JAG1_HUMAN
ID JAG1_HUMAN Reviewed; 1218 AA.
AC P78504; A0AV43; B4DYR1; E9PCF9; O14902; O15122; Q15816;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2002, sequence version 3.
DT 03-AUG-2022, entry version 224.
DE RecName: Full=Protein jagged-1;
DE Short=Jagged1;
DE Short=hJ1;
DE AltName: CD_antigen=CD339;
DE Flags: Precursor;
GN Name=JAG1; Synonyms=JAGL1;
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 1).
RX PubMed=9268641; DOI=10.1006/geno.1997.4820;
RA Oda T., Elkahloun A.G., Meltzer P.S., Chandrasekharappa S.C.;
RT "Identification and cloning of the human homolog (JAG1) of the rat Jagged1
RT gene from the Alagille syndrome critical region at 20p12.";
RL Genomics 43:376-379(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN ALGS1, AND VARIANT
RP ALGS1 CYS-184.
RC TISSUE=Bone marrow;
RX PubMed=9207788; DOI=10.1038/ng0797-243;
RA Li L., Krantz I.D., Deng Y., Genin A., Banta A.B., Collins C.C., Qi M.,
RA Trask B.J., Kuo W.L., Cochran J., Costa T., Pierpont M.E.M., Rand E.B.,
RA Piccoli D.A., Hood L., Spinner N.B.;
RT "Alagille syndrome is caused by mutations in human Jagged1, which encodes a
RT ligand for Notch1.";
RL Nat. Genet. 16:243-251(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=9462510; DOI=10.1016/s1074-7613(00)80457-4;
RA Li L., Milner L.A., Deng Y., Iwata M., Banta A.B., Graf L., Marcovina S.,
RA Friedman C., Trask B.J., Hood L., Torok-Storb B.;
RT "The human homolog of rat Jagged1 expressed by marrow stroma inhibits
RT differentiation of 32D cells through interaction with Notch1.";
RL Immunity 8:43-55(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Cervix carcinoma;
RX PubMed=10329626; DOI=10.1093/emboj/18.10.2803;
RA Bash J., Zong W.-X., Banga S., Rivera A., Ballard D.W., Ron Y., Gelinas C.;
RT "Rel/NF-kappaB can trigger the Notch signaling pathway by inducing the
RT expression of Jagged1, a ligand for Notch receptors.";
RL EMBO J. 18:2803-2811(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-1218 (ISOFORM 1).
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=8955070; DOI=10.1074/jbc.271.51.32499;
RA Zimrin A.B., Pepper M.S., McMahon G.A., Nguyen F., Montesano R., Maciag T.;
RT "An antisense oligonucleotide to the notch ligand Jagged enhances
RT fibroblast growth factor-induced angiogenesis in vitro.";
RL J. Biol. Chem. 271:32499-32502(1996).
RN [10]
RP DISEASE.
RX PubMed=9207787; DOI=10.1038/ng0797-235;
RA Oda T., Elkahloun A.G., Pike B.L., Okajima K., Krantz I.D., Genin A.,
RA Piccoli D.A., Meltzer P.S., Spinner N.B., Collins F.S.,
RA Chandrasekharappa S.C.;
RT "Mutations in the human Jagged1 gene are responsible for Alagille
RT syndrome.";
RL Nat. Genet. 16:235-242(1997).
RN [11]
RP DEVELOPMENTAL STAGE.
RX PubMed=10978356; DOI=10.1136/jmg.37.9.658;
RA Jones E.A., Clement-Jones M., Wilson D.I.;
RT "JAGGED1 expression in human embryos: correlation with the Alagille
RT syndrome phenotype.";
RL J. Med. Genet. 37:658-662(2000).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 185-335, FUNCTION, INTERACTION
RP WITH NOTCH1, DOMAIN, MUTAGENESIS OF PHE-207, AND DISULFIDE BONDS.
RX PubMed=18660822; DOI=10.1038/nsmb.1457;
RA Cordle J., Johnson S., Tay J.Z., Roversi P., Wilkin M.B., de Madrid B.H.,
RA Shimizu H., Jensen S., Whiteman P., Jin B., Redfield C., Baron M.,
RA Lea S.M., Handford P.A.;
RT "A conserved face of the Jagged/Serrate DSL domain is involved in Notch
RT trans-activation and cis-inhibition.";
RL Nat. Struct. Mol. Biol. 15:849-857(2008).
RN [14]
RP STRUCTURE BY NMR OF 252-295, DOMAIN, AND DISULFIDE BONDS.
RX PubMed=19586525; DOI=10.1186/1472-6807-9-43;
RA Pintar A., Guarnaccia C., Dhir S., Pongor S.;
RT "Exon 6 of human JAG1 encodes a conserved structural unit.";
RL BMC Struct. Biol. 9:43-43(2009).
RN [15]
RP VARIANTS ALGS1 CYS-184 AND HIS-184.
RX PubMed=9585603; DOI=10.1086/301875;
RA Krantz I.D., Colliton R.P., Genin A., Rand E.B., Li L., Piccoli D.A.,
RA Spinner N.B.;
RT "Spectrum and frequency of Jagged1 (JAG1) mutations in Alagille syndrome
RT patients and their families.";
RL Am. J. Hum. Genet. 62:1361-1369(1998).
RN [16]
RP VARIANTS ALGS1 HIS-79; THR-127; ARG-129; LEU-163; GLY-184; SER-187;
RP GLY-229; PHE-284; CYS-288; PHE-438; SER-731 AND ARG-740.
RX PubMed=10220506; DOI=10.1016/s0016-5085(99)70017-x;
RA Crosnier C., Driancourt C., Raynaud N., Dhorne-Pollet S., Pollet N.,
RA Bernard O., Hadchouel M., Meunier-Rotival M.;
RT "Mutations in JAGGED1 gene are predominantly sporadic in Alagille
RT syndrome.";
RL Gastroenterology 116:1141-1148(1999).
RN [17]
RP VARIANTS ALGS1 THR-152 AND LEU-184.
RX PubMed=10533065;
RX DOI=10.1002/(sici)1098-1004(199911)14:5<394::aid-humu5>3.0.co;2-1;
RA Pilia G., Uda M., Macis D., Frau F., Crisponi L., Balli F., Barbera C.,
RA Colombo C., Frediani T., Gatti R., Iorio R., Marazzi M.G., Marcellini M.,
RA Musumeci S., Nebbia G., Vajro P., Ruffa G., Zancan L., Cao A.,
RA DeVirgilis S.;
RT "Jagged-1 mutation analysis in Italian Alagille syndrome patients.";
RL Hum. Mutat. 14:394-400(1999).
RN [18]
RP VARIANTS ALGS1 TYR-229 AND ARG-386.
RX PubMed=11058898;
RX DOI=10.1002/1098-1004(200011)16:5<408::aid-humu5>3.0.co;2-9;
RA Heritage M.L., MacMillan J.C., Colliton R.P., Genin A., Spinner N.B.,
RA Anderson G.J.;
RT "Jagged1 (JAG1) mutation detection in an Australian Alagille syndrome
RT population.";
RL Hum. Mutat. 16:408-416(2000).
RN [19]
RP VARIANT TOF ASP-274.
RX PubMed=11152664; DOI=10.1093/hmg/10.2.163;
RA Eldadah Z.A., Hamosh A., Biery N.J., Montgomery R.A., Duke M., Elkins R.,
RA Dietz H.C.;
RT "Familial tetralogy of Fallot caused by mutation in the Jagged1 gene.";
RL Hum. Mol. Genet. 10:163-169(2001).
RN [20]
RP VARIANT ALGS1 SER-37.
RX PubMed=11157803; DOI=10.1093/hmg/10.4.405;
RA Morrissette J.J.D., Colliton R.P., Spinner N.B.;
RT "Defective intracellular transport and processing of JAG1 missense
RT mutations in Alagille syndrome.";
RL Hum. Mol. Genet. 10:405-413(2001).
RN [21]
RP VARIANTS ALGS1 PHE-220 AND ARG-753.
RX PubMed=11139247; DOI=10.1002/1098-1004(2001)17:1<72::aid-humu11>3.0.co;2-u;
RA Crosnier C., Driancourt C., Raynaud N., Hadchouel M., Meunier-Rotival M.;
RT "Fifteen novel mutations in the JAGGED1 gene of patients with Alagille
RT syndrome.";
RL Hum. Mutat. 17:72-73(2001).
RN [22]
RP VARIANTS ALGS1 ASP-33; SER-37; SER-78; ASN-181; TYR-714 AND SER-902.
RX PubMed=11180599;
RX DOI=10.1002/1098-1004(200102)17:2<151::aid-humu8>3.0.co;2-t;
RA Colliton R.P., Bason L., Lu F.-M., Piccoli D.A., Krantz I.D., Spinner N.B.;
RT "Mutation analysis of Jagged1 (JAG1) in Alagille syndrome patients.";
RL Hum. Mutat. 17:151-152(2001).
RN [23]
RP INVOLVEMENT IN DCHE, AND VARIANT DCHE TYR-234.
RX PubMed=12022040; DOI=10.1086/341327;
RA Le Caignec C., Lefevre M., Schott J.J., Chaventre A., Gayet M., Calais C.,
RA Moisan J.P.;
RT "Familial deafness, congenital heart defects, and posterior embryotoxon
RT caused by cysteine substitution in the first epidermal-growth-factor-like
RT domain of Jagged 1.";
RL Am. J. Hum. Genet. 71:180-186(2002).
RN [24]
RP VARIANTS BILIARY ATRESIA LEU-45; ASP-53; MET-65; LYS-203; ASP-690; ARG-871;
RP GLN-908; PRO-921 AND GLN-1213.
RX PubMed=12297837; DOI=10.1053/jhep.2002.35820;
RA Kohsaka T., Yuan Z.-R., Guo S.-X., Tagawa M., Nakamura A., Nakano M.,
RA Kawasasaki H., Inomata Y., Tanaka K., Miyauchi J.;
RT "The significance of human Jagged 1 mutations detected in severe cases of
RT extrahepatic biliary atresia.";
RL Hepatology 36:904-912(2002).
RN [25]
RP VARIANTS ALGS1 SER-39; HIS-184 AND ARG-913.
RX PubMed=12442286; DOI=10.1002/humu.9095;
RA Heritage M.L., MacMillan J.C., Anderson G.J.;
RT "DHPLC mutation analysis of Jagged1 (JAG1) reveals six novel mutations in
RT Australian Alagille syndrome patients.";
RL Hum. Mutat. 20:481-481(2002).
RN [26]
RP CHARACTERIZATION OF VARIANT ASP-274.
RX PubMed=12649809; DOI=10.1086/374386;
RA Lu F., Morrissette J.J.D., Spinner N.B.;
RT "Conditional JAG1 mutation shows the developing heart is more sensitive
RT than developing liver to JAG1 dosage.";
RL Am. J. Hum. Genet. 72:1065-1070(2003).
RN [27]
RP VARIANTS ALGS1 VAL-31; PRO-40; SER-75; SER-123; ARG-163; CYS-224 AND
RP LEU-269, AND VARIANT GLN-937.
RX PubMed=12497640; DOI=10.1002/humu.9102;
RA Roepke A., Kujat A., Graeber M., Giannakudis J., Hansmann I.;
RT "Identification of 36 novel Jagged1 (JAG1) mutations in patients with
RT Alagille syndrome.";
RL Hum. Mutat. 21:100-100(2003).
RN [28]
RP VARIANTS ALGS1 ASN-120 AND TYR-187.
RX PubMed=15712272; DOI=10.1002/humu.9313;
RA Jurkiewicz D., Popowska E., Glaeser C., Hansmann I., Krajewska-Walasek M.;
RT "Twelve novel JAG1 gene mutations in Polish Alagille syndrome patients.";
RL Hum. Mutat. 25:321-321(2005).
RN [29]
RP VARIANTS ALGS1 22-CYS--ARG-25 DEL; SER-33; VAL-33; ARG-92; TYR-92; PRO-155;
RP GLY-252; SER-256; ARG-271; SER-504; TYR-693; GLN-889; TYR-911 AND
RP 1055-VAL-ARG-1056 GLY DELINS, AND VARIANT LYS-818.
RX PubMed=16575836; DOI=10.1002/humu.20310;
RA Warthen D.M., Moore E.C., Kamath B.M., Morrissette J.J.D., Sanchez P.,
RA Piccoli D.A., Krantz I.D., Spinner N.B.;
RT "Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation
RT detection rate.";
RL Hum. Mutat. 27:436-443(2006).
RN [30]
RP VARIANT ALGS1 TRP-436.
RX PubMed=23801938; DOI=10.1159/000347231;
RA Vozzi D., Licastro D., Martelossi S., Athanasakis E., Gasparini P.,
RA Fabretto A.;
RT "Alagille Syndrome: A new missense mutation detected by whole-exome
RT sequencing in a case previously found to be negative by DHPLC and MLPA.";
RL Mol. Syndromol. 4:207-210(2013).
RN [31]
RP VARIANTS SER-664; GLN-937 AND GLN-1104, CHARACTERIZATION OF VARIANTS
RP SER-664 AND GLN-937, VARIANT TOF LEU-810, CHARACTERIZATION OF VARIANTS TOF
RP ASP-274 AND LEU-810, CHARACTERIZATION OF VARIANT ALGS1 SER-37,
RP CHARACTERIZATION OF VARIANT DCHE TYR-234, AND FUNCTION.
RX PubMed=20437614; DOI=10.1002/humu.21231;
RA Bauer R.C., Laney A.O., Smith R., Gerfen J., Morrissette J.J.,
RA Woyciechowski S., Garbarini J., Loomes K.M., Krantz I.D., Urban Z.,
RA Gelb B.D., Goldmuntz E., Spinner N.B.;
RT "Jagged1 (JAG1) mutations in patients with tetralogy of Fallot or pulmonic
RT stenosis.";
RL Hum. Mutat. 31:594-601(2010).
RN [32]
RP VARIANTS CMT2HH ARG-577 AND PRO-650, INVOLVEMENT IN CMT2HH, SUBCELLULAR
RP LOCATION, CHARACTERIZATION OF VARIANT ALGS1 HIS-184, AND CHARACTERIZATION
RP OF VARIANTS CMT2HH ARG-577 AND PRO-650.
RX PubMed=32065591; DOI=10.1172/jci128152;
RA Sullivan J.M., Motley W.W., Johnson J.O., Aisenberg W.H., Marshall K.L.,
RA Barwick K.E., Kong L., Huh J.S., Saavedra-Rivera P.C., McEntagart M.M.,
RA Marion M.H., Hicklin L.A., Modarres H., Baple E.L., Farah M.H.,
RA Zuberi A.R., Lutz C.M., Gaudet R., Traynor B.J., Crosby A.H., Sumner C.J.;
RT "Dominant mutations of the Notch ligand Jagged1 cause peripheral
RT neuropathy.";
RL J. Clin. Invest. 130:1506-1512(2020).
CC -!- FUNCTION: Ligand for multiple Notch receptors and involved in the
CC mediation of Notch signaling (PubMed:18660822, PubMed:20437614). May be
CC involved in cell-fate decisions during hematopoiesis (PubMed:9462510).
CC Seems to be involved in early and late stages of mammalian
CC cardiovascular development. Inhibits myoblast differentiation (By
CC similarity). Enhances fibroblast growth factor-induced angiogenesis (in
CC vitro). {ECO:0000250, ECO:0000269|PubMed:18660822,
CC ECO:0000269|PubMed:20437614, ECO:0000269|PubMed:9462510}.
CC -!- SUBUNIT: Interacts with NOTCH2 and NOTCH3 (By similarity). Interacts
CC with NOTCH1 (in the presence of calcium ions) (PubMed:18660822).
CC {ECO:0000250|UniProtKB:Q9QXX0, ECO:0000269|PubMed:18660822}.
CC -!- INTERACTION:
CC P78504; P15529: CD46; NbExp=5; IntAct=EBI-2847071, EBI-2623451;
CC P78504; P46531: NOTCH1; NbExp=6; IntAct=EBI-2847071, EBI-636374;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC Cell membrane {ECO:0000269|PubMed:32065591}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P78504-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P78504-2; Sequence=VSP_056532;
CC -!- TISSUE SPECIFICITY: Widely expressed in adult and fetal tissues. In
CC cervix epithelium expressed in undifferentiated subcolumnar reserve
CC cells and squamous metaplasia. Expression is up-regulated in cervical
CC squamous cell carcinoma. Expressed in bone marrow cell line HS-27a
CC which supports the long-term maintenance of immature progenitor cells.
CC -!- DEVELOPMENTAL STAGE: Expressed in 32-52 days embryos in the distal
CC cardiac outflow tract and pulmonary artery, major arteries, portal
CC vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas,
CC mesocardium, around the major bronchial branches, and in the neural
CC tube. {ECO:0000269|PubMed:10978356}.
CC -!- DOMAIN: The second EGF-like domain is atypical.
CC {ECO:0000269|PubMed:18660822, ECO:0000269|PubMed:19586525}.
CC -!- DISEASE: Alagille syndrome 1 (ALGS1) [MIM:118450]: A form of Alagille
CC syndrome, an autosomal dominant multisystem disorder. It is clinically
CC defined by hepatic bile duct paucity and cholestasis in association
CC with cardiac, skeletal, and ophthalmologic manifestations. There are
CC characteristic facial features and less frequent clinical involvement
CC of the renal and vascular systems. {ECO:0000269|PubMed:10220506,
CC ECO:0000269|PubMed:10533065, ECO:0000269|PubMed:11058898,
CC ECO:0000269|PubMed:11139247, ECO:0000269|PubMed:11157803,
CC ECO:0000269|PubMed:11180599, ECO:0000269|PubMed:12442286,
CC ECO:0000269|PubMed:12497640, ECO:0000269|PubMed:15712272,
CC ECO:0000269|PubMed:16575836, ECO:0000269|PubMed:20437614,
CC ECO:0000269|PubMed:23801938, ECO:0000269|PubMed:32065591,
CC ECO:0000269|PubMed:9207788, ECO:0000269|PubMed:9585603}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Tetralogy of Fallot (TOF) [MIM:187500]: A congenital heart
CC anomaly which consists of pulmonary stenosis, ventricular septal
CC defect, dextroposition of the aorta (aorta is on the right side instead
CC of the left) and hypertrophy of the right ventricle. In this condition,
CC blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into
CC the body often causing cyanosis. {ECO:0000269|PubMed:11152664,
CC ECO:0000269|PubMed:20437614}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Deafness, congenital heart defects, and posterior embryotoxon
CC (DCHE) [MIM:617992]: An autosomal dominant disease characterized by
CC mild to severe combined hearing loss, congenital heart defects, and
CC posterior embryotoxon, a corneal abnormality consisting of a central
CC collagen core surrounded by a thin layer of Descemets membrane and
CC separated from the anterior chamber by a layer of endothelium.
CC Congenital heart defects include tetralogy of Fallot, ventricular
CC septal defect, or isolated peripheral pulmonic stenosis.
CC {ECO:0000269|PubMed:12022040, ECO:0000269|PubMed:20437614}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Charcot-Marie-Tooth disease 2HH (CMT2HH) [MIM:619574]: An
CC autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a
CC disorder of the peripheral nervous system characterized by progressive
CC weakness and atrophy, initially of the peroneal muscles and later of
CC the distal muscles of the arms. Charcot-Marie-Tooth disease is
CC classified in two main groups on the basis of electrophysiologic
CC properties and histopathology: primary peripheral demyelinating
CC neuropathies (designated CMT1 when they are dominantly inherited) and
CC primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2
CC group are characterized by signs of axonal degeneration in the absence
CC of obvious myelin alterations, normal or slightly reduced nerve
CC conduction velocities, and progressive distal muscle weakness and
CC atrophy. CMT2HH is characterized by vocal fold paresis that remains
CC throughout life and may be severe. Additional features include pes
CC cavus, scoliosis, distal sensory impairment with hyporeflexia, mild
CC distal muscle weakness and atrophy primarily affecting the lower limbs,
CC although the upper limbs may also be involved.
CC {ECO:0000269|PubMed:32065591}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC51323.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/JAG1ID41029ch20p12.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
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DR EMBL; AF003837; AAC51731.1; -; mRNA.
DR EMBL; U73936; AAC52020.1; -; mRNA.
DR EMBL; AF028593; AAB84053.1; -; mRNA.
DR EMBL; U61276; AAB39007.1; -; mRNA.
DR EMBL; AK302554; BAG63823.1; -; mRNA.
DR EMBL; AL035456; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC126205; AAI26206.1; -; mRNA.
DR EMBL; BC126207; AAI26208.1; -; mRNA.
DR EMBL; U77720; AAC51323.1; ALT_FRAME; mRNA.
DR CCDS; CCDS13112.1; -. [P78504-1]
DR RefSeq; NP_000205.1; NM_000214.2. [P78504-1]
DR RefSeq; XP_016883196.1; XM_017027707.1.
DR PDB; 2KB9; NMR; -; A=252-295.
DR PDB; 2VJ2; X-ray; 2.50 A; A/B=185-335.
DR PDB; 4CBZ; X-ray; 2.50 A; A/B=32-335.
DR PDB; 4CC0; X-ray; 2.32 A; A/B=32-335.
DR PDB; 4CC1; X-ray; 2.84 A; A/B=32-335.
DR PDB; 4XI7; X-ray; 2.05 A; C=1120-1130.
DR PDB; 5BO1; X-ray; 2.56 A; A/B=186-335.
DR PDBsum; 2KB9; -.
DR PDBsum; 2VJ2; -.
DR PDBsum; 4CBZ; -.
DR PDBsum; 4CC0; -.
DR PDBsum; 4CC1; -.
DR PDBsum; 4XI7; -.
DR PDBsum; 5BO1; -.
DR AlphaFoldDB; P78504; -.
DR BMRB; P78504; -.
DR SMR; P78504; -.
DR BioGRID; 106689; 35.
DR DIP; DIP-46371N; -.
DR IntAct; P78504; 18.
DR MINT; P78504; -.
DR STRING; 9606.ENSP00000254958; -.
DR ChEMBL; CHEMBL3217396; -.
DR GlyGen; P78504; 9 sites.
DR iPTMnet; P78504; -.
DR PhosphoSitePlus; P78504; -.
DR SwissPalm; P78504; -.
DR BioMuta; JAG1; -.
DR DMDM; 20455033; -.
DR EPD; P78504; -.
DR jPOST; P78504; -.
DR MassIVE; P78504; -.
DR MaxQB; P78504; -.
DR PaxDb; P78504; -.
DR PeptideAtlas; P78504; -.
DR PRIDE; P78504; -.
DR ProteomicsDB; 5543; -.
DR ProteomicsDB; 57626; -. [P78504-1]
DR ABCD; P78504; 10 sequenced antibodies.
DR Antibodypedia; 4153; 924 antibodies from 43 providers.
DR DNASU; 182; -.
DR Ensembl; ENST00000254958.10; ENSP00000254958.4; ENSG00000101384.12. [P78504-1]
DR GeneID; 182; -.
DR KEGG; hsa:182; -.
DR MANE-Select; ENST00000254958.10; ENSP00000254958.4; NM_000214.3; NP_000205.1.
DR UCSC; uc002wnw.3; human. [P78504-1]
DR CTD; 182; -.
DR DisGeNET; 182; -.
DR GeneCards; JAG1; -.
DR GeneReviews; JAG1; -.
DR HGNC; HGNC:6188; JAG1.
DR HPA; ENSG00000101384; Low tissue specificity.
DR MalaCards; JAG1; -.
DR MIM; 118450; phenotype.
DR MIM; 187500; phenotype.
DR MIM; 601920; gene.
DR MIM; 617992; phenotype.
DR MIM; 619574; phenotype.
DR neXtProt; NX_P78504; -.
DR OpenTargets; ENSG00000101384; -.
DR Orphanet; 261600; Alagille syndrome due to 20p12 microdeletion.
DR Orphanet; 261619; Alagille syndrome due to a JAG1 point mutation.
DR Orphanet; 3303; Tetralogy of Fallot.
DR PharmGKB; PA29986; -.
DR VEuPathDB; HostDB:ENSG00000101384; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000160148; -.
DR HOGENOM; CLU_004732_0_0_1; -.
DR InParanoid; P78504; -.
DR OMA; GWGGVTC; -.
DR PhylomeDB; P78504; -.
DR TreeFam; TF351835; -.
DR PathwayCommons; P78504; -.
DR Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2660826; Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant.
DR Reactome; R-HSA-2691232; Constitutive Signaling by NOTCH1 HD Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-2979096; NOTCH2 Activation and Transmission of Signal to the Nucleus.
DR Reactome; R-HSA-8941856; RUNX3 regulates NOTCH signaling.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR Reactome; R-HSA-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR Reactome; R-HSA-9013700; NOTCH4 Activation and Transmission of Signal to the Nucleus.
DR SignaLink; P78504; -.
DR SIGNOR; P78504; -.
DR BioGRID-ORCS; 182; 25 hits in 1025 CRISPR screens.
DR ChiTaRS; JAG1; human.
DR EvolutionaryTrace; P78504; -.
DR GeneWiki; JAG1; -.
DR GenomeRNAi; 182; -.
DR Pharos; P78504; Tbio.
DR PRO; PR:P78504; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P78504; protein.
DR Bgee; ENSG00000101384; Expressed in upper leg skin and 206 other tissues.
DR ExpressionAtlas; P78504; baseline and differential.
DR Genevisible; P78504; HS.
DR GO; GO:0005912; C:adherens junction; ISS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; NAS:UniProtKB.
DR GO; GO:0016020; C:membrane; TAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008083; F:growth factor activity; NAS:UniProtKB.
DR GO; GO:0005112; F:Notch binding; IPI:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IMP:CAFA.
DR GO; GO:0005198; F:structural molecule activity; NAS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; NAS:UniProtKB.
DR GO; GO:0035909; P:aorta morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003180; P:aortic valve morphogenesis; NAS:BHF-UCL.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR GO; GO:0061309; P:cardiac neural crest cell development involved in outflow tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003215; P:cardiac right ventricle morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060411; P:cardiac septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0001709; P:cell fate determination; NAS:UniProtKB.
DR GO; GO:0061073; P:ciliary body morphogenesis; IEA:Ensembl.
DR GO; GO:0072017; P:distal tubule development; IEA:Ensembl.
DR GO; GO:0061444; P:endocardial cushion cell development; ISS:BHF-UCL.
DR GO; GO:0045446; P:endothelial cell differentiation; NAS:UniProtKB.
DR GO; GO:0030097; P:hemopoiesis; NAS:UniProtKB.
DR GO; GO:0002085; P:inhibition of neuroepithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IEA:Ensembl.
DR GO; GO:0030216; P:keratinocyte differentiation; NAS:UniProtKB.
DR GO; GO:0072070; P:loop of Henle development; IEA:Ensembl.
DR GO; GO:0002011; P:morphogenesis of an epithelial sheet; IEA:Ensembl.
DR GO; GO:0045445; P:myoblast differentiation; NAS:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; IDA:UniProtKB.
DR GO; GO:0045602; P:negative regulation of endothelial cell differentiation; IEA:Ensembl.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:2000737; P:negative regulation of stem cell differentiation; IMP:UniProtKB.
DR GO; GO:0072006; P:nephron development; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; NAS:UniProtKB.
DR GO; GO:0061101; P:neuroendocrine cell differentiation; IEA:Ensembl.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; IEP:UniProtKB.
DR GO; GO:0061314; P:Notch signaling involved in heart development; IMP:BHF-UCL.
DR GO; GO:0007219; P:Notch signaling pathway; IMP:UniProtKB.
DR GO; GO:0072015; P:podocyte development; ISS:UniProtKB.
DR GO; GO:0062043; P:positive regulation of cardiac epithelial to mesenchymal transition; ISS:BHF-UCL.
DR GO; GO:0045639; P:positive regulation of myeloid cell differentiation; IEA:Ensembl.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0061156; P:pulmonary artery morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0042127; P:regulation of cell population proliferation; NAS:UniProtKB.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:2000241; P:regulation of reproductive process; IEA:Ensembl.
DR GO; GO:0032495; P:response to muramyl dipeptide; IEA:Ensembl.
DR GO; GO:0002456; P:T cell mediated immunity; IMP:UniProtKB.
DR DisProt; DP00418; -.
DR IDEAL; IID00203; -.
DR InterPro; IPR001774; DSL.
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; IPR033108; Jag1.
DR InterPro; IPR026219; Jagged/Serrate.
DR InterPro; IPR011651; Notch_ligand_N.
DR InterPro; IPR001007; VWF_dom.
DR PANTHER; PTHR24049:SF18; PTHR24049:SF18; 3.
DR Pfam; PF01414; DSL; 1.
DR Pfam; PF00008; EGF; 10.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF12661; hEGF; 1.
DR Pfam; PF07657; MNNL; 1.
DR PRINTS; PR02059; JAGGEDFAMILY.
DR SMART; SM00051; DSL; 1.
DR SMART; SM00181; EGF; 16.
DR SMART; SM00179; EGF_CA; 14.
DR SMART; SM00214; VWC; 1.
DR SMART; SM00215; VWC_out; 1.
DR SUPFAM; SSF57184; SSF57184; 3.
DR PROSITE; PS00010; ASX_HYDROXYL; 10.
DR PROSITE; PS51051; DSL; 1.
DR PROSITE; PS00022; EGF_1; 16.
DR PROSITE; PS01186; EGF_2; 12.
DR PROSITE; PS50026; EGF_3; 15.
DR PROSITE; PS01187; EGF_CA; 8.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell membrane;
KW Charcot-Marie-Tooth disease; Deafness; Developmental protein;
KW Disease variant; Disulfide bond; EGF-like domain; Glycoprotein; Membrane;
KW Neurodegeneration; Neuropathy; Notch signaling pathway; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..1218
FT /note="Protein jagged-1"
FT /id="PRO_0000007625"
FT TOPO_DOM 34..1067
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1068..1093
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1094..1218
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 185..229
FT /note="DSL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00377"
FT DOMAIN 230..263
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 264..294
FT /note="EGF-like 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 296..334
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 336..372
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 374..410
FT /note="EGF-like 5; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 412..448
FT /note="EGF-like 6; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 450..485
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 487..523
FT /note="EGF-like 8; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 525..561
FT /note="EGF-like 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 586..627
FT /note="EGF-like 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 629..665
FT /note="EGF-like 11; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 667..703
FT /note="EGF-like 12; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 705..741
FT /note="EGF-like 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 744..780
FT /note="EGF-like 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 782..818
FT /note="EGF-like 15; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 820..856
FT /note="EGF-like 16; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 199..207
FT /note="Important for interaction with NOTCH1"
FT /evidence="ECO:0000269|PubMed:18660822"
FT REGION 1152..1218
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1152..1169
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1190..1209
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 217
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 559
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 745
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 960
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 991
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1045
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1064
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 187..196
FT DISULFID 200..212
FT DISULFID 220..229
FT DISULFID 234..245
FT DISULFID 238..251
FT DISULFID 253..262
FT DISULFID 265..276
FT DISULFID 271..282
FT DISULFID 284..293
FT DISULFID 300..312
FT DISULFID 306..322
FT DISULFID 324..333
FT DISULFID 340..351
FT /evidence="ECO:0000250"
FT DISULFID 345..360
FT /evidence="ECO:0000250"
FT DISULFID 362..371
FT /evidence="ECO:0000250"
FT DISULFID 378..389
FT /evidence="ECO:0000250"
FT DISULFID 383..398
FT /evidence="ECO:0000250"
FT DISULFID 400..409
FT /evidence="ECO:0000250"
FT DISULFID 416..427
FT /evidence="ECO:0000250"
FT DISULFID 421..436
FT /evidence="ECO:0000250"
FT DISULFID 438..447
FT /evidence="ECO:0000250"
FT DISULFID 454..464
FT /evidence="ECO:0000250"
FT DISULFID 458..473
FT /evidence="ECO:0000250"
FT DISULFID 475..484
FT /evidence="ECO:0000250"
FT DISULFID 491..502
FT /evidence="ECO:0000250"
FT DISULFID 496..511
FT /evidence="ECO:0000250"
FT DISULFID 513..522
FT /evidence="ECO:0000250"
FT DISULFID 529..540
FT /evidence="ECO:0000250"
FT DISULFID 534..549
FT /evidence="ECO:0000250"
FT DISULFID 551..560
FT /evidence="ECO:0000250"
FT DISULFID 578..605
FT /evidence="ECO:0000250"
FT DISULFID 599..615
FT /evidence="ECO:0000250"
FT DISULFID 617..626
FT /evidence="ECO:0000250"
FT DISULFID 633..644
FT /evidence="ECO:0000250"
FT DISULFID 638..653
FT /evidence="ECO:0000250"
FT DISULFID 655..664
FT /evidence="ECO:0000250"
FT DISULFID 671..682
FT /evidence="ECO:0000250"
FT DISULFID 676..691
FT /evidence="ECO:0000250"
FT DISULFID 693..702
FT /evidence="ECO:0000250"
FT DISULFID 709..720
FT /evidence="ECO:0000250"
FT DISULFID 714..729
FT /evidence="ECO:0000250"
FT DISULFID 731..740
FT /evidence="ECO:0000250"
FT DISULFID 748..759
FT /evidence="ECO:0000250"
FT DISULFID 753..768
FT /evidence="ECO:0000250"
FT DISULFID 770..779
FT /evidence="ECO:0000250"
FT DISULFID 786..797
FT /evidence="ECO:0000250"
FT DISULFID 791..806
FT /evidence="ECO:0000250"
FT DISULFID 808..817
FT /evidence="ECO:0000250"
FT DISULFID 824..835
FT /evidence="ECO:0000250"
FT DISULFID 829..844
FT /evidence="ECO:0000250"
FT DISULFID 846..855
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..159
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056532"
FT VARIANT 22..25
FT /note="Missing (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026296"
FT VARIANT 31
FT /note="A -> V (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:12497640"
FT /id="VAR_026297"
FT VARIANT 33
FT /note="G -> D (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:11180599"
FT /id="VAR_026298"
FT VARIANT 33
FT /note="G -> S (in ALGS1; dbSNP:rs876661123)"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026299"
FT VARIANT 33
FT /note="G -> V (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026300"
FT VARIANT 37
FT /note="L -> S (in ALGS1; the mutant is unable to activate
FT Notch signaling; dbSNP:rs121918352)"
FT /evidence="ECO:0000269|PubMed:11157803,
FT ECO:0000269|PubMed:11180599, ECO:0000269|PubMed:20437614"
FT /id="VAR_013186"
FT VARIANT 39
FT /note="I -> S (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:12442286"
FT /id="VAR_026301"
FT VARIANT 40
FT /note="L -> P (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:12497640"
FT /id="VAR_026302"
FT VARIANT 45
FT /note="V -> L (in biliary atresia; extrahepatic;
FT dbSNP:rs183974372)"
FT /evidence="ECO:0000269|PubMed:12297837"
FT /id="VAR_026303"
FT VARIANT 53
FT /note="N -> D (in biliary atresia; extrahepatic)"
FT /evidence="ECO:0000269|PubMed:12297837"
FT /id="VAR_026304"
FT VARIANT 65
FT /note="K -> M (in biliary atresia; extrahepatic)"
FT /evidence="ECO:0000269|PubMed:12297837"
FT /id="VAR_026305"
FT VARIANT 75
FT /note="F -> S (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:12497640"
FT /id="VAR_026306"
FT VARIANT 78
FT /note="C -> S (in ALGS1; dbSNP:rs1555830957)"
FT /evidence="ECO:0000269|PubMed:11180599"
FT /id="VAR_026307"
FT VARIANT 79
FT /note="L -> H (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:10220506"
FT /id="VAR_013187"
FT VARIANT 92
FT /note="C -> R (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026308"
FT VARIANT 92
FT /note="C -> Y (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026309"
FT VARIANT 120
FT /note="I -> N (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:15712272"
FT /id="VAR_026310"
FT VARIANT 123
FT /note="P -> S (in ALGS1; dbSNP:rs1282498658)"
FT /evidence="ECO:0000269|PubMed:12497640"
FT /id="VAR_026311"
FT VARIANT 127
FT /note="A -> T (in ALGS1; dbSNP:rs930247415)"
FT /evidence="ECO:0000269|PubMed:10220506"
FT /id="VAR_013188"
FT VARIANT 129
FT /note="P -> R (in ALGS1; dbSNP:rs1032920906)"
FT /evidence="ECO:0000269|PubMed:10220506"
FT /id="VAR_013189"
FT VARIANT 146
FT /note="V -> I (in dbSNP:rs6040067)"
FT /id="VAR_048985"
FT VARIANT 152
FT /note="I -> T (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:10533065"
FT /id="VAR_013190"
FT VARIANT 155
FT /note="A -> P (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026312"
FT VARIANT 163
FT /note="P -> L (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:10220506"
FT /id="VAR_013191"
FT VARIANT 163
FT /note="P -> R (in ALGS1; dbSNP:rs1555829676)"
FT /evidence="ECO:0000269|PubMed:12497640"
FT /id="VAR_026313"
FT VARIANT 181
FT /note="Y -> N (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:11180599"
FT /id="VAR_026314"
FT VARIANT 184
FT /note="R -> C (in ALGS1; dbSNP:rs121918350)"
FT /evidence="ECO:0000269|PubMed:9207788,
FT ECO:0000269|PubMed:9585603"
FT /id="VAR_013192"
FT VARIANT 184
FT /note="R -> G (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:10220506"
FT /id="VAR_013193"
FT VARIANT 184
FT /note="R -> H (in ALGS1; loss of expression at the cell
FT membrane; dbSNP:rs121918351)"
FT /evidence="ECO:0000269|PubMed:12442286,
FT ECO:0000269|PubMed:32065591, ECO:0000269|PubMed:9585603"
FT /id="VAR_013194"
FT VARIANT 184
FT /note="R -> L (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:10533065"
FT /id="VAR_013195"
FT VARIANT 187
FT /note="C -> S (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:10220506"
FT /id="VAR_013196"
FT VARIANT 187
FT /note="C -> Y (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:15712272"
FT /id="VAR_026315"
FT VARIANT 203
FT /note="R -> K (in biliary atresia; extrahepatic)"
FT /evidence="ECO:0000269|PubMed:12297837"
FT /id="VAR_026316"
FT VARIANT 220
FT /note="C -> F (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:11139247"
FT /id="VAR_013197"
FT VARIANT 224
FT /note="W -> C (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:12497640"
FT /id="VAR_026317"
FT VARIANT 229
FT /note="C -> G (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:10220506"
FT /id="VAR_013198"
FT VARIANT 229
FT /note="C -> Y (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:11058898"
FT /id="VAR_013199"
FT VARIANT 234
FT /note="C -> Y (in DCHE; the mutant is unable to activate
FT Notch signaling; dbSNP:rs121918353)"
FT /evidence="ECO:0000269|PubMed:12022040,
FT ECO:0000269|PubMed:20437614"
FT /id="VAR_026318"
FT VARIANT 252
FT /note="R -> G (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026319"
FT VARIANT 256
FT /note="G -> S (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026320"
FT VARIANT 269
FT /note="P -> L (in ALGS1; dbSNP:rs797044956)"
FT /evidence="ECO:0000269|PubMed:12497640"
FT /id="VAR_026321"
FT VARIANT 271
FT /note="C -> R (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026322"
FT VARIANT 274
FT /note="G -> D (in TOF; temperature sensitive mutation; the
FT protein is abnormally glycosylated and retained
FT intracellularly; unable to activate Notch signaling;
FT dbSNP:rs28939668)"
FT /evidence="ECO:0000269|PubMed:11152664,
FT ECO:0000269|PubMed:12649809, ECO:0000269|PubMed:20437614"
FT /id="VAR_013200"
FT VARIANT 284
FT /note="C -> F (in ALGS1; dbSNP:rs1555829067)"
FT /evidence="ECO:0000269|PubMed:10220506"
FT /id="VAR_013201"
FT VARIANT 288
FT /note="W -> C (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:10220506"
FT /id="VAR_013202"
FT VARIANT 386
FT /note="G -> R (in ALGS1; dbSNP:rs863223650)"
FT /evidence="ECO:0000269|PubMed:11058898"
FT /id="VAR_013203"
FT VARIANT 436
FT /note="C -> W (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:23801938"
FT /id="VAR_071513"
FT VARIANT 438
FT /note="C -> F (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:10220506"
FT /id="VAR_013204"
FT VARIANT 504
FT /note="N -> S (in ALGS1; dbSNP:rs527236046)"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026323"
FT VARIANT 577
FT /note="S -> R (in CMT2HH; decreased glycosylation;
FT decreased expression at the cell membrane due to partial
FT retention in the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:32065591"
FT /id="VAR_086413"
FT VARIANT 650
FT /note="S -> P (in CMT2HH; decreased glycosylation;
FT decreased expression at the cell membrane due to partial
FT retention in the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:32065591"
FT /id="VAR_086414"
FT VARIANT 664
FT /note="C -> S (found in a patient with pulmonary stenosis;
FT unknown pathological significance; the mutant is able to
FT activate Notch signaling)"
FT /evidence="ECO:0000269|PubMed:20437614"
FT /id="VAR_080875"
FT VARIANT 690
FT /note="Y -> D (in biliary atresia; extrahepatic)"
FT /evidence="ECO:0000269|PubMed:12297837"
FT /id="VAR_026324"
FT VARIANT 693
FT /note="C -> Y (in ALGS1; dbSNP:rs566563238)"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026325"
FT VARIANT 714
FT /note="C -> Y (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:11180599"
FT /id="VAR_026326"
FT VARIANT 731
FT /note="C -> S (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:10220506"
FT /id="VAR_013205"
FT VARIANT 740
FT /note="C -> R (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:10220506"
FT /id="VAR_013206"
FT VARIANT 753
FT /note="C -> R (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:11139247"
FT /id="VAR_013207"
FT VARIANT 810
FT /note="P -> L (in TOF; the mutant is unable to activate
FT Notch signaling; dbSNP:rs769531968)"
FT /evidence="ECO:0000269|PubMed:20437614"
FT /id="VAR_080876"
FT VARIANT 818
FT /note="R -> K"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026327"
FT VARIANT 871
FT /note="P -> R (in biliary atresia; extrahepatic;
FT dbSNP:rs35761929)"
FT /evidence="ECO:0000269|PubMed:12297837"
FT /id="VAR_026328"
FT VARIANT 889
FT /note="R -> Q (in ALGS1; unknown pathological significance;
FT dbSNP:rs149419694)"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026329"
FT VARIANT 902
FT /note="C -> S (in ALGS1; dbSNP:rs876661122)"
FT /evidence="ECO:0000269|PubMed:11180599"
FT /id="VAR_026330"
FT VARIANT 908
FT /note="H -> Q (in biliary atresia; extrahepatic)"
FT /evidence="ECO:0000269|PubMed:12297837"
FT /id="VAR_026331"
FT VARIANT 911
FT /note="C -> Y (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:16575836"
FT /id="VAR_026332"
FT VARIANT 913
FT /note="S -> R (in ALGS1)"
FT /evidence="ECO:0000269|PubMed:12442286"
FT /id="VAR_026333"
FT VARIANT 921
FT /note="L -> P (in biliary atresia; extrahepatic;
FT dbSNP:rs1305578649)"
FT /evidence="ECO:0000269|PubMed:12297837"
FT /id="VAR_026334"
FT VARIANT 937
FT /note="R -> Q (likely benign variant; the mutant is able to
FT activate Notch signaling; dbSNP:rs145895196)"
FT /evidence="ECO:0000269|PubMed:12497640,
FT ECO:0000269|PubMed:20437614"
FT /id="VAR_026335"
FT VARIANT 1055..1056
FT /note="VR -> G (in ALGS1)"
FT /id="VAR_026336"
FT VARIANT 1104
FT /note="H -> Q (found in patient with tetralogy of Fallot
FT and pulmonary stenosis; unknown pathological significance;
FT dbSNP:rs1250645531)"
FT /evidence="ECO:0000269|PubMed:20437614"
FT /id="VAR_080877"
FT VARIANT 1213
FT /note="R -> Q (in biliary atresia; extrahepatic;
FT dbSNP:rs138007561)"
FT /evidence="ECO:0000269|PubMed:12297837"
FT /id="VAR_026337"
FT MUTAGEN 207
FT /note="F->A: Strongly reduced NOTCH1 binding."
FT /evidence="ECO:0000269|PubMed:18660822"
FT CONFLICT 117
FT /note="R -> P (in Ref. 5; AAB39007)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="P -> R (in Ref. 1; AAC51731)"
FT /evidence="ECO:0000305"
FT CONFLICT 498
FT /note="N -> D (in Ref. 1; AAC51731)"
FT /evidence="ECO:0000305"
FT STRAND 33..43
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 52..57
FT /evidence="ECO:0007829|PDB:4CC0"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 73..81
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 118..124
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 130..140
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 143..147
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 150..160
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 163..172
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 174..187
FT /evidence="ECO:0007829|PDB:4CC0"
FT TURN 193..196
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 208..212
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:4CC0"
FT TURN 226..229
FT /evidence="ECO:0007829|PDB:4CC0"
FT TURN 240..242
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 257..259
FT /evidence="ECO:0007829|PDB:4CC0"
FT TURN 268..270
FT /evidence="ECO:0007829|PDB:2KB9"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 277..280
FT /evidence="ECO:0007829|PDB:2KB9"
FT STRAND 286..289
FT /evidence="ECO:0007829|PDB:2KB9"
FT TURN 290..293
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:4CC0"
FT HELIX 299..303
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 311..316
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 319..323
FT /evidence="ECO:0007829|PDB:4CC0"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:4CC0"
SQ SEQUENCE 1218 AA; 133799 MW; F36EE9FBF64DF162 CRC64;
MRSPRTRGRS GRPLSLLLAL LCALRAKVCG ASGQFELEIL SMQNVNGELQ NGNCCGGARN
PGDRKCTRDE CDTYFKVCLK EYQSRVTAGG PCSFGSGSTP VIGGNTFNLK ASRGNDRNRI
VLPFSFAWPR SYTLLVEAWD SSNDTVQPDS IIEKASHSGM INPSRQWQTL KQNTGVAHFE
YQIRVTCDDY YYGFGCNKFC RPRDDFFGHY ACDQNGNKTC MEGWMGPECN RAICRQGCSP
KHGSCKLPGD CRCQYGWQGL YCDKCIPHPG CVHGICNEPW QCLCETNWGG QLCDKDLNYC
GTHQPCLNGG TCSNTGPDKY QCSCPEGYSG PNCEIAEHAC LSDPCHNRGS CKETSLGFEC
ECSPGWTGPT CSTNIDDCSP NNCSHGGTCQ DLVNGFKCVC PPQWTGKTCQ LDANECEAKP
CVNAKSCKNL IASYYCDCLP GWMGQNCDIN INDCLGQCQN DASCRDLVNG YRCICPPGYA
GDHCERDIDE CASNPCLNGG HCQNEINRFQ CLCPTGFSGN LCQLDIDYCE PNPCQNGAQC
YNRASDYFCK CPEDYEGKNC SHLKDHCRTT PCEVIDSCTV AMASNDTPEG VRYISSNVCG
PHGKCKSQSG GKFTCDCNKG FTGTYCHENI NDCESNPCRN GGTCIDGVNS YKCICSDGWE
GAYCETNIND CSQNPCHNGG TCRDLVNDFY CDCKNGWKGK TCHSRDSQCD EATCNNGGTC
YDEGDAFKCM CPGGWEGTTC NIARNSSCLP NPCHNGGTCV VNGESFTCVC KEGWEGPICA
QNTNDCSPHP CYNSGTCVDG DNWYRCECAP GFAGPDCRIN INECQSSPCA FGATCVDEIN
GYRCVCPPGH SGAKCQEVSG RPCITMGSVI PDGAKWDDDC NTCQCLNGRI ACSKVWCGPR
PCLLHKGHSE CPSGQSCIPI LDDQCFVHPC TGVGECRSSS LQPVKTKCTS DSYYQDNCAN
ITFTFNKEMM SPGLTTEHIC SELRNLNILK NVSAEYSIYI ACEPSPSANN EIHVAISAED
IRDDGNPIKE ITDKIIDLVS KRDGNSSLIA AVAEVRVQRR PLKNRTDFLV PLLSSVLTVA
WICCLVTAFY WCLRKRRKPG SHTHSASEDN TTNNVREQLN QIKNPIEKHG ANTVPIKDYE
NKNSKMSKIR THNSEVEEDD MDKHQQKARF AKQPAYTLVD REEKPPNGTP TKHPNWTNKQ
DNRDLESAQS LNRMEYIV
