GIT2
| G protein-coupled receptor kinase interacting ArfGAP 2 | |||||||||||||
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| Identifiers | |||||||||||||
| Symbols | GIT2 ; CAT-2; CAT2 | ||||||||||||
| External IDs | OMIM: 608564 MGI: 1347053 HomoloGene: 41336 GeneCards: GIT2 Gene | ||||||||||||
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| RNA expression pattern | |||||||||||||
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| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 9815 | 26431 | |||||||||||
| Ensembl | ENSG00000139436 | ENSMUSG00000041890 | |||||||||||
| UniProt | Q14161 | Q9JLQ2 | |||||||||||
| RefSeq (mRNA) | NM_001135213 | NM_001077359 | |||||||||||
| RefSeq (protein) | NP_001128685 | NP_001070827 | |||||||||||
| Location (UCSC) | Chr 12: 110.37 – 110.43 Mb | Chr 5: 114.73 – 114.78 Mb | |||||||||||
| PubMed search | |||||||||||||
ARF GTPase-activating protein GIT2 is an enzyme that in humans is encoded by the GIT2 gene.[1][2][3]
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.[3]
Model organisms
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Abnormal[4] |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal[5] |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal[6] |
| Clinical chemistry | Abnormal[7] |
| Haematology | Abnormal[8] |
| 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[9][10] |
Model organisms have been used in the study of GIT2 function. A conditional knockout mouse line, called Git2Gt(XG510)Byg[11][12] 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.[13][14][15]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Mice lacking Git2 had no significant defects in viability or fertility,[17][18] so further tests were carried out and four significant phenotypes were reported:[9][16]
- 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.[19]
References
- ↑ Premont RT, Claing A, Vitale N, Freeman JL, Pitcher JA, Patton WA, Moss J, Vaughan M, Lefkowitz RJ (Dec 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): 14082–7. doi:10.1073/pnas.95.24.14082. PMC 24330. PMID 9826657.
- ↑ Premont RT, Claing A, Vitale N, Perry SJ, Lefkowitz RJ (Aug 2000). "The GIT family of ADP-ribosylation factor GTPase-activating proteins. Functional diversity of GIT2 through alternative splicing". J Biol Chem 275 (29): 22373–80. doi:10.1074/jbc.275.29.22373. PMID 10896954.
- ↑ 3.0 3.1 "Entrez Gene: GIT2 G protein-coupled receptor kinase interactor 2".
- ↑ "Hot plate data for Git2". Wellcome Trust Sanger Institute.
- ↑ "DEXA data for Git2". Wellcome Trust Sanger Institute.
- ↑ "Eye morphology data for Git2". Wellcome Trust Sanger Institute.
- ↑ "Clinical chemistry data for Git2". Wellcome Trust Sanger Institute.
- ↑ "Haematology data for Git2". Wellcome Trust Sanger Institute.
- ↑ 9.0 9.1 9.2 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.
- ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ↑ "International Knockout Mouse Consortium".
- ↑ "Mouse Genome Informatics".
- ↑ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ↑ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ 16.0 16.1 van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
- ↑ Wellcome Trust Sanger Institute. "Viability at Weaning Data for Git2". Mouse Resources Portal. www
.sanger ..ac .uk - ↑ Wellcome Trust Sanger Institute. "Fertility Data for Git2". Mouse Resources Portal. www
.sanger ..ac .uk - ↑ Kim, Seho; Ko Jaewon, Shin Hyewon, Lee Jae-Ran, Lim Chunghun, Han Jin-Hee, Altrock Wilko D, Garner Craig C, Gundelfinger Eckart D, Premont Richard T, Kaang Bong-Kiun, Kim Eunjoon (Feb 2003). "The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo". J. Biol. Chem. (United States) 278 (8): 6291–300. doi:10.1074/jbc.M212287200. ISSN 0021-9258. PMID 12473661.
Further reading
- Nakajima D, Okazaki N, Yamakawa H et al. (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.". DNA Res. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
- Hoefen RJ, Berk BC (2006). "The multifunctional GIT family of proteins.". J. Cell. Sci. 119 (Pt 8): 1469–75. doi:10.1242/jcs.02925. PMID 16598076.
- Maruyama K, Sugano S (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 et al. (1996). "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 Res. 2 (4): 167–74, 199–210. doi:10.1093/dnares/2.4.167. PMID 8590280.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al. (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 et al. (1999). "Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat, ARF-GAP protein: A role in cytoskeletal remodeling". J. Cell Biol. 145 (4): 851–63. doi:10.1083/jcb.145.4.851. PMC 2133183. PMID 10330411.
- Bagrodia S, Bailey D, Lenard Z et al. (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.
- Vitale N, Patton WA, Moss J et al. (2000). "GIT proteins, A novel family of phosphatidylinositol 3,4, 5-trisphosphate-stimulated GTPase-activating proteins for ARF6". J. Biol. Chem. 275 (18): 13901–6. doi:10.1074/jbc.275.18.13901. PMID 10788515.
- Hoja MR, Wahlestedt C, Höög C (2000). "A visual intracellular classification strategy for uncharacterized human proteins". Exp. Cell Res. 259 (1): 239–46. doi:10.1006/excr.2000.4948. PMID 10942595.
- Ku GM, Yablonski D, Manser E et al. (2001). "A PAK1-PIX-PKL complex is activated by the T-cell receptor independent of Nck, Slp-76 and LAT". EMBO J. 20 (3): 457–65. doi:10.1093/emboj/20.3.457. PMC 133476. PMID 11157752.
- Mazaki Y, Hashimoto S, Okawa K et al. (2001). "An ADP-ribosylation factor GTPase-activating protein Git2-short/KIAA0148 is involved in subcellular localization of paxillin and actin cytoskeletal organization". Mol. Biol. Cell 12 (3): 645–62. doi:10.1091/mbc.12.3.645. PMC 30970. PMID 11251077.
- Kim S, Ko J, Shin H et al. (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.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Brill LM, Salomon AR, Ficarro SB et al. (2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Anal. Chem. 76 (10): 2763–72. doi:10.1021/ac035352d. PMID 15144186.
- Premont RT, Perry SJ, Schmalzigaug R et al. (2005). "The GIT/PIX complex: an oligomeric assembly of GIT family ARF GTPase-activating proteins and PIX family Rac1/Cdc42 guanine nucleotide exchange factors". Cell. Signal. 16 (9): 1001–11. doi:10.1016/j.cellsig.2004.02.002. PMID 15212761.
- Jin J, Smith FD, Stark C et al. (2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Curr. Biol. 14 (16): 1436–50. doi:10.1016/j.cub.2004.07.051. PMID 15324660.