NOTC3_HUMAN
ID NOTC3_HUMAN Reviewed; 2321 AA.
AC Q9UM47; Q9UEB3; Q9UPL3; Q9Y6L8;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 08-FEB-2011, sequence version 2.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Neurogenic locus notch homolog protein 3;
DE Short=Notch 3;
DE Contains:
DE RecName: Full=Notch 3 extracellular truncation;
DE Contains:
DE RecName: Full=Notch 3 intracellular domain;
DE Flags: Precursor;
GN Name=NOTCH3;
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], AND VARIANT VAL-2223.
RX PubMed=8878478; DOI=10.1038/383707a0;
RA Joutel A., Corpechot C., Ducros A., Vahedi K., Chabriat H., Mouton P.,
RA Alamowitch S., Domenga V., Cecillion M., Marechal E., Maciazek J.,
RA Vayssiere C., Cruaud C., Cabanis E.-A., Ruchoux M.M., Weissenbach J.,
RA Bach J.-F., Bousser M.-G., Tournier-Lasserve E.;
RT "Notch3 mutations in CADASIL, a hereditary adult-onset condition causing
RT stroke and dementia.";
RL Nature 383:707-710(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Gunel M., Artavanis-Tsakonas S.;
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP IDENTIFICATION OF LIGANDS.
RX PubMed=10079256; DOI=10.1016/s0002-9440(10)65325-4;
RA Gray G.E., Mann R.S., Mitsiadis E., Henrique D., Carcangiu M.-L., Banks A.,
RA Leiman J., Ward D., Ish-Horowitz D., Artavanis-Tsakonas S.;
RT "Human ligands of the Notch receptor.";
RL Am. J. Pathol. 154:785-794(1999).
RN [5]
RP INTERACTION WITH MAML1.
RX PubMed=11101851; DOI=10.1038/82644;
RA Wu L., Aster J.C., Blacklow S.C., Lake R., Artavanis-Tsakonas S.,
RA Griffin J.D.;
RT "MAML1, a human homologue of Drosophila mastermind, is a transcriptional
RT co-activator for NOTCH receptors.";
RL Nat. Genet. 26:484-489(2000).
RN [6]
RP INTERACTION WITH MAML2 AND MAML3.
RX PubMed=12370315; DOI=10.1128/mcb.22.21.7688-7700.2002;
RA Wu L., Sun T., Kobayashi K., Gao P., Griffin J.D.;
RT "Identification of a family of mastermind-like transcriptional coactivators
RT for mammalian notch receptors.";
RL Mol. Cell. Biol. 22:7688-7700(2002).
RN [7]
RP INTERACTION WITH PSMA1.
RX PubMed=17292860; DOI=10.1016/j.bbrc.2007.01.151;
RA Zhang Y., Jia L., Lee S.J., Wang M.M.;
RT "Conserved signal peptide of Notch3 inhibits interaction with proteasome.";
RL Biochem. Biophys. Res. Commun. 355:245-251(2007).
RN [8]
RP INTERACTION WITH HIF1AN.
RX PubMed=17573339; DOI=10.1074/jbc.m704102200;
RA Coleman M.L., McDonough M.A., Hewitson K.S., Coles C., Mecinovic J.,
RA Edelmann M., Cook K.M., Cockman M.E., Lancaster D.E., Kessler B.M.,
RA Oldham N.J., Ratcliffe P.J., Schofield C.J.;
RT "Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor
RT inhibiting hypoxia-inducible factor.";
RL J. Biol. Chem. 282:24027-24038(2007).
RN [9]
RP HYDROXYLATION BY HIF1AN.
RX PubMed=18299578; DOI=10.1073/pnas.0711591105;
RA Zheng X., Linke S., Dias J.M., Zheng X., Gradin K., Wallis T.P.,
RA Hamilton B.R., Gustafsson M., Ruas J.L., Wilkins S., Bilton R.L.,
RA Brismar K., Whitelaw M.L., Pereira T., Gorman J.J., Ericson J., Peet D.J.,
RA Lendahl U., Poellinger L.;
RT "Interaction with factor inhibiting HIF-1 defines an additional mode of
RT cross-coupling between the Notch and hypoxia signaling pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:3368-3373(2008).
RN [10]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-2174, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [11]
RP INVOLVEMENT IN LMNS.
RX PubMed=25394726; DOI=10.1002/ajmg.a.36863;
RA Gripp K.W., Robbins K.M., Sobreira N.L., Witmer P.D., Bird L.M., Avela K.,
RA Makitie O., Alves D., Hogue J.S., Zackai E.H., Doheny K.F., Stabley D.L.,
RA Sol-Church K.;
RT "Truncating mutations in the last exon of NOTCH3 cause lateral meningocele
RT syndrome.";
RL Am. J. Med. Genet. A 167A:271-281(2015).
RN [12]
RP VARIANTS CADASIL1 TYR-49; CYS-71; CYS-90; CYS-110; CYS-133; CYS-141;
RP ARG-146; CYS-153; CYS-169; CYS-171; CYS-182; ARG-185; SER-212; GLY-222;
RP TYR-224; CYS-258; TYR-542; CYS-558; CYS-578; CYS-728; CYS-985; CYS-1006;
RP CYS-1031; CYS-1231 AND ARG-1261, AND VARIANTS ARG-170; LEU-496; GLN-1133;
RP MET-1183 AND VAL-2223.
RX PubMed=9388399; DOI=10.1016/s0140-6736(97)08083-5;
RA Joutel A., Vahedi K., Corpechot C., Troesch A., Chabriat H., Vayssiere C.,
RA Cruaud C., Maciazek J., Weissenbach J., Bousser M.-G., Bach J.-F.,
RA Tournier-Lasserve E.;
RT "Strong clustering and stereotyped nature of Notch3 mutations in CADASIL
RT patients.";
RL Lancet 350:1511-1515(1997).
RN [13]
RP VARIANTS CADASIL1 CYS-90; PHE-117; CYS-133; CYS-141; CYS-169; TYR-174;
RP CYS-182 AND ARG-183.
RX PubMed=10227618; DOI=10.1212/wnl.52.7.1361;
RA Dichgans M., Filippi M., Bruening R., Iannucci G., Berchtenbreiter C.,
RA Minicucci L., Uttner I., Crispin A., Ludwig H., Gasser T., Yousry T.A.;
RT "Quantitative MRI in CADASIL: correlation with disability and cognitive
RT performance.";
RL Neurology 52:1361-1367(1999).
RN [14]
RP VARIANTS CADASIL1 CYS-133; CYS-141; CYS-153; CYS-182; CYS-207; CYS-544 AND
RP ARG-1015.
RX PubMed=10371548; DOI=10.1212/wnl.52.9.1913;
RG Dutch CADASIL research group;
RA Lesnik Oberstein S.A.J., Ferrari M.D., Bakker E., van Gestel J.,
RA Kneppers A.L.J., Frants R.R., Breuning M.H., Haan J.;
RT "Diagnostic Notch3 sequence analysis in CADASIL: three new mutations in
RT Dutch patients. Dutch CADASIL Research Group.";
RL Neurology 52:1913-1915(1999).
RN [15]
RP VARIANTS CADASIL1 80-ASP--SER-84 DEL; CYS-90; PHE-93; CYS-110; PHE-117;
RP PHE-123; CYS-133; CYS-141; SER-144; TYR-144; CYS-150; 153-ARG--CYS-155 DEL;
RP CYS-153; CYS-169; TYR-174; CYS-182; ARG-183; SER-183; ARG-185 AND PHE-194.
RX PubMed=10854111; DOI=10.1038/sj.ejhg.5200460;
RA Dichgans M., Ludwig H., Mueller-Hoecker J., Messerschmidt A., Gasser T.;
RT "Small in-frame deletions and missense mutations in CADASIL: 3D models
RT predict misfolding of Notch3 EGF-like repeat domains.";
RL Eur. J. Hum. Genet. 8:280-285(2000).
RN [16]
RP VARIANT CADASIL1 PHE-144.
RX PubMed=11058919;
RX DOI=10.1002/1098-1004(200011)16:5<449::aid-humu26>3.0.co;2-i;
RA Grigg R., Lea R., Sullivan A.A., Curtain R., MacMillian J., Griffiths L.;
RT "Identification of a novel mutation C144F in the Notch3 gene in an
RT Australian CADASIL pedigree.";
RL Hum. Mutat. 16:449-450(2000).
RN [17]
RP VARIANTS CADASIL1 TYR-49; CYS-54; CYS-90; CYS-110; 114-GLY--PRO-120 DEL;
RP TYR-123; CYS-133; CYS-141; ARG-146; CYS-153; SER-162; CYS-169; TYR-174;
RP CYS-180; CYS-182; ARG-185; TYR-194; TYR-206; CYS-207; SER-212; GLY-222;
RP TYR-224; CYS-258; TYR-542; CYS-558; CYS-578; CYS-607; CYS-728; CYS-984;
RP CYS-985; CYS-1006; CYS-1031; CYS-1231 AND ARG-1261.
RX PubMed=11102981;
RX DOI=10.1002/1098-1004(200012)16:6<518::aid-humu9>3.0.co;2-q;
RA Escary J.-L., Cecillon M., Maciazek J., Lathrop M., Tournier-Lasserve E.,
RA Joutel A.;
RT "Evaluation of DHPLC analysis in mutational scanning of Notch3, a gene with
RT a high G-C content.";
RL Hum. Mutat. 16:518-526(2000).
RN [18]
RP VARIANT CADASIL1 114-GLY--PRO-120 DEL.
RX PubMed=10802807; DOI=10.1212/wnl.54.9.1874;
RA Joutel A., Chabriat H., Vahedi K., Domenga V., Vayssiere C., Ruchoux M.M.,
RA Lucas C., Leys D., Bousser M.-G., Tournier-Lasserve E.;
RT "Splice site mutation causing a seven amino acid Notch3 in-frame deletion
RT in CADASIL.";
RL Neurology 54:1874-1875(2000).
RN [19]
RP VARIANT CADASIL1 CYS-332.
RX PubMed=11559313; DOI=10.1001/archneur.58.9.1418;
RA Oliveri R.L., Muglia M., De Stefano N., Mazzei R., Labate A.,
RA Conforti F.L., Patitucci A., Gabriele A.L., Tagarelli G., Magariello A.,
RA Zappia M., Gambardella A., Federico A., Quattrone A.;
RT "A novel mutation in the Notch3 gene in an Italian family with cerebral
RT autosomal dominant arteriopathy with subcortical infarcts and
RT leukoencephalopathy: genetic and magnetic resonance spectroscopic
RT findings.";
RL Arch. Neurol. 58:1418-1422(2001).
RN [20]
RP VARIANTS CADASIL1 CYS-110; CYS-133; TRP-134; CYS-141; CYS-153; CYS-182;
RP GLY-185; CYS-207; SER-212; GLY-222; SER-428; CYS-558; CYS-985 AND CYS-1063.
RX PubMed=11755616; DOI=10.1016/s0140-6736(01)07142-2;
RA Joutel A., Favrole P., Labauge P., Chabriat H., Lescoat C., Andreux F.,
RA Domenga V., Cecillon M., Vahedi K., Ducros A., Cave-Riant F., Bousser M.G.,
RA Tournier-Lasserve E.;
RT "Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL
RT diagnosis.";
RL Lancet 358:2049-2051(2001).
RN [21]
RP VARIANT CADASIL1 TRP-134.
RX PubMed=11810186; DOI=10.1007/s004010100439;
RA Feuerhake F., Volk B., Ostertag C.B., Jungling F.D., Kassubek J.,
RA Orszagh M., Dichgans M.;
RT "Reversible coma with raised intracranial pressure: an unusual clinical
RT manifestation of CADASIL.";
RL Acta Neuropathol. 103:188-192(2002).
RN [22]
RP VARIANTS CADASIL1 ARG-76; TYR-93; TYR-128; CYS-142; ARG-194; TYR-222;
RP SER-233; ARG-251; CYS-420; GLY-440; CYS-449; CYS-953 AND CYS-1021.
RX PubMed=12146805; DOI=10.1111/j.1750-3639.2002.tb00451.x;
RA Kalimo H., Ruchoux M.-M., Viitanen M., Kalaria R.N.;
RT "CADASIL: a common form of hereditary arteriopathy causing brain infarcts
RT and dementia.";
RL Brain Pathol. 12:371-384(2002).
RN [23]
RP VARIANT CADASIL1 ARG-455.
RX PubMed=12136071; DOI=10.1212/wnl.59.2.277;
RA Arboleda-Velasquez J.F., Lopera F., Lopez E., Frosch M.P.,
RA Sepulveda-Falla D., Gutierrez J.E., Vargas S., Medina M.,
RA Martinez De Arrieta C., Lebo R.V., Slaugenhaupt S.A., Betensky R.A.,
RA Villegas A., Arcos-Burgos M., Rivera D., Restrepo J.C., Kosik K.S.;
RT "C455R notch3 mutation in a Colombian CADASIL kindred with early onset of
RT stroke.";
RL Neurology 59:277-279(2002).
RN [24]
RP VARIANT CADASIL1 TYR-67.
RX PubMed=12589106; DOI=10.3346/jkms.2003.18.1.141;
RA Moon S.-Y., Kim H.-Y., Seok J.-I., Kwon J.-C., Ki C.-S., Kim J.-W.,
RA Suh Y.-L., Na D.L.;
RT "A novel mutation (C67Y)in the NOTCH3 gene in a Korean CADASIL patient.";
RL J. Korean Med. Sci. 18:141-144(2003).
RN [25]
RP VARIANTS CADASIL1 CYS-90; CYS-133; CYS-169; ARG-174; PHE-174 AND LYS-213.
RX PubMed=12810003; DOI=10.1016/s0022-510x(03)00109-6;
RA Santa Y., Uyama E., Chui D.H., Arima M., Kotorii S., Takahashi K.,
RA Tabira T.;
RT "Genetic, clinical and pathological studies of CADASIL in Japan: a partial
RT contribution of Notch3 mutations and implications of smooth muscle cell
RT degeneration for the pathogenesis.";
RL J. Neurol. Sci. 212:79-84(2003).
RN [26]
RP VARIANTS CADASIL1 ARG-76; CYS-90; CYS-110; CYS-141; CYS-153; CYS-169;
RP CYS-182; ARG-183; CYS-189; SER-194; CYS-207; ARG-251; CYS-332; GLY-440;
RP CYS-607; CYS-953 AND CYS-1231.
RX PubMed=15229130; DOI=10.1093/brain/awh223;
RA Singhal S., Bevan S., Barrick T., Rich P., Markus H.S.;
RT "The influence of genetic and cardiovascular risk factors on the CADASIL
RT phenotype.";
RL Brain 127:2031-2038(2004).
RN [27]
RP VARIANTS CADASIL1 GLY-43; PHE-49; CYS-60; SER-65; TRP-76; 77-GLN--CYS-82
RP DEL; 80-ASP--SER-84 DEL; ARG-87; TYR-87; CYS-90; PHE-93; TRP-106; TYR-108;
RP CYS-110; PHE-117; PHE-123; CYS-133; TRP-134; CYS-141; SER-144; TYR-144;
RP CYS-145; CYS-149; CYS-150; 153-ARG--155-CYS DEL; CYS-153; SER-155; CYS-169;
RP ARG-174; TYR-174; CYS-182; ARG-183; SER-183; PHE-183; ARG-185; PHE-194;
RP TYR-201; CYS-207; TYR-233; 239-ASP--ASP-253 DEL; SER-240; ARG-245; TYR-260;
RP CYS-332; CYS-335; CYS-337; SER-379; ARG-395; CYS-421; TYR-428; ARG-440;
RP SER-446; TYR-484; TYR-495; ARG-511; TYR-549; CYS-558; CYS-985 AND TYR-1261.
RX PubMed=15364702; DOI=10.1093/brain/awh282;
RA Opherk C., Peters N., Herzog J., Luedtke R., Dichgans M.;
RT "Long-term prognosis and causes of death in CADASIL: a retrospective study
RT in 411 patients.";
RL Brain 127:2533-2539(2004).
RN [28]
RP VARIANT CADASIL1 CYS-133.
RX PubMed=15378071; DOI=10.1038/sj.ejhg.5201221;
RA Mykkaenen K., Savontaus M.L., Juvonen V., Sistonen P., Tuisku S.,
RA Tuominen S., Penttinen M., Lundkvist J., Viitanen M., Kalimo H.,
RA Peoyhoenen M.;
RT "Detection of the founder effect in Finnish CADASIL families.";
RL Eur. J. Hum. Genet. 12:813-819(2004).
RN [29]
RP CHARACTERIZATION OF VARIANTS CADASIL1 CYS-133; SER-183 AND ARG-455,
RP FUNCTION, SUBCELLULAR LOCATION, LIGAND-BINDING DOMAIN, AND PROTEOLYTIC
RP PROCESSING.
RX PubMed=15350543; DOI=10.1016/j.yexcr.2004.06.004;
RA Peters N., Opherk C., Zacherle S., Capell A., Gempel P., Dichgans M.;
RT "CADASIL-associated Notch3 mutations have differential effects both on
RT ligand binding and ligand-induced Notch3 receptor signaling through RBP-
RT Jk.";
RL Exp. Cell Res. 299:454-464(2004).
RN [30]
RP VARIANT CADASIL1 TRP-108.
RX PubMed=15300988;
RA Rojas-Marcos I., Encarnacion M., Martinez-Yelamos S., Ferrer I., Arbizu T.,
RA Gil-Peralta A., Garcia-Lozano J.R.;
RT "Gene symbol: NOTCH3. Disease: CADASIL.";
RL Hum. Genet. 115:175-175(2004).
RN [31]
RP VARIANTS CADASIL1 GLY-43; PHE-49; CYS-60; SER-65; TRP-76; 80-ASP--SER-84
RP DEL; ARG-87; CYS-90; PHE-93; TYR-108; CYS-110; PHE-117; PHE-123; CYS-133;
RP TRP-134; CYS-141; SER-144; TYR-144; CYS-149; CYS-150; CYS-153;
RP 153-ARG--CYS-155 DEL; CYS-169; ARG-174; TYR-174; CYS-182; SER-183; PHE-183;
RP ARG-185; PHE-194; CYS-207; TYR-233; SER-240; ARG-245; TYR-260;
RP 239-ASP--ASP-253 DEL; CYS-319; CYS-332; CYS-335; CYS-337; SER-379; ARG-395;
RP CYS-421; TYR-428; ARG-440; PHE-484; TYR-495; ARG-511; TYR-549; CYS-558;
RP CYS-728; SER-775; CYS-985 AND TYR-1261.
RX PubMed=16009764; DOI=10.1001/archneur.62.7.1091;
RA Peters N., Opherk C., Bergmann T., Castro M., Herzog J., Dichgans M.;
RT "Spectrum of mutations in biopsy-proven CADASIL: implications for
RT diagnostic strategies.";
RL Arch. Neurol. 62:1091-1094(2005).
RN [32]
RP VARIANT CADASIL1 CYS-118.
RX PubMed=15818833;
RA Soong B.W., Lee Y.-C., Lu Y.-C.;
RT "Gene symbol: NOTCH3. Disease: cerebral autosomal dominant arteriopathy
RT with subcortical infarcts and leukoencephalopathy.";
RL Hum. Genet. 116:242-242(2005).
RN [33]
RP VARIANT BRAIN SMALL-VESSEL-DISEASE PRO-1515.
RX PubMed=18273901; DOI=10.1002/humu.9527;
RA Fouillade C., Chabriat H., Riant F., Mine M., Arnoud M., Magy L.,
RA Bousser M.G., Tournier-Lasserve E., Joutel A.;
RT "Activating NOTCH3 mutation in a patient with small-vessel-disease of the
RT brain.";
RL Hum. Mutat. 29:452-452(2008).
RN [34]
RP VARIANT IMF2 PRO-1519.
RX PubMed=23731542; DOI=10.1016/j.ajhg.2013.04.024;
RA Martignetti J.A., Tian L., Li D., Ramirez M.C., Camacho-Vanegas O.,
RA Camacho S.C., Guo Y., Zand D.J., Bernstein A.M., Masur S.K., Kim C.E.,
RA Otieno F.G., Hou C., Abdel-Magid N., Tweddale B., Metry D., Fournet J.C.,
RA Papp E., McPherson E.W., Zabel C., Vaksmann G., Morisot C., Keating B.,
RA Sleiman P.M., Cleveland J.A., Everman D.B., Zackai E., Hakonarson H.;
RT "Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis.";
RL Am. J. Hum. Genet. 92:1001-1007(2013).
RN [35]
RP VARIANT CADASIL1 CYS-710.
RX PubMed=24000151; DOI=10.1002/humu.22432;
RA Rutten J.W., Boon E.M., Liem M.K., Dauwerse J.G., Pont M.J., Vollebregt E.,
RA Maat-Kievit A.J., Ginjaar H.B., Lakeman P., van Duinen S.G., Terwindt G.M.,
RA Lesnik Oberstein S.A.;
RT "Hypomorphic NOTCH3 alleles do not cause CADASIL in humans.";
RL Hum. Mutat. 34:1486-1489(2013).
CC -!- FUNCTION: Functions as a receptor for membrane-bound ligands Jagged1,
CC Jagged2 and Delta1 to regulate cell-fate determination
CC (PubMed:15350543). Upon ligand activation through the released notch
CC intracellular domain (NICD) it forms a transcriptional activator
CC complex with RBPJ/RBPSUH and activates genes of the enhancer of split
CC locus. Affects the implementation of differentiation, proliferation and
CC apoptotic programs (By similarity). {ECO:0000250|UniProtKB:Q9R172,
CC ECO:0000269|PubMed:15350543}.
CC -!- SUBUNIT: Heterodimer of a C-terminal fragment N(TM) and a N-terminal
CC fragment N(EC) which are probably linked by disulfide bonds (By
CC similarity). Interacts with MAML1, MAML2 and MAML3 which act as
CC transcriptional coactivators for NOTCH3. Interacts with PSMA1.
CC Interacts with HIF1AN. {ECO:0000250, ECO:0000269|PubMed:11101851,
CC ECO:0000269|PubMed:12370315, ECO:0000269|PubMed:17292860,
CC ECO:0000269|PubMed:17573339}.
CC -!- INTERACTION:
CC Q9UM47; Q9UM47: NOTCH3; NbExp=2; IntAct=EBI-1236377, EBI-1236377;
CC Q9UM47; P86480: PRR20D; NbExp=3; IntAct=EBI-1236377, EBI-12754095;
CC Q9UM47; Q9R1P4: Psma1; Xeno; NbExp=2; IntAct=EBI-1236377, EBI-991653;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15350543};
CC Single-pass type I membrane protein.
CC -!- SUBCELLULAR LOCATION: [Notch 3 intracellular domain]: Nucleus.
CC Note=Following proteolytical processing NICD is translocated to the
CC nucleus.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in fetal and adult tissues.
CC -!- DOMAIN: The EGF-like domains 10 and 11 are required for binding the
CC ligands JAG1 and DLL1. {ECO:0000269|PubMed:15350543}.
CC -!- PTM: Synthesized in the endoplasmic reticulum as an inactive form which
CC is proteolytically cleaved by a furin-like convertase in the trans-
CC Golgi network before it reaches the plasma membrane to yield an active,
CC ligand-accessible form. Cleavage results in a C-terminal fragment N(TM)
CC and a N-terminal fragment N(EC). Following ligand binding, it is
CC cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-
CC associated intermediate fragment called notch extracellular truncation
CC (NEXT). This fragment is then cleaved by presenilin dependent gamma-
CC secretase to release a notch-derived peptide containing the
CC intracellular domain (NICD) from the membrane.
CC {ECO:0000269|PubMed:15350543}.
CC -!- PTM: Phosphorylated. {ECO:0000250}.
CC -!- PTM: Hydroxylated by HIF1AN. {ECO:0000269|PubMed:18299578}.
CC -!- DISEASE: Cerebral arteriopathy, autosomal dominant, with subcortical
CC infarcts and leukoencephalopathy, 1 (CADASIL1) [MIM:125310]: A
CC cerebrovascular disease characterized by multiple subcortical infarcts,
CC pseudobulbar palsy, dementia, and the presence of granular deposits in
CC small cerebral arteries producing ischemic stroke.
CC {ECO:0000269|PubMed:10227618, ECO:0000269|PubMed:10371548,
CC ECO:0000269|PubMed:10802807, ECO:0000269|PubMed:10854111,
CC ECO:0000269|PubMed:11058919, ECO:0000269|PubMed:11102981,
CC ECO:0000269|PubMed:11559313, ECO:0000269|PubMed:11755616,
CC ECO:0000269|PubMed:11810186, ECO:0000269|PubMed:12136071,
CC ECO:0000269|PubMed:12146805, ECO:0000269|PubMed:12589106,
CC ECO:0000269|PubMed:12810003, ECO:0000269|PubMed:15229130,
CC ECO:0000269|PubMed:15300988, ECO:0000269|PubMed:15350543,
CC ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:15378071,
CC ECO:0000269|PubMed:15818833, ECO:0000269|PubMed:16009764,
CC ECO:0000269|PubMed:24000151, ECO:0000269|PubMed:9388399}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Myofibromatosis, infantile 2 (IMF2) [MIM:615293]: A rare
CC mesenchymal disorder characterized by the development of benign tumors
CC in the skin, striated muscles, bones, and, more rarely, visceral
CC organs. Subcutaneous or soft tissue nodules commonly involve the skin
CC of the head, neck, and trunk. Skeletal and muscular lesions occur in
CC about half of the patients. Lesions may be solitary or multicentric,
CC and they may be present at birth or become apparent in early infancy or
CC occasionally in adult life. Visceral lesions are associated with high
CC morbidity and mortality. {ECO:0000269|PubMed:23731542}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Lateral meningocele syndrome (LMNS) [MIM:130720]: A very rare
CC skeletal disorder with facial anomalies, hypotonia and neurologic
CC dysfunction due to meningocele, a protrusion of the meninges,
CC unaccompanied by neural tissue, through a bony defect in the skull or
CC vertebral column. LMNS facial features include hypertelorism and
CC telecanthus, high arched eyebrows, ptosis, mid-facial hypoplasia,
CC micrognathia, high and narrow palate, low-set ears and a hypotonic
CC appearance. Additional variable features are connective tissue
CC abnormalities, aortic dilation, a high-pitched nasal voice, wormian
CC bones and osteolysis. {ECO:0000269|PubMed:25394726}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the NOTCH family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NOTCH3ID41557ch19p13.html";
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; U97669; AAB91371.1; -; mRNA.
DR EMBL; AF058900; AAC14346.1; -; Genomic_DNA.
DR EMBL; AF058881; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058882; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058883; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058884; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058885; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058886; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058887; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058888; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058889; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058890; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058891; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058892; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058893; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058894; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058895; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058896; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058897; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058898; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AF058899; AAC14346.1; JOINED; Genomic_DNA.
DR EMBL; AC004257; AAC04897.1; -; Genomic_DNA.
DR EMBL; AC004663; AAC15789.1; -; Genomic_DNA.
DR CCDS; CCDS12326.1; -.
DR PIR; S78549; S78549.
DR RefSeq; NP_000426.2; NM_000435.2.
DR PDB; 4ZLP; X-ray; 2.48 A; A/B=1378-1640.
DR PDB; 5CZV; X-ray; 3.19 A; A=1378-1640.
DR PDB; 5CZX; X-ray; 2.10 A; A/B=1378-1640.
DR PDB; 6WQU; X-ray; 2.41 A; D=1665-1682.
DR PDB; 6XSW; X-ray; 2.98 A; C/F/J/X=1378-1634.
DR PDBsum; 4ZLP; -.
DR PDBsum; 5CZV; -.
DR PDBsum; 5CZX; -.
DR PDBsum; 6WQU; -.
DR PDBsum; 6XSW; -.
DR AlphaFoldDB; Q9UM47; -.
DR SMR; Q9UM47; -.
DR BioGRID; 110916; 127.
DR DIP; DIP-39827N; -.
DR ELM; Q9UM47; -.
DR IntAct; Q9UM47; 50.
DR MINT; Q9UM47; -.
DR STRING; 9606.ENSP00000263388; -.
DR BindingDB; Q9UM47; -.
DR ChEMBL; CHEMBL3407319; -.
DR GuidetoPHARMACOLOGY; 2860; -.
DR GlyGen; Q9UM47; 8 sites, 1 O-linked glycan (4 sites).
DR iPTMnet; Q9UM47; -.
DR PhosphoSitePlus; Q9UM47; -.
DR BioMuta; NOTCH3; -.
DR DMDM; 322510053; -.
DR EPD; Q9UM47; -.
DR jPOST; Q9UM47; -.
DR MassIVE; Q9UM47; -.
DR MaxQB; Q9UM47; -.
DR PaxDb; Q9UM47; -.
DR PeptideAtlas; Q9UM47; -.
DR PRIDE; Q9UM47; -.
DR ProteomicsDB; 85176; -.
DR ABCD; Q9UM47; 127 sequenced antibodies.
DR Antibodypedia; 3951; 673 antibodies from 44 providers.
DR DNASU; 4854; -.
DR Ensembl; ENST00000263388.7; ENSP00000263388.1; ENSG00000074181.9.
DR GeneID; 4854; -.
DR KEGG; hsa:4854; -.
DR MANE-Select; ENST00000263388.7; ENSP00000263388.1; NM_000435.3; NP_000426.2.
DR UCSC; uc002nan.4; human.
DR CTD; 4854; -.
DR DisGeNET; 4854; -.
DR GeneCards; NOTCH3; -.
DR GeneReviews; NOTCH3; -.
DR HGNC; HGNC:7883; NOTCH3.
DR HPA; ENSG00000074181; Low tissue specificity.
DR MalaCards; NOTCH3; -.
DR MIM; 125310; phenotype.
DR MIM; 130720; phenotype.
DR MIM; 600276; gene.
DR MIM; 615293; phenotype.
DR neXtProt; NX_Q9UM47; -.
DR OpenTargets; ENSG00000074181; -.
DR Orphanet; 136; Cerebral autosomal dominant arteriopathy-subcortical infarcts-leukoencephalopathy.
DR Orphanet; 2591; Infantile myofibromatosis.
DR Orphanet; 2789; Lateral meningocele syndrome.
DR PharmGKB; PA31685; -.
DR VEuPathDB; HostDB:ENSG00000074181; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000160234; -.
DR HOGENOM; CLU_000576_0_0_1; -.
DR InParanoid; Q9UM47; -.
DR OMA; RDCLQDA; -.
DR OrthoDB; 7525at2759; -.
DR PhylomeDB; Q9UM47; -.
DR TreeFam; TF351641; -.
DR PathwayCommons; Q9UM47; -.
DR Reactome; R-HSA-1912399; Pre-NOTCH Processing in the Endoplasmic Reticulum.
DR Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation.
DR Reactome; R-HSA-1912420; Pre-NOTCH Processing in Golgi.
DR Reactome; R-HSA-350054; Notch-HLH transcription pathway.
DR Reactome; R-HSA-5083630; Defective LFNG causes SCDO3.
DR Reactome; R-HSA-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR Reactome; R-HSA-9013508; NOTCH3 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-9017802; Noncanonical activation of NOTCH3.
DR SignaLink; Q9UM47; -.
DR SIGNOR; Q9UM47; -.
DR BioGRID-ORCS; 4854; 13 hits in 1080 CRISPR screens.
DR ChiTaRS; NOTCH3; human.
DR GeneWiki; Notch_3; -.
DR GenomeRNAi; 4854; -.
DR Pharos; Q9UM47; Tchem.
DR PRO; PR:Q9UM47; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9UM47; protein.
DR Bgee; ENSG00000074181; Expressed in popliteal artery and 195 other tissues.
DR ExpressionAtlas; Q9UM47; baseline and differential.
DR Genevisible; Q9UM47; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0038023; F:signaling receptor activity; IMP:UniProtKB.
DR GO; GO:0048844; P:artery morphogenesis; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0072104; P:glomerular capillary formation; IEA:Ensembl.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0014016; P:neuroblast differentiation; IEA:Ensembl.
DR GO; GO:0048663; P:neuron fate commitment; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR013032; EGF-like_CS.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR008297; Notch.
DR InterPro; IPR035993; Notch-like_dom_sf.
DR InterPro; IPR022331; Notch_3.
DR InterPro; IPR024600; Notch_C.
DR InterPro; IPR000800; Notch_dom.
DR InterPro; IPR010660; Notch_NOD_dom.
DR InterPro; IPR011656; Notch_NODP_dom.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF13857; Ank_5; 1.
DR Pfam; PF00008; EGF; 19.
DR Pfam; PF07645; EGF_CA; 5.
DR Pfam; PF12661; hEGF; 3.
DR Pfam; PF06816; NOD; 1.
DR Pfam; PF07684; NODP; 1.
DR Pfam; PF00066; Notch; 3.
DR PIRSF; PIRSF002279; Notch; 1.
DR PRINTS; PR01452; LNOTCHREPEAT.
DR PRINTS; PR01986; NOTCH3.
DR SMART; SM00248; ANK; 6.
DR SMART; SM01334; DUF3454; 1.
DR SMART; SM00181; EGF; 34.
DR SMART; SM00179; EGF_CA; 31.
DR SMART; SM00004; NL; 3.
DR SMART; SM01338; NOD; 1.
DR SMART; SM01339; NODP; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF57184; SSF57184; 4.
DR SUPFAM; SSF90193; SSF90193; 3.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
DR PROSITE; PS00010; ASX_HYDROXYL; 18.
DR PROSITE; PS00022; EGF_1; 33.
DR PROSITE; PS01186; EGF_2; 25.
DR PROSITE; PS50026; EGF_3; 34.
DR PROSITE; PS01187; EGF_CA; 16.
DR PROSITE; PS50258; LNR; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; ANK repeat; Cell membrane; Developmental protein;
KW Differentiation; Disease variant; Disulfide bond; EGF-like domain;
KW Glycoprotein; Membrane; Methylation; Notch signaling pathway; Nucleus;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..39
FT /evidence="ECO:0000255"
FT CHAIN 40..2321
FT /note="Neurogenic locus notch homolog protein 3"
FT /id="PRO_0000007692"
FT CHAIN 1629..2321
FT /note="Notch 3 extracellular truncation"
FT /evidence="ECO:0000250"
FT /id="PRO_0000007693"
FT CHAIN 1662..2321
FT /note="Notch 3 intracellular domain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000007694"
FT TOPO_DOM 40..1643
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1644..1664
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1665..2321
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 40..77
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 78..118
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 119..156
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 158..195
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 197..234
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 236..272
FT /note="EGF-like 6; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 274..312
FT /note="EGF-like 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 314..350
FT /note="EGF-like 8; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 351..389
FT /note="EGF-like 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 391..429
FT /note="EGF-like 10; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 431..467
FT /note="EGF-like 11; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 469..505
FT /note="EGF-like 12; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 507..543
FT /note="EGF-like 13; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 545..580
FT /note="EGF-like 14; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 582..618
FT /note="EGF-like 15; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 620..655
FT /note="EGF-like 16; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 657..693
FT /note="EGF-like 17; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 695..730
FT /note="EGF-like 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 734..770
FT /note="EGF-like 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 771..808
FT /note="EGF-like 20"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 810..847
FT /note="EGF-like 21; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 849..885
FT /note="EGF-like 22; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 887..922
FT /note="EGF-like 23; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 924..960
FT /note="EGF-like 24"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 962..998
FT /note="EGF-like 25"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1000..1034
FT /note="EGF-like 26"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1036..1082
FT /note="EGF-like 27"
FT /evidence="ECO:0000305"
FT DOMAIN 1084..1120
FT /note="EGF-like 28"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1122..1158
FT /note="EGF-like 29; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1160..1203
FT /note="EGF-like 30; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1205..1244
FT /note="EGF-like 31"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1246..1287
FT /note="EGF-like 32"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1289..1325
FT /note="EGF-like 33"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1335..1373
FT /note="EGF-like 34"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1387..1427
FT /note="LNR 1"
FT REPEAT 1428..1458
FT /note="LNR 2"
FT REPEAT 1467..1505
FT /note="LNR 3"
FT REPEAT 1838..1867
FT /note="ANK 1"
FT REPEAT 1871..1901
FT /note="ANK 2"
FT REPEAT 1905..1934
FT /note="ANK 3"
FT REPEAT 1938..1967
FT /note="ANK 4"
FT REPEAT 1971..2000
FT /note="ANK 5"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2024..2120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2190..2321
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2190..2211
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2257..2284
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2295..2312
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 1571..1572
FT /note="Cleavage; by furin-like protease"
FT /evidence="ECO:0000250"
FT MOD_RES 2174
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT CARBOHYD 1179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1336
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1438
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 43..55
FT /evidence="ECO:0000250"
FT DISULFID 49..65
FT /evidence="ECO:0000250"
FT DISULFID 67..76
FT /evidence="ECO:0000250"
FT DISULFID 82..93
FT /evidence="ECO:0000250"
FT DISULFID 87..106
FT /evidence="ECO:0000250"
FT DISULFID 108..117
FT /evidence="ECO:0000250"
FT DISULFID 123..134
FT /evidence="ECO:0000250"
FT DISULFID 128..144
FT /evidence="ECO:0000250"
FT DISULFID 146..155
FT /evidence="ECO:0000250"
FT DISULFID 162..174
FT /evidence="ECO:0000250"
FT DISULFID 168..183
FT /evidence="ECO:0000250"
FT DISULFID 185..194
FT /evidence="ECO:0000250"
FT DISULFID 201..212
FT /evidence="ECO:0000250"
FT DISULFID 206..222
FT /evidence="ECO:0000250"
FT DISULFID 224..233
FT /evidence="ECO:0000250"
FT DISULFID 240..251
FT /evidence="ECO:0000250"
FT DISULFID 245..260
FT /evidence="ECO:0000250"
FT DISULFID 262..271
FT /evidence="ECO:0000250"
FT DISULFID 278..291
FT /evidence="ECO:0000250"
FT DISULFID 285..300
FT /evidence="ECO:0000250"
FT DISULFID 302..311
FT /evidence="ECO:0000250"
FT DISULFID 318..329
FT /evidence="ECO:0000250"
FT DISULFID 323..338
FT /evidence="ECO:0000250"
FT DISULFID 340..349
FT /evidence="ECO:0000250"
FT DISULFID 355..366
FT /evidence="ECO:0000250"
FT DISULFID 360..377
FT /evidence="ECO:0000250"
FT DISULFID 379..388
FT /evidence="ECO:0000250"
FT DISULFID 395..408
FT /evidence="ECO:0000250"
FT DISULFID 402..417
FT /evidence="ECO:0000250"
FT DISULFID 419..428
FT /evidence="ECO:0000250"
FT DISULFID 435..446
FT /evidence="ECO:0000250"
FT DISULFID 440..455
FT /evidence="ECO:0000250"
FT DISULFID 457..466
FT /evidence="ECO:0000250"
FT DISULFID 473..484
FT /evidence="ECO:0000250"
FT DISULFID 478..493
FT /evidence="ECO:0000250"
FT DISULFID 495..504
FT /evidence="ECO:0000250"
FT DISULFID 511..522
FT /evidence="ECO:0000250"
FT DISULFID 516..531
FT /evidence="ECO:0000250"
FT DISULFID 533..542
FT /evidence="ECO:0000250"
FT DISULFID 549..559
FT /evidence="ECO:0000250"
FT DISULFID 554..568
FT /evidence="ECO:0000250"
FT DISULFID 570..579
FT /evidence="ECO:0000250"
FT DISULFID 586..597
FT /evidence="ECO:0000250"
FT DISULFID 591..606
FT /evidence="ECO:0000250"
FT DISULFID 608..617
FT /evidence="ECO:0000250"
FT DISULFID 624..634
FT /evidence="ECO:0000250"
FT DISULFID 629..643
FT /evidence="ECO:0000250"
FT DISULFID 645..654
FT /evidence="ECO:0000250"
FT DISULFID 661..672
FT /evidence="ECO:0000250"
FT DISULFID 666..681
FT /evidence="ECO:0000250"
FT DISULFID 683..692
FT /evidence="ECO:0000250"
FT DISULFID 699..709
FT /evidence="ECO:0000250"
FT DISULFID 704..718
FT /evidence="ECO:0000250"
FT DISULFID 720..729
FT /evidence="ECO:0000250"
FT DISULFID 738..749
FT /evidence="ECO:0000250"
FT DISULFID 743..758
FT /evidence="ECO:0000250"
FT DISULFID 760..769
FT /evidence="ECO:0000250"
FT DISULFID 775..786
FT /evidence="ECO:0000250"
FT DISULFID 780..796
FT /evidence="ECO:0000250"
FT DISULFID 798..807
FT /evidence="ECO:0000250"
FT DISULFID 814..826
FT /evidence="ECO:0000250"
FT DISULFID 820..835
FT /evidence="ECO:0000250"
FT DISULFID 837..846
FT /evidence="ECO:0000250"
FT DISULFID 853..864
FT /evidence="ECO:0000250"
FT DISULFID 858..873
FT /evidence="ECO:0000250"
FT DISULFID 875..884
FT /evidence="ECO:0000250"
FT DISULFID 891..901
FT /evidence="ECO:0000250"
FT DISULFID 896..910
FT /evidence="ECO:0000250"
FT DISULFID 912..921
FT /evidence="ECO:0000250"
FT DISULFID 928..939
FT /evidence="ECO:0000250"
FT DISULFID 933..948
FT /evidence="ECO:0000250"
FT DISULFID 950..959
FT /evidence="ECO:0000250"
FT DISULFID 966..977
FT /evidence="ECO:0000250"
FT DISULFID 971..986
FT /evidence="ECO:0000250"
FT DISULFID 988..997
FT /evidence="ECO:0000250"
FT DISULFID 1004..1015
FT /evidence="ECO:0000250"
FT DISULFID 1009..1022
FT /evidence="ECO:0000250"
FT DISULFID 1024..1033
FT /evidence="ECO:0000250"
FT DISULFID 1040..1061
FT /evidence="ECO:0000305"
FT DISULFID 1055..1070
FT /evidence="ECO:0000250"
FT DISULFID 1072..1081
FT /evidence="ECO:0000250"
FT DISULFID 1088..1099
FT /evidence="ECO:0000250"
FT DISULFID 1093..1108
FT /evidence="ECO:0000250"
FT DISULFID 1110..1119
FT /evidence="ECO:0000250"
FT DISULFID 1126..1137
FT /evidence="ECO:0000250"
FT DISULFID 1131..1146
FT /evidence="ECO:0000250"
FT DISULFID 1148..1157
FT /evidence="ECO:0000250"
FT DISULFID 1164..1182
FT /evidence="ECO:0000250"
FT DISULFID 1176..1191
FT /evidence="ECO:0000250"
FT DISULFID 1193..1202
FT /evidence="ECO:0000250"
FT DISULFID 1209..1222
FT /evidence="ECO:0000250"
FT DISULFID 1214..1232
FT /evidence="ECO:0000250"
FT DISULFID 1234..1243
FT /evidence="ECO:0000250"
FT DISULFID 1250..1261
FT /evidence="ECO:0000250"
FT DISULFID 1255..1275
FT /evidence="ECO:0000250"
FT DISULFID 1277..1286
FT /evidence="ECO:0000250"
FT DISULFID 1293..1304
FT /evidence="ECO:0000250"
FT DISULFID 1298..1313
FT /evidence="ECO:0000250"
FT DISULFID 1315..1324
FT /evidence="ECO:0000250"
FT DISULFID 1339..1350
FT /evidence="ECO:0000250"
FT DISULFID 1344..1361
FT /evidence="ECO:0000250"
FT DISULFID 1363..1372
FT /evidence="ECO:0000250"
FT DISULFID 1387..1410
FT /evidence="ECO:0000250"
FT DISULFID 1392..1405
FT /evidence="ECO:0000250"
FT DISULFID 1401..1417
FT /evidence="ECO:0000250"
FT DISULFID 1428..1451
FT /evidence="ECO:0000250"
FT DISULFID 1433..1446
FT /evidence="ECO:0000250"
FT DISULFID 1442..1458
FT /evidence="ECO:0000250"
FT DISULFID 1467..1493
FT /evidence="ECO:0000250"
FT DISULFID 1475..1488
FT /evidence="ECO:0000250"
FT DISULFID 1484..1500
FT /evidence="ECO:0000250"
FT VARIANT 43
FT /note="C -> G (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044230"
FT VARIANT 49
FT /note="C -> F (in CADASIL1; dbSNP:rs193921045)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044231"
FT VARIANT 49
FT /note="C -> Y (in CADASIL1; dbSNP:rs193921045)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:9388399"
FT /id="VAR_012871"
FT VARIANT 54
FT /note="R -> C (in CADASIL1; dbSNP:rs1555730189)"
FT /evidence="ECO:0000269|PubMed:11102981"
FT /id="VAR_044232"
FT VARIANT 60
FT /note="S -> C (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044233"
FT VARIANT 65
FT /note="C -> S (in CADASIL1; dbSNP:rs1555730176)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044234"
FT VARIANT 67
FT /note="C -> Y (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:12589106"
FT /id="VAR_044235"
FT VARIANT 71
FT /note="W -> C (in CADASIL1; dbSNP:rs28937321)"
FT /evidence="ECO:0000269|PubMed:9388399"
FT /id="VAR_012872"
FT VARIANT 76
FT /note="C -> R (in CADASIL1; dbSNP:rs1555729610)"
FT /evidence="ECO:0000269|PubMed:12146805,
FT ECO:0000269|PubMed:15229130"
FT /id="VAR_044236"
FT VARIANT 76
FT /note="C -> W (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044237"
FT VARIANT 77..82
FT /note="Missing (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702"
FT /id="VAR_044238"
FT VARIANT 80..84
FT /note="Missing (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:16009764"
FT /id="VAR_044239"
FT VARIANT 87
FT /note="C -> R (in CADASIL1; dbSNP:rs1568362232)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044240"
FT VARIANT 87
FT /note="C -> Y (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702"
FT /id="VAR_044241"
FT VARIANT 90
FT /note="R -> C (in CADASIL1; dbSNP:rs1555729604)"
FT /evidence="ECO:0000269|PubMed:10227618,
FT ECO:0000269|PubMed:10854111, ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:12810003, ECO:0000269|PubMed:15229130,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:16009764,
FT ECO:0000269|PubMed:9388399"
FT /id="VAR_012873"
FT VARIANT 93
FT /note="C -> F (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:16009764"
FT /id="VAR_044242"
FT VARIANT 93
FT /note="C -> Y (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:12146805"
FT /id="VAR_044243"
FT VARIANT 106
FT /note="C -> W (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702"
FT /id="VAR_044244"
FT VARIANT 108
FT /note="C -> W (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15300988"
FT /id="VAR_044245"
FT VARIANT 108
FT /note="C -> Y (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044246"
FT VARIANT 110
FT /note="R -> C (in CADASIL1; dbSNP:rs775836288)"
FT /evidence="ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:11102981, ECO:0000269|PubMed:11755616,
FT ECO:0000269|PubMed:15229130, ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764, ECO:0000269|PubMed:9388399"
FT /id="VAR_012874"
FT VARIANT 114..120
FT /note="Missing (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:10802807,
FT ECO:0000269|PubMed:11102981"
FT /id="VAR_012875"
FT VARIANT 117
FT /note="C -> F (in CADASIL1; dbSNP:rs773539041)"
FT /evidence="ECO:0000269|PubMed:10227618,
FT ECO:0000269|PubMed:10854111, ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044247"
FT VARIANT 118
FT /note="S -> C (in CADASIL1; dbSNP:rs1469620436)"
FT /evidence="ECO:0000269|PubMed:15818833"
FT /id="VAR_044248"
FT VARIANT 123
FT /note="C -> F (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:16009764"
FT /id="VAR_044249"
FT VARIANT 123
FT /note="C -> Y (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:11102981"
FT /id="VAR_044250"
FT VARIANT 128
FT /note="C -> Y (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:12146805"
FT /id="VAR_044251"
FT VARIANT 133
FT /note="R -> C (in CADASIL1; no effect on ligand-binding; no
FT effect on cell membrane localization; reduced proteolytic
FT processing; dbSNP:rs137852642)"
FT /evidence="ECO:0000269|PubMed:10227618,
FT ECO:0000269|PubMed:10371548, ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:11102981, ECO:0000269|PubMed:11755616,
FT ECO:0000269|PubMed:12810003, ECO:0000269|PubMed:15350543,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:15378071,
FT ECO:0000269|PubMed:16009764, ECO:0000269|PubMed:9388399"
FT /id="VAR_012876"
FT VARIANT 134
FT /note="C -> W (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:11755616,
FT ECO:0000269|PubMed:11810186, ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044252"
FT VARIANT 141
FT /note="R -> C (in CADASIL1; dbSNP:rs1174625611)"
FT /evidence="ECO:0000269|PubMed:10227618,
FT ECO:0000269|PubMed:10371548, ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:11102981, ECO:0000269|PubMed:11755616,
FT ECO:0000269|PubMed:15229130, ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764, ECO:0000269|PubMed:9388399"
FT /id="VAR_012877"
FT VARIANT 142
FT /note="F -> C (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:12146805"
FT /id="VAR_044253"
FT VARIANT 144
FT /note="C -> F (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:11058919"
FT /id="VAR_044254"
FT VARIANT 144
FT /note="C -> S (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:16009764"
FT /id="VAR_044255"
FT VARIANT 144
FT /note="C -> Y (in CADASIL1; dbSNP:rs1568361985)"
FT /evidence="ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:16009764"
FT /id="VAR_044256"
FT VARIANT 145
FT /note="S -> C (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702"
FT /id="VAR_044257"
FT VARIANT 146
FT /note="C -> R (in CADASIL1; dbSNP:rs1555729510)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:9388399"
FT /id="VAR_012878"
FT VARIANT 149
FT /note="G -> C (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044258"
FT VARIANT 150
FT /note="Y -> C (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:16009764"
FT /id="VAR_044259"
FT VARIANT 153..155
FT /note="Missing (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044260"
FT VARIANT 153
FT /note="R -> C (in CADASIL1; dbSNP:rs797045014)"
FT /evidence="ECO:0000269|PubMed:10371548,
FT ECO:0000269|PubMed:10854111, ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:11755616, ECO:0000269|PubMed:15229130,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:16009764,
FT ECO:0000269|PubMed:9388399"
FT /id="VAR_012879"
FT VARIANT 155
FT /note="C -> S (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702"
FT /id="VAR_044261"
FT VARIANT 162
FT /note="C -> S (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:11102981"
FT /id="VAR_044262"
FT VARIANT 169
FT /note="R -> C (in CADASIL1; dbSNP:rs28933696)"
FT /evidence="ECO:0000269|PubMed:10227618,
FT ECO:0000269|PubMed:10854111, ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:12810003, ECO:0000269|PubMed:15229130,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:16009764,
FT ECO:0000269|PubMed:9388399"
FT /id="VAR_012880"
FT VARIANT 170
FT /note="H -> R (in dbSNP:rs147373451)"
FT /evidence="ECO:0000269|PubMed:9388399"
FT /id="VAR_012881"
FT VARIANT 171
FT /note="G -> C (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:9388399"
FT /id="VAR_012882"
FT VARIANT 174
FT /note="C -> F (in CADASIL1; dbSNP:rs1555729486)"
FT /evidence="ECO:0000269|PubMed:12810003"
FT /id="VAR_044263"
FT VARIANT 174
FT /note="C -> R (in CADASIL1; dbSNP:rs1599394806)"
FT /evidence="ECO:0000269|PubMed:12810003,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:16009764"
FT /id="VAR_044264"
FT VARIANT 174
FT /note="C -> Y (in CADASIL1; dbSNP:rs1555729486)"
FT /evidence="ECO:0000269|PubMed:10227618,
FT ECO:0000269|PubMed:10854111, ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:16009764"
FT /id="VAR_044265"
FT VARIANT 180
FT /note="S -> C (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:11102981"
FT /id="VAR_044266"
FT VARIANT 182
FT /note="R -> C (in CADASIL1; dbSNP:rs28933697)"
FT /evidence="ECO:0000269|PubMed:10227618,
FT ECO:0000269|PubMed:10371548, ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:11102981, ECO:0000269|PubMed:11755616,
FT ECO:0000269|PubMed:15229130, ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764, ECO:0000269|PubMed:9388399"
FT /id="VAR_012883"
FT VARIANT 183
FT /note="C -> F (in CADASIL1; dbSNP:rs1568361851)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044267"
FT VARIANT 183
FT /note="C -> R (in CADASIL1; no effect on ligand-binding; no
FT effect on cell membrane localization; reduced proteolytic
FT processing)"
FT /evidence="ECO:0000269|PubMed:10227618,
FT ECO:0000269|PubMed:10854111, ECO:0000269|PubMed:15229130,
FT ECO:0000269|PubMed:15350543, ECO:0000269|PubMed:15364702"
FT /id="VAR_044268"
FT VARIANT 183
FT /note="C -> S (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:16009764"
FT /id="VAR_044269"
FT VARIANT 185
FT /note="C -> G (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:11755616"
FT /id="VAR_044270"
FT VARIANT 185
FT /note="C -> R (in CADASIL1; dbSNP:rs1568361844)"
FT /evidence="ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:11102981, ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764, ECO:0000269|PubMed:9388399"
FT /id="VAR_012884"
FT VARIANT 189
FT /note="Y -> C (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15229130"
FT /id="VAR_044271"
FT VARIANT 194
FT /note="C -> F (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:10854111,
FT ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:16009764"
FT /id="VAR_044272"
FT VARIANT 194
FT /note="C -> R (in CADASIL1; dbSNP:rs1568361818)"
FT /evidence="ECO:0000269|PubMed:12146805"
FT /id="VAR_044273"
FT VARIANT 194
FT /note="C -> S (in CADASIL1; dbSNP:rs1568361818)"
FT /evidence="ECO:0000269|PubMed:15229130"
FT /id="VAR_044274"
FT VARIANT 194
FT /note="C -> Y (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:11102981"
FT /id="VAR_044275"
FT VARIANT 201
FT /note="C -> Y (in CADASIL1; dbSNP:rs1555729468)"
FT /evidence="ECO:0000269|PubMed:15364702"
FT /id="VAR_044276"
FT VARIANT 206
FT /note="C -> Y (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:11102981"
FT /id="VAR_044277"
FT VARIANT 207
FT /note="R -> C (in CADASIL1; dbSNP:rs775267348)"
FT /evidence="ECO:0000269|PubMed:10371548,
FT ECO:0000269|PubMed:11102981, ECO:0000269|PubMed:11755616,
FT ECO:0000269|PubMed:15229130, ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044278"
FT VARIANT 212
FT /note="C -> S (in CADASIL1; dbSNP:rs1555729455)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:11755616, ECO:0000269|PubMed:9388399"
FT /id="VAR_012885"
FT VARIANT 213
FT /note="R -> K (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:12810003"
FT /id="VAR_044279"
FT VARIANT 222
FT /note="C -> G (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:11755616, ECO:0000269|PubMed:9388399"
FT /id="VAR_012886"
FT VARIANT 222
FT /note="C -> Y (in CADASIL1; dbSNP:rs1555729452)"
FT /evidence="ECO:0000269|PubMed:12146805"
FT /id="VAR_044280"
FT VARIANT 224
FT /note="C -> Y (in CADASIL1; dbSNP:rs1555729451)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:9388399"
FT /id="VAR_012887"
FT VARIANT 233
FT /note="C -> S (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:12146805"
FT /id="VAR_044281"
FT VARIANT 233
FT /note="C -> Y (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044282"
FT VARIANT 239..253
FT /note="Missing (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044283"
FT VARIANT 240
FT /note="C -> S (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044284"
FT VARIANT 245
FT /note="C -> R (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044285"
FT VARIANT 251
FT /note="C -> R (in CADASIL1; dbSNP:rs1568361608)"
FT /evidence="ECO:0000269|PubMed:12146805,
FT ECO:0000269|PubMed:15229130"
FT /id="VAR_044286"
FT VARIANT 258
FT /note="Y -> C (in CADASIL1; dbSNP:rs947976672)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:9388399"
FT /id="VAR_012888"
FT VARIANT 260
FT /note="C -> Y (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044287"
FT VARIANT 319
FT /note="A -> C (in CADASIL1; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:16009764"
FT /id="VAR_044288"
FT VARIANT 332
FT /note="R -> C (in CADASIL1; dbSNP:rs137852641)"
FT /evidence="ECO:0000269|PubMed:11559313,
FT ECO:0000269|PubMed:15229130, ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044289"
FT VARIANT 335
FT /note="S -> C (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044290"
FT VARIANT 337
FT /note="Y -> C (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044291"
FT VARIANT 379
FT /note="C -> S (in CADASIL1; dbSNP:rs1599391986)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044292"
FT VARIANT 395
FT /note="C -> R (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044293"
FT VARIANT 420
FT /note="G -> C (in CADASIL1; dbSNP:rs1323608032)"
FT /evidence="ECO:0000269|PubMed:12146805"
FT /id="VAR_044294"
FT VARIANT 421
FT /note="R -> C (in CADASIL1; dbSNP:rs1555729068)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044295"
FT VARIANT 428
FT /note="C -> S (in CADASIL1; dbSNP:rs267606915)"
FT /evidence="ECO:0000269|PubMed:11755616"
FT /id="VAR_044296"
FT VARIANT 428
FT /note="C -> Y (in CADASIL1; dbSNP:rs1568360455)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044297"
FT VARIANT 440
FT /note="C -> G (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:12146805,
FT ECO:0000269|PubMed:15229130"
FT /id="VAR_044298"
FT VARIANT 440
FT /note="C -> R (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044299"
FT VARIANT 446
FT /note="C -> S (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702"
FT /id="VAR_044300"
FT VARIANT 449
FT /note="R -> C (in CADASIL1; dbSNP:rs762734007)"
FT /evidence="ECO:0000269|PubMed:12146805"
FT /id="VAR_044301"
FT VARIANT 455
FT /note="C -> R (in CADASIL1; impaired ligand-binding;
FT strongly reduced signaling activity; no effect on cell
FT membrane localization; reduced proteolytic processing;
FT dbSNP:rs28933698)"
FT /evidence="ECO:0000269|PubMed:12136071,
FT ECO:0000269|PubMed:15350543"
FT /id="VAR_044302"
FT VARIANT 484
FT /note="C -> F (in CADASIL1; dbSNP:rs1313319587)"
FT /evidence="ECO:0000269|PubMed:16009764"
FT /id="VAR_044303"
FT VARIANT 484
FT /note="C -> Y (in CADASIL1; dbSNP:rs1313319587)"
FT /evidence="ECO:0000269|PubMed:15364702"
FT /id="VAR_044304"
FT VARIANT 495
FT /note="C -> Y (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044305"
FT VARIANT 496
FT /note="P -> L (in dbSNP:rs11670799)"
FT /evidence="ECO:0000269|PubMed:9388399"
FT /id="VAR_012889"
FT VARIANT 511
FT /note="C -> R (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044306"
FT VARIANT 542
FT /note="C -> Y (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:9388399"
FT /id="VAR_012890"
FT VARIANT 544
FT /note="R -> C (in CADASIL1; dbSNP:rs201118034)"
FT /evidence="ECO:0000269|PubMed:10371548"
FT /id="VAR_044307"
FT VARIANT 549
FT /note="C -> Y (in CADASIL1; dbSNP:rs1555728814)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044308"
FT VARIANT 558
FT /note="R -> C (in CADASIL1; dbSNP:rs75068032)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:11755616, ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764, ECO:0000269|PubMed:9388399"
FT /id="VAR_012891"
FT VARIANT 578
FT /note="R -> C (in CADASIL1; dbSNP:rs769773673)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:9388399"
FT /id="VAR_012892"
FT VARIANT 607
FT /note="R -> C (in CADASIL1; dbSNP:rs777751303)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:15229130"
FT /id="VAR_044309"
FT VARIANT 710
FT /note="Y -> C (in CADASIL1; dbSNP:rs1328784046)"
FT /evidence="ECO:0000269|PubMed:24000151"
FT /id="VAR_072080"
FT VARIANT 728
FT /note="R -> C (in CADASIL1; dbSNP:rs1057519101)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:16009764, ECO:0000269|PubMed:9388399"
FT /id="VAR_012893"
FT VARIANT 775
FT /note="C -> S (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:16009764"
FT /id="VAR_044310"
FT VARIANT 953
FT /note="G -> C (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:12146805,
FT ECO:0000269|PubMed:15229130"
FT /id="VAR_044311"
FT VARIANT 984
FT /note="F -> C (in CADASIL1; dbSNP:rs995523352)"
FT /evidence="ECO:0000269|PubMed:11102981"
FT /id="VAR_044312"
FT VARIANT 985
FT /note="R -> C (in CADASIL1; dbSNP:rs1188569102)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:11755616, ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764, ECO:0000269|PubMed:9388399"
FT /id="VAR_012894"
FT VARIANT 1006
FT /note="R -> C (in CADASIL1; dbSNP:rs1555727942)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:9388399"
FT /id="VAR_012895"
FT VARIANT 1015
FT /note="C -> R (in CADASIL1; dbSNP:rs1599382214)"
FT /evidence="ECO:0000269|PubMed:10371548"
FT /id="VAR_044313"
FT VARIANT 1020
FT /note="A -> P (in dbSNP:rs35769976)"
FT /id="VAR_044314"
FT VARIANT 1021
FT /note="Y -> C (in CADASIL1; dbSNP:rs1167405466)"
FT /evidence="ECO:0000269|PubMed:12146805"
FT /id="VAR_044315"
FT VARIANT 1031
FT /note="R -> C (in CADASIL1; dbSNP:rs1285584068)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:9388399"
FT /id="VAR_012896"
FT VARIANT 1063
FT /note="D -> C (in CADASIL1; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:11755616"
FT /id="VAR_044316"
FT VARIANT 1133
FT /note="H -> Q (in dbSNP:rs112197217)"
FT /evidence="ECO:0000269|PubMed:9388399"
FT /id="VAR_012897"
FT VARIANT 1183
FT /note="V -> M (in dbSNP:rs10408676)"
FT /evidence="ECO:0000269|PubMed:9388399"
FT /id="VAR_012898"
FT VARIANT 1231
FT /note="R -> C (in CADASIL1; dbSNP:rs201680145)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:15229130, ECO:0000269|PubMed:9388399"
FT /id="VAR_012899"
FT VARIANT 1261
FT /note="C -> R (in CADASIL1)"
FT /evidence="ECO:0000269|PubMed:11102981,
FT ECO:0000269|PubMed:9388399"
FT /id="VAR_012900"
FT VARIANT 1261
FT /note="C -> Y (in CADASIL1; dbSNP:rs1209610920)"
FT /evidence="ECO:0000269|PubMed:15364702,
FT ECO:0000269|PubMed:16009764"
FT /id="VAR_044317"
FT VARIANT 1515
FT /note="L -> P (in brain small-vessel-disease; exhibits
FT increased NOTCH3 signaling in a ligand-independent
FT fashion)"
FT /evidence="ECO:0000269|PubMed:18273901"
FT /id="VAR_044318"
FT VARIANT 1519
FT /note="L -> P (in IMF2; dbSNP:rs367543285)"
FT /evidence="ECO:0000269|PubMed:23731542"
FT /id="VAR_069927"
FT VARIANT 2223
FT /note="A -> V (in dbSNP:rs1044009)"
FT /evidence="ECO:0000269|PubMed:8878478,
FT ECO:0000269|PubMed:9388399"
FT /id="VAR_012901"
FT STRAND 1389..1391
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1392..1395
FT /evidence="ECO:0007829|PDB:6XSW"
FT STRAND 1398..1400
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1403..1405
FT /evidence="ECO:0007829|PDB:4ZLP"
FT TURN 1408..1410
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1411..1414
FT /evidence="ECO:0007829|PDB:5CZX"
FT TURN 1415..1420
FT /evidence="ECO:0007829|PDB:5CZX"
FT TURN 1424..1427
FT /evidence="ECO:0007829|PDB:5CZX"
FT TURN 1431..1433
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1434..1437
FT /evidence="ECO:0007829|PDB:5CZX"
FT STRAND 1439..1441
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1444..1446
FT /evidence="ECO:0007829|PDB:5CZX"
FT TURN 1449..1451
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1452..1456
FT /evidence="ECO:0007829|PDB:5CZX"
FT TURN 1457..1459
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1463..1465
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1469..1471
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1472..1478
FT /evidence="ECO:0007829|PDB:5CZX"
FT STRAND 1481..1483
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1486..1488
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1491..1493
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1495..1498
FT /evidence="ECO:0007829|PDB:5CZX"
FT STRAND 1510..1519
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1521..1526
FT /evidence="ECO:0007829|PDB:5CZX"
FT HELIX 1528..1539
FT /evidence="ECO:0007829|PDB:5CZX"
FT STRAND 1541..1545
FT /evidence="ECO:0007829|PDB:5CZX"
FT STRAND 1549..1551
FT /evidence="ECO:0007829|PDB:6XSW"
FT STRAND 1555..1558
FT /evidence="ECO:0007829|PDB:5CZX"
FT STRAND 1579..1587
FT /evidence="ECO:0007829|PDB:5CZX"
FT TURN 1589..1591
FT /evidence="ECO:0007829|PDB:6XSW"
FT TURN 1595..1597
FT /evidence="ECO:0007829|PDB:4ZLP"
FT STRAND 1598..1600
FT /evidence="ECO:0007829|PDB:5CZV"
FT HELIX 1604..1616
FT /evidence="ECO:0007829|PDB:5CZX"
FT STRAND 1626..1632
FT /evidence="ECO:0007829|PDB:5CZX"
SQ SEQUENCE 2321 AA; 243631 MW; 3E70EC12A59CD638 CRC64;
MGPGARGRRR RRRPMSPPPP PPPVRALPLL LLLAGPGAAA PPCLDGSPCA NGGRCTQLPS
REAACLCPPG WVGERCQLED PCHSGPCAGR GVCQSSVVAG TARFSCRCPR GFRGPDCSLP
DPCLSSPCAH GARCSVGPDG RFLCSCPPGY QGRSCRSDVD ECRVGEPCRH GGTCLNTPGS
FRCQCPAGYT GPLCENPAVP CAPSPCRNGG TCRQSGDLTY DCACLPGFEG QNCEVNVDDC
PGHRCLNGGT CVDGVNTYNC QCPPEWTGQF CTEDVDECQL QPNACHNGGT CFNTLGGHSC
VCVNGWTGES CSQNIDDCAT AVCFHGATCH DRVASFYCAC PMGKTGLLCH LDDACVSNPC
HEDAICDTNP VNGRAICTCP PGFTGGACDQ DVDECSIGAN PCEHLGRCVN TQGSFLCQCG
RGYTGPRCET DVNECLSGPC RNQATCLDRI GQFTCICMAG FTGTYCEVDI DECQSSPCVN
GGVCKDRVNG FSCTCPSGFS GSTCQLDVDE CASTPCRNGA KCVDQPDGYE CRCAEGFEGT
LCDRNVDDCS PDPCHHGRCV DGIASFSCAC APGYTGTRCE SQVDECRSQP CRHGGKCLDL
VDKYLCRCPS GTTGVNCEVN IDDCASNPCT FGVCRDGINR YDCVCQPGFT GPLCNVEINE
CASSPCGEGG SCVDGENGFR CLCPPGSLPP LCLPPSHPCA HEPCSHGICY DAPGGFRCVC
EPGWSGPRCS QSLARDACES QPCRAGGTCS SDGMGFHCTC PPGVQGRQCE LLSPCTPNPC
EHGGRCESAP GQLPVCSCPQ GWQGPRCQQD VDECAGPAPC GPHGICTNLA GSFSCTCHGG
YTGPSCDQDI NDCDPNPCLN GGSCQDGVGS FSCSCLPGFA GPRCARDVDE CLSNPCGPGT
CTDHVASFTC TCPPGYGGFH CEQDLPDCSP SSCFNGGTCV DGVNSFSCLC RPGYTGAHCQ
HEADPCLSRP CLHGGVCSAA HPGFRCTCLE SFTGPQCQTL VDWCSRQPCQ NGGRCVQTGA
YCLCPPGWSG RLCDIRSLPC REAAAQIGVR LEQLCQAGGQ CVDEDSSHYC VCPEGRTGSH
CEQEVDPCLA QPCQHGGTCR GYMGGYMCEC LPGYNGDNCE DDVDECASQP CQHGGSCIDL
VARYLCSCPP GTLGVLCEIN EDDCGPGPPL DSGPRCLHNG TCVDLVGGFR CTCPPGYTGL
RCEADINECR SGACHAAHTR DCLQDPGGGF RCLCHAGFSG PRCQTVLSPC ESQPCQHGGQ
CRPSPGPGGG LTFTCHCAQP FWGPRCERVA RSCRELQCPV GVPCQQTPRG PRCACPPGLS
GPSCRSFPGS PPGASNASCA AAPCLHGGSC RPAPLAPFFR CACAQGWTGP RCEAPAAAPE
VSEEPRCPRA ACQAKRGDQR CDRECNSPGC GWDGGDCSLS VGDPWRQCEA LQCWRLFNNS
RCDPACSSPA CLYDNFDCHA GGRERTCNPV YEKYCADHFA DGRCDQGCNT EECGWDGLDC
ASEVPALLAR GVLVLTVLLP PEELLRSSAD FLQRLSAILR TSLRFRLDAH GQAMVFPYHR
PSPGSEPRAR RELAPEVIGS VVMLEIDNRL CLQSPENDHC FPDAQSAADY LGALSAVERL
DFPYPLRDVR GEPLEPPEPS VPLLPLLVAG AVLLLVILVL GVMVARRKRE HSTLWFPEGF
SLHKDVASGH KGRREPVGQD ALGMKNMAKG ESLMGEVATD WMDTECPEAK RLKVEEPGMG
AEEAVDCRQW TQHHLVAADI RVAPAMALTP PQGDADADGM DVNVRGPDGF TPLMLASFCG
GALEPMPTEE DEADDTSASI ISDLICQGAQ LGARTDRTGE TALHLAARYA RADAAKRLLD
AGADTNAQDH SGRTPLHTAV TADAQGVFQI LIRNRSTDLD ARMADGSTAL ILAARLAVEG
MVEELIASHA DVNAVDELGK SALHWAAAVN NVEATLALLK NGANKDMQDS KEETPLFLAA
REGSYEAAKL LLDHFANREI TDHLDRLPRD VAQERLHQDI VRLLDQPSGP RSPPGPHGLG
PLLCPPGAFL PGLKAAQSGS KKSRRPPGKA GLGPQGPRGR GKKLTLACPG PLADSSVTLS
PVDSLDSPRP FGGPPASPGG FPLEGPYAAA TATAVSLAQL GGPGRAGLGR QPPGGCVLSL
GLLNPVAVPL DWARLPPPAP PGPSFLLPLA PGPQLLNPGT PVSPQERPPP YLAVPGHGEE
YPAAGAHSSP PKARFLRVPS EHPYLTPSPE SPEHWASPSP PSLSDWSEST PSPATATGAM
ATTTGALPAQ PLPLSVPSSL AQAQTQLGPQ PEVTPKRQVL A
