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Protein

GRB2-associated-binding protein 1

Gene

GAB1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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.
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

HGNCiHGNC:4066. GAB1.

Subcellular locationi

GO - Cellular componenti

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

EPDiQ13480.
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. 30 interactors.
IntActiQ13480. 61 interactors.
MINTiMINT-140909.
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_dom-like.
IPR001849. PH_domain.
PfamiView protein in Pfam
PF00169. PH. 1 hit.
SMARTiView protein in SMART
SM00233. PH. 1 hit.
SUPFAMiSSF50729. SSF50729. 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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

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: July 5, 2017
This is version 157 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

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families