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   24-JAN-2024, entry version 184.
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}.
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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; 10090-ENSMUSP00000046532; -.
DR   ProteomicsDB; 271158; -.
DR   Antibodypedia; 236; 535 antibodies from 38 providers.
DR   DNASU; 17444; -.
DR   Ensembl; ENSMUST00000043149.9; ENSMUSP00000046532.8; ENSMUSG00000042351.10.
DR   Ensembl; ENSMUST00000229980.2; ENSMUSP00000155681.2; ENSMUSG00000042351.10.
DR   GeneID; 17444; -.
DR   KEGG; mmu:17444; -.
DR   UCSC; uc007wvo.2; mouse.
DR   AGR; MGI:1333842; -.
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; 25371at2759; -.
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 80 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 56 other cell types or tissues.
DR   ExpressionAtlas; O89100; baseline and differential.
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; cd09941; SH2_Grb2_like; 1.
DR   CDD; cd11950; SH3_GRAP2_C; 1.
DR   Gene3D; 3.30.505.10; SH2 domain; 1.
DR   Gene3D; 2.30.30.40; SH3 Domains; 2.
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:SF3; GRB2-RELATED ADAPTER PROTEIN 2; 1.
DR   PANTHER; PTHR46037; PROTEIN ENHANCER OF SEVENLESS 2B; 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; SSF55550; SH2 domain; 1.
DR   SUPFAM; SSF50044; SH3-domain; 2.
DR   PROSITE; PS50001; SH2; 1.
DR   PROSITE; PS50002; SH3; 2.
DR   Genevisible; O89100; MM.
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
//