Reviewed, UniProtKB/Swiss-Prot Q9Y2X7 (GIT1_HUMAN)

Names and origin

Protein names

Recommended name:
    ARF GTPase-activating protein GIT1
      Short name=ARF GAP GIT1
Alternative name(s):
    G protein-coupled receptor kinase-interactor 1
    GRK-interacting protein 1
    Cool-associated and tyrosine-phosphorylated protein 1
      Short name=CAT-1
      Short name=CAT1

Gene names

Name:

GIT1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	761 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	GTPase-activating protein for the ADP ribosylation factor family. May serve as a scaffold to bring together molecules to form signaling modules controlling vesicle trafficking, adhesion and cytoskeletal organization. Increases the speed of cell migration, as well as the size and rate of formation of protrusions, possibly by targeting PAK1 to adhesions and the leading edge of lamellipodia. Sequesters inactive non-tyrosine-phosphorylated paxillin in cytoplasmic complexes. Ref.5
Subunit structure	Interacts with G protein-coupled receptor kinases: ADRBK1/GRK2, PPFIA1 and PPFIA4. Interacts with ARHGEF6/alpha-PIX, with ARHGEF7/beta-PIX, with PXN/paxillin and with PTK2/FAK By similarity. Component of cytoplasmic complexes, which also contain PXN, ARHGEF6 and PAK1. Interacts with TGFB1I1. Interacts with SCRIB.
Subcellular location	Cytoplasm. Note: Cycles between at least 3 distinct intracellular compartments, including focal adhesions, cytoplasmic complexes and membrane protrusions. During cell migration, when cells detach, moves from the adhesions into the cytoplasmic complexes towards the leading edge, while, when cells adhere, it is found in vinculin-containing adhesions. Recruitment to adhesions may be mediated by active tyrosine-phosphorylated paxillin. Ref.5
Domain	The paxillin-binding domain is masked in the full-length protein and is regulated by ARHGEF6 By similarity.
Post-translational modification	Phosphorylated on tyrosine residues by PTK2 and SRC in growing fibroblasts. Tyrosine-phosphorylation is increased following cell spreading on fibronectin, decreased in cells arrested in mitosis and increased in the ensuing G1 phase By similarity.
Sequence similarities	Contains 3 ANK repeats. Contains 1 Arf-GAP domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	ANK repeat Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	GTPase activation
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	regulation of ARF GTPase activity Inferred from electronic annotation. Source: InterPro regulation of G-protein coupled receptor protein signaling pathway Ref.3 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from direct assay. Source: HPA cytoskeleton Inferred from direct assay. Source: HPA focal adhesion Inferred from direct assay. Source: HPA
Molecular function	ARF GTPase activator activity Inferred from electronic annotation. Source: InterPro protein binding Ref.6 Ref.13 Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BARD1	Q99728	1	EBI-466061,EBI-473181
C1orf103	Q5T3J3	1	EBI-466061,EBI-473196
CHD3	Q12873	1	EBI-466061,EBI-523590
HTT	P42858	5	EBI-466061,EBI-466029
KIAA1377	Q9P2H0	1	EBI-466061,EBI-473176
PAK2	Q13177	1	EBI-466061,EBI-1045887

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y2X7-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9Y2X7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     134-176: SKQLHSSVRT...GTTPLHVAAK → TGHRSWATPD...VPWCPPLSSP
     177-761: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 761	761	ARF GTPase-activating protein GIT1		PRO_0000074200
Regions
	Domain	1 – 124	124	Arf-GAP
	Repeat	132 – 161	30	ANK 1
	Repeat	166 – 195	30	ANK 2
	Repeat	199 – 228	30	ANK 3
	Zinc finger	11 – 34	24	C4-type
	Region	251 – 415	165	PTK2-binding By similarity
	Region	254 – 367	114	ARHGEF6-binding By similarity
	Region	637 – 761	125	Interaction with PXN and TGFB1I1 By similarity
Amino acid modifications
	Modified residue	134	1	Phosphoserine Ref.12
	Modified residue	224	1	Phosphotyrosine By similarity
	Modified residue	361	1	Phosphoserine By similarity
	Modified residue	362	1	Phosphoserine Ref.15
	Modified residue	373	1	Phosphoserine Ref.15
	Modified residue	383	1	Phosphotyrosine Ref.15
	Modified residue	385	1	Phosphoserine Ref.15 Ref.11 Ref.14 Ref.16
	Modified residue	388	1	Phosphoserine Ref.15 Ref.11 Ref.14 Ref.16 Ref.7
	Modified residue	392	1	Phosphothreonine Ref.15
	Modified residue	410	1	Phosphoserine Ref.15
	Modified residue	508	1	Phosphoserine By similarity
	Modified residue	545	1	Phosphotyrosine Ref.9 Ref.10 Ref.18
	Modified residue	554	1	Phosphotyrosine Ref.10
	Modified residue	592	1	Phosphoserine Ref.15 Ref.11 Ref.14
	Modified residue	596	1	Phosphoserine Ref.15
	Modified residue	598	1	Phosphotyrosine Ref.11 Ref.14 Ref.8
Natural variations
	Alternative sequence	134 – 176	43	SKQLH…HVAAK → TGHRSWATPDINPHPNRATG TSALSAATLPGSQVPWCPPL SSP in isoform 2.		VSP_009666
	Alternative sequence	177 – 761	585	Missing in isoform 2.		VSP_009667
Experimental info
	Sequence conflict	121	1	P → S in AAD28046. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 15, 2004. Version 2. Checksum: 702744942A796399	FASTA	761	84,341
	10 20 30 40 50 60 MSRKGPRAEV CADCSAPDPG WASISRGVLV CDECCSVHRS LGRHISIVKH LRHSAWPPTL 70 80 90 100 110 120 LQMVHTLASN GANSIWEHSL LDPAQVQSGR RKANPQDKVH PIKSEFIRAK YQMLAFVHKL 130 140 150 160 170 180 PCRDDDGVTA KDLSKQLHSS VRTGNLETCL RLLSLGAQAN FFHPEKGTTP LHVAAKAGQT 190 200 210 220 230 240 LQAELLVVYG ADPGSPDVNG RTPIDYARQA GHHELAERLV ECQYELTDRL AFYLCGRKPD 250 260 270 280 290 300 HKNGHYIIPQ MADSLDLSEL AKAAKKKLQA LSNRLFEELA MDVYDEVDRR ENDAVWLATQ 310 320 330 340 350 360 NHSTLVTERS AVPFLPVNPE YSATRNQGRQ KLARFNAREF ATLIIDILSE AKRRQQGKSL 370 380 390 400 410 420 SSPTDNLELS LRSQSDLDDQ HDYDSVASDE DTDQEPLRST GATRSNRARS MDSSDLSDGA 430 440 450 460 470 480 VTLQEYLELK KALATSEAKV QQLMKVNSSL SDELRRLQRE IHKLQAENLQ LRQPPGPVPT 490 500 510 520 530 540 PPLPSERAEH TPMAPGGSTH RRDRQAFSMY EPGSALKPFG GPPGDELTTR LQPFHSTELE 550 560 570 580 590 600 DDAIYSVHVP AGLYRIRKGV SASAVPFTPS SPLLSCSQEG SRHTSKLSRH GSGADSDYEN 610 620 630 640 650 660 TQSGDPLLGL EGKRFLELGK EEDFHPELES LDGDLDPGLP STEDVILKTE QVTKNIQELL 670 680 690 700 710 720 RAAQEFKHDS FVPCSEKIHL AVTEMASLFP KRPALEPVRS SLRLLNASAY RLQSECRKTV 730 740 750 760 PPEPGAPVDF QLLTQQVIQC AYDIAKAAKQ LVTITTREKK Q
	Isoform 2. Checksum: 2B5BB45555AB5201	FASTA	176	19,160
	10 20 30 40 50 60 MSRKGPRAEV CADCSAPDPG WASISRGVLV CDECCSVHRS LGRHISIVKH LRHSAWPPTL 70 80 90 100 110 120 LQMVHTLASN GANSIWEHSL LDPAQVQSGR RKANPQDKVH PIKSEFIRAK YQMLAFVHKL 130 140 150 160 170 PCRDDDGVTA KDLTGHRSWA TPDINPHPNR ATGTSALSAA TLPGSQVPWC PPLSSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The GIT family of ADP-ribosylation factor GTPase-activating proteins. Functional diversity of GIT2 through alternative splicing." Premont R.T., Claing A., Vitale N., Perry S.J., Lefkowitz R.J. J. Biol. Chem. 275:22373-22380(2000) [PubMed: 10896954] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 585-761 (ISOFORM 1). Tissue: Lung and Melanoma.
[3]	"Beta2-adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein." Premont R.T., Claing A., Vitale N., Freeman J.L.R., Pitcher J.A., Patton W.A., Moss J., Vaughan M., Lefkowitz R.J. Proc. Natl. Acad. Sci. U.S.A. 95:14082-14087(1998) [PubMed: 9826657] [Abstract] Cited for: CHARACTERIZATION.
[4]	"Hic-5 interacts with GIT1 with a different binding mode from paxillin." Nishiya N., Shirai T., Suzuki W., Nose K. J. Biochem. 132:279-289(2002) [PubMed: 12153727] [Abstract] Cited for: INTERACTION WITH TGFB1I1.
[5]	"GIT1 functions in a motile, multi-molecular signaling complex that regulates protrusive activity and cell migration." Manabe R., Kovalenko M., Webb D.J., Horwitz A.R. J. Cell Sci. 115:1497-1510(2002) [PubMed: 11896197] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION IN CELL MIGRATION.
[6]	"Mammalian Scribble forms a tight complex with the betaPIX exchange factor." Audebert S., Navarro C., Nourry C., Chasserot-Golaz S., Lecine P., Bellaiche Y., Dupont J.-L., Premont R.T., Sempere C., Strub J.-M., Van Dorsselaer A., Vitale N., Borg J.-P. Curr. Biol. 14:987-995(2004) [PubMed: 15182672] [Abstract] Cited for: INTERACTION WITH SCRIB.
[7]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-388, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-598, MASS SPECTROMETRY.
[9]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-545, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-545 AND TYR-554, MASS SPECTROMETRY.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385; SER-388; SER-592 AND TYR-598, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-134, MASS SPECTROMETRY.
[13]	"Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma." Zhan L., Rosenberg A., Bergami K.C., Yu M., Xuan Z., Jaffe A.B., Allred C., Muthuswamy S.K. Cell 135:865-878(2008) [PubMed: 19041750] [Abstract] Cited for: INTERACTION WITH SCRIB.
[14]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385; SER-388; SER-592 AND TYR-598, MASS SPECTROMETRY. Tissue: Platelet.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-362; SER-373; TYR-383; SER-385; SER-388; THR-392; SER-410; SER-592 AND SER-596, MASS SPECTROMETRY.
[16]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385 AND SER-388, MASS SPECTROMETRY. Tissue: Liver.
[17]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[18]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-545, MASS SPECTROMETRY. Tissue: Mammary epithelium.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF124490 mRNA. Translation: AAD28046.1. BC006227 mRNA. Translation: AAH06227.2. BC048196 mRNA. Translation: AAH48196.1. Different initiation.
IPI	IPI00383987. IPI00384861.
RefSeq	NP_001078923.1. NP_054749.2.
UniGene	Hs.514051
3D structure databases
HSSP	HSSP built from PDB template 1OY3 based on UniProtKB Q60778.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y2X7. 24 interactions.
STRING	Q9Y2X7.
PTM databases
PhosphoSite	Q9Y2X7.
Proteomic databases
PRIDE	Q9Y2X7.
Genome annotation databases
Ensembl	ENST00000225394; ENSP00000225394; ENSG00000108262; Homo sapiens. [Genome view] ENST00000335356; ENSP00000334125; ENSG00000108262; Homo sapiens. [Genome view] ENST00000394868; ENSP00000378337; ENSG00000108262; Homo sapiens. [Genome view] ENST00000394869; ENSP00000378338; ENSG00000108262; Homo sapiens. [Genome view]
GeneID	28964.
KEGG	hsa:28964.
UCSC	uc002hef.2. human.
Organism-specific databases
CTD	28964.
GeneCards	GC17M024924.
H-InvDB	HIX0013673.
HGNC	HGNC:4272. GIT1.
HPA	HPA004059. HPA004186.
MIM	608434. gene.
PharmGKB	PA28683.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9Y2X7.
Enzyme and pathway databases
Pathway_Interaction_DB	arf6cyclingpathway. Arf6 signaling events. aurora_a_pathway. Aurora A signaling. a4b1_paxdep_pathway. Paxillin-dependent events mediated by a4b1. a4b1_paxindep_pathway. Paxillin-independent events mediated by a4b1 and a4b7.
Gene expression databases
ArrayExpress	Q9Y2X7.
Bgee	Q9Y2X7.
CleanEx	HS_GIT1.
Genevestigator	Q9Y2X7.
GermOnline	ENSG00000108262. Homo sapiens.
Family and domain databases
InterPro	IPR002110. ANK. IPR001164. ArfGAP. IPR013724. GIT_SHD. [Graphical view]
Gene3D	G3DSA:1.25.40.20. ANK. 1 hit.
Pfam	PF00023. Ank. 3 hits. PF01412. ArfGap. 1 hit. PF08518. GIT_SHD. 2 hits. [Graphical view]
PRINTS	PR00405. REVINTRACTNG.
SMART	SM00248. ANK. 3 hits. SM00105. ArfGap. 1 hit. SM00555. GIT. 2 hits. [Graphical view]
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 1 hit. PS50115. ARFGAP. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	51807.
PMAP-CutDB	Q9Y2X7.
SOURCE	Search...

Entry information

Entry name

GIT1_HUMAN

Accession

Primary (citable) accession number: Q9Y2X7
Secondary accession number(s): Q86SS0, Q9BRJ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 18, 2001
Last sequence update:	March 15, 2004
Last modified:	November 3, 2009
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.