BMPR2_HUMAN
ID BMPR2_HUMAN Reviewed; 1038 AA.
AC Q13873; Q13161; Q16569; Q4ZG08; Q53SA5; Q585T8;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 228.
DE RecName: Full=Bone morphogenetic protein receptor type-2;
DE Short=BMP type-2 receptor;
DE Short=BMPR-2;
DE EC=2.7.11.30;
DE AltName: Full=Bone morphogenetic protein receptor type II;
DE Short=BMP type II receptor;
DE Short=BMPR-II;
DE Flags: Precursor;
GN Name=BMPR2; Synonyms=PPH1;
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 2), AND ALTERNATIVE SPLICING.
RC TISSUE=Kidney;
RX PubMed=7791754; DOI=10.1128/mcb.15.7.3479;
RA Liu F., Ventura F., Doody J., Massague J.;
RT "Human type II receptor for bone morphogenic proteins (BMPs): extension of
RT the two-kinase receptor model to the BMPs.";
RL Mol. Cell. Biol. 15:3479-3486(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Substantia nigra;
RX PubMed=7644468; DOI=10.1073/pnas.92.17.7632;
RA Rosenzweig B.L., Imamura T., Okadome T., Cox G.N., Yamashita H.,
RA ten Dijke P., Heldin C., Miyazono K.;
RT "Cloning and characterization of a human type II receptor for bone
RT morphogenetic proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:7632-7636(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Skin fibroblast;
RX PubMed=7673243; DOI=10.1074/jbc.270.38.22522;
RA Nohno T., Ishikawa T., Saito T., Hosokawa K., Noji S., Wosing D.H.,
RA Rosenbaum J.S.;
RT "Identification of a human type II receptor for bone morphogenetic protein-
RT 4 that forms differential heteromeric complexes with bone morphogenetic
RT protein type I receptors.";
RL J. Biol. Chem. 270:22522-22526(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7890683; DOI=10.1074/jbc.270.10.5625;
RA Kawabata M., Chytil A., Moses H.L.;
RT "Cloning of a novel type II serine/threonine kinase receptor through
RT interaction with the type I transforming growth factor-beta receptor.";
RL J. Biol. Chem. 270:5625-5630(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-586, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-379, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [10]
RP INTERACTION WITH GDF5.
RX PubMed=21976273; DOI=10.1002/jbmr.532;
RA Schwaerzer G.K., Hiepen C., Schrewe H., Nickel J., Ploeger F., Sebald W.,
RA Mueller T., Knaus P.;
RT "New insights into the molecular mechanism of multiple synostoses syndrome
RT (SYNS): mutation within the GDF5 knuckle epitope causes noggin-
RT resistance.";
RL J. Bone Miner. Res. 27:429-442(2012).
RN [11]
RP INTERACTION WITH BMP4.
RX PubMed=29212066; DOI=10.1159/000485759;
RA Jin X., Nie E., Zhou X., Zeng A., Yu T., Zhi T., Jiang K., Wang Y.,
RA Zhang J., You Y.;
RT "Fstl1 Promotes Glioma Growth Through the BMP4/Smad1/5/8 Signaling
RT Pathway.";
RL Cell. Physiol. Biochem. 44:1616-1628(2017).
RN [12]
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 [13]
RP INTERACTION WITH SCUBE3.
RX PubMed=33308444; DOI=10.1016/j.ajhg.2020.11.015;
RG Genomics England Research Consortium;
RA Lin Y.C., Niceta M., Muto V., Vona B., Pagnamenta A.T., Maroofian R.,
RA Beetz C., van Duyvenvoorde H., Dentici M.L., Lauffer P., Vallian S.,
RA Ciolfi A., Pizzi S., Bauer P., Gruening N.M., Bellacchio E.,
RA Del Fattore A., Petrini S., Shaheen R., Tiosano D., Halloun R.,
RA Pode-Shakked B., Albayrak H.M., Isik E., Wit J.M., Dittrich M.,
RA Freire B.L., Bertola D.R., Jorge A.A.L., Barel O., Sabir A.H.,
RA Al Tenaiji A.M.J., Taji S.M., Al-Sannaa N., Al-Abdulwahed H., Digilio M.C.,
RA Irving M., Anikster Y., Bhavani G.S.L., Girisha K.M., Haaf T., Taylor J.C.,
RA Dallapiccola B., Alkuraya F.S., Yang R.B., Tartaglia M.;
RT "SCUBE3 loss-of-function causes a recognizable recessive developmental
RT disorder due to defective bone morphogenetic protein signaling.";
RL Am. J. Hum. Genet. 108:115-133(2021).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 33-131, AND DISULFIDE BONDS.
RX PubMed=17094948; DOI=10.1016/j.bbrc.2006.10.109;
RA Mace P.D., Cutfield J.F., Cutfield S.M.;
RT "High resolution structures of the bone morphogenetic protein type II
RT receptor in two crystal forms: implications for ligand binding.";
RL Biochem. Biophys. Res. Commun. 351:831-838(2006).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 189-517 IN COMPLEX WITH ADP.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the BMPR2 kinase domain.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [16]
RP VARIANTS PPH1 GLN-491 AND TRP-491.
RX PubMed=10903931; DOI=10.1086/303059;
RA Deng Z., Morse J.H., Slager S.L., Cuervo N., Moore K.J., Venetos G.,
RA Kalachikov S., Cayanis E., Fischer S.G., Barst R.J., Hodge S.E.,
RA Knowles J.A.;
RT "Familial primary pulmonary hypertension (gene PPH1) is caused by mutations
RT in the bone morphogenetic protein receptor-II gene.";
RL Am. J. Hum. Genet. 67:737-744(2000).
RN [17]
RP VARIANTS PPH1 TYR-60; TYR-117 AND ARG-483.
RX PubMed=11015450; DOI=10.1136/jmg.37.10.741;
RA Thomson J.R., Machado R.D., Pauciulo M.W., Morgan N.V., Humbert M.,
RA Elliott G.C., Ward K., Yacoub M., Mikhail G., Rogers P., Newman J.H.,
RA Wheeler L., Higenbottam T., Gibbs J.S.R., Egan J., Crozier A., Peacock A.,
RA Allcock R., Corris P., Loyd J.E., Trembath R.C., Nichols W.C.;
RT "Sporadic primary pulmonary hypertension is associated with germline
RT mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta
RT family.";
RL J. Med. Genet. 37:741-745(2000).
RN [18]
RP VARIANTS PPH1 TRP-118; TYR-347 AND GLY-485.
RX PubMed=10973254; DOI=10.1038/79226;
RA Lane K.B., Machado R.D., Pauciulo M.W., Thomson J.R., Phillips J.A. III,
RA Loyd J.E., Nichols W.C., Trembath R.C., Aldred M., Brannon C.A.,
RA Conneally P.M., Foroud T., Fretwell N., Gaddipati R., Koller D., Loyd E.J.,
RA Morgan N.V., Newman J.H., Prince M.A., Vilarino Gueell C., Wheeler L.;
RT "Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor,
RT cause familial primary pulmonary hypertension.";
RL Nat. Genet. 26:81-84(2000).
RN [19]
RP VARIANTS PPH1 ARG-123; SER-123; ARG-420 AND THR-512, VARIANT ASP-224, AND
RP CHARACTERIZATION OF VARIANT PPH1 GLY-485.
RX PubMed=11115378; DOI=10.1086/316947;
RA Machado R.D., Pauciulo M.W., Thomson J.R., Lane K.B., Morgan N.V.,
RA Wheeler L., Phillips J.A. III, Newman J.H., Williams D., Galie N.,
RA Manes A., McNeil K., Yacoub M., Mikhail G., Rogers P., Corris P.,
RA Humbert M., Donnai D., Martensson G., Tranebjaerg L., Loyd J.E.,
RA Trembath R.C., Nichols W.C.;
RT "BMPR2 haploinsufficiency as the inherited molecular mechanism for primary
RT pulmonary hypertension.";
RL Am. J. Hum. Genet. 68:92-102(2001).
RN [20]
RP VARIANTS PPH1 HIS-82; ASP-182 AND ARG-483.
RX PubMed=12358323; DOI=10.1183/09031936.02.01762002;
RA Humbert M., Deng Z., Simonneau G., Barst R.J., Sitbon O., Wolf M.,
RA Cuervo N., Moore K.J., Hodge S.E., Knowles J.A., Morse J.H.;
RT "BMPR2 germline mutations in pulmonary hypertension associated with
RT fenfluramine derivatives.";
RL Eur. Respir. J. 20:518-523(2002).
RN [21]
RP INVOLVEMENT IN PVOD1.
RX PubMed=12446270; DOI=10.1164/rccm.200208-861oc;
RA Runo J.R., Vnencak-Jones C.L., Prince M., Loyd J.E., Wheeler L.,
RA Robbins I.M., Lane K.B., Newman J.H., Johnson J., Nichols W.C.,
RA Phillips J.A. III;
RT "Pulmonary veno-occlusive disease caused by an inherited mutation in bone
RT morphogenetic protein receptor II.";
RL Am. J. Respir. Crit. Care Med. 167:889-894(2003).
RN [22]
RP VARIANT PPH1 PRO-899, AND CHARACTERIZATION OF VARIANT PPH1 PRO-899.
RX PubMed=15965979; DOI=10.1002/humu.20200;
RA Sankelo M., Flanagan J.A., Machado R., Harrison R., Rudarakanchana N.,
RA Morrell N., Dixon M., Halme M., Puolijoki H., Kere J., Elomaa O.,
RA Kupari M., Raeisaenen-Sokolowski A., Trembath R.C., Laitinen T.;
RT "BMPR2 mutations have short lifetime expectancy in primary pulmonary
RT hypertension.";
RL Hum. Mutat. 26:119-124(2005).
RN [23]
RP INVOLVEMENT IN PVOD1.
RX PubMed=16429395; DOI=10.1002/humu.20285;
RA Machado R.D., Aldred M.A., James V., Harrison R.E., Patel B.,
RA Schwalbe E.C., Gruenig E., Janssen B., Koehler R., Seeger W.,
RA Eickelberg O., Olschewski H., Elliott C.G., Glissmeyer E., Carlquist J.,
RA Kim M., Torbicki A., Fijalkowska A., Szewczyk G., Parma J.,
RA Abramowicz M.J., Galie N., Morisaki H., Kyotani S., Nakanishi N.,
RA Morisaki T., Humbert M., Simonneau G., Sitbon O., Soubrier F., Coulet F.,
RA Morrell N.W., Trembath R.C.;
RT "Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial
RT hypertension.";
RL Hum. Mutat. 27:121-132(2006).
RN [24]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-775.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [25]
RP VARIANTS PPH1 LEU-77; PHE-84; TYR-87; LEU-92; PRO-162; ASN-264 AND MET-341,
RP AND VARIANT ASN-775.
RX PubMed=24936649; DOI=10.1371/journal.pone.0100261;
RA Pousada G., Baloira A., Vilarino C., Cifrian J.M., Valverde D.;
RT "Novel mutations in BMPR2, ACVRL1 and KCNA5 genes and hemodynamic
RT parameters in patients with pulmonary arterial hypertension.";
RL PLoS ONE 9:E100261-E100261(2014).
RN [26]
RP VARIANTS PPH1 CYS-67 AND ASN-863, CHARACTERIZATION OF VARIANTS PPH1 CYS-67
RP AND ASN-863, AND SUBCELLULAR LOCATION.
RX PubMed=25187962; DOI=10.1371/journal.pone.0106703;
RA Wang H., Ji R., Meng J., Cui Q., Zou W., Li L., Wang G., Sun L., Li Z.,
RA Huo L., Fan Y., Penny D.J.;
RT "Functional changes in pulmonary arterial endothelial cells associated with
RT BMPR2 mutations.";
RL PLoS ONE 9:E106703-E106703(2014).
RN [27]
RP VARIANTS PPH1 ARG-64; PHE-84; HIS-109; ALA-138; 218-TYR--LEU-1038 DEL;
RP GLY-248; 298-TRP--LEU-1038 DEL AND ARG-467, CHARACTERIZATION OF VARIANTS
RP PPH1 ARG-64; LEU-77; TYR-87; LEU-92; HIS-109; ALA-138; PRO-162;
RP 218-TYR--LEU-1038 DEL; GLY-248; ASN-264; 298-TRP--LEU-1038 DEL; MET-341 AND
RP ARG-467, AND CHARACTERIZATION OF VARIANT ASN-775.
RX PubMed=28507310; DOI=10.1038/s41598-017-02074-8;
RA Pousada G., Lupo V., Castro-Sanchez S., Alvarez-Satta M.,
RA Sanchez-Monteagudo A., Baloira A., Espinos C., Valverde D.;
RT "Molecular and functional characterization of the BMPR2 gene in Pulmonary
RT Arterial Hypertension.";
RL Sci. Rep. 7:1923-1923(2017).
CC -!- FUNCTION: On ligand binding, forms a receptor complex consisting of two
CC type II and two type I transmembrane serine/threonine kinases. Type II
CC receptors phosphorylate and activate type I receptors which
CC autophosphorylate, then bind and activate SMAD transcriptional
CC regulators. Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is
CC weak but enhanced by the presence of type I receptors for BMPs.
CC Mediates induction of adipogenesis by GDF6.
CC {ECO:0000250|UniProtKB:O35607}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[receptor-protein] = ADP + H(+) + O-phospho-
CC L-threonyl-[receptor-protein]; Xref=Rhea:RHEA:44880, Rhea:RHEA-
CC COMP:11024, Rhea:RHEA-COMP:11025, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977,
CC ChEBI:CHEBI:456216; EC=2.7.11.30;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[receptor-protein] = ADP + H(+) + O-phospho-L-
CC seryl-[receptor-protein]; Xref=Rhea:RHEA:18673, Rhea:RHEA-COMP:11022,
CC Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
CC EC=2.7.11.30;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- SUBUNIT: Interacts with GDF5 (PubMed:21976273). Interacts with BMP4
CC (PubMed:29212066). Interacts with SCUBE3 (PubMed:33308444).
CC {ECO:0000269|PubMed:21976273, ECO:0000269|PubMed:29212066,
CC ECO:0000269|PubMed:33308444}.
CC -!- INTERACTION:
CC Q13873; P43026: GDF5; NbExp=4; IntAct=EBI-527196, EBI-8571476;
CC Q13873; Q13976: PRKG1; NbExp=2; IntAct=EBI-527196, EBI-3952014;
CC Q13873; P08607: C4bpa; Xeno; NbExp=3; IntAct=EBI-527196, EBI-527325;
CC Q13873; P68404: Prkcb; Xeno; NbExp=4; IntAct=EBI-527196, EBI-397048;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25187962};
CC Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13873-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13873-2; Sequence=VSP_054441, VSP_054442;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart and liver.
CC -!- DISEASE: Pulmonary hypertension, primary, 1 (PPH1) [MIM:178600]: A rare
CC disorder characterized by plexiform lesions of proliferating
CC endothelial cells in pulmonary arterioles. The lesions lead to elevated
CC pulmonary arterial pression, right ventricular failure, and death. The
CC disease can occur from infancy throughout life and it has a mean age at
CC onset of 36 years. Penetrance is reduced. Although familial pulmonary
CC hypertension is rare, cases secondary to known etiologies are more
CC common and include those associated with the appetite-suppressant
CC drugs. {ECO:0000269|PubMed:10903931, ECO:0000269|PubMed:10973254,
CC ECO:0000269|PubMed:11015450, ECO:0000269|PubMed:11115378,
CC ECO:0000269|PubMed:12358323, ECO:0000269|PubMed:15965979,
CC ECO:0000269|PubMed:24936649, ECO:0000269|PubMed:25187962,
CC ECO:0000269|PubMed:28507310}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Pulmonary venoocclusive disease 1, autosomal dominant (PVOD1)
CC [MIM:265450]: A disease characterized by widespread fibrous obstruction
CC and intimal thickening of septal veins and preseptal venules, a low
CC diffusing capacity for carbon monoxide, occult alveolar hemorrhage, and
CC nodular ground-glass opacities, septal lines and lymph node enlargement
CC showed by high-resolution computed tomography of the chest. It is
CC frequently associated with pulmonary capillary dilatation and
CC proliferation, and is a rare and devastating cause of pulmonary
CC hypertension. {ECO:0000269|PubMed:12446270,
CC ECO:0000269|PubMed:16429395}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. TGFB receptor subfamily. {ECO:0000305}.
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DR EMBL; U25110; AAA86519.1; -; mRNA.
DR EMBL; Z48923; CAA88759.1; -; mRNA.
DR EMBL; D50516; BAA09094.1; -; mRNA.
DR EMBL; U20165; AAC50105.1; -; mRNA.
DR EMBL; AC009960; AAX76517.1; -; Genomic_DNA.
DR EMBL; AC073410; AAX88941.1; -; Genomic_DNA.
DR EMBL; AC064836; AAY24146.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70309.1; -; Genomic_DNA.
DR EMBL; BC052985; AAH52985.1; -; mRNA.
DR CCDS; CCDS33361.1; -. [Q13873-1]
DR PIR; I38935; I38935.
DR RefSeq; NP_001195.2; NM_001204.6. [Q13873-1]
DR PDB; 2HLQ; X-ray; 1.45 A; A=33-131.
DR PDB; 3G2F; X-ray; 2.35 A; A/B=189-517.
DR PDB; 6UNP; X-ray; 2.30 A; A/B=188-529.
DR PDBsum; 2HLQ; -.
DR PDBsum; 3G2F; -.
DR PDBsum; 6UNP; -.
DR AlphaFoldDB; Q13873; -.
DR SMR; Q13873; -.
DR BioGRID; 107127; 99.
DR DIP; DIP-5794N; -.
DR ELM; Q13873; -.
DR IntAct; Q13873; 51.
DR MINT; Q13873; -.
DR STRING; 9606.ENSP00000363708; -.
DR BindingDB; Q13873; -.
DR ChEMBL; CHEMBL5467; -.
DR DrugBank; DB11639; Dibotermin alfa.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q13873; -.
DR GuidetoPHARMACOLOGY; 1794; -.
DR GlyConnect; 1046; 2 N-Linked glycans (2 sites).
DR GlyGen; Q13873; 6 sites, 3 N-linked glycans (2 sites), 2 O-linked glycans (2 sites).
DR iPTMnet; Q13873; -.
DR PhosphoSitePlus; Q13873; -.
DR BioMuta; BMPR2; -.
DR DMDM; 12643724; -.
DR CPTAC; CPTAC-2209; -.
DR EPD; Q13873; -.
DR jPOST; Q13873; -.
DR MassIVE; Q13873; -.
DR MaxQB; Q13873; -.
DR PaxDb; Q13873; -.
DR PeptideAtlas; Q13873; -.
DR PRIDE; Q13873; -.
DR ProteomicsDB; 59705; -. [Q13873-1]
DR Antibodypedia; 19946; 536 antibodies from 37 providers.
DR DNASU; 659; -.
DR Ensembl; ENST00000374574.2; ENSP00000363702.2; ENSG00000204217.16. [Q13873-2]
DR Ensembl; ENST00000374580.10; ENSP00000363708.4; ENSG00000204217.16. [Q13873-1]
DR GeneID; 659; -.
DR KEGG; hsa:659; -.
DR MANE-Select; ENST00000374580.10; ENSP00000363708.4; NM_001204.7; NP_001195.2.
DR UCSC; uc002uzf.5; human. [Q13873-1]
DR CTD; 659; -.
DR DisGeNET; 659; -.
DR GeneCards; BMPR2; -.
DR GeneReviews; BMPR2; -.
DR HGNC; HGNC:1078; BMPR2.
DR HPA; ENSG00000204217; Low tissue specificity.
DR MalaCards; BMPR2; -.
DR MIM; 178600; phenotype.
DR MIM; 265450; phenotype.
DR MIM; 600799; gene.
DR neXtProt; NX_Q13873; -.
DR OpenTargets; ENSG00000204217; -.
DR Orphanet; 275786; Drug- or toxin-induced pulmonary arterial hypertension.
DR Orphanet; 275777; Heritable pulmonary arterial hypertension.
DR Orphanet; 31837; Pulmonary venoocclusive disease.
DR PharmGKB; PA25388; -.
DR VEuPathDB; HostDB:ENSG00000204217; -.
DR eggNOG; KOG3653; Eukaryota.
DR GeneTree; ENSGT00940000156449; -.
DR HOGENOM; CLU_013015_0_0_1; -.
DR InParanoid; Q13873; -.
DR OMA; RDTHVNG; -.
DR OrthoDB; 390511at2759; -.
DR PhylomeDB; Q13873; -.
DR TreeFam; TF314724; -.
DR PathwayCommons; Q13873; -.
DR Reactome; R-HSA-201451; Signaling by BMP.
DR SignaLink; Q13873; -.
DR SIGNOR; Q13873; -.
DR BioGRID-ORCS; 659; 24 hits in 1119 CRISPR screens.
DR ChiTaRS; BMPR2; human.
DR EvolutionaryTrace; Q13873; -.
DR GeneWiki; BMPR2; -.
DR GenomeRNAi; 659; -.
DR Pharos; Q13873; Tchem.
DR PRO; PR:Q13873; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q13873; protein.
DR Bgee; ENSG00000204217; Expressed in visceral pleura and 195 other tissues.
DR ExpressionAtlas; Q13873; baseline and differential.
DR Genevisible; Q13873; HS.
DR GO; GO:0005912; C:adherens junction; IDA:BHF-UCL.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0044214; C:spanning component of plasma membrane; TAS:AgBase.
DR GO; GO:0016362; F:activin receptor activity, type II; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0036122; F:BMP binding; IPI:UniProtKB.
DR GO; GO:0098821; F:BMP receptor activity; ISS:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; IPI:ARUK-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019211; F:phosphatase activator activity; IEA:Ensembl.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IEA:Ensembl.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:ARUK-UCL.
DR GO; GO:0030546; F:signaling receptor activator activity; IEA:Ensembl.
DR GO; GO:0005024; F:transforming growth factor beta receptor activity; IBA:GO_Central.
DR GO; GO:0009952; P:anterior/posterior pattern specification; ISS:BHF-UCL.
DR GO; GO:0003176; P:aortic valve development; ISS:BHF-UCL.
DR GO; GO:0060840; P:artery development; ISS:BHF-UCL.
DR GO; GO:0060413; P:atrial septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0001568; P:blood vessel development; IBA:GO_Central.
DR GO; GO:0001974; P:blood vessel remodeling; ISS:BHF-UCL.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:BHF-UCL.
DR GO; GO:0071773; P:cellular response to BMP stimulus; IMP:BHF-UCL.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central.
DR GO; GO:0009267; P:cellular response to starvation; IEP:BHF-UCL.
DR GO; GO:0002063; P:chondrocyte development; IMP:AgBase.
DR GO; GO:0003197; P:endocardial cushion development; ISS:BHF-UCL.
DR GO; GO:0060350; P:endochondral bone morphogenesis; ISS:AgBase.
DR GO; GO:0072577; P:endothelial cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0001935; P:endothelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0060173; P:limb development; IEA:Ensembl.
DR GO; GO:0048286; P:lung alveolus development; ISS:BHF-UCL.
DR GO; GO:0001946; P:lymphangiogenesis; ISS:BHF-UCL.
DR GO; GO:0060836; P:lymphatic endothelial cell differentiation; ISS:BHF-UCL.
DR GO; GO:0001893; P:maternal placenta development; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; ISS:BHF-UCL.
DR GO; GO:0003183; P:mitral valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0003252; P:negative regulation of cell proliferation involved in heart valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:1902731; P:negative regulation of chondrocyte proliferation; IMP:AgBase.
DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IMP:BHF-UCL.
DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IMP:BHF-UCL.
DR GO; GO:0045906; P:negative regulation of vasoconstriction; ISS:BHF-UCL.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; ISS:BHF-UCL.
DR GO; GO:0048842; P:positive regulation of axon extension involved in axon guidance; IEA:Ensembl.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:UniProtKB.
DR GO; GO:0030501; P:positive regulation of bone mineralization; IMP:BHF-UCL.
DR GO; GO:0061036; P:positive regulation of cartilage development; ISS:AgBase.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IDA:UniProtKB.
DR GO; GO:0045778; P:positive regulation of ossification; ISS:BHF-UCL.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:BHF-UCL.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IGI:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0030166; P:proteoglycan biosynthetic process; ISS:AgBase.
DR GO; GO:0003177; P:pulmonary valve development; ISS:BHF-UCL.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:HGNC-UCL.
DR GO; GO:0014916; P:regulation of lung blood pressure; IMP:BHF-UCL.
DR GO; GO:0061298; P:retina vasculature development in camera-type eye; ISS:BHF-UCL.
DR GO; GO:1905314; P:semi-lunar valve development; ISS:BHF-UCL.
DR GO; GO:0007178; P:transmembrane receptor protein serine/threonine kinase signaling pathway; IDA:BHF-UCL.
DR GO; GO:0003186; P:tricuspid valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060841; P:venous blood vessel development; ISS:BHF-UCL.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR000472; Activin_recp.
DR InterPro; IPR015770; BMPR2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR InterPro; IPR000333; TGFB_receptor.
DR PANTHER; PTHR23255; PTHR23255; 1.
DR PANTHER; PTHR23255:SF97; PTHR23255:SF97; 1.
DR Pfam; PF01064; Activin_recp; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Disease variant; Disulfide bond; Glycoprotein; Kinase; Magnesium;
KW Manganese; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Receptor; Reference proteome; Serine/threonine-protein kinase; Signal;
KW Transferase; Transmembrane; Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..1038
FT /note="Bone morphogenetic protein receptor type-2"
FT /id="PRO_0000024415"
FT TOPO_DOM 27..150
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 151..171
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 172..1038
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 203..504
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 593..626
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 746..770
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 872..972
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 746..768
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 872..897
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 898..918
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 937..964
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 333
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 209..217
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|Ref.15"
FT BINDING 230
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|Ref.15"
FT BINDING 280..282
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|Ref.15"
FT BINDING 337..338
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|Ref.15"
FT BINDING 351
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|Ref.15"
FT MOD_RES 379
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 586
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 680
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35607"
FT MOD_RES 681
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35607"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 34..66
FT /evidence="ECO:0000269|PubMed:17094948,
FT ECO:0007744|PDB:2HLQ"
FT DISULFID 60..84
FT /evidence="ECO:0000269|PubMed:17094948,
FT ECO:0007744|PDB:2HLQ"
FT DISULFID 94..117
FT /evidence="ECO:0000269|PubMed:17094948,
FT ECO:0007744|PDB:2HLQ"
FT DISULFID 99..116
FT /evidence="ECO:0000269|PubMed:17094948,
FT ECO:0007744|PDB:2HLQ"
FT DISULFID 118..123
FT /evidence="ECO:0000269|PubMed:17094948,
FT ECO:0007744|PDB:2HLQ"
FT VAR_SEQ 530
FT /note="N -> R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7791754"
FT /id="VSP_054441"
FT VAR_SEQ 531..1038
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7791754"
FT /id="VSP_054442"
FT VARIANT 60
FT /note="C -> Y (in PPH1; dbSNP:rs1085307172)"
FT /evidence="ECO:0000269|PubMed:11015450"
FT /id="VAR_013670"
FT VARIANT 64
FT /note="S -> R (in PPH1; unknown pathological significance;
FT unchanged subcellular localization)"
FT /evidence="ECO:0000269|PubMed:28507310"
FT /id="VAR_079588"
FT VARIANT 67
FT /note="Y -> C (in PPH1; significant decrease in nitric
FT oxide synthesis by endothelial cells; dbSNP:rs1085307177)"
FT /evidence="ECO:0000269|PubMed:25187962"
FT /id="VAR_073041"
FT VARIANT 77
FT /note="I -> L (in PPH1; unknown pathological significance;
FT unchanged subcellular localization)"
FT /evidence="ECO:0000269|PubMed:24936649,
FT ECO:0000269|PubMed:28507310"
FT /id="VAR_079589"
FT VARIANT 82
FT /note="Q -> H (in PPH1; dbSNP:rs1085307185)"
FT /evidence="ECO:0000269|PubMed:12358323"
FT /id="VAR_033109"
FT VARIANT 84
FT /note="C -> F (in PPH1; alters alternative splicing of
FT BMPR2; dbSNP:rs1085307197)"
FT /evidence="ECO:0000269|PubMed:24936649,
FT ECO:0000269|PubMed:28507310"
FT /id="VAR_079590"
FT VARIANT 87
FT /note="H -> Y (in PPH1; unknown pathological significance;
FT unchanged subcellular localization)"
FT /evidence="ECO:0000269|PubMed:24936649,
FT ECO:0000269|PubMed:28507310"
FT /id="VAR_079591"
FT VARIANT 92
FT /note="Q -> L (in PPH1; unknown pathological significance;
FT unchanged subcellular localization)"
FT /evidence="ECO:0000269|PubMed:24936649,
FT ECO:0000269|PubMed:28507310"
FT /id="VAR_079592"
FT VARIANT 109
FT /note="Q -> H (in PPH1; unknown pathological significance;
FT unchanged subcellular localization)"
FT /evidence="ECO:0000269|PubMed:28507310"
FT /id="VAR_079593"
FT VARIANT 117
FT /note="C -> Y (in PPH1; dbSNP:rs1085307215)"
FT /evidence="ECO:0000269|PubMed:11015450"
FT /id="VAR_013671"
FT VARIANT 118
FT /note="C -> W (in PPH1; dbSNP:rs137852743)"
FT /evidence="ECO:0000269|PubMed:10973254"
FT /id="VAR_013672"
FT VARIANT 123
FT /note="C -> R (in PPH1; dbSNP:rs137852750)"
FT /evidence="ECO:0000269|PubMed:11115378"
FT /id="VAR_013673"
FT VARIANT 123
FT /note="C -> S (in PPH1; dbSNP:rs137852750)"
FT /evidence="ECO:0000269|PubMed:11115378"
FT /id="VAR_013674"
FT VARIANT 138
FT /note="P -> A (in PPH1; unknown pathological significance;
FT unchanged subcellular localization)"
FT /evidence="ECO:0000269|PubMed:28507310"
FT /id="VAR_079594"
FT VARIANT 162
FT /note="A -> P (in PPH1; unknown pathological significance;
FT unchanged subcellular localization)"
FT /evidence="ECO:0000269|PubMed:24936649,
FT ECO:0000269|PubMed:28507310"
FT /id="VAR_079595"
FT VARIANT 182
FT /note="G -> D (in PPH1; dbSNP:rs137852754)"
FT /evidence="ECO:0000269|PubMed:12358323"
FT /id="VAR_033110"
FT VARIANT 218..1038
FT /note="Missing (in PPH1; changed localization to the plasma
FT membrane)"
FT /evidence="ECO:0000269|PubMed:28507310"
FT /id="VAR_079596"
FT VARIANT 224
FT /note="E -> D (in dbSNP:rs754343081)"
FT /evidence="ECO:0000269|PubMed:11115378"
FT /id="VAR_013675"
FT VARIANT 248
FT /note="R -> G (in PPH1; unknown pathological significance;
FT unchanged subcellular localization)"
FT /evidence="ECO:0000269|PubMed:28507310"
FT /id="VAR_079597"
FT VARIANT 264
FT /note="D -> N (in PPH1; unknown pathological significance;
FT unchanged subcellular localization)"
FT /evidence="ECO:0000269|PubMed:24936649,
FT ECO:0000269|PubMed:28507310"
FT /id="VAR_079598"
FT VARIANT 298..1038
FT /note="Missing (in PPH1; loss of localization to the plasma
FT membrane; localized to the cytoplasm)"
FT /evidence="ECO:0000269|PubMed:28507310"
FT /id="VAR_079599"
FT VARIANT 341
FT /note="V -> M (in PPH1; unknown pathological significance;
FT unchanged subcellular localization; dbSNP:rs767882551)"
FT /evidence="ECO:0000269|PubMed:24936649,
FT ECO:0000269|PubMed:28507310"
FT /id="VAR_079600"
FT VARIANT 347
FT /note="C -> Y (in PPH1; dbSNP:rs137852744)"
FT /evidence="ECO:0000269|PubMed:10973254"
FT /id="VAR_013676"
FT VARIANT 420
FT /note="C -> R (in PPH1; dbSNP:rs1085307324)"
FT /evidence="ECO:0000269|PubMed:11115378"
FT /id="VAR_013677"
FT VARIANT 467
FT /note="K -> R (in PPH1; unknown pathological significance;
FT unchanged subcellular localization)"
FT /evidence="ECO:0000269|PubMed:28507310"
FT /id="VAR_079601"
FT VARIANT 483
FT /note="C -> R (in PPH1; sporadic; dbSNP:rs1085307354)"
FT /evidence="ECO:0000269|PubMed:11015450,
FT ECO:0000269|PubMed:12358323"
FT /id="VAR_013678"
FT VARIANT 485
FT /note="D -> G (in PPH1; complete loss of function;
FT dbSNP:rs137852745)"
FT /evidence="ECO:0000269|PubMed:10973254,
FT ECO:0000269|PubMed:11115378"
FT /id="VAR_013679"
FT VARIANT 491
FT /note="R -> Q (in PPH1; sporadic; dbSNP:rs137852749)"
FT /evidence="ECO:0000269|PubMed:10903931"
FT /id="VAR_013680"
FT VARIANT 491
FT /note="R -> W (in PPH1; dbSNP:rs137852746)"
FT /evidence="ECO:0000269|PubMed:10903931"
FT /id="VAR_013681"
FT VARIANT 512
FT /note="K -> T (in PPH1; dbSNP:rs1085307364)"
FT /evidence="ECO:0000269|PubMed:11115378"
FT /id="VAR_013682"
FT VARIANT 519
FT /note="N -> K (in PPH1; dbSNP:rs1085307365)"
FT /id="VAR_013683"
FT VARIANT 775
FT /note="S -> N (unchanged subcellular localization;
FT dbSNP:rs2228545)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:24936649, ECO:0000269|PubMed:28507310"
FT /id="VAR_019996"
FT VARIANT 863
FT /note="S -> N (in PPH1; abnormal subcellular localization;
FT significant increase in apoptosis of endothelial cells;
FT significant decrease in proliferation of endothelial cells;
FT significant decrease in nitric oxide synthesis by
FT endothelial cells; significant increase in endothelin 1
FT synthesis by endothelial cells; dbSNP:rs1006246556)"
FT /evidence="ECO:0000269|PubMed:25187962"
FT /id="VAR_073042"
FT VARIANT 899
FT /note="R -> P (in PPH1; leads to constitutive activation of
FT the MAPK14 pathway; dbSNP:rs137852752)"
FT /evidence="ECO:0000269|PubMed:15965979"
FT /id="VAR_033111"
FT CONFLICT 828
FT /note="G -> R (in Ref. 2; CAA88759)"
FT /evidence="ECO:0000305"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:2HLQ"
FT TURN 42..47
FT /evidence="ECO:0007829|PDB:2HLQ"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:2HLQ"
FT TURN 53..56
FT /evidence="ECO:0007829|PDB:2HLQ"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:2HLQ"
FT STRAND 66..73
FT /evidence="ECO:0007829|PDB:2HLQ"
FT STRAND 76..84
FT /evidence="ECO:0007829|PDB:2HLQ"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:2HLQ"
FT TURN 105..109
FT /evidence="ECO:0007829|PDB:2HLQ"
FT STRAND 113..118
FT /evidence="ECO:0007829|PDB:2HLQ"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:2HLQ"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:6UNP"
FT STRAND 203..211
FT /evidence="ECO:0007829|PDB:6UNP"
FT STRAND 216..222
FT /evidence="ECO:0007829|PDB:6UNP"
FT STRAND 225..233
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 237..247
FT /evidence="ECO:0007829|PDB:6UNP"
FT STRAND 260..267
FT /evidence="ECO:0007829|PDB:6UNP"
FT STRAND 273..279
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 287..293
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 298..315
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:6UNP"
FT STRAND 338..341
FT /evidence="ECO:0007829|PDB:6UNP"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:6UNP"
FT STRAND 359..362
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 380..382
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 385..388
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 394..396
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 397..417
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 421..423
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 437..440
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 446..453
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 471..481
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 488..490
FT /evidence="ECO:0007829|PDB:6UNP"
FT HELIX 494..506
FT /evidence="ECO:0007829|PDB:6UNP"
SQ SEQUENCE 1038 AA; 115201 MW; 1389923CE574B913 CRC64;
MTSSLQRPWR VPWLPWTILL VSTAAASQNQ ERLCAFKDPY QQDLGIGESR ISHENGTILC
SKGSTCYGLW EKSKGDINLV KQGCWSHIGD PQECHYEECV VTTTPPSIQN GTYRFCCCST
DLCNVNFTEN FPPPDTTPLS PPHSFNRDET IIIALASVSV LAVLIVALCF GYRMLTGDRK
QGLHSMNMME AAASEPSLDL DNLKLLELIG RGRYGAVYKG SLDERPVAVK VFSFANRQNF
INEKNIYRVP LMEHDNIARF IVGDERVTAD GRMEYLLVME YYPNGSLCKY LSLHTSDWVS
SCRLAHSVTR GLAYLHTELP RGDHYKPAIS HRDLNSRNVL VKNDGTCVIS DFGLSMRLTG
NRLVRPGEED NAAISEVGTI RYMAPEVLEG AVNLRDCESA LKQVDMYALG LIYWEIFMRC
TDLFPGESVP EYQMAFQTEV GNHPTFEDMQ VLVSREKQRP KFPEAWKENS LAVRSLKETI
EDCWDQDAEA RLTAQCAEER MAELMMIWER NKSVSPTVNP MSTAMQNERN LSHNRRVPKI
GPYPDYSSSS YIEDSIHHTD SIVKNISSEH SMSSTPLTIG EKNRNSINYE RQQAQARIPS
PETSVTSLST NTTTTNTTGL TPSTGMTTIS EMPYPDETNL HTTNVAQSIG PTPVCLQLTE
EDLETNKLDP KEVDKNLKES SDENLMEHSL KQFSGPDPLS STSSSLLYPL IKLAVEATGQ
QDFTQTANGQ ACLIPDVLPT QIYPLPKQQN LPKRPTSLPL NTKNSTKEPR LKFGSKHKSN
LKQVETGVAK MNTINAAEPH VVTVTMNGVA GRNHSVNSHA ATTQYANGTV LSGQTTNIVT
HRAQEMLQNQ FIGEDTRLNI NSSPDEHEPL LRREQQAGHD EGVLDRLVDR RERPLEGGRT
NSNNNNSNPC SEQDVLAQGV PSTAADPGPS KPRRAQRPNS LDLSATNVLD GSSIQIGEST
QDGKSGSGEK IKKRVKTPYS LKRWRPSTWV ISTESLDCEV NNNGSNRAVH SKSSTAVYLA
EGGTATTMVS KDIGMNCL
