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 27-MAR-2024, entry version 224. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 GlyCosmos; Q07008; 47 sites, No reported glycans. DR GlyGen; Q07008; 48 sites. DR iPTMnet; Q07008; -. DR PhosphoSitePlus; Q07008; -. DR PaxDb; 10116-ENSRNOP00000026212; -. DR Ensembl; ENSRNOT00000026212.8; ENSRNOP00000026212.6; ENSRNOG00000019322.8. DR GeneID; 25496; -. DR KEGG; rno:25496; -. DR UCSC; RGD:3187; rat. DR AGR; RGD:3187; -. 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; TCHEQRD; -. DR OrthoDB; 5473534at2759; -. 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 cell types or tissues. 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: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:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:RGD. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; 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:0140537; F:transcription regulator activator 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:0006915; P:apoptotic process; 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:0048754; P:branching morphogenesis of an epithelial tube; ISO:RGD. DR GO; GO:0017156; P:calcium-ion regulated exocytosis; ISO:RGD. 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; ISO:RGD. 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:0003273; P:cell migration involved in endocardial cushion formation; ISO:RGD. DR GO; GO:0008283; P:cell population proliferation; ISO:RGD. DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; ISO:RGD. DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB. 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: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; ISO:RGD. DR GO; GO:0008544; P:epidermis development; ISO:RGD. DR GO; GO:0072148; P:epithelial cell fate commitment; ISO:RGD. DR GO; GO:0050673; P:epithelial cell proliferation; ISO:RGD. 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; ISO:RGD. 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:0001554; P:luteolysis; IEP: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: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:0032966; P:negative regulation of collagen biosynthetic process; IMP:RGD. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:RGD. DR GO; GO:2001027; P:negative regulation of endothelial cell chemotaxis; ISS:UniProtKB. DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISO:RGD. 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; ISO:RGD. 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:0043069; P:negative regulation of programmed cell death; ISO:RGD. 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:0021915; P:neural tube development; ISO:RGD. DR GO; GO:0061101; P:neuroendocrine cell differentiation; ISO:RGD. 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:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB. 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:0051152; P:positive regulation of smooth muscle cell differentiation; ISO:RGD. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:RGD. DR GO; GO:0007221; P:positive regulation of transcription of Notch receptor target; IMP:RGD. 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:0061344; P:regulation of cell adhesion involved in heart morphogenesis; ISO: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; ISO:RGD. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO: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; ISO:RGD. 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: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; ISO:RGD. 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 CDD; cd00054; EGF_CA; 30. DR CDD; cd21702; JMTM_Notch1; 1. DR Gene3D; 3.30.300.320; -; 1. DR Gene3D; 3.30.70.3310; -; 1. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1. DR Gene3D; 2.10.25.10; Laminin; 35. 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 PANTHER; PTHR24049; CRUMBS FAMILY MEMBER; 1. DR PANTHER; PTHR24049:SF30; DELTA-LIKE PROTEIN; 1. DR Pfam; PF00023; Ank; 1. DR Pfam; PF12796; Ank_2; 2. DR Pfam; PF00008; EGF; 17. DR Pfam; PF07645; EGF_CA; 4. DR Pfam; PF12661; hEGF; 9. 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; PR01983; NOTCH. 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; Ankyrin repeat; 1. DR SUPFAM; SSF57196; EGF/Laminin; 18. DR SUPFAM; SSF57184; Growth factor receptor domain; 5. DR SUPFAM; SSF90193; Notch domain; 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. DR Genevisible; Q07008; RN. 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 //