NOTC4_HUMAN
ID NOTC4_HUMAN Reviewed; 2003 AA.
AC Q99466; B0V183; B0V1X5; O00306; Q5SSY7; Q99458; Q99940; Q9H3S8; Q9UII9;
AC Q9UIJ0;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Neurogenic locus notch homolog protein 4 {ECO:0000305};
DE Short=Notch 4;
DE Short=hNotch4;
DE Contains:
DE RecName: Full=Notch 4 extracellular truncation;
DE Contains:
DE RecName: Full=Notch 4 intracellular domain;
DE Flags: Precursor;
GN Name=NOTCH4 {ECO:0000312|HGNC:HGNC:7884}; Synonyms=INT3;
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 [GENOMIC DNA / MRNA] (ISOFORM 1), AND POLYMORPHISM OF
RP POLY-LEU REGION.
RC TISSUE=Placenta;
RX PubMed=9168133; DOI=10.1016/s0378-1119(96)00857-8;
RA Sugaya K., Sasanuma S., Nohata J., Kimura T., Fukagawa T., Nakamura Y.,
RA Ando A., Inoko H., Ikemura T., Mita K.;
RT "Gene organization of human NOTCH4 and (CTG)n polymorphism in this human
RT counterpart gene of mouse proto-oncogene Int3.";
RL Gene 189:235-244(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Bone marrow, and Heart;
RX PubMed=9693032; DOI=10.1006/geno.1998.5330;
RA Li L., Huang G.M., Banta A.B., Deng Y., Smith T., Dong P., Friedman C.,
RA Chen L., Trask B.J., Spies T., Rowen L., Hood L.;
RT "Cloning, characterization, and the complete 56.8-kilobase DNA sequence of
RT the human NOTCH4 gene.";
RL Genomics 51:45-58(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLN-117.
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-503, AND VARIANTS GLN-117 AND
RP GLN-317.
RA Miyagawa T., Tokunaga K., Hojho H.;
RT "Human notch4 gene variant.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
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 [7]
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).
CC -!- FUNCTION: Functions as a receptor for membrane-bound ligands Jagged1,
CC Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand
CC activation through the released notch intracellular domain (NICD) it
CC forms a transcriptional activator complex with RBPJ/RBPSUH and
CC activates genes of the enhancer of split locus. Affects the
CC implementation of differentiation, proliferation and apoptotic
CC programs. May regulate branching morphogenesis in the developing
CC vascular system (By similarity). {ECO:0000250}.
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 NOTCH4. {ECO:0000250,
CC ECO:0000269|PubMed:11101851, ECO:0000269|PubMed:12370315}.
CC -!- INTERACTION:
CC Q99466; P05067: APP; NbExp=3; IntAct=EBI-7970822, EBI-77613;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein.
CC -!- SUBCELLULAR LOCATION: [Notch 4 intracellular domain]: Nucleus.
CC Note=Following proteolytical processing NICD is translocated to the
CC nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=1;
CC IsoId=Q99466-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99466-2; Sequence=VSP_001406;
CC Name=3;
CC IsoId=Q99466-3; Sequence=VSP_001407;
CC -!- TISSUE SPECIFICITY: Highly expressed in the heart, moderately in the
CC lung and placenta and at low levels in the liver, skeletal muscle,
CC kidney, pancreas, spleen, lymph node, thymus, bone marrow and fetal
CC liver. No expression was seen in adult brain or peripheral blood
CC leukocytes.
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 (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated. {ECO:0000250}.
CC -!- POLYMORPHISM: The poly-Leu region of NOTCH4 (in the signal peptide) is
CC polymorphic and the number of Leu varies in the population (from 6 to
CC 12). {ECO:0000269|PubMed:9168133}.
CC -!- SIMILARITY: Belongs to the NOTCH family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA09708.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; D63395; BAA09708.1; ALT_FRAME; mRNA.
DR EMBL; D86566; BAA13116.1; -; Genomic_DNA.
DR EMBL; U95299; AAC32288.1; -; mRNA.
DR EMBL; U89335; AAC63097.1; -; Genomic_DNA.
DR EMBL; AL662884; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX284686; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX284927; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR812478; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR933878; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB023961; BAB20317.1; -; Genomic_DNA.
DR EMBL; AB024520; BAA88951.1; -; Genomic_DNA.
DR EMBL; AB024578; BAA88952.1; -; Genomic_DNA.
DR CCDS; CCDS34420.1; -. [Q99466-1]
DR RefSeq; NP_004548.3; NM_004557.3. [Q99466-1]
DR AlphaFoldDB; Q99466; -.
DR SMR; Q99466; -.
DR BioGRID; 110917; 8.
DR CORUM; Q99466; -.
DR ELM; Q99466; -.
DR IntAct; Q99466; 3.
DR MINT; Q99466; -.
DR STRING; 9606.ENSP00000364163; -.
DR BindingDB; Q99466; -.
DR ChEMBL; CHEMBL3407321; -.
DR GlyGen; Q99466; 6 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; Q99466; -.
DR PhosphoSitePlus; Q99466; -.
DR BioMuta; NOTCH4; -.
DR DMDM; 20139103; -.
DR jPOST; Q99466; -.
DR MassIVE; Q99466; -.
DR MaxQB; Q99466; -.
DR PaxDb; Q99466; -.
DR PeptideAtlas; Q99466; -.
DR PRIDE; Q99466; -.
DR ProteomicsDB; 78281; -. [Q99466-1]
DR ProteomicsDB; 78282; -. [Q99466-2]
DR ProteomicsDB; 78283; -. [Q99466-3]
DR ABCD; Q99466; 8 sequenced antibodies.
DR Antibodypedia; 3228; 314 antibodies from 35 providers.
DR DNASU; 4855; -.
DR Ensembl; ENST00000375023.3; ENSP00000364163.3; ENSG00000204301.6. [Q99466-1]
DR Ensembl; ENST00000425600.1; ENSP00000401321.1; ENSG00000238196.5.
DR Ensembl; ENST00000439349.2; ENSP00000408335.2; ENSG00000223355.5.
DR Ensembl; ENST00000457094.2; ENSP00000403447.2; ENSG00000234876.5. [Q99466-1]
DR GeneID; 4855; -.
DR KEGG; hsa:4855; -.
DR MANE-Select; ENST00000375023.3; ENSP00000364163.3; NM_004557.4; NP_004548.3.
DR UCSC; uc003obb.3; human. [Q99466-1]
DR CTD; 4855; -.
DR DisGeNET; 4855; -.
DR GeneCards; NOTCH4; -.
DR HGNC; HGNC:7884; NOTCH4.
DR HPA; ENSG00000204301; Tissue enhanced (adipose tissue, breast).
DR MIM; 164951; gene.
DR neXtProt; NX_Q99466; -.
DR OpenTargets; ENSG00000204301; -.
DR PharmGKB; PA31686; -.
DR VEuPathDB; HostDB:ENSG00000204301; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000163287; -.
DR HOGENOM; CLU_000576_0_0_1; -.
DR InParanoid; Q99466; -.
DR OMA; SKEPDAC; -.
DR PhylomeDB; Q99466; -.
DR TreeFam; TF351641; -.
DR PathwayCommons; Q99466; -.
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-9013695; NOTCH4 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-9013700; NOTCH4 Activation and Transmission of Signal to the Nucleus.
DR Reactome; R-HSA-9604323; Negative regulation of NOTCH4 signaling.
DR SignaLink; Q99466; -.
DR SIGNOR; Q99466; -.
DR BioGRID-ORCS; 4855; 12 hits in 1077 CRISPR screens.
DR ChiTaRS; NOTCH4; human.
DR GeneWiki; NOTCH4; -.
DR GenomeRNAi; 4855; -.
DR Pharos; Q99466; Tchem.
DR PRO; PR:Q99466; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q99466; protein.
DR Bgee; ENSG00000204301; Expressed in apex of heart and 91 other tissues.
DR ExpressionAtlas; Q99466; baseline and differential.
DR Genevisible; Q99466; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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:0005887; C:integral component of plasma membrane; TAS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; TAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005509; F:calcium ion binding; TAS:UniProtKB.
DR GO; GO:0005112; F:Notch binding; IBA:GO_Central.
DR GO; GO:0038023; F:signaling receptor activity; TAS:UniProtKB.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; NAS:UniProtKB.
DR GO; GO:0001709; P:cell fate determination; TAS:UniProtKB.
DR GO; GO:0001886; P:endothelial cell morphogenesis; IEA:Ensembl.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; IMP:ARUK-UCL.
DR GO; GO:0030097; P:hemopoiesis; TAS:UniProtKB.
DR GO; GO:0030879; P:mammary gland development; IDA:UniProtKB.
DR GO; GO:0001763; P:morphogenesis of a branching structure; ISS:UniProtKB.
DR GO; GO:0060354; P:negative regulation of cell adhesion molecule production; IMP:ARUK-UCL.
DR GO; GO:0045596; P:negative regulation of cell differentiation; NAS:UniProtKB.
DR GO; GO:2000048; P:negative regulation of cell-cell adhesion mediated by cadherin; IMP:ARUK-UCL.
DR GO; GO:0045602; P:negative regulation of endothelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:ARUK-UCL.
DR GO; GO:0007221; P:positive regulation of transcription of Notch receptor target; TAS:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; TAS:UniProtKB.
DR GO; GO:0001944; P:vasculature development; ISS:UniProtKB.
DR GO; GO:0042060; P:wound healing; 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; IPR022355; Notch_4.
DR InterPro; IPR000800; Notch_dom.
DR InterPro; IPR010660; Notch_NOD_dom.
DR InterPro; IPR011656; Notch_NODP_dom.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF00008; EGF; 12.
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; PR01987; NOTCH4.
DR SMART; SM00248; ANK; 5.
DR SMART; SM00181; EGF; 29.
DR SMART; SM00179; EGF_CA; 22.
DR SMART; SM00004; NL; 3.
DR SMART; SM01338; NOD; 1.
DR SMART; SM01339; NODP; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF57184; SSF57184; 5.
DR SUPFAM; SSF90193; SSF90193; 2.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 5.
DR PROSITE; PS00010; ASX_HYDROXYL; 11.
DR PROSITE; PS00022; EGF_1; 28.
DR PROSITE; PS01186; EGF_2; 21.
DR PROSITE; PS50026; EGF_3; 28.
DR PROSITE; PS01187; EGF_CA; 9.
DR PROSITE; PS50258; LNR; 3.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; ANK repeat; Cell membrane;
KW Developmental protein; Differentiation; Disulfide bond; EGF-like domain;
KW Glycoprotein; Membrane; Notch signaling pathway; Nucleus; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Transcription;
KW Transcription regulation; Transmembrane; Transmembrane helix;
KW Triplet repeat expansion.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..2003
FT /note="Neurogenic locus notch homolog protein 4"
FT /id="PRO_0000007701"
FT CHAIN 1432..2003
FT /note="Notch 4 extracellular truncation"
FT /evidence="ECO:0000250"
FT /id="PRO_0000007702"
FT CHAIN 1467..2003
FT /note="Notch 4 intracellular domain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000007703"
FT TOPO_DOM 24..1447
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1448..1468
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1469..2003
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..63
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 64..115
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 118..155
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 156..192
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 194..232
FT /note="EGF-like 5; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 234..274
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 276..312
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 314..353
FT /note="EGF-like 8; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 355..391
FT /note="EGF-like 9; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 392..430
FT /note="EGF-like 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 432..473
FT /note="EGF-like 11; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 475..511
FT /note="EGF-like 12; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 513..549
FT /note="EGF-like 13; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 551..587
FT /note="EGF-like 14; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 589..625
FT /note="EGF-like 15; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 626..659
FT /note="EGF-like 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 661..689
FT /note="EGF-like 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 691..727
FT /note="EGF-like 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 729..765
FT /note="EGF-like 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 767..803
FT /note="EGF-like 20"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 806..842
FT /note="EGF-like 21"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 844..880
FT /note="EGF-like 22"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 882..928
FT /note="EGF-like 23"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 930..966
FT /note="EGF-like 24"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 968..1004
FT /note="EGF-like 25"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1006..1044
FT /note="EGF-like 26"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1046..1085
FT /note="EGF-like 27"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1087..1126
FT /note="EGF-like 28"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1130..1171
FT /note="EGF-like 29"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1170..1213
FT /note="LNR 1"
FT REPEAT 1214..1250
FT /note="LNR 2"
FT REPEAT 1251..1294
FT /note="LNR 3"
FT REPEAT 1633..1665
FT /note="ANK 1"
FT REPEAT 1666..1698
FT /note="ANK 2"
FT REPEAT 1700..1732
FT /note="ANK 3"
FT REPEAT 1733..1765
FT /note="ANK 4"
FT REPEAT 1766..1798
FT /note="ANK 5"
FT REGION 1347..1371
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1485..1508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1900..1927
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1968..2003
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 664
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 714
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 964
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 28..41
FT /evidence="ECO:0000250"
FT DISULFID 35..51
FT /evidence="ECO:0000250"
FT DISULFID 53..62
FT /evidence="ECO:0000250"
FT DISULFID 68..80
FT /evidence="ECO:0000250"
FT DISULFID 74..103
FT /evidence="ECO:0000250"
FT DISULFID 105..114
FT /evidence="ECO:0000250"
FT DISULFID 122..133
FT /evidence="ECO:0000250"
FT DISULFID 127..143
FT /evidence="ECO:0000250"
FT DISULFID 145..154
FT /evidence="ECO:0000250"
FT DISULFID 160..171
FT /evidence="ECO:0000250"
FT DISULFID 165..180
FT /evidence="ECO:0000250"
FT DISULFID 182..191
FT /evidence="ECO:0000250"
FT DISULFID 198..211
FT /evidence="ECO:0000250"
FT DISULFID 205..220
FT /evidence="ECO:0000250"
FT DISULFID 222..231
FT /evidence="ECO:0000250"
FT DISULFID 238..249
FT /evidence="ECO:0000250"
FT DISULFID 243..262
FT /evidence="ECO:0000250"
FT DISULFID 264..273
FT /evidence="ECO:0000250"
FT DISULFID 280..291
FT /evidence="ECO:0000250"
FT DISULFID 285..300
FT /evidence="ECO:0000250"
FT DISULFID 302..311
FT /evidence="ECO:0000250"
FT DISULFID 318..332
FT /evidence="ECO:0000250"
FT DISULFID 326..341
FT /evidence="ECO:0000250"
FT DISULFID 343..352
FT /evidence="ECO:0000250"
FT DISULFID 359..370
FT /evidence="ECO:0000250"
FT DISULFID 364..379
FT /evidence="ECO:0000250"
FT DISULFID 381..390
FT /evidence="ECO:0000250"
FT DISULFID 396..407
FT /evidence="ECO:0000250"
FT DISULFID 401..418
FT /evidence="ECO:0000250"
FT DISULFID 420..429
FT /evidence="ECO:0000250"
FT DISULFID 436..452
FT /evidence="ECO:0000250"
FT DISULFID 446..461
FT /evidence="ECO:0000250"
FT DISULFID 463..472
FT /evidence="ECO:0000250"
FT DISULFID 479..490
FT /evidence="ECO:0000250"
FT DISULFID 484..499
FT /evidence="ECO:0000250"
FT DISULFID 501..510
FT /evidence="ECO:0000250"
FT DISULFID 517..528
FT /evidence="ECO:0000250"
FT DISULFID 522..537
FT /evidence="ECO:0000250"
FT DISULFID 539..548
FT /evidence="ECO:0000250"
FT DISULFID 555..566
FT /evidence="ECO:0000250"
FT DISULFID 560..575
FT /evidence="ECO:0000250"
FT DISULFID 577..586
FT /evidence="ECO:0000250"
FT DISULFID 593..604
FT /evidence="ECO:0000250"
FT DISULFID 598..613
FT /evidence="ECO:0000250"
FT DISULFID 615..624
FT /evidence="ECO:0000250"
FT DISULFID 629..640
FT /evidence="ECO:0000250"
FT DISULFID 634..649
FT /evidence="ECO:0000250"
FT DISULFID 651..658
FT /evidence="ECO:0000250"
FT DISULFID 665..672
FT /evidence="ECO:0000250"
FT DISULFID 667..677
FT /evidence="ECO:0000250"
FT DISULFID 679..688
FT /evidence="ECO:0000250"
FT DISULFID 695..706
FT /evidence="ECO:0000250"
FT DISULFID 700..715
FT /evidence="ECO:0000250"
FT DISULFID 717..726
FT /evidence="ECO:0000250"
FT DISULFID 733..744
FT /evidence="ECO:0000250"
FT DISULFID 738..753
FT /evidence="ECO:0000250"
FT DISULFID 755..764
FT /evidence="ECO:0000250"
FT DISULFID 771..782
FT /evidence="ECO:0000250"
FT DISULFID 776..791
FT /evidence="ECO:0000250"
FT DISULFID 793..802
FT /evidence="ECO:0000250"
FT DISULFID 810..821
FT /evidence="ECO:0000250"
FT DISULFID 815..830
FT /evidence="ECO:0000250"
FT DISULFID 832..841
FT /evidence="ECO:0000250"
FT DISULFID 848..859
FT /evidence="ECO:0000250"
FT DISULFID 853..868
FT /evidence="ECO:0000250"
FT DISULFID 870..879
FT /evidence="ECO:0000250"
FT DISULFID 886..907
FT /evidence="ECO:0000250"
FT DISULFID 901..916
FT /evidence="ECO:0000250"
FT DISULFID 918..927
FT /evidence="ECO:0000250"
FT DISULFID 934..945
FT /evidence="ECO:0000250"
FT DISULFID 939..954
FT /evidence="ECO:0000250"
FT DISULFID 956..965
FT /evidence="ECO:0000250"
FT DISULFID 972..983
FT /evidence="ECO:0000250"
FT DISULFID 977..992
FT /evidence="ECO:0000250"
FT DISULFID 994..1003
FT /evidence="ECO:0000250"
FT DISULFID 1010..1023
FT /evidence="ECO:0000250"
FT DISULFID 1015..1032
FT /evidence="ECO:0000250"
FT DISULFID 1034..1043
FT /evidence="ECO:0000250"
FT DISULFID 1050..1061
FT /evidence="ECO:0000250"
FT DISULFID 1055..1073
FT /evidence="ECO:0000250"
FT DISULFID 1075..1084
FT /evidence="ECO:0000250"
FT DISULFID 1091..1102
FT /evidence="ECO:0000250"
FT DISULFID 1096..1114
FT /evidence="ECO:0000250"
FT DISULFID 1116..1125
FT /evidence="ECO:0000250"
FT DISULFID 1134..1146
FT /evidence="ECO:0000250"
FT DISULFID 1140..1159
FT /evidence="ECO:0000250"
FT DISULFID 1161..1170
FT /evidence="ECO:0000250"
FT DISULFID 1178..1191
FT /evidence="ECO:0000250"
FT DISULFID 1187..1203
FT /evidence="ECO:0000250"
FT DISULFID 1214..1238
FT /evidence="ECO:0000250"
FT DISULFID 1220..1233
FT /evidence="ECO:0000250"
FT DISULFID 1229..1245
FT /evidence="ECO:0000250"
FT DISULFID 1251..1277
FT /evidence="ECO:0000250"
FT DISULFID 1259..1272
FT /evidence="ECO:0000250"
FT DISULFID 1268..1284
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..1414
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9693032"
FT /id="VSP_001406"
FT VAR_SEQ 378..2003
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9693032"
FT /id="VSP_001407"
FT VARIANT 117
FT /note="K -> Q (in dbSNP:rs915894)"
FT /evidence="ECO:0000269|PubMed:14574404, ECO:0000269|Ref.4"
FT /id="VAR_012866"
FT VARIANT 204
FT /note="P -> L (in dbSNP:rs2071282)"
FT /id="VAR_033828"
FT VARIANT 206
FT /note="P -> L (in dbSNP:rs2071282)"
FT /id="VAR_033829"
FT VARIANT 244
FT /note="S -> L (in dbSNP:rs8192585)"
FT /id="VAR_033830"
FT VARIANT 272
FT /note="D -> G (in dbSNP:rs520692)"
FT /id="VAR_012867"
FT VARIANT 284
FT /note="Q -> H (in dbSNP:rs520803)"
FT /id="VAR_059271"
FT VARIANT 317
FT /note="E -> Q"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_012868"
FT VARIANT 320
FT /note="T -> A (in dbSNP:rs422951)"
FT /id="VAR_012869"
FT VARIANT 534
FT /note="G -> S (in dbSNP:rs8192591)"
FT /id="VAR_033831"
FT VARIANT 809
FT /note="S -> I (in dbSNP:rs3132961)"
FT /id="VAR_048991"
FT VARIANT 851
FT /note="K -> R (in dbSNP:rs2022060)"
FT /id="VAR_012870"
FT VARIANT 942
FT /note="G -> R (in dbSNP:rs17604492)"
FT /id="VAR_048992"
FT VARIANT 1346
FT /note="R -> P (in dbSNP:rs8192573)"
FT /id="VAR_048993"
FT CONFLICT 1431
FT /note="A -> V (in Ref. 1; BAA09708)"
FT /evidence="ECO:0000305"
FT CONFLICT 1436
FT /note="A -> E (in Ref. 1; BAA09708)"
FT /evidence="ECO:0000305"
FT CONFLICT 1445
FT /note="L -> F (in Ref. 1; BAA09708)"
FT /evidence="ECO:0000305"
FT CONFLICT 1537..1539
FT /note="Missing (in Ref. 2; AAC63097)"
FT /evidence="ECO:0000305"
FT CONFLICT 1538
FT /note="G -> A (in Ref. 1; BAA09708)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2003 AA; 209622 MW; BED10283A43A0C14 CRC64;
MQPPSLLLLL LLLLLLCVSV VRPRGLLCGS FPEPCANGGT CLSLSLGQGT CQCAPGFLGE
TCQFPDPCQN AQLCQNGGSC QALLPAPLGL PSSPSPLTPS FLCTCLPGFT GERCQAKLED
PCPPSFCSKR GRCHIQASGR PQCSCMPGWT GEQCQLRDFC SANPCVNGGV CLATYPQIQC
HCPPGFEGHA CERDVNECFQ DPGPCPKGTS CHNTLGSFQC LCPVGQEGPR CELRAGPCPP
RGCSNGGTCQ LMPEKDSTFH LCLCPPGFIG PDCEVNPDNC VSHQCQNGGT CQDGLDTYTC
LCPETWTGWD CSEDVDECET QGPPHCRNGG TCQNSAGSFH CVCVSGWGGT SCEENLDDCI
AATCAPGSTC IDRVGSFSCL CPPGRTGLLC HLEDMCLSQP CHGDAQCSTN PLTGSTLCLC
QPGYSGPTCH QDLDECLMAQ QGPSPCEHGG SCLNTPGSFN CLCPPGYTGS RCEADHNECL
SQPCHPGSTC LDLLATFHCL CPPGLEGQLC EVETNECASA PCLNHADCHD LLNGFQCICL
PGFSGTRCEE DIDECRSSPC ANGGQCQDQP GAFHCKCLPG FEGPRCQTEV DECLSDPCPV
GASCLDLPGA FFCLCPSGFT GQLCEVPLCA PNLCQPKQIC KDQKDKANCL CPDGSPGCAP
PEDNCTCHHG HCQRSSCVCD VGWTGPECEA ELGGCISAPC AHGGTCYPQP SGYNCTCPTG
YTGPTCSEEM TACHSGPCLN GGSCNPSPGG YYCTCPPSHT GPQCQTSTDY CVSAPCFNGG
TCVNRPGTFS CLCAMGFQGP RCEGKLRPSC ADSPCRNRAT CQDSPQGPRC LCPTGYTGGS
CQTLMDLCAQ KPCPRNSHCL QTGPSFHCLC LQGWTGPLCN LPLSSCQKAA LSQGIDVSSL
CHNGGLCVDS GPSYFCHCPP GFQGSLCQDH VNPCESRPCQ NGATCMAQPS GYLCQCAPGY
DGQNCSKELD ACQSQPCHNH GTCTPKPGGF HCACPPGFVG LRCEGDVDEC LDQPCHPTGT
AACHSLANAF YCQCLPGHTG QWCEVEIDPC HSQPCFHGGT CEATAGSPLG FICHCPKGFE
GPTCSHRAPS CGFHHCHHGG LCLPSPKPGF PPRCACLSGY GGPDCLTPPA PKGCGPPSPC
LYNGSCSETT GLGGPGFRCS CPHSSPGPRC QKPGAKGCEG RSGDGACDAG CSGPGGNWDG
GDCSLGVPDP WKGCPSHSRC WLLFRDGQCH PQCDSEECLF DGYDCETPPA CTPAYDQYCH
DHFHNGHCEK GCNTAECGWD GGDCRPEDGD PEWGPSLALL VVLSPPALDQ QLFALARVLS
LTLRVGLWVR KDRDGRDMVY PYPGARAEEK LGGTRDPTYQ ERAAPQTQPL GKETDSLSAG
FVVVMGVDLS RCGPDHPASR CPWDPGLLLR FLAAMAAVGA LEPLLPGPLL AVHPHAGTAP
PANQLPWPVL CSPVAGVILL ALGALLVLQL IRRRRREHGA LWLPPGFTRR PRTQSAPHRR
RPPLGEDSIG LKALKPKAEV DEDGVVMCSG PEEGEEVGQA EETGPPSTCQ LWSLSGGCGA
LPQAAMLTPP QESEMEAPDL DTRGPDGVTP LMSAVCCGEV QSGTFQGAWL GCPEPWEPLL
DGGACPQAHT VGTGETPLHL AARFSRPTAA RRLLEAGANP NQPDRAGRTP LHAAVAADAR
EVCQLLLRSR QTAVDARTED GTTPLMLAAR LAVEDLVEEL IAAQADVGAR DKWGKTALHW
AAAVNNARAA RSLLQAGADK DAQDNREQTP LFLAAREGAV EVAQLLLGLG AARELRDQAG
LAPADVAHQR NHWDLLTLLE GAGPPEARHK ATPGREAGPF PRARTVSVSV PPHGGGALPR
CRTLSAGAGP RGGGACLQAR TWSVDLAARG GGAYSHCRSL SGVGAGGGPT PRGRRFSAGM
RGPRPNPAIM RGRYGVAAGR GGRVSTDDWP CDWVALGACG SASNIPIPPP CLTPSPERGS
PQLDCGPPAL QEMPINQGGE GKK
