ID NOTC2_MOUSE Reviewed; 2473 AA. AC O35516; G5E8J0; Q06008; Q60941; DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot. DT 10-APR-2019, sequence version 2. DT 27-MAR-2024, entry version 227. DE RecName: Full=Neurogenic locus notch homolog protein 2 {ECO:0000250|UniProtKB:Q04721}; DE Short=Notch 2; DE AltName: Full=Motch B {ECO:0000303|PubMed:8440332}; DE Contains: DE RecName: Full=Notch 2 extracellular truncation; DE Contains: DE RecName: Full=Notch 2 intracellular domain; DE Flags: Precursor; GN Name=Notch2 {ECO:0000312|MGI:MGI:97364}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57BL/6J; TISSUE=Thymus; RA Hamada Y., Higuchi M., Tsujimoto Y.; RT "Complete amino acid sequence and mutliform transcripts encoded by a single RT copy of mouse Notch2 gene."; RL Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 318-1520. RC STRAIN=C57BL/6 X CBA; TISSUE=Embryo; RX PubMed=8440332; DOI=10.1006/excr.1993.1044; RA Lardelli M., Lendahl U.; RT "Motch A and Motch B-two mouse Notch homologues coexpressed in a wide RT variety of tissues."; RL Exp. Cell Res. 204:364-372(1993). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1768-2156. RX PubMed=8917536; DOI=10.1073/pnas.93.23.13014; RA Milner L.A., Bigas A., Kopan R., Brashem-Stein C., Bernstein I.D., RA Martin D.I.; RT "Inhibition of granulocytic differentiation by mNotch1."; RL Proc. Natl. Acad. Sci. U.S.A. 93:13014-13019(1996). RN [6] RP FUNCTION. RX PubMed=10393120; DOI=10.1242/dev.126.15.3415; RA Hamada Y., Kadokawa Y., Okabe M., Ikawa M., Coleman J.R., Tsujimoto Y.; RT "Mutation in ankyrin repeats of the mouse Notch2 gene induces early RT embryonic lethality."; RL Development 126:3415-3424(1999). RN [7] RP DEVELOPMENTAL STAGE, AND ALTERNATIVE SPLICING. RX PubMed=7609614; DOI=10.1016/0169-328x(94)00257-f; RA Higuchi M., Kiyama H., Hayakawa T., Hamada Y., Tsujimoto Y.; RT "Differential expression of Notch1 and Notch2 in developing and adult mouse RT brain."; RL Brain Res. Mol. Brain Res. 29:263-272(1995). RN [8] RP PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF MET-1701. RX PubMed=11518718; DOI=10.1074/jbc.m107234200; RA Saxena M.T., Schroeter E.H., Mumm J.S., Kopan R.; RT "Murine notch homologs (N1-4) undergo presenilin-dependent proteolysis."; RL J. Biol. Chem. 276:40268-40273(2001). RN [9] RP PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF MET-1701. RX PubMed=11459941; DOI=10.1073/pnas.161269998; RA Mizutani T., Taniguchi Y., Aoki T., Hashimoto N., Honjo T.; RT "Conservation of the biochemical mechanisms of signal transduction among RT mammalian Notch family members."; RL Proc. Natl. Acad. Sci. U.S.A. 98:9026-9031(2001). RN [10] RP INTERACTION WITH MAML1. RX PubMed=15019995; DOI=10.1016/j.gene.2003.12.007; RA Wu L., Kobayashi K., Sun T., Gao P., Liu J., Nakamura M., Weisberg E., RA Mukhopadhyay N.K., Griffin J.D.; RT "Cloning and functional characterization of the murine mastermind-like 1 RT (Maml1) gene."; RL Gene 328:153-165(2004). RN [11] RP INTERACTION WITH HIF1AN. RX PubMed=17573339; DOI=10.1074/jbc.m704102200; RA Coleman M.L., McDonough M.A., Hewitson K.S., Coles C., Mecinovic J., RA Edelmann M., Cook K.M., Cockman M.E., Lancaster D.E., Kessler B.M., RA Oldham N.J., Ratcliffe P.J., Schofield C.J.; RT "Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor RT inhibiting hypoxia-inducible factor."; RL J. Biol. Chem. 282:24027-24038(2007). RN [12] RP FUNCTION AS POSITIVE REGULATOR OF OSTEOCLASTOGENESIS, AND INTERACTION WITH RP RELA. RX PubMed=18710934; DOI=10.1128/mcb.00299-08; RA Fukushima H., Nakao A., Okamoto F., Shin M., Kajiya H., Sakano S., RA Bigas A., Jimi E., Okabe K.; RT "The association of Notch2 and NF-kappaB accelerates RANKL-induced RT osteoclastogenesis."; RL Mol. Cell. Biol. 28:6402-6412(2008). RN [13] RP HYDROXYLATION BY HIF1AN. RX PubMed=18299578; DOI=10.1073/pnas.0711591105; RA Zheng X., Linke S., Dias J.M., Zheng X., Gradin K., Wallis T.P., RA Hamilton B.R., Gustafsson M., Ruas J.L., Wilkins S., Bilton R.L., RA Brismar K., Whitelaw M.L., Pereira T., Gorman J.J., Ericson J., Peet D.J., RA Lendahl U., Poellinger L.; RT "Interaction with factor inhibiting HIF-1 defines an additional mode of RT cross-coupling between the Notch and hypoxia signaling pathways."; RL Proc. Natl. Acad. Sci. U.S.A. 105:3368-3373(2008). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1780; SER-1843 AND SER-1846, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Kidney, and Liver; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [16] RP GLYCOSYLATION AT SER-613, AND MUTAGENESIS OF SER-614. RX PubMed=21949356; DOI=10.1073/pnas.1109696108; RA Takeuchi H., Fernandez-Valdivia R.C., Caswell D.S., Nita-Lazar A., RA Rana N.A., Garner T.P., Weldeghiorghis T.K., Macnaughtan M.A., RA Jafar-Nejad H., Haltiwanger R.S.; RT "Rumi functions as both a protein O-glucosyltransferase and a protein O- RT xylosyltransferase."; RL Proc. Natl. Acad. Sci. U.S.A. 108:16600-16605(2011). 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 (PubMed:10393120). 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 (PubMed:10393120, PubMed:18710934). Affects the CC implementation of differentiation, proliferation and apoptotic programs CC (PubMed:10393120, PubMed:18710934). May play an essential role in CC postimplantation development, probably in some aspect of cell CC specification and/or differentiation (By similarity). In collaboration CC with RELA/p65 enhances NFATc1 promoter activity and positively CC regulates RANKL-induced osteoclast differentiation (PubMed:18710934). CC Positively regulates self-renewal of liver cancer cells (By CC similarity). {ECO:0000250|UniProtKB:Q04721, CC ECO:0000269|PubMed:10393120, ECO:0000269|PubMed:18710934}. 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 MAML1, MAML2 and MAML3 which act as transcriptional coactivators CC for NOTCH2. Interacts with RELA/p65. Interacts with HIF1AN. Interacts CC (via ANK repeats) with TCIM, the interaction inhibits the nuclear CC translocation of NOTCH2 N2ICD (By similarity). Interacts with CUL1, CC RBX1, SKP1 and FBXW7 that are SCF(FBXW7) E3 ubiquitin-protein ligase CC complex components. Interacts with MINAR1; this interaction increases CC MINAR1 stability and function (By similarity). Interacts with MDK; this CC interaction mediates a nuclear accumulation of NOTCH2 and therefore CC activation of NOTCH2 signaling leading to interaction between HES1 and CC STAT3 (By similarity). Interacts with MINAR2 (By similarity). CC {ECO:0000250, ECO:0000250|UniProtKB:Q04721, CC ECO:0000269|PubMed:15019995, ECO:0000269|PubMed:17573339, CC ECO:0000269|PubMed:18710934}. CC -!- SUBCELLULAR LOCATION: [Notch 2 extracellular truncation]: Cell membrane CC {ECO:0000250|UniProtKB:Q04721}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q04721}. CC -!- SUBCELLULAR LOCATION: [Notch 2 intracellular domain]: Nucleus CC {ECO:0000250|UniProtKB:Q04721}. Cytoplasm CC {ECO:0000250|UniProtKB:Q04721}. Note=Following proteolytical processing CC NICD is translocated to the nucleus. Retained at the cytoplasm by TCIM. CC {ECO:0000250|UniProtKB:Q04721}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O35516-1; Sequence=Displayed; CC Name=2; CC IsoId=O35516-2; Sequence=VSP_001405; CC -!- TISSUE SPECIFICITY: Expressed in the brain, liver, kidney, CC neuroepithelia, somites, optic vesicles and branchial arches, but not CC heart. CC -!- DEVELOPMENTAL STAGE: Expressed in the embryonic ventricular zone, the CC postnatal ependymal cells, and the choroid plexus throughout embryonic CC and postnatal development. {ECO:0000269|PubMed:7609614}. 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 (PubMed:11459941, PubMed:11518718). Cleavage CC results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC) CC (PubMed:11459941, PubMed:11518718). Following ligand binding, it is CC cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane- CC associated intermediate fragment called notch extracellular truncation CC (NEXT) (By similarity). This fragment is then cleaved by presenilin CC dependent gamma-secretase to release a notch-derived peptide containing CC the intracellular domain (NICD) from the membrane (PubMed:11459941, CC PubMed:11518718). {ECO:0000250|UniProtKB:Q01705, CC ECO:0000269|PubMed:11459941, ECO:0000269|PubMed:11518718}. CC -!- PTM: Hydroxylated by HIF1AN. {ECO:0000269|PubMed:18299578}. CC -!- PTM: Can be either O-glucosylated or O-xylosylated at Ser-613 by CC POGLUT1. {ECO:0000269|PubMed:21949356}. CC -!- PTM: Phosphorylated by GSK3. GSK3-mediated phosphorylation is necessary CC for NOTCH2 recognition by FBXW7, ubiquitination and degradation via the CC ubiquitin proteasome pathway. {ECO:0000250|UniProtKB:Q04721}. CC -!- SIMILARITY: Belongs to the NOTCH family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA22094.1; Type=Frameshift; Evidence={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; D32210; BAA22094.1; ALT_FRAME; mRNA. DR EMBL; AC154173; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC164091; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH466620; EDL38950.1; -; Genomic_DNA. DR EMBL; X68279; CAA48340.1; -; mRNA. DR EMBL; U31881; AAC52924.1; -; mRNA. DR CCDS; CCDS51013.1; -. [O35516-1] DR PIR; A49175; A49175. DR RefSeq; NP_035058.2; NM_010928.2. [O35516-1] DR AlphaFoldDB; O35516; -. DR SMR; O35516; -. DR BioGRID; 201809; 18. DR CORUM; O35516; -. DR DIP; DIP-6008N; -. DR IntAct; O35516; 2. DR STRING; 10090.ENSMUSP00000078741; -. DR GlyCosmos; O35516; 6 sites, No reported glycans. DR GlyGen; O35516; 7 sites, 1 O-linked glycan (1 site). DR iPTMnet; O35516; -. DR PhosphoSitePlus; O35516; -. DR SwissPalm; O35516; -. DR CPTAC; non-CPTAC-3851; -. DR EPD; O35516; -. DR jPOST; O35516; -. DR MaxQB; O35516; -. DR PaxDb; 10090-ENSMUSP00000078741; -. DR PeptideAtlas; O35516; -. DR ProteomicsDB; 252844; -. [O35516-1] DR ProteomicsDB; 252845; -. [O35516-2] DR ProteomicsDB; 336721; -. DR Pumba; O35516; -. DR ABCD; O35516; 4 sequenced antibodies. DR Antibodypedia; 20208; 745 antibodies from 43 providers. DR DNASU; 18129; -. DR Ensembl; ENSMUST00000079812.8; ENSMUSP00000078741.7; ENSMUSG00000027878.12. [O35516-1] DR GeneID; 18129; -. DR KEGG; mmu:18129; -. DR UCSC; uc008qpo.1; mouse. DR AGR; MGI:97364; -. DR CTD; 4853; -. DR MGI; MGI:97364; Notch2. DR VEuPathDB; HostDB:ENSMUSG00000027878; -. DR eggNOG; KOG1217; Eukaryota. DR GeneTree; ENSGT00940000155030; -. DR HOGENOM; CLU_000576_0_0_1; -. DR InParanoid; O35516; -. DR OMA; AHMSEPP; -. DR OrthoDB; 5473534at2759; -. DR PhylomeDB; O35516; -. DR TreeFam; TF351641; -. DR BioGRID-ORCS; 18129; 7 hits in 83 CRISPR screens. DR ChiTaRS; Notch2; mouse. DR PRO; PR:O35516; -. DR Proteomes; UP000000589; Chromosome 3. DR RNAct; O35516; Protein. DR Bgee; ENSMUSG00000027878; Expressed in ciliary body and 327 other cell types or tissues. DR GO; GO:0009986; C:cell surface; ISS:UniProtKB. DR GO; GO:0005929; C:cilium; IDA:MGI. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0043235; C:receptor complex; ISO:MGI. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0051059; F:NF-kappaB binding; IPI:UniProtKB. DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central. DR GO; GO:0009887; P:animal organ morphogenesis; TAS:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:InterPro. DR GO; GO:0060413; P:atrial septum morphogenesis; ISS:BHF-UCL. DR GO; GO:0030509; P:BMP signaling pathway; IMP:MGI. DR GO; GO:0046849; P:bone remodeling; ISO:MGI. DR GO; GO:0001709; P:cell fate determination; ISO:MGI. DR GO; GO:0008283; P:cell population proliferation; IMP:MGI. DR GO; GO:0071228; P:cellular response to tumor cell; ISS:UniProtKB. DR GO; GO:1990705; P:cholangiocyte proliferation; IMP:MGI. DR GO; GO:0061073; P:ciliary body morphogenesis; IMP:MGI. DR GO; GO:0042742; P:defense response to bacterium; IMP:MGI. DR GO; GO:0007368; P:determination of left/right symmetry; IMP:MGI. DR GO; GO:0030326; P:embryonic limb morphogenesis; IGI:MGI. DR GO; GO:0010001; P:glial cell differentiation; IBA:GO_Central. DR GO; GO:0072104; P:glomerular capillary formation; IEP:UniProtKB. DR GO; GO:0001947; P:heart looping; IGI:BHF-UCL. DR GO; GO:0072574; P:hepatocyte proliferation; IMP:MGI. DR GO; GO:0006959; P:humoral immune response; IGI:MGI. DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI. DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IGI:MGI. DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB. DR GO; GO:0035622; P:intrahepatic bile duct development; IMP:MGI. DR GO; GO:0070986; P:left/right axis specification; IGI:BHF-UCL. DR GO; GO:0001889; P:liver development; IMP:MGI. DR GO; GO:0072576; P:liver morphogenesis; IMP:MGI. DR GO; GO:0002315; P:marginal zone B cell differentiation; IMP:UniProtKB. DR GO; GO:0002011; P:morphogenesis of an epithelial sheet; IMP:MGI. DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI. DR GO; GO:0043011; P:myeloid dendritic cell differentiation; IMP:MGI. DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:MGI. DR GO; GO:0007219; P:Notch signaling pathway; IDA:MGI. DR GO; GO:0060674; P:placenta blood vessel development; IMP:MGI. DR GO; GO:0001890; P:placenta development; IMP:MGI. DR GO; GO:0072015; P:podocyte development; IEP:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IGI:MGI. DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:MGI. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI. DR GO; GO:0010838; P:positive regulation of keratinocyte proliferation; ISS:UniProtKB. DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:MGI. DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IBA:GO_Central. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IDA:UniProtKB. DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISS:UniProtKB. DR GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0072014; P:proximal tubule development; IEP:UniProtKB. DR GO; GO:0003184; P:pulmonary valve morphogenesis; ISS:BHF-UCL. DR GO; GO:2001204; P:regulation of osteoclast development; ISS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:MGI. DR GO; GO:0042060; P:wound healing; IDA:UniProtKB. DR CDD; cd00054; EGF_CA; 28. DR CDD; cd21703; JMTM_Notch2; 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; IPR022336; Notch_2. 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:SF22; DROSOPHILA CRUMBS HOMOLOG; 1. DR Pfam; PF00023; Ank; 2. DR Pfam; PF12796; Ank_2; 1. DR Pfam; PF00008; EGF; 20. DR Pfam; PF07645; EGF_CA; 5. DR Pfam; PF12661; hEGF; 7. DR Pfam; PF06816; NOD; 1. DR Pfam; PF07684; NODP; 1. DR Pfam; PF00066; Notch; 3. DR PIRSF; PIRSF002279; Notch; 1. DR PRINTS; PR00010; EGFBLOOD. DR PRINTS; PR01452; LNOTCHREPEAT. DR PRINTS; PR01983; NOTCH. DR PRINTS; PR01985; NOTCH2. DR SMART; SM00248; ANK; 6. DR SMART; SM01334; DUF3454; 1. DR SMART; SM00181; EGF; 35. DR SMART; SM00179; EGF_CA; 34. 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; 20. DR SUPFAM; SSF57184; Growth factor receptor domain; 4. DR SUPFAM; SSF90193; Notch domain; 2. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 4. DR PROSITE; PS00010; ASX_HYDROXYL; 22. DR PROSITE; PS00022; EGF_1; 34. DR PROSITE; PS01186; EGF_2; 27. DR PROSITE; PS50026; EGF_3; 35. DR PROSITE; PS01187; EGF_CA; 22. DR PROSITE; PS50258; LNR; 3. PE 1: Evidence at protein level; KW Activator; Alternative splicing; ANK repeat; Cell membrane; Cytoplasm; KW Developmental protein; Differentiation; Disulfide bond; EGF-like domain; KW Glycoprotein; Membrane; Notch signaling pathway; Nucleus; Phosphoprotein; KW Receptor; Reference proteome; Repeat; Signal; Transcription; KW Transcription regulation; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT CHAIN 26..2473 FT /note="Neurogenic locus notch homolog protein 2" FT /id="PRO_0000007686" FT CHAIN 1668..2473 FT /note="Notch 2 extracellular truncation" FT /evidence="ECO:0000250|UniProtKB:Q01705" FT /id="PRO_0000007687" FT CHAIN 1699..2473 FT /note="Notch 2 intracellular domain" FT /evidence="ECO:0000305|PubMed:11459941, FT ECO:0000305|PubMed:11518718" FT /id="PRO_0000007688" FT TOPO_DOM 26..1679 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1680..1700 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1701..2473 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 26..63 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 64..102 FT /note="EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 105..143 FT /note="EGF-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 144..180 FT /note="EGF-like 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 182..219 FT /note="EGF-like 5; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 221..258 FT /note="EGF-like 6; incomplete" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 260..296 FT /note="EGF-like 7; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 298..336 FT /note="EGF-like 8; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 338..374 FT /note="EGF-like 9; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 375..413 FT /note="EGF-like 10" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 415..454 FT /note="EGF-like 11; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 456..492 FT /note="EGF-like 12; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 494..530 FT /note="EGF-like 13; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 532..568 FT /note="EGF-like 14; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 570..605 FT /note="EGF-like 15; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 607..643 FT /note="EGF-like 16; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 645..680 FT /note="EGF-like 17; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 682..718 FT /note="EGF-like 18; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 720..755 FT /note="EGF-like 19" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 757..793 FT /note="EGF-like 20; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 795..831 FT /note="EGF-like 21; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 833..871 FT /note="EGF-like 22" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 873..909 FT /note="EGF-like 23; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 911..947 FT /note="EGF-like 24; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 949..985 FT /note="EGF-like 25; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 987..1023 FT /note="EGF-like 26; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1025..1061 FT /note="EGF-like 27; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1063..1099 FT /note="EGF-like 28" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1101..1147 FT /note="EGF-like 29" FT /evidence="ECO:0000305" FT DOMAIN 1149..1185 FT /note="EGF-like 30; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1187..1223 FT /note="EGF-like 31; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1225..1262 FT /note="EGF-like 32; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1264..1302 FT /note="EGF-like 33" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1304..1343 FT /note="EGF-like 34" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1375..1412 FT /note="EGF-like 35" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REPEAT 1425..1465 FT /note="LNR 1" FT REPEAT 1466..1502 FT /note="LNR 2" FT REPEAT 1503..1544 FT /note="LNR 3" FT REPEAT 1828..1872 FT /note="ANK 1" FT REPEAT 1877..1906 FT /note="ANK 2" FT REPEAT 1910..1940 FT /note="ANK 3" FT REPEAT 1944..1973 FT /note="ANK 4" FT REPEAT 1977..2006 FT /note="ANK 5" FT REPEAT 2010..2039 FT /note="ANK 6" FT REGION 1425..1679 FT /note="Negative regulatory region (NRR)" FT /evidence="ECO:0000250" FT REGION 1755..1778 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2098..2117 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2122..2169 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2382..2473 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1762..1778 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2124..2139 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2140..2169 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2386..2404 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2421..2449 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 614 FT /note="Essential for O-xylosylation" FT /evidence="ECO:0000269|PubMed:21949356" FT MOD_RES 1718 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q04721" FT MOD_RES 1780 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319" FT MOD_RES 1803 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q04721" FT MOD_RES 1805 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04721" FT MOD_RES 1809 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q04721" FT MOD_RES 1843 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319" FT MOD_RES 1846 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319" FT MOD_RES 2071 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04721" FT MOD_RES 2079 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QW30" FT MOD_RES 2082 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04721" FT MOD_RES 2098 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q04721" FT CARBOHYD 46 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 155 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 613 FT /note="O-linked (Glc...) serine; alternate" FT /evidence="ECO:0000269|PubMed:21949356" FT CARBOHYD 613 FT /note="O-linked (Xyl...) serine; alternate" FT /evidence="ECO:0000269|PubMed:21949356" FT CARBOHYD 733 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1102 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1465 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 28..41 FT /evidence="ECO:0000250" FT DISULFID 35..51 FT /evidence="ECO:0000250" FT DISULFID 53..62 FT /evidence="ECO:0000250" FT DISULFID 68..79 FT /evidence="ECO:0000250" FT DISULFID 73..90 FT /evidence="ECO:0000250" FT DISULFID 92..101 FT /evidence="ECO:0000250" FT DISULFID 109..121 FT /evidence="ECO:0000250" FT DISULFID 115..131 FT /evidence="ECO:0000250" FT DISULFID 133..142 FT /evidence="ECO:0000250" FT DISULFID 148..159 FT /evidence="ECO:0000250" FT DISULFID 153..168 FT /evidence="ECO:0000250" FT DISULFID 170..179 FT /evidence="ECO:0000250" FT DISULFID 186..198 FT /evidence="ECO:0000250" FT DISULFID 192..207 FT /evidence="ECO:0000250" FT DISULFID 209..218 FT /evidence="ECO:0000250" FT DISULFID 230..246 FT /evidence="ECO:0000250" FT DISULFID 248..257 FT /evidence="ECO:0000250" FT DISULFID 264..275 FT /evidence="ECO:0000250" FT DISULFID 269..284 FT /evidence="ECO:0000250" FT DISULFID 286..295 FT /evidence="ECO:0000250" FT DISULFID 302..315 FT /evidence="ECO:0000250" FT DISULFID 309..324 FT /evidence="ECO:0000250" FT DISULFID 326..335 FT /evidence="ECO:0000250" FT DISULFID 342..353 FT /evidence="ECO:0000250" FT DISULFID 347..362 FT /evidence="ECO:0000250" FT DISULFID 364..373 FT /evidence="ECO:0000250" FT DISULFID 379..390 FT /evidence="ECO:0000250" FT DISULFID 384..401 FT /evidence="ECO:0000250" FT DISULFID 403..412 FT /evidence="ECO:0000250" FT DISULFID 419..433 FT /evidence="ECO:0000250" FT DISULFID 427..442 FT /evidence="ECO:0000250" FT DISULFID 444..453 FT /evidence="ECO:0000250" FT DISULFID 460..471 FT /evidence="ECO:0000250" FT DISULFID 465..480 FT /evidence="ECO:0000250" FT DISULFID 482..491 FT /evidence="ECO:0000250" FT DISULFID 498..509 FT /evidence="ECO:0000250" FT DISULFID 503..518 FT /evidence="ECO:0000250" FT DISULFID 520..529 FT /evidence="ECO:0000250" FT DISULFID 536..547 FT /evidence="ECO:0000250" FT DISULFID 541..556 FT /evidence="ECO:0000250" FT DISULFID 558..567 FT /evidence="ECO:0000250" FT DISULFID 574..584 FT /evidence="ECO:0000250" FT DISULFID 579..593 FT /evidence="ECO:0000250" FT DISULFID 595..604 FT /evidence="ECO:0000250" FT DISULFID 611..622 FT /evidence="ECO:0000250" FT DISULFID 616..631 FT /evidence="ECO:0000250" FT DISULFID 633..642 FT /evidence="ECO:0000250" FT DISULFID 649..659 FT /evidence="ECO:0000250" FT DISULFID 654..668 FT /evidence="ECO:0000250" FT DISULFID 670..679 FT /evidence="ECO:0000250" FT DISULFID 686..697 FT /evidence="ECO:0000250" FT DISULFID 691..706 FT /evidence="ECO:0000250" FT DISULFID 708..717 FT /evidence="ECO:0000250" FT DISULFID 724..734 FT /evidence="ECO:0000250" FT DISULFID 729..743 FT /evidence="ECO:0000250" FT DISULFID 745..754 FT /evidence="ECO:0000250" FT DISULFID 761..772 FT /evidence="ECO:0000250" FT DISULFID 766..781 FT /evidence="ECO:0000250" FT DISULFID 783..792 FT /evidence="ECO:0000250" FT DISULFID 799..810 FT /evidence="ECO:0000250" FT DISULFID 804..819 FT /evidence="ECO:0000250" FT DISULFID 821..830 FT /evidence="ECO:0000250" FT DISULFID 837..848 FT /evidence="ECO:0000250" FT DISULFID 842..859 FT /evidence="ECO:0000250" FT DISULFID 861..870 FT /evidence="ECO:0000250" FT DISULFID 877..888 FT /evidence="ECO:0000250" FT DISULFID 882..897 FT /evidence="ECO:0000250" FT DISULFID 899..908 FT /evidence="ECO:0000250" FT DISULFID 915..926 FT /evidence="ECO:0000250" FT DISULFID 920..935 FT /evidence="ECO:0000250" FT DISULFID 937..946 FT /evidence="ECO:0000250" FT DISULFID 953..964 FT /evidence="ECO:0000250" FT DISULFID 958..973 FT /evidence="ECO:0000250" FT DISULFID 975..984 FT /evidence="ECO:0000250" FT DISULFID 991..1002 FT /evidence="ECO:0000250" FT DISULFID 996..1011 FT /evidence="ECO:0000250" FT DISULFID 1013..1022 FT /evidence="ECO:0000250" FT DISULFID 1029..1040 FT /evidence="ECO:0000250" FT DISULFID 1034..1049 FT /evidence="ECO:0000250" FT DISULFID 1051..1060 FT /evidence="ECO:0000250" FT DISULFID 1067..1078 FT /evidence="ECO:0000250" FT DISULFID 1072..1087 FT /evidence="ECO:0000250" FT DISULFID 1089..1098 FT /evidence="ECO:0000250" FT DISULFID 1105..1126 FT /evidence="ECO:0000305" FT DISULFID 1120..1135 FT /evidence="ECO:0000250" FT DISULFID 1137..1146 FT /evidence="ECO:0000250" FT DISULFID 1153..1164 FT /evidence="ECO:0000250" FT DISULFID 1158..1173 FT /evidence="ECO:0000250" FT DISULFID 1175..1184 FT /evidence="ECO:0000250" FT DISULFID 1191..1202 FT /evidence="ECO:0000250" FT DISULFID 1196..1211 FT /evidence="ECO:0000250" FT DISULFID 1213..1222 FT /evidence="ECO:0000250" FT DISULFID 1229..1241 FT /evidence="ECO:0000250" FT DISULFID 1235..1250 FT /evidence="ECO:0000250" FT DISULFID 1252..1261 FT /evidence="ECO:0000250" FT DISULFID 1268..1281 FT /evidence="ECO:0000250" FT DISULFID 1273..1290 FT /evidence="ECO:0000250" FT DISULFID 1292..1301 FT /evidence="ECO:0000250" FT DISULFID 1308..1319 FT /evidence="ECO:0000250" FT DISULFID 1313..1331 FT /evidence="ECO:0000250" FT DISULFID 1333..1346 FT /evidence="ECO:0000250" FT DISULFID 1378..1389 FT /evidence="ECO:0000250" FT DISULFID 1383..1400 FT /evidence="ECO:0000250" FT DISULFID 1402..1411 FT /evidence="ECO:0000250" FT DISULFID 1425..1448 FT /evidence="ECO:0000250" FT DISULFID 1430..1443 FT /evidence="ECO:0000250" FT DISULFID 1439..1455 FT /evidence="ECO:0000250" FT DISULFID 1466..1489 FT /evidence="ECO:0000250" FT DISULFID 1472..1484 FT /evidence="ECO:0000250" FT DISULFID 1480..1496 FT /evidence="ECO:0000250" FT DISULFID 1503..1527 FT /evidence="ECO:0000250" FT DISULFID 1509..1522 FT /evidence="ECO:0000250" FT DISULFID 1518..1534 FT /evidence="ECO:0000250" FT DISULFID 1634..1641 FT /evidence="ECO:0000250" FT VAR_SEQ 1304..1510 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_001405" FT MUTAGEN 614 FT /note="S->A: No effect on O-glycosylation by POGLUT1. Loss FT of O-xylosylation." FT /evidence="ECO:0000269|PubMed:21949356" FT MUTAGEN 1701 FT /note="M->L: No effect on NICD processing." FT /evidence="ECO:0000269|PubMed:11459941, FT ECO:0000269|PubMed:11518718" FT MUTAGEN 1701 FT /note="M->V: Decreased NICD processing." FT /evidence="ECO:0000269|PubMed:11459941, FT ECO:0000269|PubMed:11518718" FT CONFLICT 3 FT /note="A -> D (in Ref. 1; BAA22094)" FT /evidence="ECO:0000305" FT CONFLICT 210 FT /note="P -> G (in Ref. 1; BAA22094)" FT /evidence="ECO:0000305" FT CONFLICT 224..228 FT /note="PCAPS -> RGL (in Ref. 1; BAA22094)" FT /evidence="ECO:0000305" FT CONFLICT 244 FT /note="F -> L (in Ref. 1; BAA22094)" FT /evidence="ECO:0000305" FT CONFLICT 1342 FT /note="C -> L (in Ref. 1; BAA22094)" FT /evidence="ECO:0000305" FT CONFLICT 1801 FT /note="R -> S (in Ref. 1; BAA22094)" FT /evidence="ECO:0000305" FT CONFLICT 1904 FT /note="A -> R (in Ref. 1; BAA22094)" FT /evidence="ECO:0000305" FT CONFLICT 1921 FT /note="A -> G (in Ref. 1; BAA22094)" FT /evidence="ECO:0000305" FT CONFLICT 2315 FT /note="G -> R (in Ref. 1; BAA22094)" FT /evidence="ECO:0000305" SQ SEQUENCE 2473 AA; 265633 MW; 3A9067BBE3B1F480 CRC64; MPALRPAALR ALLWLWLCGA GPAHALQCRG GQEPCVNEGT CVTYHNGTGF CRCPEGFLGE YCQHRDPCEK NRCQNGGTCV PQGMLGKATC RCAPGFTGED CQYSTSHPCF VSRPCQNGGT CHMLSRDTYE CTCQVGFTGK QCQWTDACLS HPCENGSTCT SVASQFSCKC PAGLTGQKCE ADINECDIPG RCQHGGTCLN LPGSYRCQCP QGFTGQHCDS PYVPCAPSPC VNGGTCRQTG DFTFECNCLP GFEGSTCERN IDDCPNHKCQ NGGVCVDGVN TYNCRCPPQW TGQFCTEDVD ECLLQPNACQ NGGTCTNRNG GYGCVCVNGW SGDDCSENID DCAYASCTPG STCIDRVASF SCLCPEGKAG LLCHLDDACI SNPCHKGALC DTNPLNGQYI CTCPQGYKGA DCTEDVDECA MANSNPCEHA GKCVNTDGAF HCECLKGYAG PRCEMDINEC HSDPCQNDAT CLDKIGGFTC LCMPGFKGVH CELEVNECQS NPCVNNGQCV DKVNRFQCLC PPGFTGPVCQ IDIDDCSSTP CLNGAKCIDH PNGYECQCAT GFTGILCDEN IDNCDPDPCH HGQCQDGIDS YTCICNPGYM GAICSDQIDE CYSSPCLNDG RCIDLVNGYQ CNCQPGTSGL NCEINFDDCA SNPCMHGVCV DGINRYSCVC SPGFTGQRCN IDIDECASNP CRKGATCIND VNGFRCICPE GPHHPSCYSQ VNECLSNPCI HGNCTGGLSG YKCLCDAGWV GVNCEVDKNE CLSNPCQNGG TCNNLVNGYR CTCKKGFKGY NCQVNIDECA SNPCLNQGTC FDDVSGYTCH CMLPYTGKNC QTVLAPCSPN PCENAAVCKE APNFESFSCL CAPGWQGKRC TVDVDECISK PCMNNGVCHN TQGSYVCECP PGFSGMDCEE DINDCLANPC QNGGSCVDHV NTFSCQCHPG FIGDKCQTDM NECLSEPCKN GGTCSDYVNS YTCTCPAGFH GVHCENNIDE CTESSCFNGG TCVDGINSFS CLCPVGFTGP FCLHDINECS SNPCLNAGTC VDGLGTYRCI CPLGYTGKNC QTLVNLCSRS PCKNKGTCVQ EKARPHCLCP PGWDGAYCDV LNVSCKAAAL QKGVPVEHLC QHSGICINAG NTHHCQCPLG YTGSYCEEQL DECASNPCQH GATCNDFIGG YRCECVPGYQ GVNCEYEVDE CQNQPCQNGG TCIDLVNHFK CSCPPGTRGL LCEENIDECA GGPHCLNGGQ CVDRIGGYTC RCLPGFAGER CEGDINECLS NPCSSEGSLD CVQLKNNYNC ICRSAFTGRH CETFLDVCPQ KPCLNGGTCA VASNMPDGFI CRCPPGFSGA RCQSSCGQVK CRRGEQCIHT DSGPRCFCLN PKDCESGCAS NPCQHGGTCY PQRQPPHYSC RCPPSFGGSH CELYTAPTST PPATCQSQYC ADKARDGICD EACNSHACQW DGGDCSLTME DPWANCTSTL RCWEYINNQC DEQCNTAECL FDNFECQRNS KTCKYDKYCA DHFKDNHCDQ GCNSEECGWD GLDCASDQPE NLAEGTLIIV VLLPPEQLLQ DSRSFLRALG TLLHTNLRIK QDSQGALMVY PYFGEKSAAM KKQKMTRRSL PEEQEQEQEV IGSKIFLEID NRQCVQDSDQ CFKNTDAAAA LLASHAIQGT LSYPLVSVFS ELESPRNAQL LYLLAVAVVI ILFFILLGVI MAKRKRKHGF LWLPEGFTLR RDSSNHKRRE PVGQDAVGLK NLSVQVSEAN LIGSGTSEHW VDDEGPQPKK AKAEDEALLS EDDPIDRRPW TQQHLEAADI RHTPSLALTP PQAEQEVDVL DVNVRGPDGC TPLMLASLRG GSSDLSDEDE DAEDSSANII TDLVYQGASL QAQTDRTGEM ALHLAARYSR ADAAKRLLDA GADANAQDNM GRCPLHAAVA ADAQGVFQIL IRNRVTDLDA RMNDGTTPLI LAARLAVEGM VAELINCQAD VNAVDDHGKS ALHWAAAVNN VEATLLLLKN GANRDMQDNK EETPLFLAAR EGSYEAAKIL LDHFANRDIT DHMDRLPRDV ARDRMHHDIV RLLDEYNVTP SPPGTVLTSA LSPVLCGPNR SFLSLKHTPM GKKARRPNTK STMPTSLPNL AKEAKDAKGS RRKKCLNEKV QLSESSVTLS PVDSLESPHT YVSDATSSPM ITSPGILQAS PTPLLAAAAP AAPVHTQHAL SFSNLHDMQP LAPGASTVLP SVSQLLSHHH IAPPGSSSAG SLGRLHPVPV PADWMNRVEM NETQYSEMFG MVLAPAEGAH PGIAAPQSRP PEGKHMSTQR EPLPPIVTFQ LIPKGSIAQA AGAPQTQSSC PPAVAGPLPS MYQIPEMPRL PSVAFPPTMM PQQEGQVAQT IVPTYHPFPA SVGKYPTPPS QHSYASSNAA ERTPSHGGHL QGEHPYLTPS PESPDQWSSS SPHSASDWSD VTTSPTPGGG GGGQRGPGTH MSEPPHSNMQ VYA //