ID ACVL1_HUMAN Reviewed; 503 AA. AC P37023; A6NGA8; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 15-DEC-1998, sequence version 2. DT 03-MAY-2023, entry version 232. DE RecName: Full=Serine/threonine-protein kinase receptor R3; DE Short=SKR3; DE EC=2.7.11.30; DE AltName: Full=Activin receptor-like kinase 1; DE Short=ALK-1; DE AltName: Full=TGF-B superfamily receptor type I; DE Short=TSR-I; DE Flags: Precursor; GN Name=ACVRL1; Synonyms=ACVRLK1, ALK1; 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]. RC TISSUE=Placenta; RX PubMed=8397373; RA ten Dijke P., Ichijo H., Franzen P., Schulz P., Saras J., Toyoshima H., RA Heldin C.-H., Miyazono K.; RT "Activin receptor-like kinases: a novel subclass of cell-surface receptors RT with predicted serine/threonine kinase activity."; RL Oncogene 8:2879-2887(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8242742; DOI=10.1016/0092-8674(93)90488-c; RA Attisano L., Carcamo J., Ventura F., Weis F.M., Massague J., Wrana J.L.; RT "Identification of human activin and TGF beta type I receptors that form RT heteromeric kinase complexes with type II receptors."; RL Cell 75:671-680(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HHT2 CYS-50; GLN-67; RP ILE-333; TRP-374 AND THR-424. RX PubMed=9245985; DOI=10.1086/513903; RA Berg J.N., Gallione C.J., Stenzel T.T., Johnson D.W., Allen W.P., RA Schwartz C.E., Jackson C.E., Porteous M.E.M., Marchuk D.A.; RT "The activin receptor-like kinase 1 gene: genomic structure and mutations RT in hereditary hemorrhagic telangiectasia type 2."; RL Am. J. Hum. Genet. 61:60-67(1997). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [7] RP INTERACTION WITH TSC22D1. RX PubMed=21791611; DOI=10.1128/mcb.05448-11; RA Yan X., Zhang J., Pan L., Wang P., Xue H., Zhang L., Gao X., Zhao X., RA Ning Y., Chen Y.G.; RT "TSC-22 promotes transforming growth factor beta-mediated cardiac RT myofibroblast differentiation by antagonizing Smad7 activity."; RL Mol. Cell. Biol. 31:3700-3709(2011). RN [8] RP STRUCTURE BY NMR OF 19-118, FUNCTION AS BMP9 RECEPTOR, DISULFIDE BONDS, AND RP MUTAGENESIS OF 74-ARG--LEU-76. RX PubMed=22799562; DOI=10.1021/bi300942x; RA Mahlawat P., Ilangovan U., Biswas T., Sun L.Z., Hinck A.P.; RT "Structure of the Alk1 extracellular domain and characterization of its RT bone morphogenetic protein (BMP) binding properties."; RL Biochemistry 51:6328-6341(2012). RN [9] RP X-RAY CRYSTALLOGRAPHY (3.36 ANGSTROMS) OF 22-118 IN COMPLEX WITH BMP9 AND RP ACVR2B, FUNCTION AS BMP9 AND BMP10 RECEPTOR, AND DISULFIDE BONDS. RX PubMed=22718755; DOI=10.1074/jbc.m112.377960; RA Townson S.A., Martinez-Hackert E., Greppi C., Lowden P., Sako D., Liu J., RA Ucran J.A., Liharska K., Underwood K.W., Seehra J., Kumar R., RA Grinberg A.V.; RT "Specificity and structure of a high affinity activin receptor-like kinase RT 1 (ALK1) signaling complex."; RL J. Biol. Chem. 287:27313-27325(2012). RN [10] RP VARIANTS HHT2 SER-232 DEL; ARG-376 AND GLN-411. RX PubMed=8640225; DOI=10.1038/ng0696-189; RA Johnson D.W., Berg J.N., Baldwin M.A., Gallione C.J., Marondel I., RA Yoon S.-J., Stenzel T.T., Speer M., Pericak-Vance M.A., Diamond A., RA Guttmacher A.E., Jackson C.E., Attisano L., Kucherlapati R., RA Porteous M.E.M., Marchuk D.A.; RT "Mutations in the activin receptor-like kinase 1 gene in hereditary RT haemorrhagic telangiectasia type 2."; RL Nat. Genet. 13:189-194(1996). RN [11] RP VARIANTS HHT2 TYR-51; TRP-77 AND ASP-96. RX PubMed=10694922; RX DOI=10.1002/(sici)1098-1004(1998)12:2<137::aid-humu16>3.0.co;2-j; RA Klaus D.J., Gallione C.J., Anthony K., Yeh E.Y., Yu J., Lux A., RA Johnson D.W., Marchuk D.A.; RT "Novel missense and frameshift mutations in the activin receptor-like RT kinase-1 gene in hereditary hemorrhagic telangiectasia."; RL Hum. Mutat. 12:137-137(1998). RN [12] RP VARIANTS HHT2 GLY-48-49-ALA DELINS EP; CYS-50; SER-232 DEL; ILE-333; RP TYR-344 AND ASP-407. RX PubMed=10767348; DOI=10.1093/hmg/9.8.1227; RA Abdalla S.A., Pece-Barbara N., Vera S., Tapia E., Paez E., Bernabeu C., RA Letarte M.; RT "Analysis of ALK-1 and endoglin in newborns from families with hereditary RT hemorrhagic telangiectasia type 2."; RL Hum. Mol. Genet. 9:1227-1237(2000). RN [13] RP VARIANTS HHT2 TRP-374 AND ASN-398. RX PubMed=11170071; RX DOI=10.1002/1096-8628(20010201)98:4<298::aid-ajmg1093>3.0.co;2-k; RA Kjeldsen A.D., Brusgaard K., Poulsen L., Kruse T., Rasmussen K., Green A., RA Vase P.; RT "Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic RT telangiectasia in two large Danish families."; RL Am. J. Med. Genet. 98:298-302(2001). RN [14] RP VARIANTS HHT2 ASP-254 DEL; TRP-411 AND TRP-484. RX PubMed=11484689; DOI=10.1056/nejm200108023450503; RA Trembath R.C., Thomson J.R., Machado R.D., Morgan N.V., Atkinson C., RA Winship I., Simonneau G., Galie N., Loyd J.E., Humbert M., Nichols W.C., RA Berg J., Manes A., McGaughran J., Pauciulo M., Wheeler L., Morrell N.W.; RT "Clinical and molecular genetic features of pulmonary hypertension in RT patients with hereditary hemorrhagic telangiectasia."; RL N. Engl. J. Med. 345:325-334(2001). RN [15] RP VARIANTS HHT2 ALA-179; ASP-211; TYR-344; TRP-374; GLN-374; SER-399; GLN-411 RP AND THR-487, AND CHARACTERIZATION OF VARIANTS HHT2 CYS-50; GLN-67; TRP-77; RP ALA-179; ASP-211; SER-232 DEL; ASP-254 DEL; ILE-333; TYR-344; GLN-374; RP LEU-378; GLN-411 AND THR-487. RX PubMed=14684682; DOI=10.1136/jmg.40.12.865; RA Harrison R.E., Flanagan J.A., Sankelo M., Abdalla S.A., Rowell J., RA Machado R.D., Elliott C.G., Robbins I.M., Olschewski H., McLaughlin V., RA Gruenig E., Kermeen F., Halme M., Raeisaenen-Sokolowski A., Laitinen T., RA Morrell N.W., Trembath R.C.; RT "Molecular and functional analysis identifies ALK-1 as the predominant RT cause of pulmonary hypertension related to hereditary haemorrhagic RT telangiectasia."; RL J. Med. Genet. 40:865-871(2003). RN [16] RP ERRATUM OF PUBMED:14684682. RA Harrison R.E., Flanagan J.A., Sankelo M., Abdalla S.A., Rowell J., RA Machado R.D., Elliott C.G., Robbins I.M., Olschewski H., McLaughlin V., RA Gruenig E., Kermeen F., Halme M., Raeisaenen-Sokolowski A., Laitinen T., RA Morrell N.W., Trembath R.C.; RL J. Med. Genet. 41:576-576(2004). RN [17] RP VARIANTS HHT2 ARG-48; LYS-215; ARG-223; ARG-229; SER-233 DEL; PHE-285; RP PRO-306; TYR-314; PRO-337; PRO-347; GLN-374; VAL-376; LYS-379; GLY-397; RP TRP-411; PRO-411; GLN-411; LEU-425; LEU-479; VAL-482 AND TRP-484. RX PubMed=15024723; DOI=10.1002/humu.20017; RG French Rendu-Osler network; RA Lesca G., Plauchu H., Coulet F., Lefebvre S., Plessis G., Odent S., RA Riviere S., Leheup B., Goizet C., Carette M.-F., Cordier J.-F., Pinson S., RA Soubrier F., Calender A., Giraud S.; RT "Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic RT telangiectasia in France."; RL Hum. Mutat. 23:289-299(2004). RN [18] RP VARIANTS HHT2 TRP-67; TRP-374; LYS-379; ASP-407; TRP-411; VAL-425 AND RP PHE-425 DEL. RX PubMed=15712270; DOI=10.1002/humu.9311; RA Kuehl H.K.A., Caselitz M., Hasenkamp S., Wagner S., El-Harith E.-H.A., RA Manns M.P., Stuhrmann M.; RT "Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic RT telangiectasia: identification of five novel ALK1 and one novel ENG RT mutations."; RL Hum. Mutat. 25:320-320(2005). RN [19] RP VARIANT SER-30, AND VARIANTS HHT2 TYR-34; ALA-52; ILE-197; ASP-219; RP LYS-237; LEU-260; PRO-289; ARG-344; CYS-426 AND ARG-433. RX PubMed=16752392; DOI=10.1002/humu.20342; RA Bossler A.D., Richards J., George C., Godmilow L., Ganguly A.; RT "Novel mutations in ENG and ACVRL1 identified in a series of 200 RT individuals undergoing clinical genetic testing for hereditary hemorrhagic RT telangiectasia (HHT): correlation of genotype with phenotype."; RL Hum. Mutat. 27:667-675(2006). RN [20] RP VARIANTS HHT2 GLY-50; PRO-66; ARG-69; TYR-176; LEU-233; PRO-265; PRO-403 RP AND SER-416. RX PubMed=16525724; RA Argyriou L., Twelkemeyer S., Panchulidze I., Wehner L.E., Teske U., RA Engel W., Nayernia K.; RT "Novel mutations in the ENG and ACVRL1 genes causing hereditary hemorrhagic RT teleangiectasia."; RL Int. J. Mol. Med. 17:655-659(2006). RN [21] RP VARIANTS CYS-38; PRO-138; LYS-277; PRO-342; THR-400 AND GLU-486, AND RP VARIANTS HHT2 SER-96; GLY-217; GLU-226; ARG-280; ARG-294; GLN-328; HIS-335; RP ASP-347; SER-378; ARG-424; SER-449 AND PRO-479. RX PubMed=20414677; DOI=10.1007/s00439-010-0825-4; RA Richards-Yutz J., Grant K., Chao E.C., Walther S.E., Ganguly A.; RT "Update on molecular diagnosis of hereditary hemorrhagic telangiectasia."; RL Hum. Genet. 128:61-77(2010). RN [22] RP VARIANTS ASN-8; VAL-59; VAL-159; CYS-225 AND ALA-396. 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 [23] RP VARIANTS HHT2 GLY-41; TYR-41; GLY-46; PRO-47; TYR-66; PHE-77; ASP-211; RP SER-211; VAL-245; PRO-306; VAL-313; TYR-314; SER-378; ASP-379; LYS-379; RP GLY-404; TRP-411; MET-441 AND TYR-443, VARIANTS ASP-111 AND PHE-417, RP CHARACTERIZATION OF VARIANTS HHT2 GLY-41; TYR-41; GLY-46; PRO-47; TYR-66; RP PHE-77; ASP-211; SER-211; VAL-245; PRO-306; VAL-313; TYR-314; SER-378; RP ASP-379; LYS-379; GLY-404; TRP-411; MET-441 AND TYR-443, CHARACTERIZATION RP OF VARIANTS ASP-111 AND PHE-417, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=26176610; DOI=10.1371/journal.pone.0132111; RA Alaa El Din F., Patri S., Thoreau V., Rodriguez-Ballesteros M., Hamade E., RA Bailly S., Gilbert-Dussardier B., Abou Merhi R., Kitzis A.; RT "Functional and splicing defect analysis of 23 ACVRL1 mutations in a cohort RT of patients affected by hereditary hemorrhagic telangiectasia."; RL PLoS ONE 10:E0132111-E0132111(2015). CC -!- FUNCTION: Type I receptor for TGF-beta family ligands BMP9/GDF2 and CC BMP10 and important regulator of normal blood vessel development. On CC ligand binding, forms a receptor complex consisting of two type II and CC two type I transmembrane serine/threonine kinases. Type II receptors CC phosphorylate and activate type I receptors which autophosphorylate, CC then bind and activate SMAD transcriptional regulators. May bind CC activin as well. {ECO:0000269|PubMed:22718755, CC ECO:0000269|PubMed:22799562, ECO:0000269|PubMed:26176610}. 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 TSC22D1/TSC-22. {ECO:0000269|PubMed:21791611}. CC -!- INTERACTION: CC P37023; PRO_0000033903 [Q9UK05]: GDF2; NbExp=2; IntAct=EBI-8043559, EBI-16227344; CC P37023; P02750: LRG1; NbExp=3; IntAct=EBI-8043559, EBI-9083443; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26176610}; CC Single-pass type I membrane protein {ECO:0000255}. CC -!- DISEASE: Telangiectasia, hereditary hemorrhagic, 2 (HHT2) [MIM:600376]: CC A multisystemic vascular dysplasia leading to dilation of permanent CC blood vessels and arteriovenous malformations of skin, mucosa, and CC viscera. The disease is characterized by recurrent epistaxis and CC gastro-intestinal hemorrhage. Visceral involvement includes CC arteriovenous malformations of the lung, liver, and brain. CC {ECO:0000269|PubMed:10694922, ECO:0000269|PubMed:10767348, CC ECO:0000269|PubMed:11170071, ECO:0000269|PubMed:11484689, CC ECO:0000269|PubMed:14684682, ECO:0000269|PubMed:15024723, CC ECO:0000269|PubMed:15712270, ECO:0000269|PubMed:16525724, CC ECO:0000269|PubMed:16752392, ECO:0000269|PubMed:20414677, CC ECO:0000269|PubMed:26176610, ECO:0000269|PubMed:8640225, CC ECO:0000269|PubMed:9245985}. 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}. CC -!- WEB RESOURCE: Name=Hereditary Hemorrhagic Telangiectasia and ENG; CC URL="http://arup.utah.edu/database/ACVRL1/ACVRL1_welcome.php"; 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; Z22533; CAA80255.1; -; mRNA. DR EMBL; L17075; AAA16160.1; -; mRNA. DR EMBL; U77713; AAB61900.1; -; Genomic_DNA. DR EMBL; U77707; AAB61900.1; JOINED; Genomic_DNA. DR EMBL; U77708; AAB61900.1; JOINED; Genomic_DNA. DR EMBL; U77709; AAB61900.1; JOINED; Genomic_DNA. DR EMBL; U77710; AAB61900.1; JOINED; Genomic_DNA. DR EMBL; U77711; AAB61900.1; JOINED; Genomic_DNA. DR EMBL; U77712; AAB61900.1; JOINED; Genomic_DNA. DR EMBL; AC025259; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471111; EAW58213.1; -; Genomic_DNA. DR EMBL; BC042637; AAH42637.1; -; mRNA. DR CCDS; CCDS31804.1; -. DR PIR; A49431; A49431. DR RefSeq; NP_000011.2; NM_000020.2. DR RefSeq; NP_001070869.1; NM_001077401.1. DR RefSeq; XP_005269292.1; XM_005269235.2. DR PDB; 2LCR; NMR; -; A=22-118. DR PDB; 3MY0; X-ray; 2.65 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X=195-497. DR PDB; 4FAO; X-ray; 3.36 A; C/D/I/J/O/P/U/V/c/d/i/j=22-118. DR PDB; 6SF1; X-ray; 2.80 A; A=21-118. DR PDB; 6SF2; X-ray; 3.30 A; A/D=21-118. DR PDB; 6SF3; X-ray; 2.30 A; A=21-118. DR PDB; 7PPC; X-ray; 3.60 A; E/F/G/H=22-118. DR PDBsum; 2LCR; -. DR PDBsum; 3MY0; -. DR PDBsum; 4FAO; -. DR PDBsum; 6SF1; -. DR PDBsum; 6SF2; -. DR PDBsum; 6SF3; -. DR PDBsum; 7PPC; -. DR AlphaFoldDB; P37023; -. DR BMRB; P37023; -. DR SMR; P37023; -. DR BioGRID; 106609; 32. DR DIP; DIP-5938N; -. DR IntAct; P37023; 8. DR MINT; P37023; -. DR STRING; 9606.ENSP00000373574; -. DR BindingDB; P37023; -. DR ChEMBL; CHEMBL5311; -. DR DrugBank; DB00171; ATP. DR DrugCentral; P37023; -. DR GuidetoPHARMACOLOGY; 1784; -. DR GlyCosmos; P37023; 1 site, No reported glycans. DR GlyGen; P37023; 1 site. DR iPTMnet; P37023; -. DR PhosphoSitePlus; P37023; -. DR BioMuta; ACVRL1; -. DR DMDM; 3915750; -. DR EPD; P37023; -. DR jPOST; P37023; -. DR MassIVE; P37023; -. DR PaxDb; P37023; -. DR PeptideAtlas; P37023; -. DR ProteomicsDB; 55254; -. DR ABCD; P37023; 1 sequenced antibody. DR Antibodypedia; 2055; 645 antibodies from 41 providers. DR DNASU; 94; -. DR Ensembl; ENST00000388922.9; ENSP00000373574.4; ENSG00000139567.13. DR GeneID; 94; -. DR KEGG; hsa:94; -. DR MANE-Select; ENST00000388922.9; ENSP00000373574.4; NM_000020.3; NP_000011.2. DR UCSC; uc001rzj.4; human. DR AGR; HGNC:175; -. DR CTD; 94; -. DR DisGeNET; 94; -. DR GeneCards; ACVRL1; -. DR GeneReviews; ACVRL1; -. DR HGNC; HGNC:175; ACVRL1. DR HPA; ENSG00000139567; Tissue enhanced (lung). DR MalaCards; ACVRL1; -. DR MIM; 600376; phenotype. DR MIM; 601284; gene. DR neXtProt; NX_P37023; -. DR OpenTargets; ENSG00000139567; -. DR Orphanet; 774; Hereditary hemorrhagic telangiectasia. DR Orphanet; 275777; Heritable pulmonary arterial hypertension. DR PharmGKB; PA24496; -. DR VEuPathDB; HostDB:ENSG00000139567; -. DR eggNOG; KOG2052; Eukaryota. DR GeneTree; ENSGT00940000161446; -. DR HOGENOM; CLU_000288_8_1_1; -. DR InParanoid; P37023; -. DR OMA; TIHAENQ; -. DR OrthoDB; 3900892at2759; -. DR PhylomeDB; P37023; -. DR TreeFam; TF314724; -. DR BRENDA; 2.7.10.2; 2681. DR BRENDA; 2.7.11.30; 2681. DR PathwayCommons; P37023; -. DR Reactome; R-HSA-201451; Signaling by BMP. DR SignaLink; P37023; -. DR SIGNOR; P37023; -. DR BioGRID-ORCS; 94; 32 hits in 1186 CRISPR screens. DR ChiTaRS; ACVRL1; human. DR GeneWiki; ACVRL1; -. DR GenomeRNAi; 94; -. DR Pharos; P37023; Tchem. DR PRO; PR:P37023; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P37023; protein. DR Bgee; ENSG00000139567; Expressed in right lung and 150 other tissues. DR ExpressionAtlas; P37023; baseline and differential. DR Genevisible; P37023; HS. DR GO; GO:0070724; C:BMP receptor complex; IBA:GO_Central. DR GO; GO:0009986; C:cell surface; IDA:MGI. DR GO; GO:0030425; C:dendrite; IEA:Ensembl. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0048185; F:activin binding; IDA:UniProtKB. DR GO; GO:0016361; F:activin receptor activity, type I; IDA:MGI. DR GO; GO:0005524; F:ATP binding; IDA:HGNC-UCL. DR GO; GO:0098821; F:BMP receptor activity; IMP:UniProtKB. DR GO; GO:0016301; F:kinase activity; IDA:UniProt. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:HGNC-UCL. DR GO; GO:0046332; F:SMAD binding; IDA:HGNC-UCL. DR GO; GO:0050431; F:transforming growth factor beta binding; IPI:UniProtKB. DR GO; GO:0005024; F:transforming growth factor beta receptor activity; IDA:MGI. DR GO; GO:0005025; F:transforming growth factor beta receptor activity, type I; IDA:UniProtKB. DR GO; GO:0004675; F:transmembrane receptor protein serine/threonine kinase activity; NAS:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IMP:HGNC-UCL. DR GO; GO:0060840; P:artery development; ISS:BHF-UCL. DR GO; GO:0008015; P:blood circulation; IMP:HGNC-UCL. DR GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; TAS:DFLAT. DR GO; GO:0001955; P:blood vessel maturation; TAS:DFLAT. DR GO; GO:0001974; P:blood vessel remodeling; ISS:BHF-UCL. DR GO; GO:0030509; P:BMP signaling pathway; IMP: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:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:BHF-UCL. DR GO; GO:0035912; P:dorsal aorta morphogenesis; ISS:BHF-UCL. DR GO; GO:0009953; P:dorsal/ventral pattern formation; IBA:GO_Central. DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL. DR GO; GO:0061154; P:endothelial tube morphogenesis; IMP:BHF-UCL. DR GO; GO:0007507; P:heart development; IBA:GO_Central. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0001946; P:lymphangiogenesis; ISS:BHF-UCL. DR GO; GO:0060836; P:lymphatic endothelial cell differentiation; IMP:BHF-UCL. DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IMP:BHF-UCL. DR GO; GO:0007162; P:negative regulation of cell adhesion; IMP:HGNC-UCL. DR GO; GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL. DR GO; GO:0030336; P:negative regulation of cell migration; IMP:HGNC-UCL. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:HGNC-UCL. DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; IMP:BHF-UCL. DR GO; GO:0045602; P:negative regulation of endothelial cell differentiation; IEA:Ensembl. DR GO; GO:0010596; P:negative regulation of endothelial cell migration; IDA:BHF-UCL. DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IEA:Ensembl. DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; IMP:HGNC-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; ISS:BHF-UCL. DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl. DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IDA:BHF-UCL. DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; TAS:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:HGNC-UCL. DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IEA:Ensembl. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IEA:Ensembl. DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0006468; P:protein phosphorylation; IDA:HGNC-UCL. DR GO; GO:0008217; P:regulation of blood pressure; IMP:HGNC-UCL. DR GO; GO:0043535; P:regulation of blood vessel endothelial cell migration; TAS:DFLAT. DR GO; GO:0006275; P:regulation of DNA replication; TAS:DFLAT. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:HGNC-UCL. DR GO; GO:0001936; P:regulation of endothelial cell proliferation; TAS:DFLAT. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0061298; P:retina vasculature development in camera-type eye; ISS:BHF-UCL. DR GO; GO:0007165; P:signal transduction; IDA:HGNC-UCL. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:HGNC-UCL. DR GO; GO:0060841; P:venous blood vessel development; ISS:BHF-UCL. DR GO; GO:0035313; P:wound healing, spreading of epidermal cells; IMP:HGNC-UCL. DR CDD; cd14142; STKc_ACVR1_ALK1; 1. DR Gene3D; 2.10.60.10; CD59; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR003605; GS_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR InterPro; IPR045860; Snake_toxin-like_sf. DR InterPro; IPR000333; TGFB_receptor. DR PANTHER; PTHR23255:SF66; SERINE/THREONINE-PROTEIN KINASE RECEPTOR R3; 1. DR PANTHER; PTHR23255; TRANSFORMING GROWTH FACTOR-BETA RECEPTOR TYPE I AND II; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF08515; TGF_beta_GS; 1. DR PRINTS; PR00653; ACTIVIN2R. DR SMART; SM00467; GS; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF57302; Snake toxin-like; 1. DR PROSITE; PS51256; GS; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW 3D-structure; Angiogenesis; ATP-binding; Cell membrane; Disease variant; KW Disulfide bond; Glycoprotein; Kinase; Magnesium; Manganese; Membrane; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Receptor; KW Reference proteome; Serine/threonine-protein kinase; Signal; Transferase; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..21 FT /evidence="ECO:0000255" FT CHAIN 22..503 FT /note="Serine/threonine-protein kinase receptor R3" FT /id="PRO_0000024420" FT TOPO_DOM 22..118 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 119..141 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 142..503 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 172..201 FT /note="GS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00585" FT DOMAIN 202..492 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 73..76 FT /note="Mediates specificity for BMP ligand" FT ACT_SITE 330 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 208..216 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 229 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 155 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q61288" FT MOD_RES 160 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q61288" FT MOD_RES 161 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q61288" FT CARBOHYD 98 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 34..51 FT /evidence="ECO:0000269|PubMed:22718755, FT ECO:0000269|PubMed:22799562, ECO:0007744|PDB:2LCR, FT ECO:0007744|PDB:4FAO" FT DISULFID 36..41 FT /evidence="ECO:0000269|PubMed:22718755, FT ECO:0000269|PubMed:22799562, ECO:0007744|PDB:2LCR, FT ECO:0007744|PDB:4FAO" FT DISULFID 46..69 FT /evidence="ECO:0000269|PubMed:22718755, FT ECO:0000269|PubMed:22799562, ECO:0007744|PDB:2LCR, FT ECO:0007744|PDB:4FAO" FT DISULFID 77..89 FT /evidence="ECO:0000269|PubMed:22718755, FT ECO:0000269|PubMed:22799562, ECO:0007744|PDB:2LCR, FT ECO:0007744|PDB:4FAO" FT DISULFID 90..95 FT /evidence="ECO:0000269|PubMed:22718755, FT ECO:0000269|PubMed:22799562, ECO:0007744|PDB:2LCR, FT ECO:0007744|PDB:4FAO" FT VARIANT 8 FT /note="K -> N" FT /evidence="ECO:0000269|PubMed:24936649" FT /id="VAR_079583" FT VARIANT 30 FT /note="P -> S (found in a patient with hereditary FT hemorrhagic talagiectasia; unknown pathological FT significance; dbSNP:rs149664056)" FT /evidence="ECO:0000269|PubMed:16752392" FT /id="VAR_070308" FT VARIANT 34 FT /note="C -> Y (in HHT2)" FT /evidence="ECO:0000269|PubMed:16752392" FT /id="VAR_070309" FT VARIANT 38 FT /note="S -> C" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070310" FT VARIANT 41 FT /note="C -> G (in HHT2; loss of receptor activity in FT response to BMP9; predominantly retained in the endoplasmic FT reticulum)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075231" FT VARIANT 41 FT /note="C -> Y (in HHT2; loss of receptor activity in FT response to BMP9; predominantly retained in the endoplasmic FT reticulum; dbSNP:rs1184716348)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075232" FT VARIANT 46 FT /note="C -> G (in HHT2; loss of receptor activity in FT response to BMP9; retained in the endoplasmic reticulum)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075233" FT VARIANT 47 FT /note="R -> P (in HHT2; loss of receptor activity in FT response to BMP9; retained in the endoplasmic reticulum; FT dbSNP:rs774389618)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075234" FT VARIANT 48..49 FT /note="GA -> EP (in HHT2; dbSNP:rs387906392)" FT /id="VAR_026784" FT VARIANT 48 FT /note="G -> R (in HHT2)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026785" FT VARIANT 50 FT /note="W -> C (in HHT2; retained in the endoplasmic FT reticulum; dbSNP:rs121909285)" FT /evidence="ECO:0000269|PubMed:10767348, FT ECO:0000269|PubMed:14684682, ECO:0000269|PubMed:9245985" FT /id="VAR_006204" FT VARIANT 50 FT /note="W -> G (in HHT2)" FT /evidence="ECO:0000269|PubMed:16525724" FT /id="VAR_070311" FT VARIANT 51 FT /note="C -> Y (in HHT2; dbSNP:rs863223409)" FT /evidence="ECO:0000269|PubMed:10694922" FT /id="VAR_006205" FT VARIANT 52 FT /note="T -> A (in HHT2; dbSNP:rs1131691346)" FT /evidence="ECO:0000269|PubMed:16752392" FT /id="VAR_070312" FT VARIANT 59 FT /note="E -> V (found in a patient with pulmonary arterial FT hypertension; unknown pathological significance; FT dbSNP:rs1466116430)" FT /evidence="ECO:0000269|PubMed:24936649" FT /id="VAR_079584" FT VARIANT 66 FT /note="H -> P (in HHT2)" FT /evidence="ECO:0000269|PubMed:16525724" FT /id="VAR_070313" FT VARIANT 66 FT /note="H -> Y (in HHT2; loss of receptor activity in FT response to BMP9; retained in the endoplasmic reticulum; FT dbSNP:rs1480110873)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075235" FT VARIANT 67 FT /note="R -> Q (in HHT2; retained in the endoplasmic FT reticulum; dbSNP:rs863223414)" FT /evidence="ECO:0000269|PubMed:14684682, FT ECO:0000269|PubMed:9245985" FT /id="VAR_006206" FT VARIANT 67 FT /note="R -> W (in HHT2; dbSNP:rs1085307405)" FT /evidence="ECO:0000269|PubMed:15712270" FT /id="VAR_026786" FT VARIANT 69 FT /note="C -> R (in HHT2)" FT /evidence="ECO:0000269|PubMed:16525724" FT /id="VAR_070314" FT VARIANT 77 FT /note="C -> F (in HHT2; loss of receptor activity in FT response to BMP9; retained in the endoplasmic reticulum; FT dbSNP:rs1330837892)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075236" FT VARIANT 77 FT /note="C -> W (in HHT2; retained in the endoplasmic FT reticulum)" FT /evidence="ECO:0000269|PubMed:10694922, FT ECO:0000269|PubMed:14684682" FT /id="VAR_006207" FT VARIANT 96 FT /note="N -> D (in HHT2)" FT /evidence="ECO:0000269|PubMed:10694922" FT /id="VAR_006208" FT VARIANT 96 FT /note="N -> S (in HHT2)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070315" FT VARIANT 111 FT /note="E -> D (no loss of receptor activity in response to FT BMP9; mutant protein is capable of targeting the cell FT surface appropriately; dbSNP:rs1481094868)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075237" FT VARIANT 138 FT /note="L -> P" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070316" FT VARIANT 159 FT /note="E -> V (found in a patient with pulmonary arterial FT hypertension; unknown pathological significance)" FT /evidence="ECO:0000269|PubMed:24936649" FT /id="VAR_079585" FT VARIANT 176 FT /note="D -> Y (in HHT2)" FT /evidence="ECO:0000269|PubMed:16525724" FT /id="VAR_070317" FT VARIANT 179 FT /note="D -> A (in HHT2; mutant protein is capable of FT targeting the cell surface appropriately; FT dbSNP:rs753792569)" FT /evidence="ECO:0000269|PubMed:14684682" FT /id="VAR_026787" FT VARIANT 197 FT /note="T -> I (in HHT2)" FT /evidence="ECO:0000269|PubMed:16752392" FT /id="VAR_070318" FT VARIANT 211 FT /note="G -> D (in HHT2; loss of receptor activity in FT response to BMP9; retained in the endoplasmic reticulum; FT dbSNP:rs28936687)" FT /evidence="ECO:0000269|PubMed:14684682, FT ECO:0000269|PubMed:26176610" FT /id="VAR_026788" FT VARIANT 211 FT /note="G -> S (in HHT2; loss of receptor activity in FT response to BMP9; retained in the endoplasmic reticulum)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075238" FT VARIANT 215 FT /note="E -> K (in HHT2; dbSNP:rs754283265)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026789" FT VARIANT 217 FT /note="W -> G (in HHT2)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070319" FT VARIANT 219 FT /note="G -> D (in HHT2)" FT /evidence="ECO:0000269|PubMed:16752392" FT /id="VAR_070320" FT VARIANT 223 FT /note="G -> R (in HHT2)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026790" FT VARIANT 225 FT /note="S -> C (found in a patient with pulmonary arterial FT hypertension; unknown pathological significance)" FT /evidence="ECO:0000269|PubMed:24936649" FT /id="VAR_079586" FT VARIANT 226 FT /note="V -> E (in HHT2; dbSNP:rs1565593639)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070321" FT VARIANT 229 FT /note="K -> R (in HHT2)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026791" FT VARIANT 232 FT /note="Missing (in HHT2; mutant protein is capable of FT targeting the cell surface appropriately)" FT /evidence="ECO:0000269|PubMed:10767348, FT ECO:0000269|PubMed:14684682, ECO:0000269|PubMed:8640225" FT /id="VAR_006209" FT VARIANT 233 FT /note="S -> L (in HHT2; dbSNP:rs762773076)" FT /evidence="ECO:0000269|PubMed:16525724" FT /id="VAR_070322" FT VARIANT 233 FT /note="Missing (in HHT2)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026792" FT VARIANT 237 FT /note="Q -> K (in HHT2)" FT /evidence="ECO:0000269|PubMed:16752392" FT /id="VAR_070323" FT VARIANT 245 FT /note="I -> N (in dbSNP:rs1804508)" FT /id="VAR_011717" FT VARIANT 245 FT /note="I -> V (in HHT2; no loss of receptor activity in FT response to BMP9; mutant protein is capable of targeting FT the cell surface appropriately; affects splicing by FT inducing the creation of a new donor splice site and the FT loss of the 3' end of exon 6)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075239" FT VARIANT 254 FT /note="Missing (in HHT2; retained in the endoplasmic FT reticulum; dbSNP:rs387906393)" FT /evidence="ECO:0000269|PubMed:11484689, FT ECO:0000269|PubMed:14684682" FT /id="VAR_026793" FT VARIANT 260 FT /note="I -> L (in HHT2)" FT /evidence="ECO:0000269|PubMed:16752392" FT /id="VAR_070324" FT VARIANT 265 FT /note="T -> P (in HHT2; dbSNP:rs1592223978)" FT /evidence="ECO:0000269|PubMed:16525724" FT /id="VAR_070325" FT VARIANT 277 FT /note="T -> K (found in a patient with hereditary FT hemorrhagic talagiectasia; unknown pathological FT significance)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070326" FT VARIANT 280 FT /note="H -> R (in HHT2)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070327" FT VARIANT 285 FT /note="L -> F (in HHT2; dbSNP:rs1085307410)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026794" FT VARIANT 289 FT /note="L -> P (in HHT2)" FT /evidence="ECO:0000269|PubMed:16752392" FT /id="VAR_070328" FT VARIANT 294 FT /note="L -> R (in HHT2)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070329" FT VARIANT 306 FT /note="A -> P (in HHT2; loss of receptor activity in FT response to BMP9; retained in the endoplasmic reticulum; FT dbSNP:rs1940807179)" FT /evidence="ECO:0000269|PubMed:15024723, FT ECO:0000269|PubMed:26176610" FT /id="VAR_026795" FT VARIANT 313 FT /note="L -> V (in HHT2; loss of receptor activity in FT response to BMP9; predominantly retained in the endoplasmic FT reticulum)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075240" FT VARIANT 314 FT /note="H -> Y (in HHT2; loss of receptor activity in FT response to BMP9; retained in the endoplasmic reticulum; FT dbSNP:rs1565594311)" FT /evidence="ECO:0000269|PubMed:15024723, FT ECO:0000269|PubMed:26176610" FT /id="VAR_026796" FT VARIANT 328 FT /note="H -> Q (in HHT2; dbSNP:rs1565594410)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070330" FT VARIANT 333 FT /note="S -> I (in HHT2; retained in the endoplasmic FT reticulum; dbSNP:rs863223413)" FT /evidence="ECO:0000269|PubMed:10767348, FT ECO:0000269|PubMed:14684682, ECO:0000269|PubMed:9245985" FT /id="VAR_006210" FT VARIANT 335 FT /note="N -> H (in HHT2)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070331" FT VARIANT 337 FT /note="L -> P (in HHT2; dbSNP:rs1592224349)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026797" FT VARIANT 342 FT /note="L -> P (in dbSNP:rs762287966)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070332" FT VARIANT 344 FT /note="C -> R (in HHT2; dbSNP:rs1592224412)" FT /evidence="ECO:0000269|PubMed:16752392" FT /id="VAR_070333" FT VARIANT 344 FT /note="C -> Y (in HHT2; retained in the endoplasmic FT reticulum; dbSNP:rs28936688)" FT /evidence="ECO:0000269|PubMed:10767348, FT ECO:0000269|PubMed:14684682" FT /id="VAR_026798" FT VARIANT 347 FT /note="A -> D (in HHT2)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070334" FT VARIANT 347 FT /note="A -> P (in HHT2)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026799" FT VARIANT 374 FT /note="R -> Q (in HHT2; retained in the endoplasmic FT reticulum; dbSNP:rs1060503248)" FT /evidence="ECO:0000269|PubMed:14684682, FT ECO:0000269|PubMed:15024723" FT /id="VAR_026800" FT VARIANT 374 FT /note="R -> W (in HHT2; dbSNP:rs28936401)" FT /evidence="ECO:0000269|PubMed:11170071, FT ECO:0000269|PubMed:14684682, ECO:0000269|PubMed:15712270, FT ECO:0000269|PubMed:9245985" FT /id="VAR_006211" FT VARIANT 376 FT /note="M -> R (in HHT2; dbSNP:rs28936399)" FT /evidence="ECO:0000269|PubMed:8640225" FT /id="VAR_006212" FT VARIANT 376 FT /note="M -> V (in HHT2; dbSNP:rs1555153277)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026801" FT VARIANT 378 FT /note="P -> L (in HHT2; retained in the endoplasmic FT reticulum)" FT /evidence="ECO:0000269|PubMed:14684682" FT /id="VAR_026802" FT VARIANT 378 FT /note="P -> S (in HHT2; loss of receptor activity in FT response to BMP9; retained in the endoplasmic reticulum; FT dbSNP:rs959973779)" FT /evidence="ECO:0000269|PubMed:20414677, FT ECO:0000269|PubMed:26176610" FT /id="VAR_070335" FT VARIANT 379 FT /note="E -> D (in HHT2; loss of receptor activity in FT response to BMP9; retained in the endoplasmic reticulum)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075241" FT VARIANT 379 FT /note="E -> K (in HHT2; loss of receptor activity in FT response to BMP9; retained in the endoplasmic reticulum; FT dbSNP:rs1131691686)" FT /evidence="ECO:0000269|PubMed:15024723, FT ECO:0000269|PubMed:15712270, ECO:0000269|PubMed:26176610" FT /id="VAR_026803" FT VARIANT 396 FT /note="T -> A (found in patients with pulmonary arterial FT hypertension; unknown pathological significance)" FT /evidence="ECO:0000269|PubMed:24936649" FT /id="VAR_079587" FT VARIANT 397 FT /note="D -> G (in HHT2)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026804" FT VARIANT 398 FT /note="I -> N (in HHT2; dbSNP:rs121909286)" FT /evidence="ECO:0000269|PubMed:11170071" FT /id="VAR_026805" FT VARIANT 399 FT /note="W -> S (in HHT2; dbSNP:rs121909289)" FT /evidence="ECO:0000269|PubMed:14684682" FT /id="VAR_026806" FT VARIANT 400 FT /note="A -> T (found in a patient with hereditary FT hemorrhagic talagiectasia; unknown pathological FT significance)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070336" FT VARIANT 403 FT /note="L -> P (in HHT2)" FT /evidence="ECO:0000269|PubMed:16525724" FT /id="VAR_070337" FT VARIANT 404 FT /note="V -> G (in HHT2; loss of receptor activity in FT response to BMP9; predominantly retained in the endoplasmic FT reticulum)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075242" FT VARIANT 407 FT /note="E -> D (in HHT2; dbSNP:rs1565595129)" FT /evidence="ECO:0000269|PubMed:10767348, FT ECO:0000269|PubMed:15712270" FT /id="VAR_026807" FT VARIANT 411 FT /note="R -> P (in HHT2; dbSNP:rs121909284)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026808" FT VARIANT 411 FT /note="R -> Q (in HHT2; retained in the endoplasmic FT reticulum; dbSNP:rs121909284)" FT /evidence="ECO:0000269|PubMed:14684682, FT ECO:0000269|PubMed:15024723, ECO:0000269|PubMed:8640225" FT /id="VAR_006213" FT VARIANT 411 FT /note="R -> W (in HHT2; loss of receptor activity in FT response to BMP9; predominantly retained in the endoplasmic FT reticulum; dbSNP:rs121909287)" FT /evidence="ECO:0000269|PubMed:11484689, FT ECO:0000269|PubMed:15024723, ECO:0000269|PubMed:15712270, FT ECO:0000269|PubMed:26176610" FT /id="VAR_026809" FT VARIANT 416 FT /note="G -> S (in HHT2)" FT /evidence="ECO:0000269|PubMed:16525724" FT /id="VAR_070338" FT VARIANT 417 FT /note="I -> F (no loss of receptor activity in response to FT BMP9; mutant protein is capable of targeting the cell FT surface appropriately; dbSNP:rs141653630)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075243" FT VARIANT 424 FT /note="P -> R (in HHT2; dbSNP:rs1940906429)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070339" FT VARIANT 424 FT /note="P -> T (in HHT2; dbSNP:rs1085307419)" FT /evidence="ECO:0000269|PubMed:9245985" FT /id="VAR_006214" FT VARIANT 425 FT /note="F -> L (in HHT2)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026810" FT VARIANT 425 FT /note="F -> V (in HHT2)" FT /evidence="ECO:0000269|PubMed:15712270" FT /id="VAR_026811" FT VARIANT 425 FT /note="Missing (in HHT2)" FT /evidence="ECO:0000269|PubMed:15712270" FT /id="VAR_026812" FT VARIANT 426 FT /note="Y -> C (in HHT2)" FT /evidence="ECO:0000269|PubMed:16752392" FT /id="VAR_070340" FT VARIANT 433 FT /note="P -> R (in HHT2)" FT /evidence="ECO:0000269|PubMed:16752392" FT /id="VAR_070341" FT VARIANT 441 FT /note="V -> M (in HHT2; retained in the endoplasmic FT reticulum; dbSNP:rs1565596498)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075244" FT VARIANT 443 FT /note="C -> Y (in HHT2; retained in the endoplasmic FT reticulum)" FT /evidence="ECO:0000269|PubMed:26176610" FT /id="VAR_075245" FT VARIANT 449 FT /note="P -> S (in HHT2; dbSNP:rs1940908457)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070342" FT VARIANT 479 FT /note="R -> L (in HHT2)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026813" FT VARIANT 479 FT /note="R -> P (in HHT2; dbSNP:rs1085307426)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070343" FT VARIANT 482 FT /note="A -> V (in HHT2; dbSNP:rs139142865)" FT /evidence="ECO:0000269|PubMed:15024723" FT /id="VAR_026814" FT VARIANT 484 FT /note="R -> W (in HHT2; dbSNP:rs121909288)" FT /evidence="ECO:0000269|PubMed:11484689, FT ECO:0000269|PubMed:15024723" FT /id="VAR_026815" FT VARIANT 486 FT /note="K -> E (found in a patient with hereditary FT hemorrhagic talagiectasia; unknown pathological FT significance; dbSNP:rs113700354)" FT /evidence="ECO:0000269|PubMed:20414677" FT /id="VAR_070344" FT VARIANT 487 FT /note="K -> T (in HHT2; mutant protein is capable of FT targeting the cell surface appropriately; FT dbSNP:rs1085307428)" FT /evidence="ECO:0000269|PubMed:14684682" FT /id="VAR_026816" FT MUTAGEN 74..76 FT /note="REL->DFQ: Affinity for BMP9 decreased by 200-fold." FT /evidence="ECO:0000269|PubMed:22799562" FT CONFLICT 172 FT /note="S -> T (in Ref. 1; CAA80255)" FT /evidence="ECO:0000305" FT HELIX 26..28 FT /evidence="ECO:0007829|PDB:2LCR" FT STRAND 32..35 FT /evidence="ECO:0007829|PDB:6SF3" FT STRAND 42..56 FT /evidence="ECO:0007829|PDB:6SF3" FT STRAND 59..61 FT /evidence="ECO:0007829|PDB:6SF1" FT STRAND 64..72 FT /evidence="ECO:0007829|PDB:6SF3" FT HELIX 74..78 FT /evidence="ECO:0007829|PDB:6SF3" FT STRAND 83..90 FT /evidence="ECO:0007829|PDB:6SF3" FT TURN 93..96 FT /evidence="ECO:0007829|PDB:6SF3" FT HELIX 198..201 FT /evidence="ECO:0007829|PDB:3MY0" FT STRAND 203..211 FT /evidence="ECO:0007829|PDB:3MY0" FT STRAND 214..221 FT /evidence="ECO:0007829|PDB:3MY0" FT STRAND 224..231 FT /evidence="ECO:0007829|PDB:3MY0" FT HELIX 233..235 FT /evidence="ECO:0007829|PDB:3MY0" FT HELIX 236..248 FT /evidence="ECO:0007829|PDB:3MY0" FT STRAND 259..265 FT /evidence="ECO:0007829|PDB:3MY0" FT STRAND 267..269 FT /evidence="ECO:0007829|PDB:3MY0" FT STRAND 272..278 FT /evidence="ECO:0007829|PDB:3MY0" FT HELIX 285..291 FT /evidence="ECO:0007829|PDB:3MY0" FT HELIX 296..314 FT /evidence="ECO:0007829|PDB:3MY0" FT STRAND 325..327 FT /evidence="ECO:0007829|PDB:3MY0" FT STRAND 335..338 FT /evidence="ECO:0007829|PDB:3MY0" FT STRAND 344..346 FT /evidence="ECO:0007829|PDB:3MY0" FT STRAND 353..355 FT /evidence="ECO:0007829|PDB:3MY0" FT STRAND 357..359 FT /evidence="ECO:0007829|PDB:3MY0" FT HELIX 373..375 FT /evidence="ECO:0007829|PDB:3MY0" FT HELIX 378..381 FT /evidence="ECO:0007829|PDB:3MY0" FT HELIX 390..410 FT /evidence="ECO:0007829|PDB:3MY0" FT TURN 424..428 FT /evidence="ECO:0007829|PDB:3MY0" FT HELIX 435..442 FT /evidence="ECO:0007829|PDB:3MY0" FT STRAND 455..459 FT /evidence="ECO:0007829|PDB:3MY0" FT TURN 460..462 FT /evidence="ECO:0007829|PDB:3MY0" FT HELIX 463..469 FT /evidence="ECO:0007829|PDB:3MY0" FT HELIX 476..478 FT /evidence="ECO:0007829|PDB:3MY0" FT HELIX 482..491 FT /evidence="ECO:0007829|PDB:3MY0" SQ SEQUENCE 503 AA; 56124 MW; 074522AA802325DD CRC64; MTLGSPRKGL LMLLMALVTQ GDPVKPSRGP LVTCTCESPH CKGPTCRGAW CTVVLVREEG RHPQEHRGCG NLHRELCRGR PTEFVNHYCC DSHLCNHNVS LVLEATQPPS EQPGTDGQLA LILGPVLALL ALVALGVLGL WHVRRRQEKQ RGLHSELGES SLILKASEQG DSMLGDLLDS DCTTGSGSGL PFLVQRTVAR QVALVECVGK GRYGEVWRGL WHGESVAVKI FSSRDEQSWF RETEIYNTVL LRHDNILGFI ASDMTSRNSS TQLWLITHYH EHGSLYDFLQ RQTLEPHLAL RLAVSAACGL AHLHVEIFGT QGKPAIAHRD FKSRNVLVKS NLQCCIADLG LAVMHSQGSD YLDIGNNPRV GTKRYMAPEV LDEQIRTDCF ESYKWTDIWA FGLVLWEIAR RTIVNGIVED YRPPFYDVVP NDPSFEDMKK VVCVDQQTPT IPNRLAADPV LSGLAQMMRE CWYPNPSARL TALRIKKTLQ KISNSPEKPK VIQ //