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 24-JAN-2024, entry version 199. 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; 64. 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 GlyCosmos; P13224; 1 site, No reported glycans. DR GlyGen; P13224; 4 sites, 1 O-linked glycan (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; 9606-ENSP00000383382; -. DR PeptideAtlas; P13224; -. DR ProteomicsDB; 52900; -. [P13224-1] DR ProteomicsDB; 52901; -. [P13224-2] DR Pumba; P13224; -. DR Antibodypedia; 44871; 167 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 AGR; HGNC:4440; -. DR CTD; 2812; -. DR DisGeNET; 2812; -. DR GeneCards; GP1BB; -. DR HGNC; HGNC:4440; GP1BB. DR HPA; ENSG00000203618; Tissue enriched (brain). 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; 5356136at2759; -. 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 1162 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 94 other cell types or tissues. DR GO; GO:1990779; C:glycoprotein Ib-IX-V complex; IPI:ComplexPortal. 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; ISO: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; Ribonuclease Inhibitor; 1. DR InterPro; IPR000483; Cys-rich_flank_reg_C. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR000372; LRRNT. DR PANTHER; PTHR22650; GLYCOPROTEIN IB BETA; 1. DR PANTHER; PTHR22650:SF7; PLATELET GLYCOPROTEIN IB BETA CHAIN; 1. DR SMART; SM00082; LRRCT; 1. DR SMART; SM00013; LRRNT; 1. DR SUPFAM; SSF52058; L domain-like; 1. DR Genevisible; P13224; HS. 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 //