EGLN_HUMAN
ID EGLN_HUMAN Reviewed; 658 AA.
AC P17813; Q14248; Q14926; Q5T9C0;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Endoglin;
DE AltName: CD_antigen=CD105;
DE Flags: Precursor;
GN Name=ENG; Synonyms=END;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), FUNCTION, SUBCELLULAR LOCATION,
RP SUBUNIT, AND ALTERNATIVE SPLICING.
RX PubMed=8370410; DOI=10.1002/eji.1830230943;
RA Bellon T., Corbi A., Lastres P., Cales C., Cebrian M., Vera S.,
RA Cheifetz S., Massague J., Letarte M., Bernabeu C.;
RT "Identification and expression of two forms of the human transforming
RT growth factor-beta-binding protein endoglin with distinct cytoplasmic
RT regions.";
RL Eur. J. Immunol. 23:2340-2345(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 14-658, PROTEIN SEQUENCE OF
RP 26-36 (ISOFORM LONG), SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Umbilical vein;
RX PubMed=1692830; DOI=10.1016/s0021-9258(19)38892-1;
RA Gougos A., Letarte M.;
RT "Primary structure of endoglin, an RGD-containing glycoprotein of human
RT endothelial cells.";
RL J. Biol. Chem. 265:8361-8364(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 122-378, FUNCTION, AND INVOLVEMENT IN
RP HHT1.
RX PubMed=7894484; DOI=10.1038/ng1294-345;
RA McAllister K.A., Grogg K.M., Johnson D.W., Gallione C.J., Baldwin M.A.,
RA Jackson C.E., Helmbold E.A., Markel D.S., McKinnon W.C., Murrell J.,
RA McCormick M.K., Pericak-Vance M.A., Heutink P., Oostra B.A., Haitjema T.,
RA Westerman C.J., Porteous M.E., Guttmacher A.E., Letarte M., Marchuk D.A.;
RT "Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for
RT hereditary haemorrhagic telangiectasia type 1.";
RL Nat. Genet. 8:345-351(1994).
RN [6]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=1326540; DOI=10.1016/s0021-9258(18)41732-2;
RA Cheifetz S., Bellon T., Cales C., Vera S., Bernabeu C., Massague J.,
RA Letarte M.;
RT "Endoglin is a component of the transforming growth factor-beta receptor
RT system in human endothelial cells.";
RL J. Biol. Chem. 267:19027-19030(1992).
RN [7]
RP INTERACTION WITH DYNLT4.
RX PubMed=16982625; DOI=10.1074/jbc.m608614200;
RA Meng Q.-J., Lux A., Holloschi A., Li J., Hughes J.M.X., Foerg T.,
RA McCarthy J.E.G., Heagerty A.M., Kioschis P., Hafner M., Garland J.M.;
RT "Identification of Tctex2beta, a novel dynein light chain family member
RT that interacts with different transforming growth factor-beta receptors.";
RL J. Biol. Chem. 281:37069-37080(2006).
RN [8]
RP INTERACTION WITH ARRB2, SUBCELLULAR LOCATION, FUNCTION, AND MUTAGENESIS OF
RP THR-650.
RX PubMed=17540773; DOI=10.1074/jbc.m700176200;
RA Lee N.Y., Blobe G.C.;
RT "The interaction of endoglin with beta-arrestin2 regulates transforming
RT growth factor-beta-mediated ERK activation and migration in endothelial
RT cells.";
RL J. Biol. Chem. 282:21507-21517(2007).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-134.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [10]
RP FUNCTION, AND INTERACTION WITH GDF2 AND BMP10.
RX PubMed=21737454; DOI=10.1074/jbc.m111.260133;
RA Castonguay R., Werner E.D., Matthews R.G., Presman E., Mulivor A.W.,
RA Solban N., Sako D., Pearsall R.S., Underwood K.W., Seehra J., Kumar R.,
RA Grinberg A.V.;
RT "Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10
RT via its orphan domain, inhibits blood vessel formation, and suppresses
RT tumor growth.";
RL J. Biol. Chem. 286:30034-30046(2011).
RN [11]
RP INTERACTION WITH GDF2 AND ACVRL1, AND SUBUNIT.
RX PubMed=22347366; DOI=10.1371/journal.pone.0029948;
RA Alt A., Miguel-Romero L., Donderis J., Aristorena M., Blanco F.J.,
RA Round A., Rubio V., Bernabeu C., Marina A.;
RT "Structural and functional insights into endoglin ligand recognition and
RT binding.";
RL PLoS ONE 7:E29948-E29948(2012).
RN [12]
RP FUNCTION.
RX PubMed=23300529; DOI=10.1371/journal.pone.0050920;
RA Nolan-Stevaux O., Zhong W., Culp S., Shaffer K., Hoover J.,
RA Wickramasinghe D., Ruefli-Brasse A.;
RT "Endoglin requirement for BMP9 signaling in endothelial cells reveals new
RT mechanism of action for selective anti-endoglin antibodies.";
RL PLoS ONE 7:E50920-E50920(2012).
RN [13] {ECO:0007744|PDB:5HZV, ECO:0007744|PDB:5HZW, ECO:0007744|PDB:5I04}
RP X-RAY CRYSTALLOGRAPHY (2.42 ANGSTROMS) OF 26-337, X-RAY CRYSTALLOGRAPHY
RP (2.70 ANGSTROMS) OF 338-581, X-RAY CRYSTALLOGRAPHY (4.45 ANGSTROMS) OF
RP 26-337 IN COMPLEX WITH GDF2, INTERACTION WITH GDF2 AND ACVRL1, SUBUNIT,
RP DOMAIN, DISULFIDE BONDS, AND MUTAGENESIS OF ASP-246; 270-GLN-ILE-271;
RP TYR-277; SER-278; PHE-282; PHE-290; CYS-350; CYS-382 AND CYS-516.
RX PubMed=28564608; DOI=10.1016/j.celrep.2017.05.011;
RA Saito T., Bokhove M., Croci R., Zamora-Caballero S., Han L., Letarte M.,
RA de Sanctis D., Jovine L.;
RT "Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP
RT Signaling and HHT1.";
RL Cell Rep. 19:1917-1928(2017).
RN [14]
RP VARIANT HHT1 192-ARG--PRO-198 DEL, AND VARIANT MET-5.
RX PubMed=9245986; DOI=10.1086/513906;
RA Shovlin C.L., Hughes J.M.B., Scott J., Seidman C.E., Seidman J.G.;
RT "Characterization of endoglin and identification of novel mutations in
RT hereditary hemorrhagic telangiectasia.";
RL Am. J. Hum. Genet. 61:68-79(1997).
RN [15]
RP VARIANT HHT1 ASP-160.
RX PubMed=9157574;
RA Yamaguchi H., Azuma H., Shigekiyo T., Inoue H., Saito S.;
RT "A novel missense mutation in the endoglin gene in hereditary hemorrhagic
RT telangiectasia.";
RL Thromb. Haemost. 77:243-247(1997).
RN [16]
RP VARIANTS HHT1 VAL-52; ARG-53; CYS-149 AND PRO-306.
RX PubMed=9554745;
RX DOI=10.1002/(sici)1098-1004(1998)11:4<286::aid-humu6>3.0.co;2-b;
RA Gallione C.J., Klaus D.J., Yeh E.Y., Stenzel T.T., Xue Y., Anthony K.B.,
RA McAllister K.A., Baldwin M.A., Berg J.N., Lux A., Smith J.D., Vary C.P.H.,
RA Craigen W.J., Westermann C.J.J., Warner M.L., Miller Y.E., Jackson C.E.,
RA Guttmacher A.E., Marchuk D.A.;
RT "Mutation and expression analysis of the endoglin gene in hereditary
RT hemorrhagic telangiectasia reveals null alleles.";
RL Hum. Mutat. 11:286-294(1998).
RN [17]
RP VARIANTS HHT1 VAL-52; ARG-53; CYS-149 AND PRO-221, SUBCELLULAR LOCATION,
RP AND CHARACTERIZATION OF VARIANTS HHT1 VAL-52; ARG-53; CYS-149 AND PRO-221.
RX PubMed=10545596; DOI=10.1093/hmg/8.12.2171;
RA Pece-Barbara N., Cymerman U., Vera S., Marchuk D.A., Letarte M.;
RT "Expression analysis of four endoglin missense mutations suggests that
RT haploinsufficiency is the predominant mechanism for hereditary hemorrhagic
RT telangiectasia type 1.";
RL Hum. Mol. Genet. 8:2171-2181(1999).
RN [18]
RP VARIANT HHT1 VAL-413.
RX PubMed=10982033; DOI=10.1007/s004390000326;
RA Gallione C.J., Scheessele E.A., Reinhardt D., Duits A.J., Berg J.N.,
RA Westermann C.J.J., Marchuk D.A.;
RT "Two common endoglin mutations in families with hereditary hemorrhagic
RT telangiectasia in the Netherlands Antilles: evidence for a founder
RT effect.";
RL Hum. Genet. 107:40-44(2000).
RN [19]
RP VARIANT HHT1 ARG-53, AND TISSUE SPECIFICITY.
RX PubMed=10625079; DOI=10.1203/00006450-200001000-00008;
RA Cymerman U., Vera S., Pece-Barbara N., Bourdeau A., White R.I. Jr.,
RA Dunn J., Letarte M.;
RT "Identification of hereditary hemorrhagic telangiectasia type 1 in newborns
RT by protein expression and mutation analysis of endoglin.";
RL Pediatr. Res. 47:24-35(2000).
RN [20]
RP VARIANTS HHT1 PRO-8; PHE-49; ARG-107; CYS-207 DEL; THR-263; ARG-232-233-THR
RP DEL; ILE-263 DEL; SER-412 AND MET-504.
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 [21]
RP VARIANTS HHT1 PRO-221 AND ILE-263 DEL, AND VARIANT LEU-615.
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 [22]
RP VARIANTS HHT1 ASP-11; ASP-105; GLU-175; THR-220; ASP-308; SER-363; TRP-437;
RP SER-490; HIS-529; PRO-547 AND ASP-604.
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 [23]
RP VARIANTS HHT1 193-THR-LEU-194 DELINS VAL-LEU-GLN AND ASP-545.
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 [24]
RP VARIANTS PRO-150; PRO-205; MET-236; MET-315; GLU-374; ARG-414; SER-545;
RP TYR-549 AND ALA-561, AND VARIANTS HHT1 GLN-221; GLU-238; SER-263; ARG-269;
RP TYR-394; PRO-529 AND ARG-603.
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).
CC -!- FUNCTION: Vascular endothelium glycoprotein that plays an important
CC role in the regulation of angiogenesis (PubMed:21737454,
CC PubMed:23300529). Required for normal structure and integrity of adult
CC vasculature (PubMed:7894484). Regulates the migration of vascular
CC endothelial cells (PubMed:17540773). Required for normal extraembryonic
CC angiogenesis and for embryonic heart development (By similarity). May
CC regulate endothelial cell shape changes in response to blood flow,
CC which drive vascular remodeling and establishment of normal vascular
CC morphology during angiogenesis (By similarity). May play a critical
CC role in the binding of endothelial cells to integrins and/or other RGD
CC receptors (PubMed:1692830). Acts as TGF-beta coreceptor and is involved
CC in the TGF-beta/BMP signaling cascade that ultimately leads to the
CC activation of SMAD transcription factors (PubMed:8370410,
CC PubMed:21737454, PubMed:22347366, PubMed:23300529). Required for
CC GDF2/BMP9 signaling through SMAD1 in endothelial cells and modulates
CC TGFB1 signaling through SMAD3 (PubMed:21737454, PubMed:22347366,
CC PubMed:23300529). {ECO:0000250|UniProtKB:Q63961,
CC ECO:0000269|PubMed:17540773, ECO:0000269|PubMed:21737454,
CC ECO:0000269|PubMed:23300529, ECO:0000269|PubMed:7894484,
CC ECO:0000269|PubMed:8370410, ECO:0000305|PubMed:1692830}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:8370410, PubMed:1326540,
CC PubMed:21737454, PubMed:22347366, PubMed:28564608). Forms a heteromeric
CC complex with the signaling receptors for transforming growth factor-
CC beta: TGFBR1 and/or TGFBR2 (PubMed:1326540). It is able to bind TGFB1
CC and TGFB2 with high affinity, but not TGFB3 (PubMed:8370410,
CC PubMed:1326540). Interacts with GDF2, forming a heterotetramer with a
CC 2:2 stoichiometry (PubMed:21737454, PubMed:22347366, PubMed:28564608).
CC Interacts with ACVRL1 (PubMed:22347366, PubMed:28564608). Can form a
CC heteromeric complex with GDF2 and ACVRL1 (PubMed:28564608). Interacts
CC with BMP10 (PubMed:21737454). Interacts with DYNLT4 (PubMed:16982625).
CC Interacts with ARRB2 (PubMed:17540773). {ECO:0000269|PubMed:1326540,
CC ECO:0000269|PubMed:16982625, ECO:0000269|PubMed:17540773,
CC ECO:0000269|PubMed:21737454, ECO:0000269|PubMed:22347366,
CC ECO:0000269|PubMed:28564608, ECO:0000269|PubMed:8370410}.
CC -!- INTERACTION:
CC P17813; P17813: ENG; NbExp=2; IntAct=EBI-2834630, EBI-2834630;
CC P17813; PRO_0000033903 [Q9UK05]: GDF2; NbExp=10; IntAct=EBI-2834630, EBI-16227344;
CC P17813; P08648: ITGA5; NbExp=4; IntAct=EBI-2834630, EBI-1382311;
CC P17813; P05556: ITGB1; NbExp=3; IntAct=EBI-2834630, EBI-703066;
CC P17813; P17931: LGALS3; NbExp=5; IntAct=EBI-2834630, EBI-1170392;
CC P17813; P01137: TGFB1; NbExp=2; IntAct=EBI-2834630, EBI-779636;
CC P17813; P19474: TRIM21; NbExp=6; IntAct=EBI-2834630, EBI-81290;
CC P17813-1; P02750: LRG1; NbExp=4; IntAct=EBI-16065304, EBI-9083443;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10545596,
CC ECO:0000269|PubMed:1326540, ECO:0000269|PubMed:1692830,
CC ECO:0000269|PubMed:17540773, ECO:0000269|PubMed:8370410}; Single-pass
CC type I membrane protein {ECO:0000305|PubMed:1692830,
CC ECO:0000305|PubMed:8370410}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P17813-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P17813-2; Sequence=VSP_004233;
CC -!- TISSUE SPECIFICITY: Detected on umbilical veil endothelial cells
CC (PubMed:10625079). Detected in placenta (at protein level)
CC (PubMed:1692830). Detected on endothelial cells (PubMed:1692830).
CC {ECO:0000269|PubMed:10625079, ECO:0000269|PubMed:1692830}.
CC -!- DOMAIN: The ZP domain mediates dimerization.
CC {ECO:0000269|PubMed:28564608}.
CC -!- DOMAIN: The N-terminal OR region is composed of two intertwined domains
CC (OR1 and OR2) with a common, novel fold. Each contains 12 beta-strands
CC that form a parallel beta-helix-like structure, plus a single alpha-
CC helix. The OR1 region mediates interaction with GDF2.
CC {ECO:0000269|PubMed:28564608}.
CC -!- DISEASE: Telangiectasia, hereditary hemorrhagic, 1 (HHT1) [MIM:187300]:
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:10545596, ECO:0000269|PubMed:10625079,
CC ECO:0000269|PubMed:10982033, 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:7894484, ECO:0000269|PubMed:9157574,
CC ECO:0000269|PubMed:9245986, ECO:0000269|PubMed:9554745}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ENGID40452ch9q34.html";
CC -!- WEB RESOURCE: Name=Hereditary Hemorrhagic Telangiectasia and ENG;
CC URL="http://arup.utah.edu/database/ENG/ENG_welcome.php";
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DR EMBL; X72012; CAA50891.1; -; mRNA.
DR EMBL; AL157935; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL162586; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW87702.1; -; Genomic_DNA.
DR EMBL; J05481; AAA35800.1; -; mRNA.
DR EMBL; U37439; AAC63386.1; -; Genomic_DNA.
DR EMBL; AF036969; AAC63386.1; JOINED; Genomic_DNA.
DR EMBL; U37447; AAC63386.1; JOINED; Genomic_DNA.
DR EMBL; AF036970; AAC63386.1; JOINED; Genomic_DNA.
DR EMBL; U37446; AAC63386.1; JOINED; Genomic_DNA.
DR EMBL; U37445; AAC63386.1; JOINED; Genomic_DNA.
DR EMBL; AF036971; AAC63386.1; JOINED; Genomic_DNA.
DR EMBL; U37442; AAC63386.1; JOINED; Genomic_DNA.
DR EMBL; U37441; AAC63386.1; JOINED; Genomic_DNA.
DR CCDS; CCDS48029.1; -. [P17813-1]
DR CCDS; CCDS6880.1; -. [P17813-2]
DR PIR; S50831; S50831.
DR RefSeq; NP_000109.1; NM_000118.3. [P17813-2]
DR RefSeq; NP_001108225.1; NM_001114753.2. [P17813-1]
DR RefSeq; NP_001265067.1; NM_001278138.1.
DR PDB; 5HZV; X-ray; 2.70 A; A=338-581.
DR PDB; 5HZW; X-ray; 4.45 A; A=26-337.
DR PDB; 5I04; X-ray; 2.42 A; A=26-337.
DR PDBsum; 5HZV; -.
DR PDBsum; 5HZW; -.
DR PDBsum; 5I04; -.
DR AlphaFoldDB; P17813; -.
DR SASBDB; P17813; -.
DR SMR; P17813; -.
DR BioGRID; 108337; 203.
DR CORUM; P17813; -.
DR DIP; DIP-6246N; -.
DR IntAct; P17813; 225.
DR MINT; P17813; -.
DR STRING; 9606.ENSP00000362299; -.
DR ChEMBL; CHEMBL3712885; -.
DR DrugBank; DB06322; Carotuximab.
DR GuidetoPHARMACOLOGY; 2895; -.
DR GlyGen; P17813; 9 sites, 2 O-linked glycans (4 sites).
DR iPTMnet; P17813; -.
DR PhosphoSitePlus; P17813; -.
DR SwissPalm; P17813; -.
DR BioMuta; ENG; -.
DR DMDM; 3041681; -.
DR EPD; P17813; -.
DR jPOST; P17813; -.
DR MassIVE; P17813; -.
DR MaxQB; P17813; -.
DR PaxDb; P17813; -.
DR PeptideAtlas; P17813; -.
DR PRIDE; P17813; -.
DR ProteomicsDB; 53517; -. [P17813-1]
DR ProteomicsDB; 53518; -. [P17813-2]
DR ABCD; P17813; 1 sequenced antibody.
DR Antibodypedia; 2321; 2452 antibodies from 53 providers.
DR DNASU; 2022; -.
DR Ensembl; ENST00000344849.4; ENSP00000341917.3; ENSG00000106991.14. [P17813-2]
DR Ensembl; ENST00000373203.9; ENSP00000362299.4; ENSG00000106991.14. [P17813-1]
DR GeneID; 2022; -.
DR KEGG; hsa:2022; -.
DR MANE-Select; ENST00000373203.9; ENSP00000362299.4; NM_001114753.3; NP_001108225.1.
DR UCSC; uc004bsj.6; human. [P17813-1]
DR CTD; 2022; -.
DR DisGeNET; 2022; -.
DR GeneCards; ENG; -.
DR GeneReviews; ENG; -.
DR HGNC; HGNC:3349; ENG.
DR HPA; ENSG00000106991; Tissue enhanced (heart).
DR MalaCards; ENG; -.
DR MIM; 131195; gene.
DR MIM; 187300; phenotype.
DR neXtProt; NX_P17813; -.
DR OpenTargets; ENSG00000106991; -.
DR Orphanet; 231160; Familial cerebral saccular aneurysm.
DR Orphanet; 329971; Generalized juvenile polyposis/juvenile polyposis coli.
DR Orphanet; 774; Hereditary hemorrhagic telangiectasia.
DR Orphanet; 275777; Heritable pulmonary arterial hypertension.
DR PharmGKB; PA27785; -.
DR VEuPathDB; HostDB:ENSG00000106991; -.
DR eggNOG; ENOG502RZQ9; Eukaryota.
DR GeneTree; ENSGT00530000063861; -.
DR InParanoid; P17813; -.
DR OMA; YIYLHTR; -.
DR OrthoDB; 122304at2759; -.
DR PhylomeDB; P17813; -.
DR TreeFam; TF337375; -.
DR PathwayCommons; P17813; -.
DR SignaLink; P17813; -.
DR SIGNOR; P17813; -.
DR BioGRID-ORCS; 2022; 12 hits in 1077 CRISPR screens.
DR ChiTaRS; ENG; human.
DR GeneWiki; Endoglin; -.
DR GenomeRNAi; 2022; -.
DR Pharos; P17813; Tbio.
DR PRO; PR:P17813; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P17813; protein.
DR Bgee; ENSG00000106991; Expressed in right lung and 185 other tissues.
DR ExpressionAtlas; P17813; baseline and differential.
DR Genevisible; P17813; HS.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0072563; C:endothelial microparticle; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0043235; C:receptor complex; IPI:BHF-UCL.
DR GO; GO:0048185; F:activin binding; TAS:BHF-UCL.
DR GO; GO:0015026; F:coreceptor activity; IDA:BHF-UCL.
DR GO; GO:0005534; F:galactose binding; IDA:BHF-UCL.
DR GO; GO:0005539; F:glycosaminoglycan binding; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0050431; F:transforming growth factor beta binding; IPI:BHF-UCL.
DR GO; GO:0005024; F:transforming growth factor beta receptor activity; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; NAS:BHF-UCL.
DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; IPI:BHF-UCL.
DR GO; GO:0005114; F:type II transforming growth factor beta receptor binding; IPI:BHF-UCL.
DR GO; GO:0048844; P:artery morphogenesis; ISS:BHF-UCL.
DR GO; GO:0055009; P:atrial cardiac muscle tissue morphogenesis; ISS:BHF-UCL.
DR GO; GO:1905222; P:atrioventricular canal morphogenesis; ISS:BHF-UCL.
DR GO; GO:0030509; P:BMP signaling pathway; TAS:BHF-UCL.
DR GO; GO:0060348; P:bone development; IEA:Ensembl.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003209; P:cardiac atrium morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003208; P:cardiac ventricle morphogenesis; ISS:BHF-UCL.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0060326; P:cell chemotaxis; IMP:BHF-UCL.
DR GO; GO:0016477; P:cell migration; IMP:BHF-UCL.
DR GO; GO:0003273; P:cell migration involved in endocardial cushion formation; IEA:Ensembl.
DR GO; GO:0048870; P:cell motility; IMP:BHF-UCL.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0022009; P:central nervous system vasculogenesis; IMP:BHF-UCL.
DR GO; GO:0070483; P:detection of hypoxia; IDA:BHF-UCL.
DR GO; GO:0035912; P:dorsal aorta morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; IBA:GO_Central.
DR GO; GO:0003198; P:epithelial to mesenchymal transition involved in endocardial cushion formation; ISS:BHF-UCL.
DR GO; GO:0070278; P:extracellular matrix constituent secretion; IEA:Ensembl.
DR GO; GO:0022617; P:extracellular matrix disassembly; IMP:BHF-UCL.
DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
DR GO; GO:0030336; P:negative regulation of cell migration; IDA:BHF-UCL.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:BHF-UCL.
DR GO; GO:0051001; P:negative regulation of nitric-oxide synthase activity; IMP:BHF-UCL.
DR GO; GO:0060394; P:negative regulation of pathway-restricted SMAD protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:BHF-UCL.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; 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:0032967; P:positive regulation of collagen biosynthetic process; IEA:Ensembl.
DR GO; GO:1905007; P:positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; ISS:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IGI:BHF-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:1905065; P:positive regulation of vascular associated smooth muscle cell differentiation; ISS:BHF-UCL.
DR GO; GO:0030155; P:regulation of cell adhesion; TAS:BHF-UCL.
DR GO; GO:0042127; P:regulation of cell population proliferation; TAS:BHF-UCL.
DR GO; GO:0042325; P:regulation of phosphorylation; TAS:BHF-UCL.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:HGNC-UCL.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IDA:HGNC-UCL.
DR GO; GO:0031960; P:response to corticosteroid; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IDA:BHF-UCL.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0048745; P:smooth muscle tissue development; ISS:BHF-UCL.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0097084; P:vascular associated smooth muscle cell development; ISS:BHF-UCL.
DR GO; GO:0001570; P:vasculogenesis; IMP:BHF-UCL.
DR GO; GO:0048845; P:venous blood vessel morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; ISS:BHF-UCL.
DR GO; GO:0042060; P:wound healing; IMP:BHF-UCL.
DR InterPro; IPR001507; ZP_dom.
DR Pfam; PF00100; Zona_pellucida; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Angiogenesis; Cell adhesion;
KW Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond;
KW Glycoprotein; Membrane; Phosphoprotein; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:1692830"
FT CHAIN 26..658
FT /note="Endoglin"
FT /id="PRO_0000021156"
FT TOPO_DOM 26..586
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 587..611
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 612..658
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 363..533
FT /note="ZP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00375,
FT ECO:0000305|PubMed:28564608"
FT REGION 26..337
FT /note="Required for interaction with GDF2"
FT /evidence="ECO:0000269|PubMed:21737454,
FT ECO:0000269|PubMed:22347366, ECO:0000269|PubMed:28564608"
FT REGION 26..46
FT /note="OR1, N-terminal part"
FT /evidence="ECO:0000269|PubMed:28564608"
FT REGION 47..199
FT /note="OR2"
FT /evidence="ECO:0000269|PubMed:28564608"
FT REGION 200..330
FT /note="OR1, C-terminal part"
FT /evidence="ECO:0000269|PubMed:28564608"
FT REGION 270..282
FT /note="Essential for interaction with GDF2"
FT /evidence="ECO:0000269|PubMed:28564608"
FT REGION 626..658
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 399..401
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT COMPBIAS 632..658
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 646
FT /note="Phosphoserine; by TGFBR1"
FT /evidence="ECO:0000250|UniProtKB:Q63961"
FT MOD_RES 649
FT /note="Phosphoserine; by TGFBR1"
FT /evidence="ECO:0000250|UniProtKB:Q63961"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 307
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 30..207
FT /evidence="ECO:0000269|PubMed:28564608,
FT ECO:0007744|PDB:5HZW, ECO:0007744|PDB:5I04"
FT DISULFID 53..182
FT /evidence="ECO:0000269|PubMed:28564608,
FT ECO:0007744|PDB:5HZW, ECO:0007744|PDB:5I04"
FT DISULFID 242..330
FT /evidence="ECO:0000269|PubMed:28564608,
FT ECO:0007744|PDB:5HZW"
FT DISULFID 350..382
FT /evidence="ECO:0000269|PubMed:28564608,
FT ECO:0007744|PDB:5HZV"
FT DISULFID 363..442
FT /evidence="ECO:0000269|PubMed:28564608,
FT ECO:0007744|PDB:5HZV"
FT DISULFID 394..412
FT /evidence="ECO:0000269|PubMed:28564608,
FT ECO:0007744|PDB:5HZV"
FT DISULFID 493..549
FT /evidence="ECO:0000269|PubMed:28564608,
FT ECO:0007744|PDB:5HZV"
FT DISULFID 516
FT /note="Interchain"
FT /evidence="ECO:0000305|PubMed:28564608"
FT VAR_SEQ 619..658
FT /note="SPSKREPVVAVAAPASSESSSTNHSIGSTQSTPCSTSSMA -> EYPRPPQ
FT (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:8370410"
FT /id="VSP_004233"
FT VARIANT 5
FT /note="T -> M (in dbSNP:rs35400405)"
FT /evidence="ECO:0000269|PubMed:9245986"
FT /id="VAR_005192"
FT VARIANT 8
FT /note="L -> P (in HHT1; dbSNP:rs1564466414)"
FT /evidence="ECO:0000269|PubMed:15024723"
FT /id="VAR_026774"
FT VARIANT 11
FT /note="A -> D (in HHT1)"
FT /evidence="ECO:0000269|PubMed:16752392"
FT /id="VAR_070279"
FT VARIANT 49
FT /note="V -> F (in HHT1; dbSNP:rs1252348200)"
FT /evidence="ECO:0000269|PubMed:15024723"
FT /id="VAR_026775"
FT VARIANT 52
FT /note="G -> V (in HHT1; impairs protein folding; abolishes
FT expression at the cell surface)"
FT /evidence="ECO:0000269|PubMed:10545596,
FT ECO:0000269|PubMed:9554745"
FT /id="VAR_005193"
FT VARIANT 53
FT /note="C -> R (in HHT1; impairs protein folding; abolishes
FT expression at the cell surface)"
FT /evidence="ECO:0000269|PubMed:10545596,
FT ECO:0000269|PubMed:10625079, ECO:0000269|PubMed:9554745"
FT /id="VAR_005194"
FT VARIANT 105
FT /note="V -> D (in HHT1; dbSNP:rs1588585880)"
FT /evidence="ECO:0000269|PubMed:16752392"
FT /id="VAR_070280"
FT VARIANT 107
FT /note="L -> R (in HHT1)"
FT /evidence="ECO:0000269|PubMed:15024723"
FT /id="VAR_026776"
FT VARIANT 149
FT /note="W -> C (in HHT1; impairs protein folding; nearly
FT abolishes expression at the cell surface;
FT dbSNP:rs878853657)"
FT /evidence="ECO:0000269|PubMed:10545596,
FT ECO:0000269|PubMed:9554745"
FT /id="VAR_005195"
FT VARIANT 150
FT /note="A -> P (found in a family with hereditary
FT hemorrhagic talagiectasia; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070281"
FT VARIANT 160
FT /note="A -> D (in HHT1)"
FT /evidence="ECO:0000269|PubMed:9157574"
FT /id="VAR_009120"
FT VARIANT 175
FT /note="A -> E (in HHT1)"
FT /evidence="ECO:0000269|PubMed:16752392"
FT /id="VAR_070282"
FT VARIANT 192..198
FT /note="Missing (in HHT1)"
FT /evidence="ECO:0000269|PubMed:9245986"
FT /id="VAR_005196"
FT VARIANT 193..194
FT /note="TL -> VLQ (in HHT1)"
FT /evidence="ECO:0000269|PubMed:16525724"
FT /id="VAR_070283"
FT VARIANT 205
FT /note="R -> P"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070284"
FT VARIANT 207
FT /note="Missing (in HHT1)"
FT /evidence="ECO:0000269|PubMed:15024723"
FT /id="VAR_026777"
FT VARIANT 220
FT /note="I -> T (in HHT1; dbSNP:rs1588582695)"
FT /evidence="ECO:0000269|PubMed:16752392"
FT /id="VAR_070285"
FT VARIANT 221
FT /note="L -> P (in HHT1; impairs protein folding; strongly
FT reduces expression at the cell surface;
FT dbSNP:rs1554810378)"
FT /evidence="ECO:0000269|PubMed:10545596,
FT ECO:0000269|PubMed:15712270"
FT /id="VAR_009121"
FT VARIANT 221
FT /note="L -> Q (in HHT1)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070286"
FT VARIANT 232..233
FT /note="Missing (in HHT1)"
FT /id="VAR_026778"
FT VARIANT 236
FT /note="V -> M (found in a patient with hereditary
FT hemorrhagic talagiectasia; unknown pathological
FT significance; dbSNP:rs754136153)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070287"
FT VARIANT 238
FT /note="V -> E (in HHT1; dbSNP:rs1060501415)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070288"
FT VARIANT 263
FT /note="I -> S (in HHT1)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070289"
FT VARIANT 263
FT /note="I -> T (in HHT1)"
FT /evidence="ECO:0000269|PubMed:15024723"
FT /id="VAR_026780"
FT VARIANT 263
FT /note="Missing (in HHT1)"
FT /evidence="ECO:0000269|PubMed:15024723,
FT ECO:0000269|PubMed:15712270"
FT /id="VAR_026779"
FT VARIANT 269
FT /note="M -> R (in HHT1)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070290"
FT VARIANT 306
FT /note="L -> P (in HHT1)"
FT /evidence="ECO:0000269|PubMed:9554745"
FT /id="VAR_005197"
FT VARIANT 308
FT /note="A -> D (in HHT1)"
FT /evidence="ECO:0000269|PubMed:16752392"
FT /id="VAR_070291"
FT VARIANT 315
FT /note="V -> M (found in a family with hereditary
FT hemorrhagic talagiectasia; unknown pathological
FT significance; dbSNP:rs763508329)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070292"
FT VARIANT 363
FT /note="C -> S (in HHT1; dbSNP:rs1588580782)"
FT /evidence="ECO:0000269|PubMed:16752392"
FT /id="VAR_070293"
FT VARIANT 366
FT /note="D -> H (in dbSNP:rs1800956)"
FT /id="VAR_014764"
FT VARIANT 374
FT /note="K -> E (found in a patient with hereditary
FT hemorrhagic talagiectasia; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070294"
FT VARIANT 394
FT /note="C -> Y (in HHT1)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070295"
FT VARIANT 412
FT /note="C -> S (in HHT1)"
FT /evidence="ECO:0000269|PubMed:15024723"
FT /id="VAR_026781"
FT VARIANT 413
FT /note="G -> V (in HHT1; dbSNP:rs121918401)"
FT /evidence="ECO:0000269|PubMed:10982033"
FT /id="VAR_037140"
FT VARIANT 414
FT /note="M -> R (found in a patient with hereditary
FT hemorrhagic talagiectasia; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070296"
FT VARIANT 437
FT /note="R -> W (in HHT1; dbSNP:rs1434169817)"
FT /evidence="ECO:0000269|PubMed:16752392"
FT /id="VAR_070297"
FT VARIANT 490
FT /note="L -> S (in HHT1; dbSNP:rs763475207)"
FT /evidence="ECO:0000269|PubMed:16752392"
FT /id="VAR_070298"
FT VARIANT 504
FT /note="V -> M (in HHT1; dbSNP:rs116330805)"
FT /evidence="ECO:0000269|PubMed:15024723"
FT /id="VAR_026782"
FT VARIANT 529
FT /note="R -> H (in HHT1; dbSNP:rs863223538)"
FT /evidence="ECO:0000269|PubMed:16752392"
FT /id="VAR_070299"
FT VARIANT 529
FT /note="R -> P (in HHT1)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070300"
FT VARIANT 545
FT /note="G -> D (in HHT1)"
FT /evidence="ECO:0000269|PubMed:16525724"
FT /id="VAR_070301"
FT VARIANT 545
FT /note="G -> S (in dbSNP:rs142896669)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070302"
FT VARIANT 547
FT /note="L -> P (in HHT1)"
FT /evidence="ECO:0000269|PubMed:16752392"
FT /id="VAR_070303"
FT VARIANT 549
FT /note="C -> Y (found in a patient with hereditary
FT hemorrhagic talagiectasia; unknown pathological
FT significance; dbSNP:rs1060501421)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070304"
FT VARIANT 561
FT /note="D -> A (in dbSNP:rs375965489)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070305"
FT VARIANT 603
FT /note="G -> R (in HHT1)"
FT /evidence="ECO:0000269|PubMed:20414677"
FT /id="VAR_070306"
FT VARIANT 604
FT /note="A -> D (in HHT1)"
FT /evidence="ECO:0000269|PubMed:16752392"
FT /id="VAR_070307"
FT VARIANT 615
FT /note="S -> L (in dbSNP:rs148002300)"
FT /evidence="ECO:0000269|PubMed:15712270"
FT /id="VAR_026783"
FT MUTAGEN 246
FT /note="D->A: No effect on interaction with GDF2."
FT /evidence="ECO:0000269|PubMed:28564608"
FT MUTAGEN 269
FT /note="M->A: Impairs protein folding, but does not abolish
FT interaction with GDF2."
FT /evidence="ECO:0000269|PubMed:28564608"
FT MUTAGEN 270..271
FT /note="QI->AA: Loss of interaction with GDF2."
FT /evidence="ECO:0000269|PubMed:28564608"
FT MUTAGEN 277
FT /note="Y->A: No effect on interaction with GDF2."
FT /evidence="ECO:0000269|PubMed:28564608"
FT MUTAGEN 278
FT /note="S->P: Loss of interaction with GDF2."
FT /evidence="ECO:0000269|PubMed:28564608"
FT MUTAGEN 282
FT /note="F->V: Loss of interaction with GDF2."
FT /evidence="ECO:0000269|PubMed:28564608"
FT MUTAGEN 290
FT /note="F->A: No effect on interaction with GDF2."
FT /evidence="ECO:0000269|PubMed:28564608"
FT MUTAGEN 350
FT /note="C->S: Impairs protein folding. Impairs protein
FT folding; when associated with C-382."
FT /evidence="ECO:0000269|PubMed:28564608"
FT MUTAGEN 382
FT /note="C->S: Impairs protein folding. Impairs protein
FT folding; when associated with C-350."
FT /evidence="ECO:0000269|PubMed:28564608"
FT MUTAGEN 516
FT /note="C->S: Loss of dimerization via ZP domain."
FT /evidence="ECO:0000269|PubMed:28564608"
FT MUTAGEN 650
FT /note="T->A: Loss of interaction with ARRB2."
FT /evidence="ECO:0000269|PubMed:17540773"
FT CONFLICT 14
FT /note="L -> G (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 122..130
FT /note="SSLVTFQEP -> FQPGHLPRA (in Ref. 5)"
FT /evidence="ECO:0000305"
FT TURN 37..39
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 40..54
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 61..70
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 94..103
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:5I04"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 125..129
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 132..137
FT /evidence="ECO:0007829|PDB:5I04"
FT HELIX 143..151
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 156..171
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 193..200
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 205..208
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 217..224
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 232..240
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 249..254
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 259..267
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 270..279
FT /evidence="ECO:0007829|PDB:5I04"
FT HELIX 296..305
FT /evidence="ECO:0007829|PDB:5I04"
FT STRAND 309..327
FT /evidence="ECO:0007829|PDB:5I04"
FT HELIX 352..358
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 360..363
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 365..373
FT /evidence="ECO:0007829|PDB:5HZV"
FT HELIX 374..379
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 384..388
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 400..408
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 415..417
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 420..431
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 436..443
FT /evidence="ECO:0007829|PDB:5HZV"
FT TURN 445..447
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 448..459
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 465..467
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 473..481
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 484..496
FT /evidence="ECO:0007829|PDB:5HZV"
FT TURN 499..501
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 503..508
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 517..519
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 524..526
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 529..532
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 538..540
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 543..555
FT /evidence="ECO:0007829|PDB:5HZV"
FT HELIX 560..562
FT /evidence="ECO:0007829|PDB:5HZV"
FT STRAND 564..574
FT /evidence="ECO:0007829|PDB:5HZV"
SQ SEQUENCE 658 AA; 70578 MW; 49CA2CE013298D17 CRC64;
MDRGTLPLAV ALLLASCSLS PTSLAETVHC DLQPVGPERG EVTYTTSQVS KGCVAQAPNA
ILEVHVLFLE FPTGPSQLEL TLQASKQNGT WPREVLLVLS VNSSVFLHLQ ALGIPLHLAY
NSSLVTFQEP PGVNTTELPS FPKTQILEWA AERGPITSAA ELNDPQSILL RLGQAQGSLS
FCMLEASQDM GRTLEWRPRT PALVRGCHLE GVAGHKEAHI LRVLPGHSAG PRTVTVKVEL
SCAPGDLDAV LILQGPPYVS WLIDANHNMQ IWTTGEYSFK IFPEKNIRGF KLPDTPQGLL
GEARMLNASI VASFVELPLA SIVSLHASSC GGRLQTSPAP IQTTPPKDTC SPELLMSLIQ
TKCADDAMTL VLKKELVAHL KCTITGLTFW DPSCEAEDRG DKFVLRSAYS SCGMQVSASM
ISNEAVVNIL SSSSPQRKKV HCLNMDSLSF QLGLYLSPHF LQASNTIEPG QQSFVQVRVS
PSVSEFLLQL DSCHLDLGPE GGTVELIQGR AAKGNCVSLL SPSPEGDPRF SFLLHFYTVP
IPKTGTLSCT VALRPKTGSQ DQEVHRTVFM RLNIISPDLS GCTSKGLVLP AVLGITFGAF
LIGALLTAAL WYIYSHTRSP SKREPVVAVA APASSESSST NHSIGSTQST PCSTSSMA
