GIT2 is an enzyme that in humans is encoded by the GIT2 gene.

Function

This gene encodes a member of the GIT protein family. GIT proteins interact with G protein-coupled receptor kinases and possess ADP-ribosylation factor (ARF) GTPase-activating protein (GAP) activity. This gene undergoes extensive alternative splicing; although ten transcript variants have been described, the full length sequence has been determined for only four variants. The various isoforms have functional differences, with respect to ARF GAP activity and to G protein-coupled receptor kinase 2 binding.

Model organisms

Git2 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Abnormal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal
Haematology	Abnormal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Normal
Skin Histopathology	Normal
Brain histopathology	Abnormal
All tests and analysis from

Model organisms have been used in the study of GIT2 function. A conditional knockout mouse line, called Git2^Gt(XG510)Byg was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Mice lacking Git2 had no significant defects in viability or fertility, so further tests were carried out and four significant phenotypes were reported:

• Mutant mice had differences in their clinical blood chemistry compared to wildtype control mice.
• Mutant male mice had a decrease in white blood cell count.
• An increased thickness in hippocampus was observed.
• Mutant female mice were slower to respond to heat when placed on a hotplate.

Interactions

GIT2 has been shown to interact with GIT1.

Further reading

• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (Jun 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
• Hoefen RJ, Berk BC (Apr 2006). "The multifunctional GIT family of proteins". Journal of Cell Science. 119 (Pt 8): 1469–75. doi:10.1242/jcs.02925. PMID 16598076.
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Nagase T, Seki N, Tanaka A, Ishikawa K, Nomura N (Aug 1995). "Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1". DNA Research. 2 (4): 167–74, 199–210. doi:10.1093/dnares/2.4.167. PMID 8590280.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Turner CE, Brown MC, Perrotta JA, Riedy MC, Nikolopoulos SN, McDonald AR, Bagrodia S, Thomas S, Leventhal PS (May 1999). "Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat, ARF-GAP protein: A role in cytoskeletal remodeling". The Journal of Cell Biology. 145 (4): 851–63. doi:10.1083/jcb.145.4.851. PMC 2133183. PMID 10330411.
• Bagrodia S, Bailey D, Lenard Z, Hart M, Guan JL, Premont RT, Taylor SJ, Cerione RA (Aug 1999). "A tyrosine-phosphorylated protein that binds to an important regulatory region on the cool family of p21-activated kinase-binding proteins". The Journal of Biological Chemistry. 274 (32): 22393–400. doi:10.1074/jbc.274.32.22393. PMID 10428811.
• Vitale N, Patton WA, Moss J, Vaughan M, Lefkowitz RJ, Premont RT (May 2000). "GIT proteins, A novel family of phosphatidylinositol 3,4, 5-trisphosphate-stimulated GTPase-activating proteins for ARF6". The Journal of Biological Chemistry. 275 (18): 13901–6. doi:10.1074/jbc.275.18.13901. PMID 10788515.
• Hoja MR, Wahlestedt C, Höög C (Aug 2000). "A visual intracellular classification strategy for uncharacterized human proteins". Experimental Cell Research. 259 (1): 239–46. doi:10.1006/excr.2000.4948. PMID 10942595.
• Ku GM, Yablonski D, Manser E, Lim L, Weiss A (Feb 2001). "A PAK1-PIX-PKL complex is activated by the T-cell receptor independent of Nck, Slp-76 and LAT". The EMBO Journal. 20 (3): 457–65. doi:10.1093/emboj/20.3.457. PMC 133476. PMID 11157752.
• Mazaki Y, Hashimoto S, Okawa K, Tsubouchi A, Nakamura K, Yagi R, Yano H, Kondo A, Iwamatsu A, Mizoguchi A, Sabe H (Mar 2001). "An ADP-ribosylation factor GTPase-activating protein Git2-short/KIAA0148 is involved in subcellular localization of paxillin and actin cytoskeletal organization". Molecular Biology of the Cell. 12 (3): 645–62. doi:10.1091/mbc.12.3.645. PMC 30970. PMID 11251077.
• Kim S, Ko J, Shin H, Lee JR, Lim C, Han JH, Altrock WD, Garner CC, Gundelfinger ED, Premont RT, Kaang BK, Kim E (Feb 2003). "The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo". The Journal of Biological Chemistry. 278 (8): 6291–300. doi:10.1074/jbc.M212287200. PMID 12473661.
• Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC (May 2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Analytical Chemistry. 76 (10): 2763–72. doi:10.1021/ac035352d. PMID 15144186.
• Premont RT, Perry SJ, Schmalzigaug R, Roseman JT, Xing Y, Claing A (Sep 2004). "The GIT/PIX complex: an oligomeric assembly of GIT family ARF GTPase-activating proteins and PIX family Rac1/Cdc42 guanine nucleotide exchange factors". Cellular Signalling. 16 (9): 1001–11. doi:10.1016/j.cellsig.2004.02.002. PMID 15212761.
• Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, Metalnikov P, O'Donnell P, Taylor P, Taylor L, Zougman A, Woodgett JR, Langeberg LK, Scott JD, Pawson T (Aug 2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Current Biology. 14 (16): 1436–50. doi:10.1016/j.cub.2004.07.051. PMID 15324660.