NOTC2_MOUSE
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 03-AUG-2022, entry version 218.
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). {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};
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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; 17.
DR CORUM; O35516; -.
DR DIP; DIP-6008N; -.
DR IntAct; O35516; 2.
DR STRING; 10090.ENSMUSP00000078741; -.
DR GlyGen; O35516; 6 sites.
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; O35516; -.
DR PeptideAtlas; O35516; -.
DR PRIDE; O35516; -.
DR ProteomicsDB; 252844; -. [O35516-1]
DR ProteomicsDB; 252845; -. [O35516-2]
DR ProteomicsDB; 336721; -.
DR ABCD; O35516; 4 sequenced antibodies.
DR Antibodypedia; 20208; 658 antibodies from 43 providers.
DR DNASU; 18129; -.
DR Ensembl; ENSMUST00000079812; ENSMUSP00000078741; ENSMUSG00000027878. [O35516-1]
DR GeneID; 18129; -.
DR KEGG; mmu:18129; -.
DR UCSC; uc008qpo.1; mouse.
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; PGYEGNH; -.
DR OrthoDB; 7525at2759; -.
DR PhylomeDB; O35516; -.
DR TreeFam; TF351641; -.
DR BioGRID-ORCS; 18129; 7 hits in 78 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 325 other 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:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0051059; F:NF-kappaB binding; IPI:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; IEA:InterPro.
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:0007417; P:central nervous system development; IBA:GO_Central.
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: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: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; ISS:UniProtKB.
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: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:0072014; P:proximal tubule development; IEP:UniProtKB.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; ISO:MGI.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; ISS:UniProtKB.
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:0001501; P:skeletal system development; IBA:GO_Central.
DR GO; GO:0042060; P:wound healing; IDA:UniProtKB.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR013032; EGF-like_CS.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR008297; Notch.
DR InterPro; IPR035993; Notch-like_dom_sf.
DR InterPro; 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 Pfam; PF12796; Ank_2; 1.
DR Pfam; PF13857; Ank_5; 1.
DR Pfam; PF00008; EGF; 24.
DR Pfam; PF07645; EGF_CA; 5.
DR Pfam; PF12661; hEGF; 3.
DR Pfam; PF06816; NOD; 1.
DR Pfam; PF07684; NODP; 1.
DR Pfam; PF00066; Notch; 3.
DR PIRSF; PIRSF002279; Notch; 1.
DR PRINTS; PR01452; LNOTCHREPEAT.
DR PRINTS; 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; SSF48403; 1.
DR SUPFAM; SSF57184; SSF57184; 4.
DR SUPFAM; SSF90193; SSF90193; 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
