G6B_MOUSE
ID G6B_MOUSE Reviewed; 242 AA.
AC D7PDD4;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Megakaryocyte and platelet inhibitory receptor G6b {ECO:0000250|UniProtKB:O95866};
DE AltName: Full=ITIM-receptor G6b-B {ECO:0000303|PubMed:23112346};
DE AltName: Full=Immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing platelet receptor {ECO:0000303|PubMed:23112346};
DE Flags: Precursor;
GN Name=Mpig6b {ECO:0000250|UniProtKB:O95866};
GN Synonyms=AU023871 {ECO:0000312|MGI:MGI:2146995},
GN G6b {ECO:0000312|MGI:MGI:2146995}, G6b-B {ECO:0000303|PubMed:23112346};
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], DISRUPTION PHENOTYPE, FUNCTION, TISSUE
RP SPECIFICITY, GLYCOSYLATION, PHOSPHORYLATION, INTERACTION WITH PTPN6 AND
RP PTPN11, AND DOMAIN.
RX PubMed=23112346; DOI=10.1126/scisignal.2002936;
RA Mazharian A., Wang Y.J., Mori J., Bem D., Finney B., Heising S., Gissen P.,
RA White J.G., Berndt M.C., Gardiner E.E., Nieswandt B., Douglas M.R.,
RA Campbell R.D., Watson S.P., Senis Y.A.;
RT "Mice lacking the ITIM-containing receptor G6b-B exhibit
RT macrothrombocytopenia and aberrant platelet function.";
RL Sci. Signal. 5:RA78-RA78(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
CC -!- FUNCTION: Inhibitory receptor that acts as a critical regulator of
CC hematopoietic lineage differentiation, megakaryocyte function and
CC platelet production (PubMed:23112346). Inhibits platelet aggregation
CC and activation by agonists such as ADP and collagen-related peptide (By
CC similarity). This regulation of megakaryocate function as well as
CC platelet production ann activation is done through the inhibition (via
CC the 2 ITIM motifs) of the receptors CLEC1B and GP6:FcRgamma signaling
CC (PubMed:23112346). Appears to operate in a calcium-independent manner
CC (By similarity). {ECO:0000250|UniProtKB:O95866,
CC ECO:0000269|PubMed:23112346}.
CC -!- SUBUNIT: Interacts (via ITIM motif) with PTPN6 and PTPN11
CC (PubMed:23112346). Binds to heparin (By similarity).
CC {ECO:0000250|UniProtKB:O95866, ECO:0000269|PubMed:23112346}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:23112346};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:O95866,
CC ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in mature megakaryocytes and platelets.
CC Not expressed by immature megakaryocytes.
CC {ECO:0000269|PubMed:23112346}.
CC -!- DOMAIN: Contains both a transmembrane region and 2 copies of a
CC cytoplasmic motif that is referred to as the immunoreceptor tyrosine-
CC based inhibitor motif (ITIM). This motif is involved in modulation of
CC cellular responses. The phosphorylated ITIM motif can bind the SH2
CC domain of several SH2-containing phosphatases. The 2 ITIM motifs of
CC isoform B are required for the inhibition of CLEC1B and GP6:FCER1G
CC signaling and platelet activation. {ECO:0000305|PubMed:23112346}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:23112346}.
CC -!- PTM: May be O-glycosylated. {ECO:0000250|UniProtKB:O95866}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:23112346}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice exhibit macrothrombocytopenia
CC (reduced platelet numbers and the presence of enlarged platelets) and a
CC susceptibility to bleeding because of defective platelet production and
CC function. They show an increased platelet turnover leading to reduced
CC platelet numbers. Their megakaryocytes exhibit reduced integrin-
CC mediated functions, defective formation of proplatelets as well as an
CC increased metalloproteinase production. {ECO:0000269|PubMed:23112346}.
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DR EMBL; AC087117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; GU269270; ADD91692.1; -; mRNA.
DR CCDS; CCDS57071.1; -.
DR RefSeq; NP_001177941.1; NM_001191012.1.
DR AlphaFoldDB; D7PDD4; -.
DR SMR; D7PDD4; -.
DR STRING; 10090.ENSMUSP00000094950; -.
DR GlyGen; D7PDD4; 2 sites.
DR iPTMnet; D7PDD4; -.
DR PhosphoSitePlus; D7PDD4; -.
DR MaxQB; D7PDD4; -.
DR PaxDb; D7PDD4; -.
DR PRIDE; D7PDD4; -.
DR ProteomicsDB; 273020; -.
DR Antibodypedia; 27557; 92 antibodies from 18 providers.
DR Ensembl; ENSMUST00000174190; ENSMUSP00000133377; ENSMUSG00000073414.
DR GeneID; 106722; -.
DR KEGG; mmu:106722; -.
DR UCSC; uc012aqy.1; mouse.
DR CTD; 80739; -.
DR MGI; MGI:2146995; Mpig6b.
DR VEuPathDB; HostDB:ENSMUSG00000073414; -.
DR eggNOG; ENOG502TEAD; Eukaryota.
DR GeneTree; ENSGT00390000017793; -.
DR HOGENOM; CLU_101026_0_0_1; -.
DR InParanoid; D7PDD4; -.
DR OMA; YMALRRP; -.
DR OrthoDB; 1224317at2759; -.
DR PhylomeDB; D7PDD4; -.
DR Reactome; R-MMU-114604; GPVI-mediated activation cascade.
DR BioGRID-ORCS; 106722; 2 hits in 72 CRISPR screens.
DR PRO; PR:D7PDD4; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; D7PDD4; protein.
DR Bgee; ENSMUSG00000073414; Expressed in bone marrow and 38 other tissues.
DR ExpressionAtlas; D7PDD4; baseline and differential.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0007596; P:blood coagulation; IMP:MGI.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IMP:MGI.
DR GO; GO:0035855; P:megakaryocyte development; IMP:MGI.
DR GO; GO:0030219; P:megakaryocyte differentiation; ISS:UniProtKB.
DR GO; GO:0009968; P:negative regulation of signal transduction; ISS:UniProtKB.
DR GO; GO:0030220; P:platelet formation; IMP:MGI.
DR InterPro; IPR028070; G6B.
DR PANTHER; PTHR37347; PTHR37347; 1.
DR Pfam; PF15096; G6B; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..242
FT /note="Megakaryocyte and platelet inhibitory receptor G6b"
FT /id="PRO_5009689216"
FT TRANSMEM 141..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 210..215
FT /note="ITIM motif"
FT /evidence="ECO:0000303|PubMed:23112346"
FT MOTIF 236..241
FT /note="ITIM motif"
FT /evidence="ECO:0000303|PubMed:23112346"
FT MOD_RES 212
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O95866"
FT CARBOHYD 32
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 242 AA; 26010 MW; 99FDE8AEA82A5F9F CRC64;
MALVLPLLPL LLSKVQGNPE VSLEGSPGDR VNLSCIGVSD PTRWAWAPSF PACKGLSKGR
RPILWASTRG TPTVLQHFSG RLRSLDNGIK RLELLLSAGD SGTFFCKGRH ENESRTVLQV
LGDKAGCRPA GSTHGYEYPK VLIPLLGVGL VLGLGVAGVV WRRRRLSPPP PPPPPPGPLP
TFAPVINAEP QRPLEQESKI SGHLDQEPSL HYADLDHSVL GRHRRMSTVV SGDASTVYAV
VV
