O75791 (GRAP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	GRAP2
Synonyms:	GADS, GRB2L, GRID

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	330 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Interacts with SLP-76 to regulate NF-AT activation. Binds to tyrosine-phosphorylated shc.
Subunit structure	Interacts with phosphorylated LIME1 upon TCR activation By similarity. Interacts with phosphorylated LAT and LAX1 upon TCR activation. Interacts with SHB. Interacts with PTPN23. Ref.12 Ref.13 Ref.14 Ref.20
Subcellular location	Nucleus. Cytoplasm. Endosome Ref.20.
Sequence similarities	Belongs to the GRB2/sem-5/DRK family. Contains 1 SH2 domain. Contains 2 SH3 domains.

Ontologies

Keywords
Cellular component	Cytoplasm Endosome Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat SH2 domain SH3 domain
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Traceable author statement Ref.1. Source: ProtInc T cell costimulation Traceable author statement. Source: Reactome T cell receptor signaling pathway Traceable author statement. Source: Reactome cell-cell signaling Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome endosome Inferred from direct assay Ref.20. Source: UniProtKB nucleus Inferred from direct assay Ref.20. Source: UniProtKB
Molecular_function	SH3/SH2 adaptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PTPN23	Q9H3S7	5	EBI-740418,EBI-724478

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 330	330	GRB2-related adapter protein 2		PRO_0000088208
Regions
	Domain	1 – 56	56	SH3 1
	Domain	58 – 149	92	SH2
	Domain	271 – 330	60	SH3 2
Amino acid modifications
	Modified residue	45	1	Phosphotyrosine Ref.16 Ref.18
	Modified residue	106	1	N6-acetyllysine Ref.19
	Modified residue	262	1	Phosphothreonine Ref.15 Ref.16 Ref.17
Natural variations
	Natural variant	319	1	L → F. Ref.4 Corresponds to variant rs12759 [ dbSNP | Ensembl ].		VAR_012079

Sequences

	Sequence		Length	Mass (Da)
	O75791 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 74F4C8D0EBB56D55	FASTA	330	37,909
	10 20 30 40 50 60 MEAVAKFDFT ASGEDELSFH TGDVLKILSN QEEWFKAELG SQEGYVPKNF IDIQFPKWFH 70 80 90 100 110 120 EGLSRHQAEN LLMGKEVGFF IIRASQSSPG DFSISVRHED DVQHFKVMRD NKGNYFLWTE 130 140 150 160 170 180 KFPSLNKLVD YYRTNSISRQ KQIFLRDRTR EDQGHRGNSL DRRSQGGPHL SGAVGEEIRP 190 200 210 220 230 240 SMNRKLSDHP PTLPLQQHQH QPQPPQYAPA PQQLQQPPQQ RYLQHHHFHQ ERRGGSLDIN 250 260 270 280 290 300 DGHCGTGLGS EMNAALMHRR HTDPVQLQAA GRVRWARALY DFEALEDDEL GFHSGEVVEV 310 320 330 LDSSNPSWWT GRLHNKLGLF PANYVAPMTR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1." Qiu M., Hua S., Agrawal M., Li G., Cai J., Chan E., Zhou H., Luo Y., Liu M. Biochem. Biophys. Res. Commun. 253:443-447(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation." Law C.-L., Ewings M.K., Chaudhary P.M., Solow S.A., Yun T.J., Marshall A.J., Hood L., Clark E.A. J. Exp. Med. 189:1243-1253(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT." Asada H., Ishii N., Sasaki Y., Endo K., Kasai H., Tanaka N., Takeshita T., Tsuchiya S., Konno T., Sugamura K. J. Exp. Med. 189:1383-1390(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28." Ellis J.H., Ashman C., Burden M.N., Kilpatrick K.E., Morse M.A., Hamblin P.A. J. Immunol. 164:5805-5814(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PHE-319.
[5]	"Genomic organization and restricted expression of the human Mona/Gads gene suggests regulation by two specific promoters." Guyot B., Arnaud S., Phothirath P., Bourette R.P., Grasset M.F., Rigal D., Mouchiroud G. Gene 290:173-179(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	Frearson J. Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Blood.
[7]	"Cloning of the human and mouse growth factor receptor binding protein like genes." Kedra D., Dumanski J.P. Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[8]	"GrbX, new recruited signaling gene having homology with Grb2." Teramoto T., Nagashima M., Terai S., Thorgeirsson S.S. Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[9]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[10]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	"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]. Tissue: Lung and Spleen.
[12]	"Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell antigen receptor-mediated signaling." Zhang W., Trible R.P., Zhu M., Liu S.K., McGlade C.J., Samelson L.E. J. Biol. Chem. 275:23355-23361(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LAT.
[13]	"Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells." Lindholm C.K., Henriksson M.L., Hallberg B., Welsh M. Eur. J. Biochem. 269:3279-3288(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SHB.
[14]	"Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling." Zhu M., Janssen E., Leung K., Zhang W. J. Biol. Chem. 277:46151-46158(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LAX1.
[15]	"Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry." Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C. Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-262, MASS SPECTROMETRY.
[16]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-45 AND THR-262, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[17]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-262, MASS SPECTROMETRY. Tissue: Platelet.
[18]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-45, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[19]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-106, MASS SPECTROMETRY.
[20]	"Histidine domain-protein tyrosine phosphatase interacts with Grb2 and GrpL." Tanase C.A. PLoS ONE 5:E14339-E14339(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTPN23, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. Z82206 Genomic DNA. Translation: CAI42713.1. BC025692 mRNA. Translation: AAH25692.1. BC026002 mRNA. Translation: AAH26002.1.
IPI	IPI00026928.
PIR	JE0376.
RefSeq	NP_004801.1. NM_004810.2.
UniGene	Hs.517499.
3D structure databases
ProteinModelPortal	O75791.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-38435N.
IntAct	O75791. 12 interactions.
MINT	MINT-140970.
STRING	9606.ENSP00000339186.
PTM databases
PhosphoSite	O75791.
Proteomic databases
PaxDb	O75791.
PRIDE	O75791.
Protocols and materials databases
DNASU	9402.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000344138; ENSP00000339186; ENSG00000100351. ENST00000407075; ENSP00000385607; ENSG00000100351.
GeneID	9402.
KEGG	hsa:9402.
UCSC	uc003ayh.2. human.
Organism-specific databases
CTD	9402.
GeneCards	GC22P040297.
HGNC	HGNC:4563. GRAP2.
HPA	CAB022073. HPA005788.
MIM	604518. gene.
neXtProt	NX_O75791.
PharmGKB	PA28959.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG272892.
HOGENOM	HOG000251625.
HOVERGEN	HBG005404.
InParanoid	O75791.
KO	K07366.
OMA	HTGDILK.
OrthoDB	EOG4BCDND.
PhylomeDB	O75791.
Enzyme and pathway databases
Pathway_Interaction_DB	tcrjnkpathway. JNK signaling in the CD4+ TCR pathway. kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit). tcrpathway. TCR signaling in naive CD4+ T cells. cd8tcrpathway. TCR signaling in naive CD8+ T cells.
Reactome	REACT_111102. Signal Transduction. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	O75791.
Bgee	O75791.
CleanEx	HS_GRAP2.
Genevestigator	O75791.
GermOnline	ENSG00000100351. Homo sapiens.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR000980. SH2. IPR001452. SH3_domain. [Graphical view]
Pfam	PF00017. SH2. 1 hit. PF00018. SH3_1. 2 hits. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00452. SH3DOMAIN.
SMART	SM00252. SH2. 1 hit. SM00326. SH3. 2 hits. [Graphical view]
SUPFAM	SSF50044. SH3. 2 hits.
PROSITE	PS50001. SH2. 1 hit. PS50002. SH3. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	GRAP2. human.
GenomeRNAi	9402.
NextBio	35223.
PMAP-CutDB	O75791.
SOURCE	Search...

Entry information

Entry name

GRAP2_HUMAN

Accession

Primary (citable) accession number: O75791
Secondary accession number(s): O43726, Q9NRB7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 130 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.