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 05-DEC-2018, entry version 206. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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): RT extension of 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 RT protein-4 that forms differential heteromeric complexes with bone RT morphogenetic 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 RT 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., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA 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., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA 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., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-586, AND IDENTIFICATION RP BY 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 RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-379, AND IDENTIFICATION RP BY 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., RA Sebald W., Mueller T., Knaus P.; RT "New insights into the molecular mechanism of multiple synostoses RT syndrome (SYNS): mutation within the GDF5 knuckle epitope causes RT noggin-resistance."; RL J. Bone Miner. Res. 27:429-442(2012). RN [11] 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [12] 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 [13] 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 [14] 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 RT mutations in the bone morphogenetic protein receptor-II gene."; RL Am. J. Hum. Genet. 67:737-744(2000). RN [15] 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., RA Peacock A., Allcock R., Corris P., Loyd J.E., Trembath R.C., RA 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- RT beta family."; RL J. Med. Genet. 37:741-745(2000). RN [16] 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., RA Phillips J.A. III, Loyd J.E., Nichols W.C., Trembath R.C., Aldred M., RA Brannon C.A., Conneally P.M., Foroud T., Fretwell N., Gaddipati R., RA Koller D., Loyd E.J., Morgan N.V., Newman J.H., Prince M.A., RA Vilarino Gueell C., Wheeler L.; RT "Heterozygous germline mutations in BMPR2, encoding a TGF-beta RT receptor, cause familial primary pulmonary hypertension."; RL Nat. Genet. 26:81-84(2000). RN [17] RP VARIANTS PPH1 ARG-123; SER-123; ARG-420 AND THR-512, VARIANT ASP-224, RP AND 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 RT primary pulmonary hypertension."; RL Am. J. Hum. Genet. 68:92-102(2001). RN [18] 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 [19] 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 RT bone morphogenetic protein receptor II."; RL Am. J. Respir. Crit. Care Med. 167:889-894(2003). RN [20] 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 [21] 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., RA Carlquist J., Kim M., Torbicki A., Fijalkowska A., Szewczyk G., RA Parma J., Abramowicz M.J., Galie N., Morisaki H., Kyotani S., RA Nakanishi N., Morisaki T., Humbert M., Simonneau G., Sitbon O., RA Soubrier F., Coulet F., Morrell N.W., Trembath R.C.; RT "Mutations of the TGF-beta type II receptor BMPR2 in pulmonary RT arterial hypertension."; RL Hum. Mutat. 27:121-132(2006). RN [22] 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., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [23] RP VARIANTS PPH1 LEU-77; PHE-84; TYR-87; LEU-92; PRO-162; ASN-264 AND RP MET-341, 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 [24] RP VARIANTS PPH1 CYS-67 AND ASN-863, CHARACTERIZATION OF VARIANTS PPH1 RP CYS-67 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., RA Li Z., Huo L., Fan Y., Penny D.J.; RT "Functional changes in pulmonary arterial endothelial cells associated RT with BMPR2 mutations."; RL PLoS ONE 9:E106703-E106703(2014). RN [25] 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 RP VARIANTS PPH1 ARG-64; LEU-77; TYR-87; LEU-92; HIS-109; ALA-138; RP PRO-162; 218-TYR--LEU-1038 DEL; GLY-248; ASN-264; 298-TRP--LEU-1038 RP DEL; MET-341 AND 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 RT Pulmonary Arterial Hypertension."; RL Sci. Rep. 7:1923-1923(2017). CC -!- FUNCTION: On ligand binding, forms a receptor complex consisting CC of two type II and two type I transmembrane serine/threonine CC kinases. Type II receptors phosphorylate and activate type I CC receptors which autophosphorylate, then bind and activate SMAD CC transcriptional regulators. Binds to BMP7, BMP2 and, less CC efficiently, BMP4. Binding is weak but enhanced by the presence of CC type I receptors for BMPs. Mediates induction of adipogenesis by CC GDF6. {ECO:0000250|UniProtKB:O35607}. CC -!- CATALYTIC ACTIVITY: CC Reaction=[receptor-protein]-L-threonine + ATP = [receptor- CC protein]-O-phospho-L-threonine + ADP + H(+); CC Xref=Rhea:RHEA:44880, Rhea:RHEA-COMP:11024, Rhea:RHEA- CC COMP:11025, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.30; CC -!- CATALYTIC ACTIVITY: CC Reaction=[receptor-protein]-L-serine + ATP = [receptor-protein]-O- CC phospho-L-serine + ADP + H(+); Xref=Rhea:RHEA:18673, Rhea:RHEA- CC COMP:11022, Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, CC ChEBI:CHEBI:456216; 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. {ECO:0000269|PubMed:21976273}. CC -!- INTERACTION: CC P08607:C4bpa (xeno); NbExp=3; IntAct=EBI-527196, EBI-527325; CC P43026:GDF5; NbExp=4; IntAct=EBI-527196, EBI-8571476; CC P68404:Prkcb (xeno); NbExp=4; IntAct=EBI-527196, EBI-397048; CC Q13976:PRKG1; NbExp=2; IntAct=EBI-527196, EBI-3952014; 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 CC rare disorder characterized by plexiform lesions of proliferating CC endothelial cells in pulmonary arterioles. The lesions lead to CC elevated pulmonary arterial pression, right ventricular failure, CC and death. The disease can occur from infancy throughout life and CC it has a mean age at onset of 36 years. Penetrance is reduced. CC Although familial pulmonary hypertension is rare, cases secondary CC to known etiologies are more common and include those associated CC with the appetite-suppressant drugs. {ECO:0000269|PubMed:10903931, CC ECO:0000269|PubMed:10973254, ECO:0000269|PubMed:11015450, CC ECO:0000269|PubMed:11115378, ECO:0000269|PubMed:12358323, CC ECO:0000269|PubMed:15965979, ECO:0000269|PubMed:24936649, CC ECO:0000269|PubMed:25187962, ECO:0000269|PubMed:28507310}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Pulmonary venoocclusive disease 1, autosomal dominant CC (PVOD1) [MIM:265450]: A disease characterized by widespread CC fibrous obstruction and intimal thickening of septal veins and CC preseptal venules, a low diffusing capacity for carbon monoxide, CC occult alveolar hemorrhage, and nodular ground-glass opacities, CC septal lines and lymph node enlargement showed by high-resolution CC computed tomography of the chest. It is frequently associated with CC pulmonary capillary dilatation and proliferation, and is a rare CC and devastating cause of pulmonary hypertension. CC {ECO:0000269|PubMed:12446270, ECO:0000269|PubMed:16429395}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr CC protein kinase family. TGFB receptor subfamily. {ECO:0000305}. 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; 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 UniGene; Hs.471119; -. DR PDB; 2HLQ; X-ray; 1.45 A; A=33-131. DR PDB; 3G2F; X-ray; 2.35 A; A/B=189-517. DR PDBsum; 2HLQ; -. DR PDBsum; 3G2F; -. DR ProteinModelPortal; Q13873; -. DR SMR; Q13873; -. DR BioGrid; 107127; 58. DR DIP; DIP-5794N; -. DR ELM; Q13873; -. DR IntAct; Q13873; 37. DR MINT; Q13873; -. DR STRING; 9606.ENSP00000363708; -. DR BindingDB; Q13873; -. DR ChEMBL; CHEMBL5467; -. DR GuidetoPHARMACOLOGY; 1794; -. DR GlyConnect; 1046; -. DR iPTMnet; Q13873; -. DR PhosphoSitePlus; Q13873; -. DR BioMuta; BMPR2; -. DR DMDM; 12643724; -. DR EPD; Q13873; -. DR MaxQB; Q13873; -. DR PaxDb; Q13873; -. DR PeptideAtlas; Q13873; -. DR PRIDE; Q13873; -. DR ProteomicsDB; 59705; -. DR DNASU; 659; -. DR Ensembl; ENST00000374574; ENSP00000363702; ENSG00000204217. [Q13873-2] DR Ensembl; ENST00000374580; ENSP00000363708; ENSG00000204217. [Q13873-1] DR GeneID; 659; -. DR KEGG; hsa:659; -. DR UCSC; uc002uzf.5; human. [Q13873-1] DR CTD; 659; -. DR DisGeNET; 659; -. DR EuPathDB; HostDB:ENSG00000204217.12; -. DR GeneCards; BMPR2; -. DR GeneReviews; BMPR2; -. DR HGNC; HGNC:1078; BMPR2. DR HPA; HPA017385; -. DR HPA; HPA049014; -. 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 eggNOG; KOG3653; Eukaryota. DR eggNOG; ENOG410XS2Z; LUCA. DR GeneTree; ENSGT00940000156449; -. DR HOGENOM; HOG000043088; -. DR HOVERGEN; HBG096378; -. DR InParanoid; Q13873; -. DR KO; K04671; -. DR OMA; ANTVAHR; -. DR OrthoDB; EOG091G03YO; -. DR PhylomeDB; Q13873; -. DR TreeFam; TF314724; -. DR Reactome; R-HSA-201451; Signaling by BMP. DR SignaLink; Q13873; -. DR SIGNOR; Q13873; -. DR ChiTaRS; BMPR2; human. DR EvolutionaryTrace; Q13873; -. DR GeneWiki; BMPR2; -. DR GenomeRNAi; 659; -. DR PRO; PR:Q13873; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; ENSG00000204217; Expressed in 220 organ(s), highest expression level in upper lobe of lung. DR CleanEx; HS_BMPR2; -. DR ExpressionAtlas; Q13873; baseline and differential. DR Genevisible; Q13873; HS. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. DR GO; GO:0009925; C:basal plasma membrane; IEA:Ensembl. DR GO; GO:0005901; C:caveola; IEA:Ensembl. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0005913; C:cell-cell adherens junction; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; 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:0043025; C:neuronal cell body; IEA:Ensembl. 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:0019838; F:growth factor binding; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0046332; F:SMAD binding; IBA:GO_Central. DR GO; GO:0005026; F:transforming growth factor beta receptor activity, type II; IBA:GO_Central. DR GO; GO:0005024; F:transforming growth factor beta-activated receptor activity; IBA:GO_Central. DR GO; GO:0009952; P:anterior/posterior pattern specification; 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:0001974; P:blood vessel remodeling; ISS:BHF-UCL. DR GO; GO:0030509; P:BMP signaling pathway; IDA:BHF-UCL. DR GO; GO:0007420; P:brain development; IEA:Ensembl. DR GO; GO:0071773; P:cellular response to BMP stimulus; IMP:BHF-UCL. 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: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:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL. DR GO; GO:0003148; P:outflow tract septum morphogenesis; ISS:BHF-UCL. DR GO; GO:0007389; P:pattern specification process; IBA:GO_Central. 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:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0030166; P:proteoglycan biosynthetic process; ISS:AgBase. DR GO; GO:0042127; P:regulation of cell proliferation; IMP:HGNC. 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:0006366; P:transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IBA:GO_Central. 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 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; IPR000333; TGFB_receptor. DR PANTHER; PTHR23255; PTHR23255; 1. DR PANTHER; PTHR23255:SF63; PTHR23255:SF63; 1. DR Pfam; PF01064; Activin_recp; 1. DR Pfam; PF00069; Pkinase; 1. DR SUPFAM; SSF56112; SSF56112; 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 Complete proteome; Disease mutation; Disulfide bond; Glycoprotein; KW Kinase; Magnesium; Manganese; Membrane; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Polymorphism; Receptor; KW Reference proteome; Serine/threonine-protein kinase; Signal; KW Transferase; Transmembrane; Transmembrane helix. FT SIGNAL 1 26 {ECO:0000255}. FT CHAIN 27 1038 Bone morphogenetic protein receptor type- FT 2. FT /FTId=PRO_0000024415. FT TOPO_DOM 27 150 Extracellular. {ECO:0000255}. FT TRANSMEM 151 171 Helical. {ECO:0000255}. FT TOPO_DOM 172 1038 Cytoplasmic. {ECO:0000255}. FT DOMAIN 203 504 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 209 217 ATP. {ECO:0000305|Ref.13}. FT NP_BIND 280 282 ATP. {ECO:0000305|Ref.13}. FT NP_BIND 337 338 ATP. {ECO:0000305|Ref.13}. FT COMPBIAS 547 550 Poly-Ser. FT COMPBIAS 610 618 Poly-Thr. FT COMPBIAS 901 908 Poly-Asn. FT ACT_SITE 333 333 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT BINDING 230 230 ATP. {ECO:0000305|Ref.13}. FT BINDING 351 351 ATP. {ECO:0000305|Ref.13}. FT MOD_RES 379 379 Phosphothreonine. FT {ECO:0000244|PubMed:19369195}. FT MOD_RES 586 586 Phosphoserine. FT {ECO:0000244|PubMed:18691976}. FT MOD_RES 680 680 Phosphoserine. FT {ECO:0000250|UniProtKB:O35607}. FT MOD_RES 681 681 Phosphoserine. FT {ECO:0000250|UniProtKB:O35607}. FT CARBOHYD 55 55 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 110 110 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 126 126 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 34 66 {ECO:0000244|PDB:2HLQ, FT ECO:0000269|PubMed:17094948}. FT DISULFID 60 84 {ECO:0000244|PDB:2HLQ, FT ECO:0000269|PubMed:17094948}. FT DISULFID 94 117 {ECO:0000244|PDB:2HLQ, FT ECO:0000269|PubMed:17094948}. FT DISULFID 99 116 {ECO:0000244|PDB:2HLQ, FT ECO:0000269|PubMed:17094948}. FT DISULFID 118 123 {ECO:0000244|PDB:2HLQ, FT ECO:0000269|PubMed:17094948}. FT VAR_SEQ 530 530 N -> R (in isoform 2). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:7791754}. FT /FTId=VSP_054441. FT VAR_SEQ 531 1038 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:7791754}. FT /FTId=VSP_054442. FT VARIANT 60 60 C -> Y (in PPH1; dbSNP:rs1085307172). FT {ECO:0000269|PubMed:11015450}. FT /FTId=VAR_013670. FT VARIANT 64 64 S -> R (in PPH1; unknown pathological FT significance; unchanged subcellular FT localization). FT {ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079588. FT VARIANT 67 67 Y -> C (in PPH1; significant decrease in FT nitric oxide synthesis by endothelial FT cells; dbSNP:rs1085307177). FT {ECO:0000269|PubMed:25187962}. FT /FTId=VAR_073041. FT VARIANT 77 77 I -> L (in PPH1; unknown pathological FT significance; unchanged subcellular FT localization). FT {ECO:0000269|PubMed:24936649, FT ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079589. FT VARIANT 82 82 Q -> H (in PPH1; dbSNP:rs1085307185). FT {ECO:0000269|PubMed:12358323}. FT /FTId=VAR_033109. FT VARIANT 84 84 C -> F (in PPH1; alters alternative FT splicing of BMPR2; dbSNP:rs1085307197). FT {ECO:0000269|PubMed:24936649, FT ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079590. FT VARIANT 87 87 H -> Y (in PPH1; unknown pathological FT significance; unchanged subcellular FT localization). FT {ECO:0000269|PubMed:24936649, FT ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079591. FT VARIANT 92 92 Q -> L (in PPH1; unknown pathological FT significance; unchanged subcellular FT localization). FT {ECO:0000269|PubMed:24936649, FT ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079592. FT VARIANT 109 109 Q -> H (in PPH1; unknown pathological FT significance; unchanged subcellular FT localization). FT {ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079593. FT VARIANT 117 117 C -> Y (in PPH1). FT {ECO:0000269|PubMed:11015450}. FT /FTId=VAR_013671. FT VARIANT 118 118 C -> W (in PPH1; dbSNP:rs137852743). FT {ECO:0000269|PubMed:10973254}. FT /FTId=VAR_013672. FT VARIANT 123 123 C -> R (in PPH1; dbSNP:rs137852750). FT {ECO:0000269|PubMed:11115378}. FT /FTId=VAR_013673. FT VARIANT 123 123 C -> S (in PPH1; dbSNP:rs137852750). FT {ECO:0000269|PubMed:11115378}. FT /FTId=VAR_013674. FT VARIANT 138 138 P -> A (in PPH1; unknown pathological FT significance; unchanged subcellular FT localization). FT {ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079594. FT VARIANT 162 162 A -> P (in PPH1; unknown pathological FT significance; unchanged subcellular FT localization). FT {ECO:0000269|PubMed:24936649, FT ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079595. FT VARIANT 182 182 G -> D (in PPH1; dbSNP:rs137852754). FT {ECO:0000269|PubMed:12358323}. FT /FTId=VAR_033110. FT VARIANT 218 1038 Missing (in PPH1; changed localization to FT the plasma membrane). FT {ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079596. FT VARIANT 224 224 E -> D (in dbSNP:rs754343081). FT {ECO:0000269|PubMed:11115378}. FT /FTId=VAR_013675. FT VARIANT 248 248 R -> G (in PPH1; unknown pathological FT significance; unchanged subcellular FT localization). FT {ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079597. FT VARIANT 264 264 D -> N (in PPH1; unknown pathological FT significance; unchanged subcellular FT localization). FT {ECO:0000269|PubMed:24936649, FT ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079598. FT VARIANT 298 1038 Missing (in PPH1; loss of localization to FT the plasma membrane; localized to the FT cytoplasm). FT {ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079599. FT VARIANT 341 341 V -> M (in PPH1; unknown pathological FT significance; unchanged subcellular FT localization; dbSNP:rs767882551). FT {ECO:0000269|PubMed:24936649, FT ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079600. FT VARIANT 347 347 C -> Y (in PPH1; dbSNP:rs137852744). FT {ECO:0000269|PubMed:10973254}. FT /FTId=VAR_013676. FT VARIANT 420 420 C -> R (in PPH1; dbSNP:rs1085307324). FT {ECO:0000269|PubMed:11115378}. FT /FTId=VAR_013677. FT VARIANT 467 467 K -> R (in PPH1; unknown pathological FT significance; unchanged subcellular FT localization). FT {ECO:0000269|PubMed:28507310}. FT /FTId=VAR_079601. FT VARIANT 483 483 C -> R (in PPH1; sporadic; FT dbSNP:rs1085307354). FT {ECO:0000269|PubMed:11015450, FT ECO:0000269|PubMed:12358323}. FT /FTId=VAR_013678. FT VARIANT 485 485 D -> G (in PPH1; complete loss of FT function; dbSNP:rs137852745). FT {ECO:0000269|PubMed:10973254, FT ECO:0000269|PubMed:11115378}. FT /FTId=VAR_013679. FT VARIANT 491 491 R -> Q (in PPH1; sporadic; FT dbSNP:rs137852749). FT {ECO:0000269|PubMed:10903931}. FT /FTId=VAR_013680. FT VARIANT 491 491 R -> W (in PPH1; dbSNP:rs137852746). FT {ECO:0000269|PubMed:10903931}. FT /FTId=VAR_013681. FT VARIANT 512 512 K -> T (in PPH1; dbSNP:rs1085307364). FT {ECO:0000269|PubMed:11115378}. FT /FTId=VAR_013682. FT VARIANT 519 519 N -> K (in PPH1; dbSNP:rs1085307365). FT /FTId=VAR_013683. FT VARIANT 775 775 S -> N (polymorphism; unchanged FT subcellular localization; FT dbSNP:rs2228545). FT {ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:24936649, FT ECO:0000269|PubMed:28507310}. FT /FTId=VAR_019996. FT VARIANT 863 863 S -> N (in PPH1; abnormal subcellular FT localization; significant increase in FT apoptosis of endothelial cells; FT significant decrease in proliferation of FT endothelial cells; significant decrease FT in nitric oxide synthesis by endothelial FT cells; significant increase in endothelin FT 1 synthesis by endothelial cells; FT dbSNP:rs1006246556). FT {ECO:0000269|PubMed:25187962}. FT /FTId=VAR_073042. FT VARIANT 899 899 R -> P (in PPH1; leads to constitutive FT activation of the MAPK14 pathway; FT dbSNP:rs137852752). FT {ECO:0000269|PubMed:15965979}. FT /FTId=VAR_033111. FT CONFLICT 828 828 G -> R (in Ref. 2; CAA88759). FT {ECO:0000305}. FT STRAND 33 35 {ECO:0000244|PDB:2HLQ}. FT TURN 42 47 {ECO:0000244|PDB:2HLQ}. FT HELIX 48 50 {ECO:0000244|PDB:2HLQ}. FT TURN 53 56 {ECO:0000244|PDB:2HLQ}. FT STRAND 57 59 {ECO:0000244|PDB:2HLQ}. FT STRAND 66 73 {ECO:0000244|PDB:2HLQ}. FT STRAND 76 84 {ECO:0000244|PDB:2HLQ}. FT STRAND 90 92 {ECO:0000244|PDB:2HLQ}. FT TURN 105 109 {ECO:0000244|PDB:2HLQ}. FT STRAND 113 118 {ECO:0000244|PDB:2HLQ}. FT HELIX 123 125 {ECO:0000244|PDB:2HLQ}. FT STRAND 202 211 {ECO:0000244|PDB:3G2F}. FT STRAND 213 222 {ECO:0000244|PDB:3G2F}. FT STRAND 225 233 {ECO:0000244|PDB:3G2F}. FT HELIX 234 236 {ECO:0000244|PDB:3G2F}. FT HELIX 237 247 {ECO:0000244|PDB:3G2F}. FT STRAND 260 267 {ECO:0000244|PDB:3G2F}. FT STRAND 273 279 {ECO:0000244|PDB:3G2F}. FT HELIX 287 293 {ECO:0000244|PDB:3G2F}. FT HELIX 298 316 {ECO:0000244|PDB:3G2F}. FT HELIX 322 324 {ECO:0000244|PDB:3G2F}. FT STRAND 338 341 {ECO:0000244|PDB:3G2F}. FT STRAND 347 349 {ECO:0000244|PDB:3G2F}. FT STRAND 359 362 {ECO:0000244|PDB:3G2F}. FT HELIX 380 382 {ECO:0000244|PDB:3G2F}. FT HELIX 385 388 {ECO:0000244|PDB:3G2F}. FT HELIX 394 396 {ECO:0000244|PDB:3G2F}. FT HELIX 397 417 {ECO:0000244|PDB:3G2F}. FT HELIX 421 423 {ECO:0000244|PDB:3G2F}. FT HELIX 437 440 {ECO:0000244|PDB:3G2F}. FT HELIX 446 453 {ECO:0000244|PDB:3G2F}. FT HELIX 471 483 {ECO:0000244|PDB:3G2F}. FT HELIX 488 490 {ECO:0000244|PDB:3G2F}. FT HELIX 494 506 {ECO:0000244|PDB:3G2F}. 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 //