GP1BB_HUMAN
ID GP1BB_HUMAN Reviewed; 206 AA.
AC P13224; Q14422; Q8NG40;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Platelet glycoprotein Ib beta chain;
DE Short=GP-Ib beta;
DE Short=GPIb-beta;
DE Short=GPIbB;
DE AltName: Full=Antigen CD42b-beta;
DE AltName: CD_antigen=CD42c;
DE Flags: Precursor;
GN Name=GP1BB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND GLYCOSYLATION AT ASN-66.
RX PubMed=3353370; DOI=10.1073/pnas.85.7.2135;
RA Lopez J.A., Chung D.W., Fujikawa K., Hagen F.S., Davie E.W., Roth G.J.;
RT "The alpha and beta chains of human platelet glycoprotein Ib are both
RT transmembrane proteins containing a leucine-rich amino acid sequence.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:2135-2139(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Brain;
RX PubMed=8021244; DOI=10.1016/s0021-9258(17)32456-0;
RA Yagi M., Edelhoff S., Disteche C.M., Roth G.J.;
RT "Structural characterization and chromosomal location of the gene encoding
RT human platelet glycoprotein Ib beta.";
RL J. Biol. Chem. 269:17424-17427(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Umbilical vein;
RX PubMed=8200976; DOI=10.1172/jci117249;
RA Kelly M.D., Essex D.W., Shapiro S.S., Meloni F.J., Druck T., Huebner K.,
RA Konkle B.A.;
RT "Complementary DNA cloning of the alternatively expressed endothelial cell
RT glycoprotein Ib beta (GPIb beta) and localization of the GPIb beta gene to
RT chromosome 22.";
RL J. Clin. Invest. 93:2417-2424(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9022087; DOI=10.1172/jci119188;
RA Zieger B., Hashimoto Y., Ware J.;
RT "Alternative expression of platelet glycoprotein Ib(beta) mRNA from an
RT adjacent 5' gene with an imperfect polyadenylation signal sequence.";
RL J. Clin. Invest. 99:520-525(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 11-206, AND VARIANTS BSS CYS-113 AND
RP PRO-133.
RX PubMed=9116284;
RA Kunishima S., Lopez J.A., Kobayashi S., Imai N., Kamiya T., Saito H.,
RA Naoe T.;
RT "Missense mutations of the glycoprotein (GP) Ib beta gene impairing the
RT GPIb alpha/beta disulfide linkage in a family with giant platelet
RT disorder.";
RL Blood 89:2404-2412(1997).
RN [6]
RP PROTEIN SEQUENCE OF 27-40, AND SIGNAL SEQUENCE CLEAVAGE SITE.
RX PubMed=3632685; DOI=10.1016/0006-291x(87)90963-6;
RA Canfield V.A., Ozols J., Nugent D., Roth G.J.;
RT "Isolation and characterization of the alpha and beta chains of human
RT platelet glycoprotein Ib.";
RL Biochem. Biophys. Res. Commun. 147:526-534(1987).
RN [7]
RP PROTEIN SEQUENCE OF 83-92 AND 190-200.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [8]
RP PHOSPHORYLATION AT SER-191, AND PROTEIN SEQUENCE OF 186-200.
RX PubMed=2504723; DOI=10.1016/s0021-9258(19)84882-2;
RA Wardell M.R., Reynolds C.C., Berndt M.C., Wallace R.W., Fox J.E.B.;
RT "Platelet glycoprotein Ib beta is phosphorylated on serine 166 by cyclic
RT AMP-dependent protein kinase.";
RL J. Biol. Chem. 264:15656-15661(1989).
RN [9]
RP SUBUNIT, AND INTERCHAIN DISULFIDE BOND.
RX PubMed=17008541; DOI=10.1182/blood-2006-05-024091;
RA Luo S.Z., Mo X., Afshar-Kharghan V., Srinivasan S., Lopez J.A., Li R.;
RT "Glycoprotein Ibalpha forms disulfide bonds with 2 glycoprotein Ibbeta
RT subunits in the resting platelet.";
RL Blood 109:603-609(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using sequential
RT IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-191 AND THR-193, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [12]
RP INTERACTION WITH TRAF4.
RX PubMed=20946164; DOI=10.1111/j.1538-7836.2010.04091.x;
RA Arthur J.F., Shen Y., Gardiner E.E., Coleman L., Murphy D., Kenny D.,
RA Andrews R.K., Berndt M.C.;
RT "TNF receptor-associated factor 4 (TRAF4) is a novel binding partner of
RT glycoprotein Ib and glycoprotein VI in human platelets.";
RL J. Thromb. Haemost. 9:163-172(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-191 AND THR-193, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-191 AND THR-193, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.24 ANGSTROMS) OF 26-146, GLYCOSYLATION AT ASN-66,
RP AND DISULFIDE BONDS.
RX PubMed=21908432; DOI=10.1182/blood-2011-05-356253;
RA McEwan P.A., Yang W., Carr K.H., Mo X., Zheng X., Li R., Emsley J.;
RT "Quaternary organization of GPIb-IX complex and insights into Bernard-
RT Soulier syndrome revealed by the structures of GPIbbeta and a GPIbbeta/GPIX
RT chimera.";
RL Blood 118:5292-5301(2011).
CC -!- FUNCTION: Gp-Ib, a surface membrane protein of platelets, participates
CC in the formation of platelet plugs by binding to von Willebrand factor,
CC which is already bound to the subendothelium.
CC -!- SUBUNIT: Two GP-Ib beta are disulfide-linked to one GP-Ib alpha. GP-IX
CC is complexed with the GP-Ib heterodimer via a non covalent linkage.
CC Interacts with TRAF4 (PubMed:20946164). {ECO:0000269|PubMed:17008541,
CC ECO:0000269|PubMed:20946164, ECO:0000269|PubMed:21908432}.
CC -!- INTERACTION:
CC P13224; P07359: GP1BA; NbExp=6; IntAct=EBI-2833037, EBI-297082;
CC P13224; P13224: GP1BB; NbExp=2; IntAct=EBI-2833037, EBI-2833037;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P13224-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P13224-2; Sequence=VSP_032671;
CC -!- TISSUE SPECIFICITY: Expressed in heart and brain.
CC {ECO:0000269|PubMed:8200976}.
CC -!- DISEASE: Bernard-Soulier syndrome (BSS) [MIM:231200]: A coagulation
CC disorder characterized by a prolonged bleeding time, unusually large
CC platelets, thrombocytopenia, and impaired prothrombin consumption.
CC {ECO:0000269|PubMed:9116284}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Platelet activation apparently involves disruption of
CC the macromolecular complex of GP-Ib with the platelet glycoprotein IX
CC (GP-IX) and dissociation of GP-Ib from the actin-binding protein.
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; J03259; AAA52594.1; -; mRNA.
DR EMBL; AF006988; AAC39781.1; -; Genomic_DNA.
DR EMBL; L20860; AAA20398.1; -; mRNA.
DR EMBL; U59632; AAB93437.1; -; mRNA.
DR EMBL; AB086231; BAC00777.1; -; Genomic_DNA.
DR CCDS; CCDS42980.1; -. [P13224-1]
DR PIR; A54137; NBHUIB.
DR PIR; I55604; I55604.
DR RefSeq; NP_000398.1; NM_000407.4. [P13224-1]
DR PDB; 3REZ; X-ray; 2.35 A; A/B/C/D=26-146.
DR PDB; 3RFE; X-ray; 1.24 A; A/B=26-146.
DR PDBsum; 3REZ; -.
DR PDBsum; 3RFE; -.
DR AlphaFoldDB; P13224; -.
DR SMR; P13224; -.
DR BioGRID; 109074; 62.
DR ComplexPortal; CPX-114; Glycoprotein Ib-IX-V complex.
DR ComplexPortal; CPX-117; Glycoprotein Ib-IX-V-Filamin-A complex.
DR IntAct; P13224; 27.
DR MINT; P13224; -.
DR STRING; 9606.ENSP00000383382; -.
DR GlyGen; P13224; 2 sites.
DR iPTMnet; P13224; -.
DR PhosphoSitePlus; P13224; -.
DR BioMuta; GP1BB; -.
DR DMDM; 121532; -.
DR OGP; P13224; -.
DR jPOST; P13224; -.
DR MassIVE; P13224; -.
DR MaxQB; P13224; -.
DR PaxDb; P13224; -.
DR PeptideAtlas; P13224; -.
DR PRIDE; P13224; -.
DR ProteomicsDB; 52900; -. [P13224-1]
DR ProteomicsDB; 52901; -. [P13224-2]
DR Antibodypedia; 44871; 148 antibodies from 28 providers.
DR DNASU; 2812; -.
DR Ensembl; ENST00000366425.4; ENSP00000383382.2; ENSG00000203618.6. [P13224-1]
DR GeneID; 2812; -.
DR KEGG; hsa:2812; -.
DR MANE-Select; ENST00000366425.4; ENSP00000383382.2; NM_000407.5; NP_000398.1.
DR UCSC; uc062bnf.1; human. [P13224-1]
DR CTD; 2812; -.
DR DisGeNET; 2812; -.
DR GeneCards; GP1BB; -.
DR HGNC; HGNC:4440; GP1BB.
DR HPA; ENSG00000203618; Tissue enhanced (brain, heart muscle).
DR MalaCards; GP1BB; -.
DR MIM; 138720; gene.
DR MIM; 231200; phenotype.
DR neXtProt; NX_P13224; -.
DR OpenTargets; ENSG00000203618; -.
DR Orphanet; 567; 22q11.2 deletion syndrome.
DR Orphanet; 140957; Autosomal dominant macrothrombocytopenia.
DR Orphanet; 274; Bernard-Soulier syndrome.
DR Orphanet; 853; Fetal and neonatal alloimmune thrombocytopenia.
DR PharmGKB; PA179; -.
DR VEuPathDB; HostDB:ENSG00000203618; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00530000064244; -.
DR HOGENOM; CLU_094615_0_0_1; -.
DR InParanoid; P13224; -.
DR OMA; HLQGRII; -.
DR OrthoDB; 217854at2759; -.
DR PhylomeDB; P13224; -.
DR PathwayCommons; P13224; -.
DR Reactome; R-HSA-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-HSA-430116; GP1b-IX-V activation signalling.
DR Reactome; R-HSA-75892; Platelet Adhesion to exposed collagen.
DR Reactome; R-HSA-76009; Platelet Aggregation (Plug Formation).
DR Reactome; R-HSA-9673221; Defective F9 activation.
DR SignaLink; P13224; -.
DR SIGNOR; P13224; -.
DR BioGRID-ORCS; 2812; 33 hits in 1075 CRISPR screens.
DR GeneWiki; GP1BB; -.
DR GenomeRNAi; 2812; -.
DR Pharos; P13224; Tbio.
DR PRO; PR:P13224; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P13224; protein.
DR Bgee; ENSG00000203618; Expressed in monocyte and 93 other tissues.
DR Genevisible; P13224; HS.
DR GO; GO:1990779; C:glycoprotein Ib-IX-V complex; IPI:ComplexPortal.
DR GO; GO:0005887; C:integral component of plasma membrane; NAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; NAS:ProtInc.
DR GO; GO:0007597; P:blood coagulation, intrinsic pathway; IPI:ComplexPortal.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; NAS:ProtInc.
DR GO; GO:0035855; P:megakaryocyte development; IC:ComplexPortal.
DR GO; GO:0030168; P:platelet activation; NAS:UniProtKB.
DR GO; GO:0010572; P:positive regulation of platelet activation; IDA:ComplexPortal.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:ComplexPortal.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000372; LRRNT.
DR Pfam; PF01463; LRRCT; 1.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00013; LRRNT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Bernard Soulier syndrome;
KW Blood coagulation; Cell adhesion; Direct protein sequencing;
KW Disease variant; Disulfide bond; Glycoprotein; Hemostasis;
KW Leucine-rich repeat; Membrane; Phosphoprotein; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:3632685"
FT CHAIN 26..206
FT /note="Platelet glycoprotein Ib beta chain"
FT /id="PRO_0000021345"
FT TOPO_DOM 27..147
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..172
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 173..206
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..55
FT /note="LRRNT"
FT REPEAT 60..83
FT /note="LRR"
FT DOMAIN 89..143
FT /note="LRRCT"
FT MOD_RES 191
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:2504723,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 193
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21908432,
FT ECO:0000269|PubMed:3353370"
FT DISULFID 26..32
FT /evidence="ECO:0000269|PubMed:21908432"
FT DISULFID 30..39
FT /evidence="ECO:0000269|PubMed:21908432"
FT DISULFID 93..118
FT /evidence="ECO:0000269|PubMed:21908432"
FT DISULFID 95..141
FT /evidence="ECO:0000269|PubMed:21908432"
FT DISULFID 147
FT /note="Interchain (with C-500 or C-501 in GP1BA)"
FT /evidence="ECO:0000269|PubMed:21908432"
FT VAR_SEQ 1..3
FT /note="MGS -> MIPSRHTMLRFLPVVNAASCPGDRRTMLVNVAAGVRVLRVPLRAG
FT GSGSLSGLRPPAIVCYLPLQRASAASGLFLARPQHCGRCGRGRGGAALSLGSPAYASRC
FT RVSRAAVFSPWAPVSLESGRAPGCSLGRPGLRGALVVWLQLGETWVRLRGDFQPACGVV
FT RVERLAGYRDAGHQGLDGAGPAVWVLRDVAQVPADRSAYCGASLA (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:8200976"
FT /id="VSP_032671"
FT VARIANT 113
FT /note="Y -> C (in BSS; dbSNP:rs121909750)"
FT /evidence="ECO:0000269|PubMed:9116284"
FT /id="VAR_025000"
FT VARIANT 133
FT /note="A -> P (in BSS; dbSNP:rs121909751)"
FT /evidence="ECO:0000269|PubMed:9116284"
FT /id="VAR_025001"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:3RFE"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:3RFE"
FT TURN 46..48
FT /evidence="ECO:0007829|PDB:3RFE"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:3RFE"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:3RFE"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:3RFE"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:3RFE"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:3RFE"
FT HELIX 98..105
FT /evidence="ECO:0007829|PDB:3RFE"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:3RFE"
FT STRAND 117..121
FT /evidence="ECO:0007829|PDB:3REZ"
FT TURN 122..126
FT /evidence="ECO:0007829|PDB:3RFE"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:3RFE"
FT HELIX 134..139
FT /evidence="ECO:0007829|PDB:3RFE"
SQ SEQUENCE 206 AA; 21718 MW; B5E81EB6F57DE0D9 CRC64;
MGSGPRGALS LLLLLLAPPS RPAAGCPAPC SCAGTLVDCG RRGLTWASLP TAFPVDTTEL
VLTGNNLTAL PPGLLDALPA LRTAHLGANP WRCDCRLVPL RAWLAGRPER APYRDLRCVA
PPALRGRLLP YLAEDELRAA CAPGPLCWGA LAAQLALLGL GLLHALLLVL LLCRLRRLRA
RARARAAARL SLTDPLVAER AGTDES
