NOTC1_RAT
ID NOTC1_RAT Reviewed; 2531 AA.
AC Q07008; F1M9E7;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2013, sequence version 3.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Neurogenic locus notch homolog protein 1;
DE Short=Notch 1;
DE Contains:
DE RecName: Full=Notch 1 extracellular truncation;
DE Short=NEXT;
DE Contains:
DE RecName: Full=Notch 1 intracellular domain;
DE Short=NICD;
DE Flags: Precursor;
GN Name=Notch1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Schwann cell;
RX PubMed=1764995; DOI=10.1242/dev.113.1.199;
RA Weinmaster G., Roberts V.J., Lemke G.;
RT "A homolog of Drosophila Notch expressed during mammalian development.";
RL Development 113:199-205(1991).
RN [2]
RP SEQUENCE REVISION TO 1652-1653.
RA Weinmaster G.;
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION.
RX PubMed=11182080; DOI=10.1016/s0896-6273(01)00179-9;
RA Tanigaki K., Nogaki F., Takahashi J., Tashiro K., Kurooka H., Honjo T.;
RT "Notch1 and Notch3 instructively restrict bFGF-responsive multipotent
RT neural progenitor cells to an astroglial fate.";
RL Neuron 29:45-55(2001).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=1295745; DOI=10.1242/dev.116.4.931;
RA Weinmaster G., Roberts V.J., Lemke G.;
RT "Notch2: a second mammalian Notch gene.";
RL Development 116:931-941(1992).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=11438922; DOI=10.1002/cne.1059.abs;
RA Irvin D.K., Zurcher S.D., Nguyen T., Weinmaster G., Kornblum H.I.;
RT "Expression patterns of Notch1, Notch2, and Notch3 suggest multiple
RT functional roles for the Notch-DSL signaling system during brain
RT development.";
RL J. Comp. Neurol. 436:167-181(2001).
RN [8] {ECO:0007744|PDB:4XL1, ECO:0007744|PDB:4XLW}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 412-526 IN COMPLEX WITH DLL4 AND
RP CALCIUM, GLYCOSYLATION AT SER-435; SER-458; THR-466 AND SER-496, AND
RP DISULFIDE BONDS.
RX PubMed=25700513; DOI=10.1126/science.1261093;
RA Luca V.C., Jude K.M., Pierce N.W., Nachury M.V., Fischer S., Garcia K.C.;
RT "Structural biology. Structural basis for Notch1 engagement of Delta-like
RT 4.";
RL Science 347:847-853(2015).
CC -!- FUNCTION: Functions as a receptor for membrane-bound ligands Jagged-1
CC (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate
CC determination (By similarity). Upon ligand activation through the
CC released notch intracellular domain (NICD) it forms a transcriptional
CC activator complex with RBPJ/RBPSUH and activates genes of the enhancer
CC of split locus (By similarity). Affects the implementation of
CC differentiation, proliferation and apoptotic programs (By similarity).
CC Involved in angiogenesis; negatively regulates endothelial cell
CC proliferation and migration and angiogenic sprouting (By similarity).
CC Involved in the maturation of both CD4(+) and CD8(+) cells in the
CC thymus (By similarity). Important for follicular differentiation and
CC possibly cell fate selection within the follicle (By similarity).
CC During cerebellar development, functions as a receptor for neuronal
CC DNER and is involved in the differentiation of Bergmann glia
CC (PubMed:11182080). Represses neuronal and myogenic differentiation (By
CC similarity). May play an essential role in postimplantation
CC development, probably in some aspect of cell specification and/or
CC differentiation (By similarity). May be involved in mesoderm
CC development, somite formation and neurogenesis (By similarity). May
CC enhance HIF1A function by sequestering HIF1AN away from HIF1A (By
CC similarity). Required for the THBS4 function in regulating protective
CC astrogenesis from the subventricular zone (SVZ) niche after injury (By
CC similarity). Involved in determination of left/right symmetry by
CC modulating the balance between motile and immotile (sensory) cilia at
CC the left-right organiser (LRO) (By similarity).
CC {ECO:0000250|UniProtKB:Q01705, ECO:0000269|PubMed:11182080}.
CC -!- SUBUNIT: Heterodimer of a C-terminal fragment N(TM) and an N-terminal
CC fragment N(EC) which are probably linked by disulfide bonds. Interacts
CC with DNER, DTX1, DTX2 and RBPJ/RBPSUH. Also interacts with MAML1, MAML2
CC and MAML3 which act as transcriptional coactivators for NOTCH1. Notch 1
CC intracellular domain interacts with SNW1; the interaction involves
CC multimerized NOTCH1 NICD and is implicated in a formation of an
CC intermediate preactivation complex which associates with DNA-bound CBF-
CC 1/RBPJ. The activated membrane-bound form interacts with AAK1 which
CC promotes NOTCH1 stabilization. Forms a trimeric complex with FBXW7 and
CC SGK1. Interacts with HIF1AN. HIF1AN negatively regulates the function
CC of notch intracellular domain (NICD), accelerating myogenic
CC differentiation. Interacts (via NICD) with SNAI1 (via zinc fingers);
CC the interaction induces SNAI1 degradation via MDM2-mediated
CC ubiquitination and inhibits SNAI1-induced cell invasion. Interacts (via
CC NICD) with MDM2A. Interacts (via NICD) with BCL6; the interaction
CC decreases MAML1 recruitment by NOTCH1 NICD on target genes DNA and
CC inhibits NOTCH1 transcractivation activity (By similarity). Interacts
CC with THBS4 (By similarity). Interacts (via the EGF-like repeat region)
CC with CCN3 (via CTCK domain) (By similarity). Interacts (via EGF-like
CC domains) with DLL4 (via N-terminal DSL and MNNL domains)
CC (PubMed:25700513). Interacts with ZMIZ1 (By similarity). Interacts (via
CC NICD domain) with MEGF10 (via the cytoplasmic domain). Interacts with
CC DLL1 and JAG1 (By similarity). Interacts (via NICD domain) with PRAG1
CC (By similarity). Forms a complex with PRAG1, N1ICD and MAML1, in a
CC MAML1-dependent manner (By similarity). Interacts (via transmembrane
CC region) with PSEN1; the interaction is direct (By similarity).
CC Interacts with ZFP64 (By similarity). {ECO:0000250|UniProtKB:P46531,
CC ECO:0000250|UniProtKB:Q01705, ECO:0000269|PubMed:25700513}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q01705};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q01705}.
CC -!- SUBCELLULAR LOCATION: [Notch 1 intracellular domain]: Nucleus
CC {ECO:0000250|UniProtKB:Q01705}. Note=Following proteolytical processing
CC NICD is translocated to the nucleus. Nuclear location may require
CC MEGF10. {ECO:0000250|UniProtKB:Q01705}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain, kidney and spleen.
CC Expressed in postnatal central nervous system (CNS) germinal zones and,
CC in early postnatal life, within numerous cells throughout the CNS.
CC Found in both subventricular and ventricular germinal zones.
CC {ECO:0000269|PubMed:11438922, ECO:0000269|PubMed:1295745}.
CC -!- DEVELOPMENTAL STAGE: In the embryo, highest levels occur between days
CC 12 and 14 and decrease rapidly to much lower levels in the adult.
CC -!- DOMAIN: Interaction with PSEN1 causes partial unwinding of the
CC transmembrane helix, facilitating access to the scissile peptide bond.
CC {ECO:0000250|UniProtKB:P46531}.
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 ADAM17 to yield a membrane-associated intermediate fragment
CC called notch extracellular truncation (NEXT). Following endocytosis,
CC this fragment is then cleaved by one of the catalytic subunits of
CC gamma-secretase (PSEN1 or PSEN2) to release a Notch-derived peptide
CC containing the intracellular domain (NICD) from the membrane.
CC {ECO:0000250|UniProtKB:Q01705}.
CC -!- PTM: Phosphorylated. {ECO:0000250}.
CC -!- PTM: O-glycosylated on the EGF-like domains. O-glucosylated at Ser-435
CC by KDELC1 and KDELC2 (By similarity). Contains both O-linked fucose and
CC O-linked glucose in the EGF-like domains 11, 12 and 13, which are
CC interacting with the residues on DLL4 (PubMed:25700513). O-linked
CC glycosylation by GALNT11 is involved in determination of left/right
CC symmetry: glycosylation promotes activation of NOTCH1, possibly by
CC promoting cleavage by ADAM17, modulating the balance between motile and
CC immotile (sensory) cilia at the left-right organiser (LRO). MFNG-,
CC RFNG- and LFNG-mediated modification of O-fucose residues at specific
CC EGF-like domains results in inhibition of its activation by JAG1 and
CC enhancement of its activation by DLL1 via an increased binding to DLL1
CC (By similarity). {ECO:0000250|UniProtKB:P46531,
CC ECO:0000250|UniProtKB:Q01705, ECO:0000269|PubMed:25700513}.
CC -!- PTM: Ubiquitinated. Undergoes 'Lys-29'-linked polyubiquitination by
CC ITCH; promotes the lysosomal degradation of non-activated internalized
CC NOTCH1. Monoubiquitination at Lys-1749 is required for activation by
CC gamma-secretase cleavage, it promotes interaction with AAK1, which
CC stabilizes it. Deubiquitination by EIF3F is necessary for nuclear
CC import of activated Notch. {ECO:0000250|UniProtKB:Q01705}.
CC -!- PTM: Hydroxylated at Asn-1945 and Asn-2012 by HIF1AN. Hydroxylation
CC reduces affinity for HI1AN and may thus indirectly modulate negative
CC regulation of NICD (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the NOTCH family. {ECO:0000305}.
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DR EMBL; X57405; CAA40667.1; -; mRNA.
DR EMBL; AABR06021907; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06021908; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474001; EDL93491.1; -; Genomic_DNA.
DR PIR; S18188; S18188.
DR RefSeq; NP_001099191.1; NM_001105721.1.
DR PDB; 4XL1; X-ray; 2.30 A; A/D=412-526.
DR PDB; 4XLW; X-ray; 3.39 A; A/C/E/G=412-526.
DR PDB; 5UK5; X-ray; 2.51 A; A=295-488.
DR PDBsum; 4XL1; -.
DR PDBsum; 4XLW; -.
DR PDBsum; 5UK5; -.
DR AlphaFoldDB; Q07008; -.
DR SMR; Q07008; -.
DR BioGRID; 247529; 1.
DR IntAct; Q07008; 3.
DR STRING; 10116.ENSRNOP00000026212; -.
DR GlyGen; Q07008; 48 sites.
DR iPTMnet; Q07008; -.
DR PhosphoSitePlus; Q07008; -.
DR PaxDb; Q07008; -.
DR PRIDE; Q07008; -.
DR Ensembl; ENSRNOT00000026212; ENSRNOP00000026212; ENSRNOG00000019322.
DR GeneID; 25496; -.
DR KEGG; rno:25496; -.
DR UCSC; RGD:3187; rat.
DR CTD; 4851; -.
DR RGD; 3187; Notch1.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000157157; -.
DR HOGENOM; CLU_000576_0_0_1; -.
DR InParanoid; Q07008; -.
DR OMA; IAGYSCE; -.
DR OrthoDB; 7525at2759; -.
DR TreeFam; TF351641; -.
DR PRO; PR:Q07008; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Proteomes; UP000234681; Chromosome 3.
DR Bgee; ENSRNOG00000019322; Expressed in lung and 19 other tissues.
DR Genevisible; Q07008; RN.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:RGD.
DR GO; GO:0005912; C:adherens junction; ISS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0071944; C:cell periphery; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0002193; C:MAML1-RBP-Jkappa- ICN1 complex; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0031490; F:chromatin DNA binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISS:UniProtKB.
DR GO; GO:0004857; F:enzyme inhibitor activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005112; F:Notch binding; ISO:RGD.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:RGD.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:WormBase.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0003180; P:aortic valve morphogenesis; ISO:RGD.
DR GO; GO:1902263; P:apoptotic process involved in embryonic digit morphogenesis; ISO:RGD.
DR GO; GO:0060842; P:arterial endothelial cell differentiation; ISO:RGD.
DR GO; GO:0048708; P:astrocyte differentiation; IDA:RGD.
DR GO; GO:0003162; P:atrioventricular node development; ISO:RGD.
DR GO; GO:0003181; P:atrioventricular valve morphogenesis; ISO:RGD.
DR GO; GO:0009912; P:auditory receptor cell fate commitment; ISO:RGD.
DR GO; GO:0007409; P:axonogenesis; ISO:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISO:RGD.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; IEA:Ensembl.
DR GO; GO:0003209; P:cardiac atrium morphogenesis; ISO:RGD.
DR GO; GO:0003207; P:cardiac chamber formation; ISO:RGD.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0003214; P:cardiac left ventricle morphogenesis; ISO:RGD.
DR GO; GO:0060379; P:cardiac muscle cell myoblast differentiation; IEA:Ensembl.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; ISO:RGD.
DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; ISO:RGD.
DR GO; GO:0003213; P:cardiac right atrium morphogenesis; ISO:RGD.
DR GO; GO:0003219; P:cardiac right ventricle formation; ISO:RGD.
DR GO; GO:0060411; P:cardiac septum morphogenesis; ISO:RGD.
DR GO; GO:0060948; P:cardiac vascular smooth muscle cell development; ISO:RGD.
DR GO; GO:0003208; P:cardiac ventricle morphogenesis; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; ISO:RGD.
DR GO; GO:0021515; P:cell differentiation in spinal cord; IEP:RGD.
DR GO; GO:0045165; P:cell fate commitment; ISO:RGD.
DR GO; GO:0001708; P:cell fate specification; ISO:RGD.
DR GO; GO:0003273; P:cell migration involved in endocardial cushion formation; ISO:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; ISO:RGD.
DR GO; GO:0071228; P:cellular response to tumor cell; ISO:RGD.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0072044; P:collecting duct development; ISO:RGD.
DR GO; GO:0007386; P:compartment pattern specification; ISO:RGD.
DR GO; GO:0060982; P:coronary artery morphogenesis; ISO:RGD.
DR GO; GO:0003182; P:coronary sinus valve morphogenesis; ISO:RGD.
DR GO; GO:0003169; P:coronary vein morphogenesis; ISO:RGD.
DR GO; GO:0007368; P:determination of left/right symmetry; ISO:RGD.
DR GO; GO:0072017; P:distal tubule development; ISO:RGD.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; ISO:RGD.
DR GO; GO:0030326; P:embryonic limb morphogenesis; ISO:RGD.
DR GO; GO:0060956; P:endocardial cell differentiation; ISO:RGD.
DR GO; GO:0003197; P:endocardial cushion development; ISO:RGD.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISO:RGD.
DR GO; GO:0003157; P:endocardium development; ISO:RGD.
DR GO; GO:0003160; P:endocardium morphogenesis; ISO:RGD.
DR GO; GO:0007492; P:endoderm development; ISO:RGD.
DR GO; GO:0009957; P:epidermal cell fate specification; IEA:Ensembl.
DR GO; GO:0008544; P:epidermis development; ISO:RGD.
DR GO; GO:0072148; P:epithelial cell fate commitment; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0003198; P:epithelial to mesenchymal transition involved in endocardial cushion formation; ISO:RGD.
DR GO; GO:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0007440; P:foregut morphogenesis; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0010001; P:glial cell differentiation; ISO:RGD.
DR GO; GO:0072144; P:glomerular mesangial cell development; ISO:RGD.
DR GO; GO:0003241; P:growth involved in heart morphogenesis; ISO:RGD.
DR GO; GO:0031069; P:hair follicle morphogenesis; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0001947; P:heart looping; ISO:RGD.
DR GO; GO:0061384; P:heart trabecula morphogenesis; ISO:RGD.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; ISO:RGD.
DR GO; GO:0006959; P:humoral immune response; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; ISO:RGD.
DR GO; GO:0002085; P:inhibition of neuroepithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0097400; P:interleukin-17-mediated signaling pathway; ISO:RGD.
DR GO; GO:0030216; P:keratinocyte differentiation; ISO:RGD.
DR GO; GO:0070986; P:left/right axis specification; ISO:RGD.
DR GO; GO:0001889; P:liver development; ISO:RGD.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:0014031; P:mesenchymal cell development; ISO:RGD.
DR GO; GO:0003192; P:mitral valve formation; ISO:RGD.
DR GO; GO:2000811; P:negative regulation of anoikis; ISO:RGD.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; ISO:RGD.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISO:RGD.
DR GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; ISO:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; ISO:RGD.
DR GO; GO:0043086; P:negative regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:0060354; P:negative regulation of cell adhesion molecule production; ISO:RGD.
DR GO; GO:0060548; P:negative regulation of cell death; ISO:RGD.
DR GO; GO:0045596; P:negative regulation of cell differentiation; ISO:RGD.
DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0003252; P:negative regulation of cell proliferation involved in heart valve morphogenesis; ISO:RGD.
DR GO; GO:2000048; P:negative regulation of cell-cell adhesion mediated by cadherin; ISO:RGD.
DR GO; GO:0010812; P:negative regulation of cell-substrate adhesion; ISO:RGD.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:2001027; P:negative regulation of endothelial cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0003332; P:negative regulation of extracellular matrix constituent secretion; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; ISS:UniProtKB.
DR GO; GO:0045608; P:negative regulation of inner ear auditory receptor cell differentiation; ISO:RGD.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; ISO:RGD.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; ISS:UniProtKB.
DR GO; GO:0050768; P:negative regulation of neurogenesis; ISS:UniProtKB.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IMP:RGD.
DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0030279; P:negative regulation of ossification; ISO:RGD.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:RGD.
DR GO; GO:0046533; P:negative regulation of photoreceptor cell differentiation; ISO:RGD.
DR GO; GO:2000974; P:negative regulation of pro-B cell differentiation; ISS:UniProtKB.
DR GO; GO:2000737; P:negative regulation of stem cell differentiation; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0021915; P:neural tube development; ISO:RGD.
DR GO; GO:0061101; P:neuroendocrine cell differentiation; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; ISO:RGD.
DR GO; GO:0048663; P:neuron fate commitment; ISO:RGD.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; ISO:RGD.
DR GO; GO:0061314; P:Notch signaling involved in heart development; ISS:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:WormBase.
DR GO; GO:0003270; P:Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation; ISO:RGD.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEP:RGD.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISO:RGD.
DR GO; GO:0003344; P:pericardium morphogenesis; ISO:RGD.
DR GO; GO:1903849; P:positive regulation of aorta morphogenesis; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:1902339; P:positive regulation of apoptotic process involved in morphogenesis; ISO:RGD.
DR GO; GO:0048711; P:positive regulation of astrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0062043; P:positive regulation of cardiac epithelial to mesenchymal transition; IGI:BHF-UCL.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IMP:RGD.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:RGD.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0045687; P:positive regulation of glial cell differentiation; IMP:RGD.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; ISO:RGD.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IMP:RGD.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISO:RGD.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISO:RGD.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:RGD.
DR GO; GO:0061419; P:positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; ISS:UniProtKB.
DR GO; GO:0007221; P:positive regulation of transcription of Notch receptor target; IMP:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; ISO:RGD.
DR GO; GO:0050434; P:positive regulation of viral transcription; ISO:RGD.
DR GO; GO:0060740; P:prostate gland epithelium morphogenesis; ISO:RGD.
DR GO; GO:0030163; P:protein catabolic process; ISO:RGD.
DR GO; GO:0006606; P:protein import into nucleus; ISO:RGD.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; ISO:RGD.
DR GO; GO:0003264; P:regulation of cardioblast proliferation; IMP:RGD.
DR GO; GO:0030334; P:regulation of cell migration; ISO:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; ISO:RGD.
DR GO; GO:0060768; P:regulation of epithelial cell proliferation involved in prostate gland development; ISO:RGD.
DR GO; GO:1901201; P:regulation of extracellular matrix assembly; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0045607; P:regulation of inner ear auditory receptor cell differentiation; ISO:RGD.
DR GO; GO:0050767; P:regulation of neurogenesis; ISO:RGD.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; ISO:RGD.
DR GO; GO:0014807; P:regulation of somitogenesis; ISO:RGD.
DR GO; GO:0072091; P:regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0031960; P:response to corticosteroid; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0032495; P:response to muramyl dipeptide; ISO:RGD.
DR GO; GO:0042670; P:retinal cone cell differentiation; IEA:Ensembl.
DR GO; GO:0060528; P:secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development; ISO:RGD.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; ISO:RGD.
DR GO; GO:0001501; P:skeletal system development; IBA:GO_Central.
DR GO; GO:0048103; P:somatic stem cell division; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; IMP:RGD.
DR GO; GO:0002040; P:sprouting angiogenesis; ISO:RGD.
DR GO; GO:0072538; P:T-helper 17 type immune response; ISO:RGD.
DR GO; GO:0042246; P:tissue regeneration; IEP:RGD.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0035148; P:tube formation; ISS:UniProtKB.
DR GO; GO:0060979; P:vasculogenesis involved in coronary vascular morphogenesis; ISO:RGD.
DR GO; GO:0048845; P:venous blood vessel morphogenesis; ISO:RGD.
DR GO; GO:0060843; P:venous endothelial cell differentiation; ISO:RGD.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISO:RGD.
DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; ISO:RGD.
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; IPR022362; Notch_1.
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; 2.
DR Pfam; PF00008; EGF; 20.
DR Pfam; PF07645; EGF_CA; 5.
DR Pfam; PF12661; hEGF; 4.
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; PR01984; NOTCH1.
DR SMART; SM00248; ANK; 6.
DR SMART; SM01334; DUF3454; 1.
DR SMART; SM00181; EGF; 36.
DR SMART; SM00179; EGF_CA; 32.
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; 3.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
DR PROSITE; PS00010; ASX_HYDROXYL; 22.
DR PROSITE; PS00022; EGF_1; 35.
DR PROSITE; PS01186; EGF_2; 27.
DR PROSITE; PS50026; EGF_3; 36.
DR PROSITE; PS01187; EGF_CA; 21.
DR PROSITE; PS50258; LNR; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Angiogenesis; ANK repeat; Calcium; Cell membrane;
KW Developmental protein; Differentiation; Disulfide bond; EGF-like domain;
KW Glycoprotein; Hydroxylation; Isopeptide bond; Membrane; Metal-binding;
KW Notch signaling pathway; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Transcription;
KW Transcription regulation; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..2531
FT /note="Neurogenic locus notch homolog protein 1"
FT /id="PRO_0000007680"
FT CHAIN 1711..2531
FT /note="Notch 1 extracellular truncation"
FT /evidence="ECO:0000250"
FT /id="PRO_0000007681"
FT CHAIN 1744..2531
FT /note="Notch 1 intracellular domain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000007682"
FT TOPO_DOM 19..1725
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1726..1746
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P46531"
FT TOPO_DOM 1747..2531
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 20..58
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 59..99
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 102..139
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 140..176
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 178..216
FT /note="EGF-like 5; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 218..255
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 257..293
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 295..333
FT /note="EGF-like 8; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 335..371
FT /note="EGF-like 9; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 372..410
FT /note="EGF-like 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 412..450
FT /note="EGF-like 11; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 452..488
FT /note="EGF-like 12; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 490..526
FT /note="EGF-like 13; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 528..564
FT /note="EGF-like 14; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 566..601
FT /note="EGF-like 15; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 603..639
FT /note="EGF-like 16; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 641..676
FT /note="EGF-like 17; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 678..714
FT /note="EGF-like 18; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 716..751
FT /note="EGF-like 19; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 753..789
FT /note="EGF-like 20; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 791..827
FT /note="EGF-like 21; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 829..867
FT /note="EGF-like 22"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 869..905
FT /note="EGF-like 23; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 907..943
FT /note="EGF-like 24"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 945..981
FT /note="EGF-like 25; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 983..1019
FT /note="EGF-like 26"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1021..1057
FT /note="EGF-like 27; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1059..1095
FT /note="EGF-like 28"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1097..1143
FT /note="EGF-like 29"
FT /evidence="ECO:0000305"
FT DOMAIN 1145..1181
FT /note="EGF-like 30; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1183..1219
FT /note="EGF-like 31; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1221..1265
FT /note="EGF-like 32; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1267..1305
FT /note="EGF-like 33"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1307..1346
FT /note="EGF-like 34"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1348..1384
FT /note="EGF-like 35"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1387..1426
FT /note="EGF-like 36"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1449..1489
FT /note="LNR 1"
FT REPEAT 1490..1531
FT /note="LNR 2"
FT REPEAT 1532..1571
FT /note="LNR 3"
FT REPEAT 1917..1946
FT /note="ANK 1"
FT REPEAT 1950..1980
FT /note="ANK 2"
FT REPEAT 1984..2013
FT /note="ANK 3"
FT REPEAT 2017..2046
FT /note="ANK 4"
FT REPEAT 2050..2079
FT /note="ANK 5"
FT REGION 420..421
FT /note="Interaction with DLL4"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT REGION 448..452
FT /note="Interaction with DLL4"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT REGION 1718..1750
FT /note="Interaction with PSEN1"
FT /evidence="ECO:0000250|UniProtKB:P46531"
FT REGION 1770..1798
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1937..1945
FT /note="HIF1AN-binding"
FT /evidence="ECO:0000250"
FT REGION 2004..2012
FT /note="HIF1AN-binding"
FT /evidence="ECO:0000250"
FT REGION 2141..2185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2382..2428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2440..2531
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2160..2177
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2382..2404
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2440..2482
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2490..2524
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 432
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT BINDING 435
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT BINDING 452
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT BINDING 453
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT BINDING 455
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT BINDING 469
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT BINDING 470
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT BINDING 490
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT BINDING 491
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT BINDING 493
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT BINDING 507
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT BINDING 508
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT BINDING 1457
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT BINDING 1460
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT BINDING 1475
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT BINDING 1478
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT SITE 469
FT /note="Interaction with DLL4"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT SITE 1654..1655
FT /note="Cleavage; by furin-like protease"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT SITE 1710..1711
FT /note="Cleavage; by ADAM17"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT MOD_RES 1851
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT MOD_RES 1945
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN"
FT /evidence="ECO:0000250"
FT MOD_RES 2012
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN"
FT /evidence="ECO:0000250"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 65
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 73
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 116
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 146
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 194
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 232
FT /note="O-linked (Fuc...) threonine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 232
FT /note="O-linked (GalNAc...) threonine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 311
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 341
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 349
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 378
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 435
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT CARBOHYD 458
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:25700513"
FT CARBOHYD 466
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT CARBOHYD 496
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:25700513"
FT CARBOHYD 534
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 609
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 617
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 647
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 692
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 722
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 759
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 767
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 784
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 797
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 805
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 888
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 900
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 921
FT /note="O-linked (Fuc) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 951
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 959
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 997
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1027
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1035
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1065
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1159
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1189
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1197
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1273
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1362
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1379
FT /note="O-linked (GlcNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1402
FT /note="O-linked (Fuc...) threonine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1402
FT /note="O-linked (GalNAc...) threonine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1489
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1587
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1715
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P46531"
FT DISULFID 24..37
FT /evidence="ECO:0000250"
FT DISULFID 31..46
FT /evidence="ECO:0000250"
FT DISULFID 48..57
FT /evidence="ECO:0000250"
FT DISULFID 63..74
FT /evidence="ECO:0000250"
FT DISULFID 68..87
FT /evidence="ECO:0000250"
FT DISULFID 89..98
FT /evidence="ECO:0000250"
FT DISULFID 106..117
FT /evidence="ECO:0000250"
FT DISULFID 111..127
FT /evidence="ECO:0000250"
FT DISULFID 129..138
FT /evidence="ECO:0000250"
FT DISULFID 144..155
FT /evidence="ECO:0000250"
FT DISULFID 149..164
FT /evidence="ECO:0000250"
FT DISULFID 166..175
FT /evidence="ECO:0000250"
FT DISULFID 182..195
FT /evidence="ECO:0000250"
FT DISULFID 189..204
FT /evidence="ECO:0000250"
FT DISULFID 206..215
FT /evidence="ECO:0000250"
FT DISULFID 222..233
FT /evidence="ECO:0000250"
FT DISULFID 227..243
FT /evidence="ECO:0000250"
FT DISULFID 245..254
FT /evidence="ECO:0000250"
FT DISULFID 261..272
FT /evidence="ECO:0000250"
FT DISULFID 266..281
FT /evidence="ECO:0000250"
FT DISULFID 283..292
FT /evidence="ECO:0000250"
FT DISULFID 299..312
FT /evidence="ECO:0000250"
FT DISULFID 306..321
FT /evidence="ECO:0000250"
FT DISULFID 323..332
FT /evidence="ECO:0000250"
FT DISULFID 339..350
FT /evidence="ECO:0000250"
FT DISULFID 344..359
FT /evidence="ECO:0000250"
FT DISULFID 361..370
FT /evidence="ECO:0000250"
FT DISULFID 376..387
FT /evidence="ECO:0000250"
FT DISULFID 381..398
FT /evidence="ECO:0000250"
FT DISULFID 400..409
FT /evidence="ECO:0000250"
FT DISULFID 416..429
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT DISULFID 423..438
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT DISULFID 440..449
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT DISULFID 456..467
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT DISULFID 461..476
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT DISULFID 478..487
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT DISULFID 494..505
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT DISULFID 499..514
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT DISULFID 516..525
FT /evidence="ECO:0000269|PubMed:25700513,
FT ECO:0007744|PDB:4XL1"
FT DISULFID 532..543
FT /evidence="ECO:0000250"
FT DISULFID 537..552
FT /evidence="ECO:0000250"
FT DISULFID 554..563
FT /evidence="ECO:0000250"
FT DISULFID 570..580
FT /evidence="ECO:0000250"
FT DISULFID 575..589
FT /evidence="ECO:0000250"
FT DISULFID 591..600
FT /evidence="ECO:0000250"
FT DISULFID 607..618
FT /evidence="ECO:0000250"
FT DISULFID 612..627
FT /evidence="ECO:0000250"
FT DISULFID 629..638
FT /evidence="ECO:0000250"
FT DISULFID 645..655
FT /evidence="ECO:0000250"
FT DISULFID 650..664
FT /evidence="ECO:0000250"
FT DISULFID 666..675
FT /evidence="ECO:0000250"
FT DISULFID 682..693
FT /evidence="ECO:0000250"
FT DISULFID 687..702
FT /evidence="ECO:0000250"
FT DISULFID 704..713
FT /evidence="ECO:0000250"
FT DISULFID 720..730
FT /evidence="ECO:0000250"
FT DISULFID 725..739
FT /evidence="ECO:0000250"
FT DISULFID 741..750
FT /evidence="ECO:0000250"
FT DISULFID 757..768
FT /evidence="ECO:0000250"
FT DISULFID 762..777
FT /evidence="ECO:0000250"
FT DISULFID 779..788
FT /evidence="ECO:0000250"
FT DISULFID 795..806
FT /evidence="ECO:0000250"
FT DISULFID 800..815
FT /evidence="ECO:0000250"
FT DISULFID 817..826
FT /evidence="ECO:0000250"
FT DISULFID 833..844
FT /evidence="ECO:0000250"
FT DISULFID 838..855
FT /evidence="ECO:0000250"
FT DISULFID 857..866
FT /evidence="ECO:0000250"
FT DISULFID 873..884
FT /evidence="ECO:0000250"
FT DISULFID 878..893
FT /evidence="ECO:0000250"
FT DISULFID 895..904
FT /evidence="ECO:0000250"
FT DISULFID 911..922
FT /evidence="ECO:0000250"
FT DISULFID 916..931
FT /evidence="ECO:0000250"
FT DISULFID 933..942
FT /evidence="ECO:0000250"
FT DISULFID 949..960
FT /evidence="ECO:0000250"
FT DISULFID 954..969
FT /evidence="ECO:0000250"
FT DISULFID 971..980
FT /evidence="ECO:0000250"
FT DISULFID 987..998
FT /evidence="ECO:0000250"
FT DISULFID 992..1007
FT /evidence="ECO:0000250"
FT DISULFID 1009..1018
FT /evidence="ECO:0000250"
FT DISULFID 1025..1036
FT /evidence="ECO:0000250"
FT DISULFID 1030..1045
FT /evidence="ECO:0000250"
FT DISULFID 1047..1056
FT /evidence="ECO:0000250"
FT DISULFID 1063..1074
FT /evidence="ECO:0000250"
FT DISULFID 1068..1083
FT /evidence="ECO:0000250"
FT DISULFID 1085..1094
FT /evidence="ECO:0000250"
FT DISULFID 1101..1122
FT /evidence="ECO:0000305"
FT DISULFID 1116..1131
FT /evidence="ECO:0000250"
FT DISULFID 1133..1142
FT /evidence="ECO:0000250"
FT DISULFID 1149..1160
FT /evidence="ECO:0000250"
FT DISULFID 1154..1169
FT /evidence="ECO:0000250"
FT DISULFID 1171..1180
FT /evidence="ECO:0000250"
FT DISULFID 1187..1198
FT /evidence="ECO:0000250"
FT DISULFID 1192..1207
FT /evidence="ECO:0000250"
FT DISULFID 1209..1218
FT /evidence="ECO:0000250"
FT DISULFID 1225..1244
FT /evidence="ECO:0000250"
FT DISULFID 1238..1253
FT /evidence="ECO:0000250"
FT DISULFID 1255..1264
FT /evidence="ECO:0000250"
FT DISULFID 1271..1284
FT /evidence="ECO:0000250"
FT DISULFID 1276..1293
FT /evidence="ECO:0000250"
FT DISULFID 1295..1304
FT /evidence="ECO:0000250"
FT DISULFID 1311..1322
FT /evidence="ECO:0000250"
FT DISULFID 1316..1334
FT /evidence="ECO:0000250"
FT DISULFID 1336..1345
FT /evidence="ECO:0000250"
FT DISULFID 1352..1363
FT /evidence="ECO:0000250"
FT DISULFID 1357..1372
FT /evidence="ECO:0000250"
FT DISULFID 1374..1383
FT /evidence="ECO:0000250"
FT DISULFID 1391..1403
FT /evidence="ECO:0000250"
FT DISULFID 1397..1414
FT /evidence="ECO:0000250"
FT DISULFID 1416..1425
FT /evidence="ECO:0000250"
FT DISULFID 1449..1472
FT /evidence="ECO:0000250"
FT DISULFID 1454..1467
FT /evidence="ECO:0000250"
FT DISULFID 1463..1479
FT /evidence="ECO:0000250"
FT DISULFID 1490..1514
FT /evidence="ECO:0000250"
FT DISULFID 1496..1509
FT /evidence="ECO:0000250"
FT DISULFID 1505..1521
FT /evidence="ECO:0000250"
FT DISULFID 1536..1549
FT /evidence="ECO:0000250"
FT DISULFID 1545..1561
FT /evidence="ECO:0000250"
FT CROSSLNK 1749
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CONFLICT 309
FT /note="G -> A (in Ref. 1; CAA40667)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="E -> D (in Ref. 1; CAA40667)"
FT /evidence="ECO:0000305"
FT CONFLICT 402
FT /note="S -> R (in Ref. 1; CAA40667)"
FT /evidence="ECO:0000305"
FT CONFLICT 577
FT /note="Y -> I (in Ref. 1; CAA40667)"
FT /evidence="ECO:0000305"
FT CONFLICT 951
FT /note="S -> T (in Ref. 1; CAA40667)"
FT /evidence="ECO:0000305"
FT CONFLICT 1339
FT /note="G -> R (in Ref. 1; CAA40667)"
FT /evidence="ECO:0000305"
FT CONFLICT 1435
FT /note="G -> A (in Ref. 1; CAA40667)"
FT /evidence="ECO:0000305"
FT CONFLICT 1595..1596
FT /note="EL -> DV (in Ref. 1; CAA40667)"
FT /evidence="ECO:0000305"
FT CONFLICT 2501
FT /note="P -> R (in Ref. 1; CAA40667)"
FT /evidence="ECO:0000305"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:5UK5"
FT TURN 307..309
FT /evidence="ECO:0007829|PDB:5UK5"
FT STRAND 311..314
FT /evidence="ECO:0007829|PDB:5UK5"
FT STRAND 319..322
FT /evidence="ECO:0007829|PDB:5UK5"
FT STRAND 327..331
FT /evidence="ECO:0007829|PDB:5UK5"
FT STRAND 349..353
FT /evidence="ECO:0007829|PDB:5UK5"
FT STRAND 356..360
FT /evidence="ECO:0007829|PDB:5UK5"
FT STRAND 366..370
FT /evidence="ECO:0007829|PDB:5UK5"
FT HELIX 375..378
FT /evidence="ECO:0007829|PDB:5UK5"
FT STRAND 386..389
FT /evidence="ECO:0007829|PDB:5UK5"
FT TURN 391..393
FT /evidence="ECO:0007829|PDB:5UK5"
FT STRAND 396..399
FT /evidence="ECO:0007829|PDB:5UK5"
FT STRAND 404..406
FT /evidence="ECO:0007829|PDB:5UK5"
FT HELIX 415..418
FT /evidence="ECO:0007829|PDB:4XL1"
FT TURN 424..426
FT /evidence="ECO:0007829|PDB:4XL1"
FT STRAND 428..432
FT /evidence="ECO:0007829|PDB:4XL1"
FT STRAND 435..439
FT /evidence="ECO:0007829|PDB:4XL1"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:4XL1"
FT TURN 455..458
FT /evidence="ECO:0007829|PDB:4XL1"
FT STRAND 466..470
FT /evidence="ECO:0007829|PDB:4XL1"
FT STRAND 473..477
FT /evidence="ECO:0007829|PDB:4XL1"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:4XL1"
FT TURN 493..496
FT /evidence="ECO:0007829|PDB:4XL1"
FT STRAND 504..507
FT /evidence="ECO:0007829|PDB:4XL1"
FT STRAND 512..515
FT /evidence="ECO:0007829|PDB:4XL1"
FT TURN 522..525
FT /evidence="ECO:0007829|PDB:4XL1"
SQ SEQUENCE 2531 AA; 270822 MW; 3E61AE863AA237F2 CRC64;
MPRLLAPLLC LTLLPALAAR GLRCSQPSGT CLNGGRCEVA NGTEACVCSG AFVGQRCQDP
SPCLSTPCKN AGTCYVVDHG GIVDYACSCP LGFSGPLCLT PLANACLANP CRNGGTCDLL
TLTEYKCRCP PGWSGKSCQQ ADPCASNPCA NGGQCLPFES SYICGCPPGF HGPTCRQDVN
ECSQNPGLCR HGGTCHNEIG SYRCACRATH TGPHCELPYV PCSPSPCQNG GTCRPTGDTT
HECACLPGFA GQNCEENVDD CPGNNCKNGG ACVDGVNTYN CRCPPEWTGQ YCTEDVDECQ
LMPNACQNGG TCHNSHGGYN CVCVNGWTGE DCSENIDDCA SAACFQGATC HDRVASFYCE
CPHGRTGLLC HLNDACISNP CNEGSNCDTN PVNGKAICTC PSGYTGPACS QDVDECALGA
NPCEHAGKCL NTLGSFECQC LQGYTGPRCE IDVNECISNP CQNDATCLDQ IGEFQCICMP
GYEGVYCEIN TDECASSPCL HNGRCVDKIN EFLCQCPKGF SGHLCQYDVD ECASTPCKNG
AKCLDGPNTY TCVCTEGYTG THCEVDIDEC DPDPCHYGLC KDGVATFTCL CQPGYTGHHC
ETNINECHSQ PCRHGGTCQD RDNYYLCLCL KGTTGPNCEI NLDDCASNPC DSGTCLDKID
GYECACEPGY TGSMCNVNID ECAGSPCHNG GTCEDGIAGF TCRCPEGYHD PTCLSEVNEC
NSNPCIHGAC RDGLNGYKCD CAPGWSGTNC DINNNECESN PCVNGGTCKD MTSGYVCTCR
EGFSGPNCQT NINECASNPC LNQGTCIDDV AGYKCNCPLP YTGATCEVVL APCATSPCKN
SGVCKESEDY ESFSCVCPTG WQGQTCEIDI NECVKSPCRH GASCQNTNGS YRCLCQAGYT
GRNCESDIDD CRPNPCHNGG SCTDGVNAAF CDCLPGFQGA FCEEDINECA SNPCQNGANC
TDCVDSYTCT CPTGFNGIHC ENNTPDCTES SCFNGGTCVD GINSFTCLCP PGFTGSYCQY
DVNECDSRPC LHGGTCQDSY GTYKCTCPQG YTGLNCQNLV RWCDSAPCKN GGKCWQTNTQ
YHCECRSGWT GFNCDVLSVS CEVAAQKRGI DVTLLCQHGG LCVDEEDKHY CHCQAGYTGS
YCEDEVDECS PNPCQNGATC TDYLGGFSCK CVAGYHGSNC SEEINECLSQ PCQNGGTCID
LTNTYKCSCP RGTQGVHCEI NVDDCHPPLD PASRSPKCFN NGTCVDQVGG YTCTCPPGFV
GERCEGDVNE CLSNPCDPRG TQNCVQRVND FHCECRAGHT GRRCESVING CRGKPCRNGG
VCAVASNTAR GFICRCPAGF EGATCENDAR TCGSLRCLNG GTCISGPRSP TCLCLGSFTG
PECQFPASSP CVGSNPCYNQ GTCEPTSESP FYRCLCPAKF NGLLCHILDY SFTGGAGRDI
PPPQIEEACE LPECQEDAGN KVCNLQCNNH ACGWDGGDCS LNFNDPWKNC TQSLQCWKYF
SDGHCDSQCN SAGCLFDGFD CQLTEGQCNP LYDQYCKDHF SDGHCDQGCN SAECEWDGLD
CAEHVPERLA AGTLVLVVLL PPDQLRNNSF HFLRELSHVL HTNVVFKRDA QGQQMIFPYY
GREEELRKHP IKRSAVGWAT TSLLPGTNGG RQRRELDPMD IHGSIVYLEI DNRQCVQSSS
QCFQSATDVA AFLGALASLG SLNIPYKIEA VKSETVEPPL PSQLHLMYVA AAAFVLLFFV
GCGVLLSRKR RRQHGQLWFP EGFKVSEASK KKRREPLGED SVGLKPLKNA SDGALMDDNQ
NEWGDEDLET KKFRFEEPVV LPDLDDQTDH RQWTQQHLDA ADLRVSAMAP TPPQGEVDAD
CMDVNVRGPD GFTPLMIASC SGGGLETGNS EEEEDAPAVI SDFIYQGASL HNQTDRTGET
ALHLAARYSR SDAAKRLLEA SADANIQDNM GRTPLHAAVS ADAQGVFQIL LRNRATDLDA
RMHDGTTPLI LAARLAVEGM LEDLINSHAD VNAVDDLGKS ALHWAAAVNN VDAAVVLLKN
GANKDMQNNK EETPLFLAAR EGSYETAKVL LDHFANRDIT DHMDRLPRDI AQERMHHDIV
RLLDEYNLVR SPQLHGTALG GTPTLSPTLC SPNGYLGNLK SATQGKKARK PSTKGLACSS
KEAKDLKARR KKSQDGKGCL LDSSSMLSPV DSLESPHGYL SDVASPPLLP SPFQQSPSMP
LSHLPGMPDT HLGISHLNVA AKPEMAALAG GSRLAFEPPP PRLSHLPVAS SASTVLSTNG
TGAMNFTVGA PASLNGQCEW LPRLQNGMVP SQYNPLRPGV TPGTLSTQAA GLQHGMMGPI
HSSLSTNTLS PIIYQGLPNT RLATQPHLVQ TQQVQPQNLQ IQPQNLQPPS QPHLSVSSAA
NGHLGRSFLS GEPSQADVQP LGPSSLPVHT ILPQESQALP TSLPSSMVPP MTTTQFLTPP
SQHSYSSSPV DNTPSHQLQV PEHPFLTPSP ESPDQWSSSS PHSNISDWSE GISSPPTSMP
SQITHIPEAF K
