GIT2

ARF GTPase-activating protein GIT2 is an enzyme that in humans is encoded by the GIT2 gene.[5][6][7]

GIT2
Identifiers
Aliases	GIT2, CAT-2, CAT2, PKL, GIT ArfGAP 2
External IDs	OMIM: 608564 MGI: 1347053 HomoloGene: 41336 GeneCards: GIT2
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q24.11 Start 109,929,802 bp[1] End 109,996,389 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 F Start 114,727,407 bp[2] End 114,775,517 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • metal ion binding • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity Cellular component • focal adhesion • nucleoplasm Biological process • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • regulation of G-protein coupled receptor protein signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	9815	26431
Ensembl	ENSG00000139436	ENSMUSG00000041890
UniProt	Q14161	Q9JLQ2
RefSeq (mRNA)	NM_001135213 NM_001135214 NM_014776 NM_057169 NM_057170 NM_139201 NM_001330153 NM_001330154	NM_001077359 NM_001077360 NM_019834 NM_001347400
RefSeq (protein)	NP_001128685 NP_001128686 NP_001317082 NP_001317083 NP_055591 NP_476510 NP_476511 NP_631940	NP_001070827 NP_001070828 NP_001334329 NP_062808
Location (UCSC)	Chr 12: 109.93 – 110 Mb	Chr 5: 114.73 – 114.78 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[7]

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[8]
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal[9]
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal[10]
Clinical chemistry	Abnormal[11]
Haematology	Abnormal[12]
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[13][14]

Model organisms have been used in the study of GIT2 function. A conditional knockout mouse line, called Git2^Gt(XG510)Byg[15][16] 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.[17][18][19]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[13][20] Mice lacking Git2 had no significant defects in viability or fertility,[21][22] so further tests were carried out and four significant phenotypes were reported:[13][20]

• 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.[23]

References

1. GRCh38: Ensembl release 89: ENSG00000139436 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000041890 - 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 (Nov 1998). "beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein". Proceedings of the National Academy of Sciences of the United States of America. 95 (24): 14082–7. doi:10.1073/pnas.95.24.14082. PMC 24330. PMID 9826657.
6. Premont RT, Claing A, Vitale N, Perry SJ, Lefkowitz RJ (Jul 2000). "The GIT family of ADP-ribosylation factor GTPase-activating proteins. Functional diversity of GIT2 through alternative splicing". The Journal of Biological Chemistry. 275 (29): 22373–80. doi:10.1074/jbc.275.29.22373. PMID 10896954.
7. "Entrez Gene: GIT2 G protein-coupled receptor kinase interactor 2".
8. "Hot plate data for Git2". Wellcome Trust Sanger Institute.
9. "DEXA data for Git2". Wellcome Trust Sanger Institute.
10. "Eye morphology data for Git2". Wellcome Trust Sanger Institute.
11. "Clinical chemistry data for Git2". Wellcome Trust Sanger Institute.
12. "Haematology data for Git2". Wellcome Trust Sanger Institute.
13. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
14. Mouse Resources Portal, Wellcome Trust Sanger Institute.
15. "International Knockout Mouse Consortium".
16. "Mouse Genome Informatics".
17. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
18. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
19. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
20. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
21. Wellcome Trust Sanger Institute. "Viability at Weaning Data for Git2". Mouse Resources Portal. www.sanger.ac.uk. External link in |publisher= (help)
22. Wellcome Trust Sanger Institute. "Fertility Data for Git2". Mouse Resources Portal. www.sanger.ac.uk. External link in |publisher= (help)
23. 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.

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.