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Protein

GRB2-associated-binding protein 1

Gene

GAB1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Adapter protein that plays a role in intracellular signaling cascades triggered by activated receptor-type kinases. Plays a role in FGFR1 signaling. Probably involved in signaling by the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR).

GO - Molecular functioni

GO - Biological processi

  • actin cytoskeleton reorganization Source: BHF-UCL
  • angiogenesis Source: BHF-UCL
  • axon guidance Source: Reactome
  • cell proliferation Source: ProtInc
  • endothelial cell chemotaxis to vascular endothelial growth factor Source: BHF-UCL
  • epidermal growth factor receptor signaling pathway Source: Reactome
  • ERBB2 signaling pathway Source: Reactome
  • insulin receptor signaling pathway Source: ProtInc
  • positive regulation of angiogenesis Source: BHF-UCL
  • positive regulation of cell migration by vascular endothelial growth factor signaling pathway Source: BHF-UCL
  • positive regulation of protein kinase B signaling Source: Reactome
  • vascular endothelial growth factor signaling pathway Source: BHF-UCL

Enzyme and pathway databases

ReactomeiR-HSA-109704 PI3K Cascade
R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-180292 GAB1 signalosome
R-HSA-1963642 PI3K events in ERBB2 signaling
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5637810 Constitutive Signaling by EGFRvIII
R-HSA-5654689 PI-3K cascade:FGFR1
R-HSA-5654695 PI-3K cascade:FGFR2
R-HSA-5654710 PI-3K cascade:FGFR3
R-HSA-5654720 PI-3K cascade:FGFR4
R-HSA-5655253 Signaling by FGFR2 in disease
R-HSA-5655291 Signaling by FGFR4 in disease
R-HSA-5655302 Signaling by FGFR1 in disease
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8851907 MET activates PI3K/AKT signaling
R-HSA-8853334 Signaling by FGFR3 fusions in cancer
R-HSA-8853338 Signaling by FGFR3 point mutants in cancer
R-HSA-8853659 RET signaling
R-HSA-8865999 MET activates PTPN11
R-HSA-8875555 MET activates RAP1 and RAC1
R-HSA-8875656 MET receptor recycling
R-HSA-9028335 Activated NTRK2 signals through PI3K
SignaLinkiQ13480
SIGNORiQ13480

Names & Taxonomyi

Protein namesi
Recommended name:
GRB2-associated-binding protein 1
Alternative name(s):
GRB2-associated binder 1
Growth factor receptor bound protein 2-associated protein 1
Gene namesi
Name:GAB1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000109458.8
HGNCiHGNC:4066 GAB1
MIMi604439 gene
neXtProtiNX_Q13480

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

DisGeNETi2549
OpenTargetsiENSG00000109458
PharmGKBiPA28477

Polymorphism and mutation databases

BioMutaiGAB1
DMDMi90180201

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000502822 – 694GRB2-associated-binding protein 1Add BLAST693

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei251PhosphoserineCombined sources1
Modified residuei253PhosphoserineCombined sources1
Modified residuei266PhosphoserineCombined sources1
Modified residuei304PhosphoserineCombined sources1
Modified residuei387PhosphothreonineCombined sources1
Modified residuei402PhosphoserineCombined sources1
Modified residuei454PhosphoserineBy similarity1
Modified residuei627PhosphotyrosineCombined sources1
Modified residuei638PhosphothreonineCombined sources1
Modified residuei651PhosphoserineCombined sources1
Modified residuei659PhosphotyrosineCombined sources1
Modified residuei683PhosphoserineCombined sources1
Isoform 2 (identifier: Q13480-2)
Modified residuei547PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated in response to FGFR1 activation. Phosphorylated on tyrosine residue(s) by the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR). Tyrosine phosphorylation of GAB1 mediates interaction with several proteins that contain SH2 domains. Phosphorylated on tyrosine residues by HCK upon IL6 signaling.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ13480
PaxDbiQ13480
PeptideAtlasiQ13480
PRIDEiQ13480

PTM databases

iPTMnetiQ13480
PhosphoSitePlusiQ13480

Expressioni

Gene expression databases

BgeeiENSG00000109458
CleanExiHS_GAB1
ExpressionAtlasiQ13480 baseline and differential
GenevisibleiQ13480 HS

Organism-specific databases

HPAiHPA049599

Interactioni

Subunit structurei

Interacts with GRB2 and with other SH2-containing proteins. Interacts with phosphorylated LAT2. Interacts with PTPRJ. Identified in a complex containing FRS2, GRB2, GAB1, PIK3R1 and SOS1. Interacts (phosphorylated) with PTPN11. Interacts with HCK.3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • SH3/SH2 adaptor activity Source: ProtInc

Protein-protein interaction databases

BioGridi108824, 33 interactors
CORUMiQ13480
ELMiQ13480
IntActiQ13480, 62 interactors
MINTiQ13480
STRINGi9606.ENSP00000262995

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4QSYX-ray2.10B621-633[»]
ProteinModelPortaliQ13480
SMRiQ13480
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini5 – 116PHPROSITE-ProRule annotationAdd BLAST112

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi449 – 540Pro-richAdd BLAST92

Sequence similaritiesi

Belongs to the GAB family.Curated

Phylogenomic databases

eggNOGiENOG410IEIX Eukaryota
ENOG4111RDE LUCA
GeneTreeiENSGT00510000046662
HOGENOMiHOG000236270
HOVERGENiHBG051685
InParanoidiQ13480
KOiK09593
OMAiVNGFFQQ
OrthoDBiEOG091G03BY
PhylomeDBiQ13480
TreeFamiTF329487

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
PfamiView protein in Pfam
PF00169 PH, 1 hit
SMARTiView protein in SMART
SM00233 PH, 1 hit
PROSITEiView protein in PROSITE
PS50003 PH_DOMAIN, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13480-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSGGEVVCSG WLRKSPPEKK LKRYAWKRRW FVLRSGRLTG DPDVLEYYKN
60 70 80 90 100
DHAKKPIRII DLNLCQQVDA GLTFNKKEFE NSYIFDINTI DRIFYLVADS
110 120 130 140 150
EEEMNKWVRC ICDICGFNPT EEDPVKPPGS SLQAPADLPL AINTAPPSTQ
160 170 180 190 200
ADSSSATLPP PYQLINVPPH LETLGIQEDP QDYLLLINCQ SKKPEPTRTH
210 220 230 240 250
ADSAKSTSSE TDCNDNVPSH KNPASSQSKH GMNGFFQQQM IYDSPPSRAP
260 270 280 290 300
SASVDSSLYN LPRSYSHDVL PKVSPSSTEA DGELYVFNTP SGTSSVETQM
310 320 330 340 350
RHVSISYDIP PTPGNTYQIP RTFPEGTLGQ TSKLDTIPDI PPPRPPKPHP
360 370 380 390 400
AHDRSPVETC SIPRTASDTD SSYCIPTAGM SPSRSNTIST VDLNKLRKDA
410 420 430 440 450
SSQDCYDIPR AFPSDRSSSL EGFHNHFKVK NVLTVGSVSS EELDENYVPM
460 470 480 490 500
NPNSPPRQHS SSFTEPIQEA NYVPMTPGTF DFSSFGMQVP PPAHMGFRSS
510 520 530 540 550
PKTPPRRPVP VADCEPPPVD RNLKPDRKVK PAPLEIKPLP EWEELQAPVR
560 570 580 590 600
SPITRSFARD SSRFPMSPRP DSVHSTTSSS DSHDSEENYV PMNPNLSSED
610 620 630 640 650
PNLFGSNSLD GGSSPMIKPK GDKQVEYLDL DLDSGKSTPP RKQKSSGSGS
660 670 680 690
SVADERVDYV VVDQQKTLAL KSTREAWTDG RQSTESETPA KSVK
Length:694
Mass (Da):76,616
Last modified:February 7, 2006 - v2
Checksum:iE0FAC78772B6677B
GO
Isoform 2 (identifier: Q13480-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     528-528: K → KGQSPKILRLKPHGLERTDSQTIGDFATRRK

Show »
Length:724
Mass (Da):80,005
Checksum:iEAA4573B9E5A25B9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti204A → G in AAC50380 (PubMed:8596638).Curated1
Sequence conflicti213C → S in AAC50380 (PubMed:8596638).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03613283Y → C in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_025261311P → L1 PublicationCorresponds to variant dbSNP:rs28925904Ensembl.1
Natural variantiVAR_053096377T → I. Corresponds to variant dbSNP:rs2229879Ensembl.1
Natural variantiVAR_036133387T → N in a breast cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_017137528K → KGQSPKILRLKPHGLERTDS QTIGDFATRRK in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43885 mRNA Translation: AAC50380.1
DQ021880 Genomic DNA Translation: AAY26398.1
AK289767 mRNA Translation: BAF82456.1
AC097658 Genomic DNA No translation available.
AC104685 Genomic DNA Translation: AAY40964.1
CH471056 Genomic DNA Translation: EAX05072.1
BC064848 mRNA Translation: AAH64848.1
CCDSiCCDS3759.1 [Q13480-1]
CCDS3760.1 [Q13480-2]
PIRiS68442
RefSeqiNP_002030.2, NM_002039.3 [Q13480-1]
NP_997006.1, NM_207123.2 [Q13480-2]
UniGeneiHs.618456
Hs.80720

Genome annotation databases

EnsembliENST00000262994; ENSP00000262994; ENSG00000109458 [Q13480-1]
ENST00000262995; ENSP00000262995; ENSG00000109458 [Q13480-2]
GeneIDi2549
KEGGihsa:2549
UCSCiuc003ijd.4 human [Q13480-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGAB1_HUMAN
AccessioniPrimary (citable) accession number: Q13480
Secondary accession number(s): A8K152, Q4W5G2, Q6P1W2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: February 7, 2006
Last modified: May 23, 2018
This is version 166 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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