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Reviewed, UniProtKB/Swiss-Prot Q9Y2X7 (GIT1_HUMAN)

Last modified November 3, 2009. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length761 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 761761ARF GTPase-activating protein GIT1
PRO_0000074200

Regions

Domain1 – 124124Arf-GAP
Repeat132 – 16130ANK 1
Repeat166 – 19530ANK 2
Repeat199 – 22830ANK 3
Zinc finger11 – 3424C4-type
Region251 – 415165PTK2-binding By similarity
Region254 – 367114ARHGEF6-binding By similarity
Region637 – 761125Interaction with PXN and TGFB1I1 By similarity

Amino acid modifications

Modified residue1341Phosphoserine Ref.12
Modified residue2241Phosphotyrosine By similarity
Modified residue3611Phosphoserine By similarity
Modified residue3621Phosphoserine Ref.15
Modified residue3731Phosphoserine Ref.15
Modified residue3831Phosphotyrosine Ref.15
Modified residue3851Phosphoserine Ref.15 Ref.11 Ref.14 Ref.16
Modified residue3881Phosphoserine Ref.15 Ref.11 Ref.14 Ref.16 Ref.7
Modified residue3921Phosphothreonine Ref.15
Modified residue4101Phosphoserine Ref.15
Modified residue5081Phosphoserine By similarity
Modified residue5451Phosphotyrosine Ref.9 Ref.10 Ref.18
Modified residue5541Phosphotyrosine Ref.10
Modified residue5921Phosphoserine Ref.15 Ref.11 Ref.14
Modified residue5961Phosphoserine Ref.15
Modified residue5981Phosphotyrosine Ref.11 Ref.14 Ref.8

Natural variations

Alternative sequence134 – 17643SKQLH…HVAAK → TGHRSWATPDINPHPNRATG TSALSAATLPGSQVPWCPPL SSP in isoform 2.
VSP_009666
Alternative sequence177 – 761585Missing in isoform 2.
VSP_009667

Experimental info

Sequence conflict1211P → S in AAD28046. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 15, 2004. Version 2.
Checksum: 702744942A796399

FASTA76184,341
        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 

« Hide

Isoform 2.

Checksum: 2B5BB45555AB5201
Show »

FASTA17619,160

References

« Hide '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

AF124490 mRNA. Translation: AAD28046.1.
BC006227 mRNA. Translation: AAH06227.2.
BC048196 mRNA. Translation: AAH48196.1. Different initiation.
IPIIPI00383987.
IPI00384861.
RefSeqNP_001078923.1.
NP_054749.2.
UniGeneHs.514051

3D structure databases

HSSPHSSP built from PDB template 1OY3 based on UniProtKB Q60778.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9Y2X7. 24 interactions.
STRINGQ9Y2X7.

PTM databases

PhosphoSiteQ9Y2X7.

Proteomic databases

PRIDEQ9Y2X7.

Genome annotation databases

EnsemblENST00000225394; 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]
GeneID28964.
KEGGhsa:28964.
UCSCuc002hef.2. human.

Organism-specific databases

CTD28964.
GeneCardsGC17M024924.
H-InvDBHIX0013673.
HGNCHGNC:4272. GIT1.
HPAHPA004059.
HPA004186.
MIM608434. gene.
PharmGKBPA28683.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ9Y2X7.

Enzyme and pathway databases

Pathway_Interaction_DBarf6cyclingpathway. 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

ArrayExpressQ9Y2X7.
BgeeQ9Y2X7.
CleanExHS_GIT1.
GenevestigatorQ9Y2X7.
GermOnlineENSG00000108262. Homo sapiens.

Family and domain databases

InterProIPR002110. ANK.
IPR001164. ArfGAP.
IPR013724. GIT_SHD.
[Graphical view]
Gene3DG3DSA:1.25.40.20. ANK. 1 hit.
PfamPF00023. Ank. 3 hits.
PF01412. ArfGap. 1 hit.
PF08518. GIT_SHD. 2 hits.
[Graphical view]
PRINTSPR00405. REVINTRACTNG.
SMARTSM00248. ANK. 3 hits.
SM00105. ArfGap. 1 hit.
SM00555. GIT. 2 hits.
[Graphical view]
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 1 hit.
PS50115. ARFGAP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio51807.
PMAP-CutDBQ9Y2X7.
SOURCESearch...

Entry information

Entry nameGIT1_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny 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.

Relevant documents

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents