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Protein

GRB2-related adapter protein 2

Gene

GRAP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Interacts with SLP-76 to regulate NF-AT activation. Binds to tyrosine-phosphorylated shc.

GO - Molecular functioni

  • SH3/SH2 adaptor activity Source: ProtInc

GO - Biological processi

  • cell-cell signaling Source: ProtInc
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • Ras protein signal transduction Source: ProtInc
  • T cell costimulation Source: Reactome
  • T cell receptor signaling pathway Source: Reactome
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-1433557. Signaling by SCF-KIT.
R-HSA-202433. Generation of second messenger molecules.
R-HSA-2424491. DAP12 signaling.
R-HSA-2871796. FCERI mediated MAPK activation.
R-HSA-2871809. FCERI mediated Ca+2 mobilization.
R-HSA-389356. CD28 co-stimulation.
SignaLinkiO75791.

Names & Taxonomyi

Protein namesi
Recommended name:
GRB2-related adapter protein 2
Alternative name(s):
Adapter protein GRID
GRB-2-like protein
Short name:
GRB2L
GRBLG
GRBX
Grf40 adapter protein
Short name:
Grf-40
Growth factor receptor-binding protein
Hematopoietic cell-associated adapter protein GrpL
P38
Protein GADS
SH3-SH2-SH3 adapter Mona
Gene namesi
Name:GRAP2
Synonyms:GADS, GRB2L, GRID
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:4563. GRAP2.

Subcellular locationi

  • Nucleus 1 Publication
  • Cytoplasm 1 Publication
  • Endosome 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • endosome Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi9402.
OpenTargetsiENSG00000100351.
PharmGKBiPA28959.

Polymorphism and mutation databases

BioMutaiGRAP2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000882081 – 330GRB2-related adapter protein 2Add BLAST330

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei45PhosphotyrosineCombined sources1
Modified residuei106N6-acetyllysineCombined sources1
Modified residuei187PhosphoserineBy similarity1
Modified residuei236PhosphoserineBy similarity1
Modified residuei262PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiO75791.
PeptideAtlasiO75791.
PRIDEiO75791.

PTM databases

iPTMnetiO75791.
PhosphoSitePlusiO75791.

Miscellaneous databases

PMAP-CutDBO75791.

Expressioni

Gene expression databases

BgeeiENSG00000100351.
CleanExiHS_GRAP2.
ExpressionAtlasiO75791. baseline and differential.
GenevisibleiO75791. HS.

Organism-specific databases

HPAiCAB022073.
HPA005788.

Interactioni

Subunit structurei

Interacts with phosphorylated LIME1 upon TCR activation (By similarity). Interacts with phosphorylated LAT and LAX1 upon TCR activation. Interacts with SHB. Interacts with PTPN23.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
EGFRP005332EBI-740418,EBI-297353
ERBB2P046262EBI-740418,EBI-641062
GAREM1Q9H7063EBI-740418,EBI-3440103
Kcnma1Q084603EBI-740418,EBI-1633915From a different organism.
KITP107212EBI-740418,EBI-1379503
LCP2Q1309419EBI-740418,EBI-346946
LNX1Q8TBB14EBI-740418,EBI-739832
PTPN23Q9H3S78EBI-740418,EBI-724478
SPRY2O435973EBI-740418,EBI-742487

GO - Molecular functioni

  • SH3/SH2 adaptor activity Source: ProtInc

Protein-protein interaction databases

BioGridi114799. 49 interactors.
DIPiDIP-38435N.
IntActiO75791. 56 interactors.
MINTiMINT-140970.
STRINGi9606.ENSP00000339186.

Structurei

3D structure databases

ProteinModelPortaliO75791.
SMRiO75791.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 56SH3 1PROSITE-ProRule annotationAdd BLAST56
Domaini58 – 149SH2PROSITE-ProRule annotationAdd BLAST92
Domaini271 – 330SH3 2PROSITE-ProRule annotationAdd BLAST60

Sequence similaritiesi

Belongs to the GRB2/sem-5/DRK family.Curated
Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 2 SH3 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG3601. Eukaryota.
ENOG410XR1G. LUCA.
GeneTreeiENSGT00820000126999.
HOGENOMiHOG000251625.
HOVERGENiHBG005404.
InParanoidiO75791.
KOiK07366.
OMAiLSSQEEW.
OrthoDBiEOG091G0HWS.
PhylomeDBiO75791.
TreeFamiTF354288.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
PF00018. SH3_1. 2 hits.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 2 hits.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50002. SH3. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: O75791-1) [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
MEAVAKFDFT ASGEDELSFH TGDVLKILSN QEEWFKAELG SQEGYVPKNF
60 70 80 90 100
IDIQFPKWFH EGLSRHQAEN LLMGKEVGFF IIRASQSSPG DFSISVRHED
110 120 130 140 150
DVQHFKVMRD NKGNYFLWTE KFPSLNKLVD YYRTNSISRQ KQIFLRDRTR
160 170 180 190 200
EDQGHRGNSL DRRSQGGPHL SGAVGEEIRP SMNRKLSDHP PTLPLQQHQH
210 220 230 240 250
QPQPPQYAPA PQQLQQPPQQ RYLQHHHFHQ ERRGGSLDIN DGHCGTGLGS
260 270 280 290 300
EMNAALMHRR HTDPVQLQAA GRVRWARALY DFEALEDDEL GFHSGEVVEV
310 320 330
LDSSNPSWWT GRLHNKLGLF PANYVAPMTR
Length:330
Mass (Da):37,909
Last modified:November 1, 1998 - v1
Checksum:i74F4C8D0EBB56D55
GO
Isoform 2 (identifier: O75791-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: MEAVAKFDFT...NQEEWFKAEL → MVSRRPLSTP...ELPRGLLHLC
     40-152: Missing.

Note: No experimental confirmation available.
Show »
Length:217
Mass (Da):24,382
Checksum:iEC20AF61B4EFCD49
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012079319L → F.1 PublicationCorresponds to variant rs12759dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0552341 – 39MEAVA…FKAEL → MVSRRPLSTPGRELTHGQGG WLLHHPGQPELPRGLLHLC in isoform 2. 1 PublicationAdd BLAST39
Alternative sequenceiVSP_05523540 – 152Missing in isoform 2. 1 PublicationAdd BLAST113

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF102694 mRNA. Translation: AAD04926.1.
AF129476 mRNA. Translation: AAD41782.1.
AF042380 mRNA. Translation: AAC69273.1.
AF236119 mRNA. Translation: AAF60319.1.
AF236120 mRNA. Translation: AAF60320.1.
AF121002 mRNA. Translation: AAF31758.1.
AY069959 mRNA. Translation: AAL58573.1.
Y18051 mRNA. Translation: CAA77021.1.
AJ011736 mRNA. Translation: CAA09757.1.
AF090456 mRNA. Translation: AAD13027.1.
CR456498 mRNA. Translation: CAG30384.1.
AK303470 mRNA. Translation: BAH13969.1.
Z82206 Genomic DNA. Translation: CAI42713.1.
BC025692 mRNA. Translation: AAH25692.1.
BC026002 mRNA. Translation: AAH26002.1.
CCDSiCCDS13999.1. [O75791-1]
PIRiJE0376.
RefSeqiNP_001278753.1. NM_001291824.1. [O75791-1]
NP_001278754.1. NM_001291825.1. [O75791-1]
NP_001278757.1. NM_001291828.1. [O75791-2]
NP_004801.1. NM_004810.3. [O75791-1]
UniGeneiHs.517499.

Genome annotation databases

EnsembliENST00000344138; ENSP00000339186; ENSG00000100351. [O75791-1]
ENST00000407075; ENSP00000385607; ENSG00000100351. [O75791-1]
GeneIDi9402.
KEGGihsa:9402.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF102694 mRNA. Translation: AAD04926.1.
AF129476 mRNA. Translation: AAD41782.1.
AF042380 mRNA. Translation: AAC69273.1.
AF236119 mRNA. Translation: AAF60319.1.
AF236120 mRNA. Translation: AAF60320.1.
AF121002 mRNA. Translation: AAF31758.1.
AY069959 mRNA. Translation: AAL58573.1.
Y18051 mRNA. Translation: CAA77021.1.
AJ011736 mRNA. Translation: CAA09757.1.
AF090456 mRNA. Translation: AAD13027.1.
CR456498 mRNA. Translation: CAG30384.1.
AK303470 mRNA. Translation: BAH13969.1.
Z82206 Genomic DNA. Translation: CAI42713.1.
BC025692 mRNA. Translation: AAH25692.1.
BC026002 mRNA. Translation: AAH26002.1.
CCDSiCCDS13999.1. [O75791-1]
PIRiJE0376.
RefSeqiNP_001278753.1. NM_001291824.1. [O75791-1]
NP_001278754.1. NM_001291825.1. [O75791-1]
NP_001278757.1. NM_001291828.1. [O75791-2]
NP_004801.1. NM_004810.3. [O75791-1]
UniGeneiHs.517499.

3D structure databases

ProteinModelPortaliO75791.
SMRiO75791.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114799. 49 interactors.
DIPiDIP-38435N.
IntActiO75791. 56 interactors.
MINTiMINT-140970.
STRINGi9606.ENSP00000339186.

PTM databases

iPTMnetiO75791.
PhosphoSitePlusiO75791.

Polymorphism and mutation databases

BioMutaiGRAP2.

Proteomic databases

PaxDbiO75791.
PeptideAtlasiO75791.
PRIDEiO75791.

Protocols and materials databases

DNASUi9402.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344138; ENSP00000339186; ENSG00000100351. [O75791-1]
ENST00000407075; ENSP00000385607; ENSG00000100351. [O75791-1]
GeneIDi9402.
KEGGihsa:9402.

Organism-specific databases

CTDi9402.
DisGeNETi9402.
GeneCardsiGRAP2.
HGNCiHGNC:4563. GRAP2.
HPAiCAB022073.
HPA005788.
MIMi604518. gene.
neXtProtiNX_O75791.
OpenTargetsiENSG00000100351.
PharmGKBiPA28959.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3601. Eukaryota.
ENOG410XR1G. LUCA.
GeneTreeiENSGT00820000126999.
HOGENOMiHOG000251625.
HOVERGENiHBG005404.
InParanoidiO75791.
KOiK07366.
OMAiLSSQEEW.
OrthoDBiEOG091G0HWS.
PhylomeDBiO75791.
TreeFamiTF354288.

Enzyme and pathway databases

ReactomeiR-HSA-1433557. Signaling by SCF-KIT.
R-HSA-202433. Generation of second messenger molecules.
R-HSA-2424491. DAP12 signaling.
R-HSA-2871796. FCERI mediated MAPK activation.
R-HSA-2871809. FCERI mediated Ca+2 mobilization.
R-HSA-389356. CD28 co-stimulation.
SignaLinkiO75791.

Miscellaneous databases

ChiTaRSiGRAP2. human.
GeneWikiiGRAP2.
GenomeRNAii9402.
PMAP-CutDBO75791.
PROiO75791.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100351.
CleanExiHS_GRAP2.
ExpressionAtlasiO75791. baseline and differential.
GenevisibleiO75791. HS.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
PF00018. SH3_1. 2 hits.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 2 hits.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50002. SH3. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGRAP2_HUMAN
AccessioniPrimary (citable) accession number: O75791
Secondary accession number(s): B7Z8I3, O43726, Q9NRB7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1998
Last modified: November 30, 2016
This is version 165 of the entry and version 1 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: 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. SIMILARITY comments
    Index of protein domains and families

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.