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Megakaryocyte and platelet inhibitory receptor G6b (ITIM-receptor G6b-B) (Immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing platelet receptor)

 G6B_MOUSE               Reviewed;         242 AA.
D7PDD4;
07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
10-AUG-2010, sequence version 1.
23-MAY-2018, entry version 56.
RecName: Full=Megakaryocyte and platelet inhibitory receptor G6b {ECO:0000250|UniProtKB:O95866};
AltName: Full=ITIM-receptor G6b-B {ECO:0000303|PubMed:23112346};
AltName: Full=Immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing platelet receptor {ECO:0000303|PubMed:23112346};
Flags: Precursor;
Name=Mpig6b {ECO:0000250|UniProtKB:O95866};
Synonyms=AU023871 {ECO:0000312|MGI:MGI:2146995},
G6b {ECO:0000312|MGI:MGI:2146995},
G6b-B {ECO:0000303|PubMed:23112346};
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], DISRUPTION PHENOTYPE, FUNCTION, TISSUE
SPECIFICITY, GLYCOSYLATION, PHOSPHORYLATION, INTERACTION WITH PTPN6
AND PTPN11, AND DOMAIN.
PubMed=23112346; DOI=10.1126/scisignal.2002936;
Mazharian A., Wang Y.J., Mori J., Bem D., Finney B., Heising S.,
Gissen P., White J.G., Berndt M.C., Gardiner E.E., Nieswandt B.,
Douglas M.R., Campbell R.D., Watson S.P., Senis Y.A.;
"Mice lacking the ITIM-containing receptor G6b-B exhibit
macrothrombocytopenia and aberrant platelet function.";
Sci. Signal. 5:RA78-RA78(2012).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=C57BL/6J;
PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S.,
She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
Lindblad-Toh K., Eichler E.E., Ponting C.P.;
"Lineage-specific biology revealed by a finished genome assembly of
the mouse.";
PLoS Biol. 7:E1000112-E1000112(2009).
-!- FUNCTION: Inhibitory receptor that acts as a critical regulator of
hematopoietic lineage differentiation, megakaryocyte function and
platelet production (PubMed:23112346). Inhibits platelet
aggregation and activation by agonists such as ADP and collagen-
related peptide (By similarity). This regulation of megakaryocate
function as well as platelet production ann activation is done
through the inhibition (via the 2 ITIM motifs) of the receptors
CLEC1B and GP6:FcRgamma signaling (PubMed:23112346). Appears to
operate in a calcium-independent manner (By similarity).
{ECO:0000250|UniProtKB:O95866, ECO:0000269|PubMed:23112346}.
-!- SUBUNIT: Interacts (via ITIM motif) with PTPN6 and PTPN11
(PubMed:23112346). Binds to heparin (By similarity).
{ECO:0000250|UniProtKB:O95866, ECO:0000269|PubMed:23112346}.
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:23112346};
Single-pass type I membrane protein {ECO:0000250|UniProtKB:O95866,
ECO:0000255}.
-!- TISSUE SPECIFICITY: Espressed in mature megakaryocytes and
platelets. Not expressed by immature megakaryocytes.
{ECO:0000269|PubMed:23112346}.
-!- DOMAIN: Contains both a transmembrane region and 2 copies of a
cytoplasmic motif that is referred to as the immunoreceptor
tyrosine-based inhibitor motif (ITIM). This motif is involved in
modulation of cellular responses. The phosphorylated ITIM motif
can bind the SH2 domain of several SH2-containing phosphatases.
The 2 ITIM motifs of isoform B are required for the inhibition of
CLEC1B and GP6:FCER1G signaling and platelet activation.
{ECO:0000305|PubMed:23112346}.
-!- PTM: N-glycosylated. {ECO:0000269|PubMed:23112346}.
-!- PTM: May be O-glycosylated. {ECO:0000250|UniProtKB:O95866}.
-!- PTM: Phosphorylated. {ECO:0000269|PubMed:23112346}.
-!- DISRUPTION PHENOTYPE: Mutant mice exhibit macrothrombocytopenia
(reduced platelet numbers and the presence of enlarged platelets)
and a susceptibility to bleeding because of defective platelet
production and function. They show an increased platelet turnover
leading to reduced platelet numbers. Their megakaryocytes exhibit
reduced integrin-mediated functions, defective formation of
proplatelets as well as an increased metalloproteinase production.
{ECO:0000269|PubMed:23112346}.
-----------------------------------------------------------------------
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EMBL; AC087117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; GU269270; ADD91692.1; -; mRNA.
CCDS; CCDS57071.1; -.
RefSeq; NP_001177941.1; NM_001191012.1.
UniGene; Mm.390956; -.
ProteinModelPortal; D7PDD4; -.
STRING; 10090.ENSMUSP00000133377; -.
iPTMnet; D7PDD4; -.
PhosphoSitePlus; D7PDD4; -.
MaxQB; D7PDD4; -.
PaxDb; D7PDD4; -.
PRIDE; D7PDD4; -.
Ensembl; ENSMUST00000174190; ENSMUSP00000133377; ENSMUSG00000073414.
GeneID; 106722; -.
KEGG; mmu:106722; -.
UCSC; uc012aqy.1; mouse.
CTD; 80739; -.
MGI; MGI:2146995; Mpig6b.
eggNOG; ENOG410IYA7; Eukaryota.
eggNOG; ENOG41118MY; LUCA.
GeneTree; ENSGT00390000017793; -.
OMA; RTYCKAP; -.
OrthoDB; EOG091G0N3N; -.
Reactome; R-MMU-114604; GPVI-mediated activation cascade.
PRO; PR:D7PDD4; -.
Proteomes; UP000000589; Chromosome 17.
Bgee; ENSMUSG00000073414; -.
ExpressionAtlas; D7PDD4; baseline and differential.
GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; ISO:MGI.
GO; GO:0007596; P:blood coagulation; IMP:MGI.
GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
GO; GO:0007229; P:integrin-mediated signaling pathway; IMP:MGI.
GO; GO:0035855; P:megakaryocyte development; IMP:MGI.
GO; GO:0030219; P:megakaryocyte differentiation; ISS:UniProtKB.
GO; GO:0009968; P:negative regulation of signal transduction; ISS:UniProtKB.
GO; GO:0030220; P:platelet formation; IMP:MGI.
InterPro; IPR028070; G6B.
PANTHER; PTHR37347; PTHR37347; 1.
Pfam; PF15096; G6B; 1.
1: Evidence at protein level;
Cell membrane; Complete proteome; Glycoprotein; Membrane;
Phosphoprotein; Receptor; Reference proteome; Signal; Transmembrane;
Transmembrane helix.
SIGNAL 1 17 {ECO:0000255}.
CHAIN 18 242 Megakaryocyte and platelet inhibitory
receptor G6b.
/FTId=PRO_5009689216.
TRANSMEM 141 161 Helical. {ECO:0000255}.
MOTIF 210 215 ITIM motif.
{ECO:0000303|PubMed:23112346}.
MOTIF 236 241 ITIM motif.
{ECO:0000303|PubMed:23112346}.
MOD_RES 212 212 Phosphotyrosine.
{ECO:0000250|UniProtKB:O95866}.
CARBOHYD 32 32 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 112 112 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
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


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