NOTC2_RAT
ID NOTC2_RAT Reviewed; 2471 AA.
AC Q9QW30;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Neurogenic locus notch homolog protein 2 {ECO:0000250|UniProtKB:Q04721};
DE Short=Notch 2;
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|RGD:3188};
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=Brain;
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 [2]
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 [3]
RP PHOSPHORYLATION AT SER-2078, AND MUTAGENESIS OF SER-2078 AND SER-2090.
RX PubMed=11577080; DOI=10.1074/jbc.m104703200;
RA Ingles-Esteve J., Espinosa L., Milner L.A., Caelles C., Bigas A.;
RT "Phosphorylation of Ser2078 modulates the Notch2 function in 32D cell
RT differentiation.";
RL J. Biol. Chem. 276:44873-44880(2001).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1845, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. Upon ligand activation through the released notch
CC intracellular domain (NICD) it forms a transcriptional activator
CC complex with RBPJ/RBPSUH and activates genes of the enhancer of split
CC locus. Affects the implementation of differentiation, proliferation and
CC apoptotic programs (By similarity). Involved in bone remodeling and
CC homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter
CC activity and positively regulates RANKL-induced osteoclast
CC differentiation. Positively regulates self-renewal of liver cancer
CC cells (By similarity). {ECO:0000250|UniProtKB:O35516,
CC ECO:0000250|UniProtKB:Q04721}.
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 (By
CC similarity). Interacts with MAML1, MAML2 and MAML3 which act as
CC transcriptional coactivators for NOTCH2. Interacts with RELA/p65 (By
CC similarity). Interacts with HIF1AN. Interacts (via ANK repeats) with
CC TCIM, the interaction inhibits the nuclear translocation of NOTCH2
CC N2ICD (By similarity). Interacts with CUL1, RBX1, SKP1 and FBXW7 that
CC are SCF(FBXW7) E3 ubiquitin-protein ligase complex components.Interacts
CC with MINAR1; this interaction increases MINAR1 stability and function
CC (By similarity). Interacts with MDK; this interaction mediates a
CC nuclear accumulation of NOTCH2 and therefore activation of NOTCH2
CC signaling leading to interaction between HES1 and STAT3 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q04721}.
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 -!- TISSUE SPECIFICITY: Highly expressed in the spleen and choroid plexus
CC in the brain. Expressed in postnatal central nervous system (CNS)
CC germinal zones and, in early postnatal life, within numerous cells
CC throughout the CNS. It is more highly localized to ventricular germinal
CC zones. Also found in the heart, liver and kidney.
CC {ECO:0000269|PubMed:11438922}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the brain during E14 and E17.
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) (By similarity). Following ligand
CC binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a
CC membrane-associated intermediate fragment called notch extracellular
CC truncation (NEXT) (By similarity). This fragment is then cleaved by
CC presenilin dependent gamma-secretase to release a notch-derived peptide
CC containing the intracellular domain (NICD) from the membrane (By
CC similarity). {ECO:0000250|UniProtKB:O35516,
CC ECO:0000250|UniProtKB:Q01705}.
CC -!- PTM: Phosphorylated. G-CSF treatment of myeloid cells specifically
CC promotes Ser-2078 phosphorylation, which inactivates Notch2 and permits
CC differentiation. {ECO:0000269|PubMed:11577080}.
CC -!- PTM: Hydroxylated by HIF1AN. {ECO:0000250|UniProtKB:Q04721}.
CC -!- PTM: Can be either O-glucosylated or O-xylosylated at Ser-613 by
CC POGLUT1. {ECO:0000250|UniProtKB:O35516}.
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 ---------------------------------------------------------------------------
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; M93661; AAK13558.1; -; mRNA.
DR PIR; A49128; A49128.
DR AlphaFoldDB; Q9QW30; -.
DR SMR; Q9QW30; -.
DR STRING; 10116.ENSRNOP00000025718; -.
DR GlyGen; Q9QW30; 6 sites.
DR iPTMnet; Q9QW30; -.
DR PhosphoSitePlus; Q9QW30; -.
DR PaxDb; Q9QW30; -.
DR PRIDE; Q9QW30; -.
DR UCSC; RGD:3188; rat.
DR RGD; 3188; Notch2.
DR eggNOG; KOG1217; Eukaryota.
DR InParanoid; Q9QW30; -.
DR PhylomeDB; Q9QW30; -.
DR PRO; PR:Q9QW30; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005929; C:cilium; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0051059; F:NF-kappaB binding; ISO:RGD.
DR GO; GO:0038023; F:signaling receptor activity; TAS:RGD.
DR GO; GO:0009887; P:animal organ morphogenesis; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:InterPro.
DR GO; GO:0060413; P:atrial septum morphogenesis; ISO:RGD.
DR GO; GO:0046849; P:bone remodeling; ISO:RGD.
DR GO; GO:0001709; P:cell fate determination; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0061073; P:ciliary body morphogenesis; ISO:RGD.
DR GO; GO:0042742; P:defense response to bacterium; ISO:RGD.
DR GO; GO:0007368; P:determination of left/right symmetry; ISO:RGD.
DR GO; GO:0030326; P:embryonic limb morphogenesis; ISO:RGD.
DR GO; GO:0072104; P:glomerular capillary formation; ISO:RGD.
DR GO; GO:0001947; P:heart looping; ISO:RGD.
DR GO; GO:0072574; P:hepatocyte proliferation; 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:0035622; P:intrahepatic bile duct development; 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:0072576; P:liver morphogenesis; ISO:RGD.
DR GO; GO:0002315; P:marginal zone B cell differentiation; ISS:UniProtKB.
DR GO; GO:0002011; P:morphogenesis of an epithelial sheet; ISO:RGD.
DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR GO; GO:0043011; P:myeloid dendritic cell differentiation; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0007219; P:Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0060674; P:placenta blood vessel development; ISO:RGD.
DR GO; GO:0001890; P:placenta development; ISO:RGD.
DR GO; GO:0072015; P:podocyte development; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0010838; P:positive regulation of keratinocyte proliferation; ISS:UniProtKB.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISO:RGD.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISS:UniProtKB.
DR GO; GO:0072014; P:proximal tubule development; ISO:RGD.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0001501; P:skeletal system development; IBA:GO_Central.
DR GO; GO:0042246; P:tissue regeneration; IEP:RGD.
DR GO; GO:0042060; P:wound healing; IEP: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; 22.
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; 33.
DR SMART; SM00004; NL; 3.
DR SMART; SM01338; NOD; 1.
DR SMART; SM01339; NODP; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF57184; SSF57184; 6.
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; 26.
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; ANK repeat; Cell membrane; Cytoplasm; Developmental protein;
KW Differentiation; Disulfide bond; EGF-like domain; Glycoprotein; Membrane;
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..25
FT /evidence="ECO:0000255"
FT CHAIN 26..2471
FT /note="Neurogenic locus notch homolog protein 2"
FT /id="PRO_0000007689"
FT CHAIN 1666..2471
FT /note="Notch 2 extracellular truncation"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT /id="PRO_0000007690"
FT CHAIN 1697..2471
FT /note="Notch 2 intracellular domain"
FT /evidence="ECO:0000250|UniProtKB:O35516"
FT /id="PRO_0000007691"
FT TOPO_DOM 26..1677
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1678..1698
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1699..2471
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"
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 1374..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 1827..1871
FT /note="ANK 1"
FT REPEAT 1876..1905
FT /note="ANK 2"
FT REPEAT 1909..1939
FT /note="ANK 3"
FT REPEAT 1943..1972
FT /note="ANK 4"
FT REPEAT 1976..2005
FT /note="ANK 5"
FT REPEAT 2009..2038
FT /note="ANK 6"
FT REGION 1425..1677
FT /note="Negative regulatory region (NRR)"
FT /evidence="ECO:0000250"
FT REGION 1751..1788
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1794..1813
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2097..2116
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2380..2471
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1760..1788
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2384..2402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2419..2447
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 614
FT /note="Essential for O-xylosylation"
FT /evidence="ECO:0000250|UniProtKB:O35516"
FT MOD_RES 1716
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q04721"
FT MOD_RES 1779
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35516"
FT MOD_RES 1802
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q04721"
FT MOD_RES 1804
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04721"
FT MOD_RES 1808
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q04721"
FT MOD_RES 1842
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35516"
FT MOD_RES 1845
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 2070
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04721"
FT MOD_RES 2078
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11577080"
FT MOD_RES 2081
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04721"
FT MOD_RES 2097
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:0000250|UniProtKB:O35516"
FT CARBOHYD 613
FT /note="O-linked (Xyl...) serine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O35516"
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 225..236
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..1342
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 1632..1639
FT /evidence="ECO:0000250"
FT MUTAGEN 2078
FT /note="S->A: Permits Notch2 inhibitory activity upon G-CSF
FT action on myeloid cells."
FT /evidence="ECO:0000269|PubMed:11577080"
FT MUTAGEN 2090
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:11577080"
SQ SEQUENCE 2471 AA; 265370 MW; 7D5C8E18DDE95FE8 CRC64;
MPALRPAALR ALLWLWLCGA GPAHALQCRG GQEPCVNEGT CVTYHNGTGY CRCPEGFLGE
YCQHRDPCEK NRCQNGGTCV TQAMLGKATC RCAPGFTGED CQYSTSHPCF VSRPCQNGGT
CHMLSWDTYE CTCQVGFTGK QCQWTDVCLS HPCENGSTCS SVANQFSCRC PAGITGQKCD
ADINECDIPG RCQHGGTCLN LPGSYRCQCP QRFTGQHCDS PYVPCAPSPC VNGGTCRQTG
DFTSECHCLP GFEGSNCERN IDDCPNHKCQ NGGVCVDGVN TYNCRCPPQW TGQFCTEDVD
ECLLQPNACQ NGGTCTNRNG GYGCVCVNGW SGDDCSENID DCAFASCTPG STCIDRVASF
SCLCPEGKAG LLCHLDDACI SNPCHKGALC DTNPLNGQYI CTCPQAYKGA DCTEDVDECA
MANSNPCEHA GKCVNTDGAF HCECLKGYAG PRCEMDINEC HSDPCQNDAT CLDKIGGFTC
LCMPGFKGVH CELEVNECQS NPCVNNGQCV DKVNRFQCLC PPGFTGPVCQ IDIDDCSSTP
CLNGAKCIDH PNGYECQCAT GFTGTLCDEN IDNCDPDPCH HGQCQDGIDS YTCICNPGYM
GAICSDQIDE CYSSPCLNDG RCIDLVNGYQ CNCQPGTSGL NCEINFDDCA SNPCLHGACV
DGINRYSCVC SPGFTGQRCN IDIDECASNP CRKDATCIND VNGFRCMCPE GPHHPSCYSQ
VNECLSSPCI HGNCTGGLSG YKCLCDAGWV GINCEVDKNE CLSNPCQNGG TCNNLVNGYR
CTCKKGFKGY NCQVNIDECA SNPCLNQGTC LDDVSGYTCH CMLPYTGKNC QTVLAPCSPN
PCENAAVCKE APNFESFTCL CAPGWQGQRC TVDVDECVSK PCMNNGICHN TQGSYMCECP
PGFSGMDCEE DINDCLANPC QNGGSCVDKV NTFSCLCLPG FVGDKCQTDM NECLSEPCKN
GGTCSDYVNS YTCTCPAGFH GVHCENNIDE CTESSCFNGG TCVDGINSFS CLCPVGFTGP
FCLHDINECS SNPCLNSGTC VDGLGTYRCT CPLGYTGKNC QTLVNLCSPS PCKNKGTCAQ
EKARPRCLCP PGWDGAYCDV LNVSCKAAAL QKGVPVEHLC QHSGICINAG NTHHCQCPLG
YTGSYCEEQL DECASNPCQH GATCSDFIGG YRCECVPGYQ GVNCEYEVDE CQNQPCQNGG
TCIDLVNHFK CSCPPGTRGL LCEENIDDCA GAPHCLNGGQ CVDRIGGYSC RCLPGFAGER
CEGDINECLS NPCSSEGSLD CIQLKNNYQC VCRSAFTGRH CETFLDVCPQ KPCLNGGTCA
VASNVPDGFI CRCPPGFSGA RCQSSCGQVK CRRGEQCVHT ASGPHCFCPN HKDCESGCAS
NPCQHGGTCY PQRQPPYYSC RCSPPFWGSH CESYTAPTST PPATCLSQYC ADKARDGICD
EACNSHACQW DGGDCSLTME DPWANCTSSL RCWEYINNQC DELCNTAECL FDNFECQRNS
KTCKYDKYCA DHFKDNHCDK GCNNEECGWD GLDCAADQPE NLAEGILVIV VLLPPEQLLQ
DSRSFLRALG TLLHTNLRIK QDSQGALMVY PYYGEKSAAM KKQKVARRSL PDEQEQEIIG
SKVFLEIDNR QCVQDSDQCF KNTDAAAALL ASHAIQGTLS YPLVSVVSES EDPRNTPLLY
LLAVAVVIIL FLILLGVIMA KRKRKHGFLW LPEGFTLRRD SSNHKRREPV GQDAVGLKNL
SVQVSEANLI GSTTSEHWGD DEGPQPKKAK AEDDEALLSE DDPVDRRPWT QQHLEAADIR
RTPSLALTPP QAEQEVDVLD VNVRGPDGCT PLMLASLRGG SSDLSDEDED AEDSSANIIT
DLVYQGASLQ AQTDRTGEMA LHLAARYSRA DAAKRLLDAG ADANAQDNMG RCPLHAAVAA
DAQGVFQILI RNRVTDLDAR MNDGTTPLIL AARLAVEGMV AELINCQADV NAVDDHGKSA
LHWAAAVNNV EATLLLLKNG ANRDMQDNKE ETPLFLAARE GSYEAAKILL DHFANRDITD
HMDRLPRDVA RDRMHHDIVR LLDEYNVTPS PPGTVLTSAL SPVLCGPNRS FLSLKHTPMG
KKARRPNTKS TMPTSLPNLA KEAKDVKGSR RKKCLNEKVQ LSESSVTLSP VDSLESPHTY
VSDATSSPMI TSPGILQASP TPLLAAAPAA PVHAQHALSF SNLHEMQPLR PGASTVLPSV
SQLLSHHHIV PPGSGSAGSL GRLHSVPVPS DWMNRVEMSE TQYSEMFGMV LAPAEGTHPG
MAAPQSRAPE GKPIPTQREP LPPIVTFQLI PKGSLAQAAG APQTQSGCPP AVAGPLPSMY
QIPEMARLPS VAFPPTMMPQ QEGQVAQTIV PTYHPFPASV GKYPTPPSQH SYASSNAAER
TPNHGGHLQG EHPYLTPSPE SPDQWSSSSP HSASDWSDVT TSPTPGGGGG GQRGPGTHMS
EPPHSNMQVY A
