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Q9UQC2 (GAB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
GRB2-associated-binding protein 2
Alternative name(s):
GRB2-associated binder 2
Growth factor receptor bound protein 2-associated protein 2
pp100
Gene names
Name:GAB2
Synonyms:KIAA0571
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length676 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Adapter protein which acts downstream of several membrane receptors including cytokine, antigen, hormone, cell matrix and growth factor receptors to regulate multiple signaling pathways. Regulates osteoclast differentiation mediating the TNFRSF11A/RANK signaling. In allergic response, it plays a role in mast cells activation and degranulation through PI-3-kinase regulation. Also involved in the regulation of cell proliferation and hematopoiesis. Ref.8 Ref.9

Subunit structure

Interacts with SHC1; may mediate interaction with receptors By similarity. Interacts with SYK By similarity. Interacts with PI-3 kinase. Interacts with GRB2 (via SH3 2 domain). Interacts (phosphorylated) with PTPN11. Interacts with TNFRSF11A (via cytoplasmic domain). Interacts (phosphorylated) with 14-3-3 family proteins SFN, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ and YWHAZ; prevents interaction with GRB2 and attenuates GAB2 signaling. Interacts with HCK. Ref.1 Ref.7 Ref.8 Ref.9

Subcellular location

Cytoplasm. Cell membrane Ref.9.

Domain

The SH3-binding motifs mediate interaction with SHC1 and GRB2 By similarity.

The PH domain mediates phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,4-bisphosphate binding By similarity.

Post-translational modification

Phosphorylated on tyrosine residue(s) by the thrombopoietin receptor (TPOR), stem cell factor receptor (SCFR), and T-cell and B-cell antigen receptors, gp130, IL-2R and IL-3R By similarity. Phosphorylated upon stimulation of TNFRSF11A/RANK by TNFSF11/RANKL By similarity. Phosphorylated upon EGF stimulation. Phosphorylated on tyrosine residues by HCK upon IL6 signaling. Ref.7 Ref.9

Dephosphorylated by PTPN11. Ref.7 Ref.9

Sequence similarities

Belongs to the GAB family.

Contains 1 PH domain.

Sequence caution

The sequence BAA25497.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UQC2-1)

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: Q9UQC2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 676676GRB2-associated-binding protein 2
PRO_0000050285

Regions

Domain6 – 117112PH
Motif351 – 3588SH3-binding
Motif510 – 51910SH3-binding

Amino acid modifications

Modified residue1331Phosphoserine Ref.9
Modified residue1401Phosphoserine Ref.9
Modified residue1411Phosphoserine Ref.9
Modified residue1481Phosphoserine Ref.9
Modified residue1491Phosphoserine Ref.9
Modified residue1591Phosphoserine Ref.9
Modified residue1641Phosphoserine Ref.9
Modified residue2101Phosphoserine Ref.9
Modified residue2181Phosphoserine Ref.9
Modified residue2231Phosphoserine Ref.9
Modified residue2641Phosphoserine Ref.9
Modified residue2651Phosphothreonine By similarity
Modified residue2661Phosphotyrosine By similarity
Modified residue2781Phosphothreonine Ref.9
Modified residue2811Phosphoserine Ref.9
Modified residue2871Phosphothreonine Ref.9
Modified residue2931Phosphotyrosine Ref.9
Modified residue3311Phosphothreonine Ref.9
Modified residue3851Phosphothreonine Ref.9
Modified residue3911Phosphothreonine Ref.9
Modified residue4051Phosphoserine Ref.9
Modified residue4521Phosphotyrosine By similarity
Modified residue4801Phosphoserine Ref.9
Modified residue5431Phosphoserine Ref.9 Ref.10
Modified residue6221Phosphoserine Ref.9
Modified residue6231Phosphoserine Ref.9

Natural variations

Alternative sequence1 – 3838Missing in isoform 2.
VSP_038520
Natural variant3201P → L.
Corresponds to variant rs2279374 [ dbSNP | Ensembl ].
VAR_053097
Natural variant3441P → L.
Corresponds to variant rs2279374 [ dbSNP | Ensembl ].
VAR_020407

Experimental info

Mutagenesis2101S → A or E: Impaired interaction with 14-3-3 proteins and increased EGF-independent cell proliferation; when associated with A-391. Ref.9
Mutagenesis3911T → A or E: Impaired interaction with 14-3-3 proteins and increased EGF-independent cell proliferation; when associated with A-210. Ref.9

Secondary structure

... 676
Helix Strand Turn

Details...

Sequences

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

Last modified May 1, 2000. Version 1.
Checksum: 107623FD07D884C9

FASTA67674,458
        10         20         30         40         50         60 
MSGGGDVVCT GWLRKSPPEK KLRRYAWKKR WFILRSGRMS GDPDVLEYYK NDHSKKPLRI 

        70         80         90        100        110        120 
INLNFCEQVD AGLTFNKKEL QDSFVFDIKT SERTFYLVAE TEEDMNKWVQ SICQICGFNQ 

       130        140        150        160        170        180 
AEESTDSLRN VSSAGHGPRS SPAELSSSSQ HLLRERKSSA PSHSSQPTLF TFEPPVSNHM 

       190        200        210        220        230        240 
QPTLSTSAPQ EYLYLHQCIS RRAENARSAS FSQGTRASFL MRSDTAVQKL AQGNGHCVNG 

       250        260        270        280        290        300 
ISGQVHGFYS LPKPSRHNTE FRDSTYDLPR SLASHGHTKG SLTGSETDNE DVYTFKTPSN 

       310        320        330        340        350        360 
TLCREFGDLL VDNMDVPATP LSAYQIPRTF TLDKNHNAMT VATPGDSAIA PPPRPPKPSQ 

       370        380        390        400        410        420 
AETPRWGSPQ QRPPISENSR SVAATIPRRN TLPAMDNSRL HRASSCETYE YPQRGGESAG 

       430        440        450        460        470        480 
RSAESMSDGV GSFLPGKMIV GRSDSTNSED NYVPMNPGSS TLLAMERAGD NSQSVYIPMS 

       490        500        510        520        530        540 
PGAHHFDSLG YPSTTLPVHR GPSRGSEIQP PPVNRNLKPD RKAKPTPLDL RNNTVIDELP 

       550        560        570        580        590        600 
FKSPITKSWS RANHTFNSSS SQYCRPISTQ SITSTDSGDS EENYVPMQNP VSASPVPSGT 

       610        620        630        640        650        660 
NSPAPKKSTG SVDYLALDFQ PSSPSPHRKP STSSVTSDEK VDYVQVDKEK TQALQNTMQE 

       670 
WTDVRQSSEP SKGAKL 

« Hide

Isoform 2 [UniParc].

Checksum: EA3BCC63C00BBAF0
Show »

FASTA63869,968

References

« Hide 'large scale' references
[1]"Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors."
Nishida K., Yoshida Y., Itoh M., Fukada T., Ohtani T., Shirogane T., Atsumi T., Takahashi-Tezuka M., Ishihara K., Hibi M., Hirano T.
Blood 93:1809-1816(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH PTPN11.
Tissue: Myeloma.
[2]"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[3]Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[4]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[7]"Critical role for hematopoietic cell kinase (Hck)-mediated phosphorylation of Gab1 and Gab2 docking proteins in interleukin 6-induced proliferation and survival of multiple myeloma cells."
Podar K., Mostoslavsky G., Sattler M., Tai Y.T., Hayashi T., Catley L.P., Hideshima T., Mulligan R.C., Chauhan D., Anderson K.C.
J. Biol. Chem. 279:21658-21665(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY HCK, INTERACTION WITH HCK; CRKL PTPN11 AND GRB2.
[8]"The molecular scaffold Gab2 is a crucial component of RANK signaling and osteoclastogenesis."
Wada T., Nakashima T., Oliveira-dos-Santos A.J., Gasser J., Hara H., Schett G., Penninger J.M.
Nat. Med. 11:394-399(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TNFRSF11A.
[9]"Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein."
Brummer T., Larance M., Herrera Abreu M.T., Lyons R.J., Timpson P., Emmerich C.H., Fleuren E.D.G., Lehrbach G.M., Schramek D., Guilhaus M., James D.E., Daly R.J.
EMBO J. 27:2305-2316(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EGFR; GRB2; PTPN11; PI-3 KINASE; SFN; SHC1; YWHAB; YWHAE; YWHAG; YWHAH; YWHAQ AND YWHAZ, MUTAGENESIS OF SER-210 AND THR-391, PHOSPHORYLATION AT SER-133; SER-140; SER-141; SER-148; SER-149; SER-159; SER-164; SER-210; SER-218; SER-223; SER-264; THR-278; SER-281; THR-287; TYR-293; THR-331; THR-385; THR-391; SER-405; SER-480; SER-543; SER-622 AND SER-623.
[10]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-543, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2."
Harkiolaki M., Tsirka T., Lewitzky M., Simister P.C., Joshi D., Bird L.E., Jones E.Y., O'Reilly N., Feller S.M.
Structure 17:809-822(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 350-358 IN COMPLEX WITH GRB2, X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 508-522 IN COMPLEX WITH GRB2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB018413 mRNA. Translation: BAA76737.1.
AB011143 mRNA. Translation: BAA25497.2. Different initiation.
AP002985 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW75057.1.
CH471076 Genomic DNA. Translation: EAW75058.1.
BC131711 mRNA. Translation: AAI31712.1.
BC152459 mRNA. Translation: AAI52460.1.
RefSeqNP_036428.1. NM_012296.3.
NP_536739.1. NM_080491.2.
UniGeneHs.429434.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2VWFX-ray1.58B508-522[»]
2W0ZX-ray1.70B350-358[»]
ProteinModelPortalQ9UQC2.
SMRQ9UQC2. Positions 27-112.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115181. 31 interactions.
DIPDIP-36653N.
IntActQ9UQC2. 12 interactions.
MINTMINT-123618.
STRING9606.ENSP00000302452.

PTM databases

PhosphoSiteQ9UQC2.

Polymorphism databases

DMDM46396035.

Proteomic databases

PaxDbQ9UQC2.
PRIDEQ9UQC2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000340149; ENSP00000343959; ENSG00000033327. [Q9UQC2-2]
ENST00000361507; ENSP00000354952; ENSG00000033327. [Q9UQC2-1]
GeneID9846.
KEGGhsa:9846.
UCSCuc001ozg.3. human. [Q9UQC2-1]

Organism-specific databases

CTD9846.
GeneCardsGC11M077926.
HGNCHGNC:14458. GAB2.
HPACAB022159.
HPA000271.
MIM606203. gene.
neXtProtNX_Q9UQC2.
PharmGKBPA28478.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG83177.
HOGENOMHOG000236270.
HOVERGENHBG051685.
KOK08091.
OMAMQPTLST.
OrthoDBEOG7T4MJJ.
PhylomeDBQ9UQC2.
TreeFamTF329487.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkQ9UQC2.

Gene expression databases

ArrayExpressQ9UQC2.
BgeeQ9UQC2.
CleanExHS_GAB2.
GenevestigatorQ9UQC2.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
[Graphical view]
PfamPF00169. PH. 1 hit.
[Graphical view]
SMARTSM00233. PH. 1 hit.
[Graphical view]
PROSITEPS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGAB2. human.
EvolutionaryTraceQ9UQC2.
GeneWikiGAB2.
GenomeRNAi9846.
NextBio37106.
PROQ9UQC2.
SOURCESearch...

Entry information

Entry nameGAB2_HUMAN
AccessionPrimary (citable) accession number: Q9UQC2
Secondary accession number(s): A2RRM2 expand/collapse secondary AC list , A6NEW9, A7MD36, O60317
Entry history
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM