GRAP2_MOUSE
ID GRAP2_MOUSE Reviewed; 322 AA.
AC O89100;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=GRB2-related adaptor protein 2;
DE AltName: Full=Adapter protein GRID;
DE AltName: Full=GADS protein;
DE AltName: Full=GRB-2-like protein;
DE Short=GRB2L;
DE AltName: Full=GRB-2-related monocytic adapter protein;
DE Short=MONA;
DE Short=Monocytic adapter;
DE AltName: Full=GRBLG;
DE AltName: Full=Growth factor receptor-binding protein;
DE AltName: Full=Hematopoietic cell-associated adaptor protein GrpL;
GN Name=Grap2; Synonyms=Gads, Grb2l, Grid, Mona;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9857184; DOI=10.1093/emboj/17.24.7273;
RA Bourette R.P., Arnaud S., Myles G.M., Blanchet J.P., Rohrschneider L.R.,
RA Mouchiroud G.;
RT "Mona, a novel hematopoietic-specific adaptor interacting with the
RT macrophage colony-stimulating factor receptor, is implicated in
RT monocyte/macrophage development.";
RL EMBO J. 17:7273-7281(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9872323; DOI=10.1038/sj.onc.1202337;
RA Liu S.K., McGlade C.J.;
RT "Gads is a novel SH2 and SH3 domain-containing adaptor protein that binds
RT to tyrosine-phosphorylated Shc.";
RL Oncogene 17:3073-3082(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10209041; DOI=10.1084/jem.189.8.1243;
RA Law C.-L., Ewings M.K., Chaudhary P.M., Solow S.A., Yun T.J.,
RA Marshall A.J., Hood L., Clark E.A.;
RT "GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate
RT nuclear factor of activated T cell activation.";
RL J. Exp. Med. 189:1243-1253(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10820259; DOI=10.4049/jimmunol.164.11.5805;
RA Ellis J.H., Ashman C., Burden M.N., Kilpatrick K.E., Morse M.A.,
RA Hamblin P.A.;
RT "GRID: a novel Grb-2-related adapter protein that interacts with the
RT activated T cell costimulatory receptor CD28.";
RL J. Immunol. 164:5805-5814(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kedra D., Dumanski J.P.;
RT "Cloning of the human and mouse growth factor receptor binding protein like
RT genes.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH LIME1.
RX PubMed=14610044; DOI=10.1084/jem.20030232;
RA Hur E.M., Son M., Lee O.-H., Choi Y.B., Park C., Lee H., Yun Y.;
RT "LIME, a novel transmembrane adaptor protein, associates with p56lck and
RT mediates T cell activation.";
RL J. Exp. Med. 198:1463-1473(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186; SER-230 AND THR-254, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Interacts with SLP-76 to regulate NF-AT activation. Binds to
CC tyrosine-phosphorylated shc.
CC -!- SUBUNIT: Interacts with phosphorylated LAT and LAX1 upon TCR
CC activation. Interacts with SHB. Interacts with PTPN23 (By similarity).
CC Interacts with phosphorylated LIME1 upon TCR activation. {ECO:0000250,
CC ECO:0000269|PubMed:14610044}.
CC -!- INTERACTION:
CC O89100; Q60787: Lcp2; NbExp=7; IntAct=EBI-642151, EBI-5324248;
CC O89100; Q6PB44: Ptpn23; NbExp=3; IntAct=EBI-642151, EBI-4284816;
CC O89100; Q13094: LCP2; Xeno; NbExp=4; IntAct=EBI-642151, EBI-346946;
CC O89100; Q9H3S7: PTPN23; Xeno; NbExp=3; IntAct=EBI-642151, EBI-724478;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC Endosome {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the GRB2/sem-5/DRK family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF055465; AAD08803.1; -; mRNA.
DR EMBL; AF053405; AAC98669.1; -; mRNA.
DR EMBL; AF129477; AAD41783.1; -; mRNA.
DR EMBL; AF236118; AAF60318.1; -; mRNA.
DR EMBL; AJ011735; CAA09756.1; -; mRNA.
DR EMBL; BC052496; AAH52496.1; -; mRNA.
DR CCDS; CCDS27663.1; -.
DR RefSeq; NP_001276371.1; NM_001289442.1.
DR RefSeq; NP_034945.1; NM_010815.3.
DR PDB; 1H3H; NMR; -; A=263-322.
DR PDB; 1OEB; X-ray; 1.76 A; A/B=265-322.
DR PDB; 1R1P; X-ray; 1.80 A; A/B/C/D=50-147.
DR PDB; 1R1Q; X-ray; 1.80 A; A/B=50-147.
DR PDB; 1R1S; X-ray; 1.90 A; A/C/E/G=50-147.
DR PDB; 1UTI; X-ray; 1.50 A; A=265-322.
DR PDB; 2D0N; X-ray; 1.57 A; A/C=267-322.
DR PDB; 2W10; X-ray; 1.90 A; A/B=265-322.
DR PDBsum; 1H3H; -.
DR PDBsum; 1OEB; -.
DR PDBsum; 1R1P; -.
DR PDBsum; 1R1Q; -.
DR PDBsum; 1R1S; -.
DR PDBsum; 1UTI; -.
DR PDBsum; 2D0N; -.
DR PDBsum; 2W10; -.
DR AlphaFoldDB; O89100; -.
DR SMR; O89100; -.
DR BioGRID; 201466; 9.
DR DIP; DIP-41343N; -.
DR IntAct; O89100; 15.
DR MINT; O89100; -.
DR STRING; 10090.ENSMUSP00000046532; -.
DR iPTMnet; O89100; -.
DR PhosphoSitePlus; O89100; -.
DR EPD; O89100; -.
DR jPOST; O89100; -.
DR PaxDb; O89100; -.
DR PRIDE; O89100; -.
DR ProteomicsDB; 271158; -.
DR Antibodypedia; 236; 503 antibodies from 38 providers.
DR DNASU; 17444; -.
DR Ensembl; ENSMUST00000043149; ENSMUSP00000046532; ENSMUSG00000042351.
DR Ensembl; ENSMUST00000229980; ENSMUSP00000155681; ENSMUSG00000042351.
DR GeneID; 17444; -.
DR KEGG; mmu:17444; -.
DR UCSC; uc007wvo.2; mouse.
DR CTD; 9402; -.
DR MGI; MGI:1333842; Grap2.
DR VEuPathDB; HostDB:ENSMUSG00000042351; -.
DR eggNOG; KOG3601; Eukaryota.
DR GeneTree; ENSGT00940000157307; -.
DR HOGENOM; CLU_073617_0_0_1; -.
DR InParanoid; O89100; -.
DR OMA; VAKFDFM; -.
DR OrthoDB; 1091250at2759; -.
DR PhylomeDB; O89100; -.
DR TreeFam; TF354288; -.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR Reactome; R-MMU-202433; Generation of second messenger molecules.
DR Reactome; R-MMU-2424491; DAP12 signaling.
DR Reactome; R-MMU-2871796; FCERI mediated MAPK activation.
DR Reactome; R-MMU-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-MMU-389356; CD28 co-stimulation.
DR Reactome; R-MMU-9607240; FLT3 Signaling.
DR BioGRID-ORCS; 17444; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Grap2; mouse.
DR EvolutionaryTrace; O89100; -.
DR PRO; PR:O89100; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; O89100; protein.
DR Bgee; ENSMUSG00000042351; Expressed in thymus and 55 other tissues.
DR ExpressionAtlas; O89100; baseline and differential.
DR Genevisible; O89100; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IBA:GO_Central.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd11950; SH3_GRAP2_C; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR IDEAL; IID50062; -.
DR InterPro; IPR035646; GRAP2_C_SH3.
DR InterPro; IPR043539; Grb2-like.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR46037; PTHR46037; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 2.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 2.
DR SUPFAM; SSF50044; SSF50044; 2.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Endosome; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; SH2 domain; SH3 domain.
FT CHAIN 1..322
FT /note="GRB2-related adaptor protein 2"
FT /id="PRO_0000088209"
FT DOMAIN 1..56
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 58..149
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 263..322
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 143..216
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 45
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O75791"
FT MOD_RES 106
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O75791"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 230
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 254
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT TURN 54..58
FT /evidence="ECO:0007829|PDB:1R1P"
FT HELIX 65..73
FT /evidence="ECO:0007829|PDB:1R1P"
FT STRAND 79..84
FT /evidence="ECO:0007829|PDB:1R1P"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:1R1P"
FT STRAND 92..97
FT /evidence="ECO:0007829|PDB:1R1P"
FT STRAND 99..106
FT /evidence="ECO:0007829|PDB:1R1P"
FT STRAND 115..119
FT /evidence="ECO:0007829|PDB:1R1P"
FT STRAND 121..124
FT /evidence="ECO:0007829|PDB:1R1P"
FT HELIX 125..132
FT /evidence="ECO:0007829|PDB:1R1P"
FT STRAND 137..141
FT /evidence="ECO:0007829|PDB:1R1P"
FT STRAND 267..272
FT /evidence="ECO:0007829|PDB:1UTI"
FT STRAND 278..281
FT /evidence="ECO:0007829|PDB:1H3H"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:1H3H"
FT STRAND 289..294
FT /evidence="ECO:0007829|PDB:1UTI"
FT STRAND 297..305
FT /evidence="ECO:0007829|PDB:1UTI"
FT STRAND 308..313
FT /evidence="ECO:0007829|PDB:1UTI"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:1UTI"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:1UTI"
SQ SEQUENCE 322 AA; 36810 MW; 736311D0640CD3D0 CRC64;
MEATAKFDFM ASGEDELSFR TGDILKILSN QEEWLKAELG SQEGYVPKNF IDIEFPEWFH
EGLSRHQAEN LLMGKDIGFF IIRASQSSPG DFSISVRHED DVQHFKVMRD TKGNYFLWTE
KFPSLNKLVD YYRTTSISKQ KQVFLRDGTQ DQGHRGNSLD RRSQGGPHPS GTVGEEIRPS
VNRKLSDHLP LGPQQFHPHQ QPSPQFTPGP QPPQQQRYLQ HFHQDRRGGS LDINDGHCGL
GSEVNATLMH RRHTDPVQLQ AAGRVRWARA LYDFEALEED ELGFRSGEVV EVLDSSNPSW
WTGRLHNKLG LFPANYVAPM MR
