ID BMPR2_HUMAN Reviewed; 1038 AA. AC Q13873; Q16569; Q4ZG08; Q53SA5; Q585T8; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 2. DT 05-APR-2011, entry version 127. 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]. RC TISSUE=Substantia nigra; RX MEDLINE=95372334; 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 [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Skin fibroblast; RX MEDLINE=95403457; 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 [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=95197572; 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 [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-586; SER-680; SER-681; RP SER-757 AND SER-863, AND MASS SPECTROMETRY. 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375; THR-379; SER-513; RP SER-515; SER-680; SER-757 AND SER-862, AND MASS SPECTROMETRY. 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 [8] 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 [9] RP VARIANTS PPH1 GLN-491 AND TRP-491. RX MEDLINE=20395844; 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 [10] RP VARIANTS PPH1 TYR-60; TYR-117 AND ARG-483. RX MEDLINE=20473811; 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 [11] RP VARIANTS PPH1 TRP-118; TYR-347 AND GLY-485. RX MEDLINE=20428187; 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 [12] RP VARIANTS PPH1 ARG-123; SER-123; ARG-420 AND THR-512, VARIANT ASP-224, RP AND CHARACTERIZATION OF VARIANT PPH1 GLY-485. RX MEDLINE=21063176; 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 [13] 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 [14] RP INVOLVEMENT IN PVOD. RX PubMed=12446270; 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 [15] 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 [16] RP INVOLVEMENT IN PVOD. 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 [17] 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). 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 BMP-7, BMP-2 and, less CC efficiently, BMP-4. Binding is weak but enhanced by the presence CC of type I receptors for BMPs. CC -!- CATALYTIC ACTIVITY: ATP + [receptor-protein] = ADP + [receptor- CC protein] phosphate. CC -!- COFACTOR: Magnesium or manganese (By similarity). CC -!- INTERACTION: CC Q91X48:C4bp (xeno); NbExp=1; IntAct=EBI-527196, EBI-527325; CC P68404:Prkcb (xeno); NbExp=2; IntAct=EBI-527196, EBI-397048; CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane CC protein. CC -!- TISSUE SPECIFICITY: Highly expressed in heart and liver. CC -!- DISEASE: Defects in BMPR2 are the cause of primary pulmonary CC hypertension (PPH1) [MIM:178600]. PPH1 is a rare autosomal CC dominant disorder characterized by plexiform lesions of CC proliferating endothelial cells in pulmonary arterioles. The CC lesions lead to elevated pulmonary arterial pression, right CC ventricular failure, and death. The disease can occur from infancy CC throughout life and it has a mean age at onset of 36 years. CC Penetrance is reduced. Although familial PPH1 is rare, cases CC secondary to known etiologies are more common and include those CC associated with the appetite-suppressant drugs. CC -!- DISEASE: Defects in BMPR2 are a cause of pulmonary venoocclusive CC disease (PVOD) [MIM:265450]. PVOD is a rare form of pulmonary CC hypertension in which the vascular changes originate in the small CC pulmonary veins and venules. The pathogenesis is unknown and any CC link with PPH1 has been speculative. The finding of PVOD CC associated with a BMPR2 mutation reveals a possible pathogenetic CC connection with PPH1. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr CC protein kinase family. TGFB receptor subfamily. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/BMPR2"; 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; 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; BC052985; AAH52985.1; -; mRNA. DR IPI; IPI00783156; -. DR PIR; I38935; I38935. DR RefSeq; NP_001195.2; NM_001204.6. 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; 33-131, 197-510. DR DIP; DIP-5794N; -. DR DIP; DIP-5941N; -. DR DIP; DIP-5942N; -. DR IntAct; Q13873; 38. DR STRING; Q13873; -. DR PhosphoSite; Q13873; -. DR PRIDE; Q13873; -. DR Ensembl; ENST00000374574; ENSP00000363702; ENSG00000204217. DR Ensembl; ENST00000374580; ENSP00000363708; ENSG00000204217. DR Ensembl; ENST00000445231; ENSP00000401728; ENSG00000204217. DR GeneID; 659; -. DR KEGG; hsa:659; -. DR UCSC; uc002uzf.2; human. DR CTD; 659; -. DR GeneCards; GC02P195088; -. DR H-InvDB; HIX0002749; -. DR HGNC; HGNC:1078; BMPR2. DR HPA; HPA017385; -. DR MIM; 178600; phenotype. DR MIM; 265450; phenotype. DR MIM; 600799; gene. DR neXtProt; NX_Q13873; -. DR Orphanet; 422; Idiopathic and/or familial pulmonary arterial hypertension. DR Orphanet; 31837; Pulmonary venoocclusive disease. DR PharmGKB; PA25388; -. DR GeneTree; ENSGT00560000076906; -. DR HOGENOM; HBG447050; -. DR HOVERGEN; HBG050705; -. DR InParanoid; Q13873; -. DR OMA; GPTPVCL; -. DR OrthoDB; EOG470TGJ; -. DR BRENDA; 2.7.11.30; 247. DR Pathway_Interaction_DB; bmppathway; BMP receptor signaling. DR Reactome; REACT_12034; Signaling by BMP. DR NextBio; 2680; -. DR ArrayExpress; Q13873; -. DR Bgee; Q13873; -. DR CleanEx; HS_BMPR2; -. DR Genevestigator; Q13873; -. DR GermOnline; ENSG00000204217; Homo sapiens. DR GO; GO:0005887; C:integral to plasma membrane; IDA:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0005024; F:transforming growth factor beta receptor activity; IEA:InterPro. DR GO; GO:0009952; P:anterior/posterior pattern formation; ISS:BHF-UCL. DR GO; GO:0030509; P:BMP signaling pathway; IDA:BHF-UCL. DR GO; GO:0009267; P:cellular response to starvation; IEP:BHF-UCL. DR GO; GO:0048286; P:lung alveolus development; ISS:BHF-UCL. DR GO; GO:0001707; P:mesoderm formation; ISS:BHF-UCL. DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB. 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: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: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: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:0014916; P:regulation of lung blood pressure; IMP:BHF-UCL. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IMP:BHF-UCL. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; ISS:BHF-UCL. DR InterPro; IPR000472; Activin_rcpt. DR InterPro; IPR015770; BMPRII. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_cat_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR017442; Se/Thr_prot_kinase-like_dom. DR PANTHER; PTHR23255:SF12; BMPRII; 1. DR Pfam; PF01064; Activin_recp; 1. DR Pfam; PF00069; Pkinase; 1. DR SUPFAM; SSF56112; Kinase_like; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; FALSE_NEG. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Complete proteome; Disease mutation; KW Disulfide bond; Glycoprotein; Kinase; Magnesium; Manganese; Membrane; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism; KW Receptor; Serine/threonine-protein kinase; Signal; Transferase; KW Transmembrane; Transmembrane helix. FT SIGNAL 1 26 Potential. FT CHAIN 27 1038 Bone morphogenetic protein receptor type- FT 2. FT /FTId=PRO_0000024415. FT TOPO_DOM 27 150 Extracellular (Potential). FT TRANSMEM 151 171 Helical; (Potential). FT TOPO_DOM 172 1038 Cytoplasmic (Potential). FT DOMAIN 203 504 Protein kinase. FT NP_BIND 209 217 ATP. FT NP_BIND 280 282 ATP. FT NP_BIND 337 338 ATP. 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 (By similarity). FT BINDING 230 230 ATP. FT BINDING 351 351 ATP. FT MOD_RES 375 375 Phosphoserine. FT MOD_RES 379 379 Phosphothreonine. FT MOD_RES 513 513 Phosphoserine. FT MOD_RES 515 515 Phosphoserine. FT MOD_RES 586 586 Phosphoserine. FT MOD_RES 680 680 Phosphoserine. FT MOD_RES 681 681 Phosphoserine. FT MOD_RES 757 757 Phosphoserine. FT MOD_RES 862 862 Phosphoserine. FT MOD_RES 863 863 Phosphoserine. FT CARBOHYD 55 55 N-linked (GlcNAc...) (Potential). FT CARBOHYD 110 110 N-linked (GlcNAc...) (Potential). FT CARBOHYD 126 126 N-linked (GlcNAc...) (Potential). FT DISULFID 34 66 By similarity. FT DISULFID 94 117 By similarity. FT VARIANT 60 60 C -> Y (in PPH1). FT /FTId=VAR_013670. FT VARIANT 82 82 Q -> H (in PPH1). FT /FTId=VAR_033109. FT VARIANT 117 117 C -> Y (in PPH1). FT /FTId=VAR_013671. FT VARIANT 118 118 C -> W (in PPH1). FT /FTId=VAR_013672. FT VARIANT 123 123 C -> R (in PPH1). FT /FTId=VAR_013673. FT VARIANT 123 123 C -> S (in PPH1). FT /FTId=VAR_013674. FT VARIANT 182 182 G -> D (in PPH1). FT /FTId=VAR_033110. FT VARIANT 224 224 E -> D. FT /FTId=VAR_013675. FT VARIANT 347 347 C -> Y (in PPH1). FT /FTId=VAR_013676. FT VARIANT 420 420 C -> R (in PPH1). FT /FTId=VAR_013677. FT VARIANT 483 483 C -> R (in PPH1; sporadic). FT /FTId=VAR_013678. FT VARIANT 485 485 D -> G (in PPH1; complete loss of FT function). FT /FTId=VAR_013679. FT VARIANT 491 491 R -> Q (in PPH1; sporadic). FT /FTId=VAR_013680. FT VARIANT 491 491 R -> W (in PPH1). FT /FTId=VAR_013681. FT VARIANT 512 512 K -> T (in PPH1). FT /FTId=VAR_013682. FT VARIANT 519 519 N -> K (in PPH1). FT /FTId=VAR_013683. FT VARIANT 775 775 S -> N (in dbSNP:rs2228545). FT /FTId=VAR_019996. FT VARIANT 899 899 R -> P (in PPH1; leads to constitutive FT activation of the MAPK14 pathway). FT /FTId=VAR_033111. FT CONFLICT 828 828 G -> R (in Ref. 1; CAA88759). FT STRAND 228 233 FT HELIX 234 236 FT HELIX 237 247 FT STRAND 260 262 FT STRAND 264 267 FT STRAND 273 279 FT HELIX 287 293 FT HELIX 298 309 FT HELIX 313 316 FT STRAND 338 341 FT STRAND 347 349 FT HELIX 380 382 FT HELIX 385 388 FT HELIX 394 396 FT HELIX 397 408 FT HELIX 412 417 FT HELIX 421 423 FT TURN 435 439 FT HELIX 446 453 FT HELIX 471 483 FT HELIX 488 490 FT HELIX 494 506 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 //