Reviewed, UniProtKB/Swiss-Prot O75791 (GRAP2_HUMAN)

Names and origin

Protein names

Recommended name:
    GRB2-related adapter protein 2
Alternative name(s):
    Protein GADS
    Growth factor receptor-binding protein
    GRBLG
    Grf40 adapter protein
      Short name=Grf-40
    GRB-2-like protein
      Short name=GRB2L
    GRBX
    P38
    Hematopoietic cell-associated adapter protein GrpL
    Adapter protein GRID
    SH3-SH2-SH3 adapter Mona

Gene names

Name:	GRAP2
Synonyms:	GADS, GRB2L, GRID

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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. Ref.12 Ref.13 Ref.14
Sequence similarities	Belongs to the GRB2/sem-5/DRK family. Contains 1 SH2 domain. Contains 2 SH3 domains.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Domain	Repeat SH2 domain SH3 domain
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	Ras protein signal transduction Ref.1 Traceable author statement. Source: ProtInc cell-cell signaling Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytosol Inferred from Experiment. Source: Reactome
Molecular function	SH3/SH2 adaptor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

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.18 Ref.15 Ref.17
Natural variations
	Natural variant	319	1	L → F: dbSNP rs12759. Ref.4		VAR_012079

Sequences

	Sequence		Length	Mass (Da)
	O75791-1 [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: 9878555] [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: 10209041] [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: 10224278] [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: 10820259] [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: 12062812] [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: 15461802] [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: 10591208] [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: 15489334] [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 angigen 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: 10811803] [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: 12084069] [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: 12359715] [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: 12522270] [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: 15144186] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-45, MASS SPECTROMETRY. Tissue: 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: 18088087] [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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-45 AND THR-262, MASS SPECTROMETRY. Tissue: 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., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-106, MASS SPECTROMETRY.
+	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.
UniGene	Hs.517499
3D structure databases
SMR	O75791. Positions 3-137, 46-188, 271-330.
ModBase	Search...
Protein-protein interaction databases
IntAct	O75791. 10 interactions.
STRING	O75791.
PTM databases
PhosphoSite	O75791.
Proteomic databases
PRIDE	O75791.
Genome annotation databases
Ensembl	ENST00000344138; ENSP00000339186; ENSG00000100351; Homo sapiens. [Genome view] ENST00000407075; ENSP00000385607; ENSG00000100351; Homo sapiens. [Genome view]
GeneID	9402.
KEGG	hsa:9402.
UCSC	uc003ayh.1. human.
Organism-specific databases
CTD	9402.
GeneCards	GC22P038621.
H-InvDB	HIX0016498. HIX0080261.
HGNC	HGNC:4563. GRAP2.
HPA	CAB022073. HPA005788.
MIM	604518. gene.
PharmGKB	PA28959.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07021.
HOGENOM	HBG715336.
HOVERGEN	O75791.
InParanoid	O75791.
OMA	LSFHTGD.
OrthoDB	EOG92FW3G.
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_6900. Signaling in Immune system.
Gene expression databases
ArrayExpress	O75791.
Bgee	O75791.
CleanEx	HS_GRAP2.
Genevestigator	O75791.
GermOnline	ENSG00000100351. Homo sapiens.
Family and domain databases
InterPro	IPR000980. SH2. IPR001452. SH3_domain. IPR020473. SH3_region. [Graphical view]
Gene3D	G3DSA:3.30.505.10. SH2. 1 hit.
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]
PROSITE	PS50001. SH2. 1 hit. PS50002. SH3. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
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:	January 19, 2010
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.