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Protein

Megakaryocyte and platelet inhibitory receptor G6b

Gene

MPIG6B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Inhibitory receptor that acts as a critical regulator of hematopoietic lineage differentiation, megakaryocyte function and platelet production (PubMed:12665801, PubMed:17311996, PubMed:27743390). Inhibits platelet aggregation and activation by agonists such as ADP and collagen-related peptide (PubMed:12665801). 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:17311996). Appears to operate in a calcium-independent manner (PubMed:12665801).3 Publications
Isoform B, displayed in this entry, is the only isoform to contain both a transmembrane region and 2 immunoreceptor tyrosine-based inhibitor motifs (ITIMs) and, thus, the only one which probably has a role of inhibitory receptor. Isoform A may be the activating counterpart of isoform B.1 Publication

GO - Molecular functioni

GO - Biological processi

  • blood coagulation Source: UniProtKB
  • erythrocyte differentiation Source: UniProtKB
  • integrin-mediated signaling pathway Source: UniProtKB
  • megakaryocyte development Source: UniProtKB
  • megakaryocyte differentiation Source: UniProtKB
  • negative regulation of signal transduction Source: UniProtKB
  • platelet activation Source: Reactome
  • platelet formation Source: UniProtKB

Keywordsi

Molecular functionHeparin-binding, Receptor

Enzyme and pathway databases

ReactomeiR-HSA-114604. GPVI-mediated activation cascade.

Names & Taxonomyi

Protein namesi
Recommended name:
Megakaryocyte and platelet inhibitory receptor G6bImported
Alternative name(s):
Protein G6bCurated
Gene namesi
Name:MPIG6BImported
Synonyms:C6orf25Imported, G6BImported, G6B-B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000204420.8.
HGNCiHGNC:13937. MPIG6B.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini18 – 142Extracellular1 PublicationSequence analysisAdd BLAST125
Transmembranei143 – 163HelicalSequence analysisAdd BLAST21
Topological domaini164 – 241Cytoplasmic1 PublicationSequence analysisAdd BLAST78

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Thrombocytopenia, anemia, and myelofibrosis (THAMY)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by thrombocytopenia, increased number of giant platelets, and anemia manifesting in early childhood. Bone marrow biopsy shows increased number of megakaryocytes and reticular fibrosis consistent with myelofibrosis.
See also OMIM:617441
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078570108 – 241Missing in THAMY; increased protein degradation; decreased enhancement of hematopoietic lineage differentiation. 1 PublicationAdd BLAST134

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi211Y → F: Abolishes the inhibitory effect against ligand-induced activation of PLCG2 by CLEC1B and GP6:FCER1G; when associated with F-237. 1 Publication1
Mutagenesisi211Y → F: Loss of tyrosine phosphorylation and loss of interaction with PTPN6 and PTPN11. 1 Publication1
Mutagenesisi237Y → F: Abolishes the inhibitory effect against ligand-induced activation of PLCG2 by CLEC1B and GP6:FCER1G; when associted with F-237. 1 Publication1
Mutagenesisi237Y → F: Reduced level of tyrosine phosphorylation and interaction with PTPN6 and PTPN11. 1 Publication1

Organism-specific databases

DisGeNETi80739.
MIMi617441. phenotype.
OpenTargetsiENSG00000204420.
PharmGKBiPA25926.

Polymorphism and mutation databases

BioMutaiG6B.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 171 PublicationAdd BLAST17
ChainiPRO_000002131218 – 241Megakaryocyte and platelet inhibitory receptor G6bAdd BLAST224

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi32N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei211Phosphotyrosine1 Publication1

Post-translational modificationi

All isoforms are N-glycosylated.2 Publications
Isoform E is O-glycosylated.1 Publication
Phosphorylated.2 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO95866.
PeptideAtlasiO95866.
PRIDEiO95866.

PTM databases

iPTMnetiO95866.
PhosphoSitePlusiO95866.

Expressioni

Tissue specificityi

Expressed in platelets. Expressed in a restricted set of hematopoietic cell lines including the erythroleukemia cell line K-562 and the T-cell leukemia cell lines MOLT-4 and Jurkat. Not detected in the monocyte-like cell line U-937, the B-cell-like cell line Raji, the fibroblast cell lines TK and HeLa, or the natural killer cell lines NKL, NK 62 and YT.2 Publications

Gene expression databases

BgeeiENSG00000204420.
ExpressionAtlasiO95866. baseline and differential.
GenevisibleiO95866. HS.

Organism-specific databases

HPAiHPA073017.

Interactioni

Subunit structurei

Interacts (via ITIM motif) with PTPN6 and PTPN11 (PubMed:11544253, PubMed:23112346). Binds to heparin (PubMed:15848171).1 Publication3 Publications

Protein-protein interaction databases

BioGridi123283. 2 interactors.
IntActiO95866. 3 interactors.
MINTiMINT-8020429.
STRINGi9606.ENSP00000364964.

Structurei

3D structure databases

ProteinModelPortaliO95866.
SMRiO95866.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi209 – 214ITIM motif1 Publication6
Motifi235 – 240ITIM motif1 Publication6

Domaini

Isoform B, displayed in this entry, is the only one of the isoforms to contain 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.1 Publication

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IYA7. Eukaryota.
ENOG41118MY. LUCA.
GeneTreeiENSGT00390000017793.
HOVERGENiHBG080566.
InParanoidiO95866.
OMAiRTYCKAP.
OrthoDBiEOG09370O4K.
PhylomeDBiO95866.
TreeFamiTF337394.

Family and domain databases

InterProiView protein in InterPro
IPR028070. G6B.
PfamiView protein in Pfam
PF15096. G6B. 1 hit.

Sequences (7)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform B1 Publication (identifier: O95866-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAVFLQLLPL LLSRAQGNPG ASLDGRPGDR VNLSCGGVSH PIRWVWAPSF
60 70 80 90 100
PACKGLSKGR RPILWASSSG TPTVPPLQPF VGRLRSLDSG IRRLELLLSA
110 120 130 140 150
GDSGTFFCKG RHEDESRTVL HVLGDRTYCK APGPTHGSVY PQLLIPLLGA
160 170 180 190 200
GLVLGLGALG LVWWLHRRLP PQPIRPLPRF APLVKTEPQR PVKEEEPKIP
210 220 230 240
GDLDQEPSLL YADLDHLALS RPRRLSTADP ADASTIYAVV V
Length:241
Mass (Da):26,163
Last modified:May 1, 1999 - v1
Checksum:iC1390699EAA109BD
GO
Isoform A1 Publication (identifier: O95866-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     182-241: PLVKTEPQRP...DASTIYAVVV → LSPPHSSTCE...APPAVHSGPC

Show »
Length:237
Mass (Da):25,003
Checksum:i109526EF36D3B6CF
GO
Isoform C1 Publication (identifier: O95866-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     138-180: SVYPQLLIPLLGAGLVLGLGALGLVWWLHRRLPPQPIRPLPRF → ACPRNRFDHSLDLLCPPHI

Show »
Length:217
Mass (Da):23,573
Checksum:i826F70FE5B45B9A0
GO
Isoform D1 Publication (identifier: O95866-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     137-241: GSVYPQLLIP...DASTIYAVVV → ALSPPHSSTC...APPAVHSGPC

Show »
Length:193
Mass (Da):20,169
Checksum:iE490E4D05BAF1652
GO
Isoform E1 Publication (identifier: O95866-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     137-180: Missing.

Show »
Length:197
Mass (Da):21,329
Checksum:i9183A850EEA4CB82
GO
Isoform F1 Publication (identifier: O95866-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     181-241: APLVKTEPQR...DASTIYAVVV → GETNSTPFSF...SPSFSSVPPT

Show »
Length:225
Mass (Da):24,225
Checksum:i1C0BF72C6E0D7CE2
GO
Isoform G1 Publication (identifier: O95866-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     182-241: PLVKTEPQRP...DASTIYAVVV → LSPPHSSTCE...TGKGMGMGRG

Show »
Length:222
Mass (Da):23,578
Checksum:i6253F93B2D56D1A6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti137 – 138GS → ID in CAI18409 (PubMed:14574404).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078570108 – 241Missing in THAMY; increased protein degradation; decreased enhancement of hematopoietic lineage differentiation. 1 PublicationAdd BLAST134
Natural variantiVAR_051004175R → G1 PublicationCorresponds to variant dbSNP:rs11575845Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_014172137 – 241GSVYP…YAVVV → ALSPPHSSTCENRAPEASKG GRAQDSRGPGPGTEPALCGS GPSSPQQAPPAVHSGPC in isoform D. 1 PublicationAdd BLAST105
Alternative sequenceiVSP_014173137 – 180Missing in isoform E. 1 PublicationAdd BLAST44
Alternative sequenceiVSP_014174138 – 180SVYPQ…PLPRF → ACPRNRFDHSLDLLCPPHI in isoform C. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_014175181 – 241APLVK…YAVVV → GETNSTPFSFSYMPTPHPSI PESEPLLGADTLVTFSPSFS SVPPT in isoform F. 1 PublicationAdd BLAST61
Alternative sequenceiVSP_014176182 – 241PLVKT…YAVVV → LSPPHSSTCENRAPEASKGG RAQDSRGPGPGTEPALCGSG PSSPQQAPPAVHSGPC in isoform A. 1 PublicationAdd BLAST60
Alternative sequenceiVSP_014177182 – 241PLVKT…YAVVV → LSPPHSSTCENRAPEASKGG RAQDSRGPGPGTGKGMGMGR G in isoform G. 2 PublicationsAdd BLAST60

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ292259 mRNA. Translation: CAC83497.1.
AJ292260 mRNA. Translation: CAC83496.1.
AJ292261 mRNA. Translation: CAC83498.1.
AJ292262 mRNA. Translation: CAC83502.1.
AJ292263 mRNA. Translation: CAC83499.1.
AJ292264 mRNA. Translation: CAC83500.1.
AJ292265 mRNA. Translation: CAC83501.1.
AF129756 Genomic DNA. Translation: AAD18075.1.
BA000025 Genomic DNA. Translation: BAB63378.1.
AL670886 Genomic DNA. Translation: CAI17813.2.
AL670886 Genomic DNA. Translation: CAI17814.2.
AL670886 Genomic DNA. Translation: CAI17815.1.
AL670886 Genomic DNA. Translation: CAI17816.2.
AL670886 Genomic DNA. Translation: CAI17818.2.
AL662899 Genomic DNA. Translation: CAI18406.2.
AL662899 Genomic DNA. Translation: CAI18407.2.
AL662899 Genomic DNA. Translation: CAI18408.1.
AL662899 Genomic DNA. Translation: CAI18409.2.
AL662899 Genomic DNA. Translation: CAI18412.2.
BX248244 Genomic DNA. Translation: CAM26092.1.
BX248244 Genomic DNA. Translation: CAM26093.1.
BX248244 Genomic DNA. Translation: CAM26094.1.
BX248244 Genomic DNA. Translation: CAM26095.1.
BX248244 Genomic DNA. Translation: CAM26096.1.
AL844216 Genomic DNA. Translation: CAM45767.1.
AL844216 Genomic DNA. Translation: CAM45768.1.
AL844216 Genomic DNA. Translation: CAM45769.1.
AL844216 Genomic DNA. Translation: CAM45770.1.
AL844216 Genomic DNA. Translation: CAM45771.1.
CR354443 Genomic DNA. Translation: CAQ07017.1.
CR354443 Genomic DNA. Translation: CAQ07020.1.
CR354443 Genomic DNA. Translation: CAQ07021.1.
CR936239 Genomic DNA. Translation: CAQ08890.1.
CR936239 Genomic DNA. Translation: CAQ08892.1.
CR936239 Genomic DNA. Translation: CAQ08893.1.
CR936239 Genomic DNA. Translation: CAQ08894.1.
CR759787 Genomic DNA. Translation: CAQ10105.1.
CR759787 Genomic DNA. Translation: CAQ10107.1.
CR759787 Genomic DNA. Translation: CAQ10108.1.
CR759787 Genomic DNA. Translation: CAQ10109.1.
CH471081 Genomic DNA. Translation: EAX03493.1.
CH471081 Genomic DNA. Translation: EAX03494.1.
CH471081 Genomic DNA. Translation: EAX03497.1.
CH471081 Genomic DNA. Translation: EAX03498.1.
BC113719 mRNA. Translation: AAI13720.1.
BC113721 mRNA. Translation: AAI13722.1.
CCDSiCCDS34405.1. [O95866-5]
CCDS34406.1. [O95866-2]
CCDS34407.1. [O95866-7]
CCDS4715.1. [O95866-1]
CCDS4716.1. [O95866-3]
CCDS4717.1. [O95866-4]
RefSeqiNP_079536.2. NM_025260.3. [O95866-2]
NP_612116.1. NM_138272.2. [O95866-1]
NP_612117.1. NM_138273.2. [O95866-3]
NP_612118.1. NM_138274.2. [O95866-4]
NP_612119.1. NM_138275.2. [O95866-5]
NP_612121.1. NM_138277.2. [O95866-7]
UniGeneiHs.247879.

Genome annotation databases

EnsembliENST00000375804; ENSP00000364962; ENSG00000204420. [O95866-4]
ENST00000375805; ENSP00000364963; ENSG00000204420. [O95866-3]
ENST00000375806; ENSP00000364964; ENSG00000204420. [O95866-1]
ENST00000375809; ENSP00000364967; ENSG00000204420. [O95866-2]
ENST00000375810; ENSP00000364968; ENSG00000204420. [O95866-7]
ENST00000375814; ENSP00000364972; ENSG00000204420. [O95866-5]
ENST00000383410; ENSP00000372902; ENSG00000206396. [O95866-5]
ENST00000383411; ENSP00000372903; ENSG00000206396. [O95866-3]
ENST00000383412; ENSP00000372904; ENSG00000206396. [O95866-2]
ENST00000400067; ENSP00000382940; ENSG00000206396. [O95866-4]
ENST00000400071; ENSP00000382944; ENSG00000206396. [O95866-1]
ENST00000411608; ENSP00000392961; ENSG00000228090. [O95866-4]
ENST00000415728; ENSP00000408430; ENSG00000224393. [O95866-1]
ENST00000415984; ENSP00000394082; ENSG00000237459. [O95866-5]
ENST00000417610; ENSP00000412747; ENSG00000230060. [O95866-4]
ENST00000422012; ENSP00000398061; ENSG00000230060. [O95866-3]
ENST00000425998; ENSP00000392917; ENSG00000224393. [O95866-4]
ENST00000426729; ENSP00000390272; ENSG00000230060. [O95866-2]
ENST00000428302; ENSP00000404519; ENSG00000231003. [O95866-2]
ENST00000431888; ENSP00000390821; ENSG00000230060. [O95866-5]
ENST00000433769; ENSP00000413647; ENSG00000228090. [O95866-5]
ENST00000435007; ENSP00000401892; ENSG00000231003. [O95866-3]
ENST00000436030; ENSP00000406706; ENSG00000231003. [O95866-1]
ENST00000437153; ENSP00000412937; ENSG00000231003. [O95866-4]
ENST00000440063; ENSP00000388982; ENSG00000237459. [O95866-4]
ENST00000444404; ENSP00000415282; ENSG00000237459. [O95866-2]
ENST00000445381; ENSP00000396823; ENSG00000224393. [O95866-3]
ENST00000447587; ENSP00000416447; ENSG00000237459. [O95866-1]
ENST00000449633; ENSP00000388484; ENSG00000231003. [O95866-5]
ENST00000451549; ENSP00000395801; ENSG00000224393. [O95866-2]
ENST00000455185; ENSP00000414824; ENSG00000224393. [O95866-5]
ENST00000457450; ENSP00000395279; ENSG00000237459. [O95866-3]
ENST00000457884; ENSP00000391097; ENSG00000230060. [O95866-1]
GeneIDi80739.
KEGGihsa:80739.
UCSCiuc003nwk.4. human. [O95866-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiG6B_HUMAN
AccessioniPrimary (citable) accession number: O95866
Secondary accession number(s): A2BEZ1
, A2BEZ2, A2BEZ3, A2BEZ4, A2BEZ5, B0UXC4, B0UXC7, B0UXC8, B0V024, B0V026, Q14CK2, Q96A86, Q96A87, Q96A88, Q96A89, Q96A90, Q96A91
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 21, 2005
Last sequence update: May 1, 1999
Last modified: October 25, 2017
This is version 129 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot