ACVL1_HUMAN
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-AUG-2022, entry version 228.
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 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 [8]
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 [9]
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 [10]
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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 -!- 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 PDBsum; 2LCR; -.
DR PDBsum; 3MY0; -.
DR PDBsum; 4FAO; -.
DR PDBsum; 6SF1; -.
DR PDBsum; 6SF2; -.
DR PDBsum; 6SF3; -.
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 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 PRIDE; P37023; -.
DR ProteomicsDB; 55254; -.
DR ABCD; P37023; 1 sequenced antibody.
DR Antibodypedia; 2055; 614 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 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; CQGTWCT; -.
DR OrthoDB; 776697at2759; -.
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; 20 hits in 1108 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:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
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: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: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:0045893; P:positive regulation of transcription, DNA-templated; IDA:HGNC-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:0001936; P:regulation of endothelial cell proliferation; TAS:DFLAT.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:HGNC-UCL.
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 Gene3D; 2.10.60.10; -; 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; PTHR23255; 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; SSF56112; 1.
DR SUPFAM; SSF57302; SSF57302; 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 /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)"
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)"
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
