NOTC1_CRIGR
ID NOTC1_CRIGR Reviewed; 2527 AA.
AC G3I6Z6;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2013, sequence version 2.
DT 03-AUG-2022, entry version 55.
DE RecName: Full=Neurogenic locus notch homolog protein 1;
DE Short=Notch 1;
DE Contains:
DE RecName: Full=Notch 1 extracellular truncation;
DE Short=NEXT;
DE Contains:
DE RecName: Full=Notch 1 intracellular domain;
DE Short=NICD;
DE Flags: Precursor;
GN Name=NOTCH1;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21804562; DOI=10.1038/nbt.1932;
RA Xu X., Nagarajan H., Lewis N.E., Pan S., Cai Z., Liu X., Chen W., Xie M.,
RA Wang W., Hammond S., Andersen M.R., Neff N., Passarelli B., Koh W.,
RA Fan H.C., Wang J., Gui Y., Lee K.H., Betenbaugh M.J., Quake S.R.,
RA Famili I., Palsson B.O., Wang J.;
RT "The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line.";
RL Nat. Biotechnol. 29:735-741(2011).
RN [2]
RP GLYCOSYLATION.
RX PubMed=10734111; DOI=10.1074/jbc.275.13.9604;
RA Moloney D.J., Shair L.H., Lu F.M., Xia J., Locke R., Matta K.L.,
RA Haltiwanger R.S.;
RT "Mammalian Notch1 is modified with two unusual forms of O-linked
RT glycosylation found on epidermal growth factor-like modules.";
RL J. Biol. Chem. 275:9604-9611(2000).
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. Involved in angiogenesis; negatively regulates
CC endothelial cell proliferation and migration and angiogenic sprouting.
CC Involved in the maturation of both CD4(+) and CD8(+) cells in the
CC thymus. Important for follicular differentiation and possibly cell fate
CC selection within the follicle. During cerebellar development, functions
CC as a receptor for neuronal DNER and is involved in the differentiation
CC of Bergmann glia. Represses neuronal and myogenic differentiation. May
CC play an essential role in postimplantation development, probably in
CC some aspect of cell specification and/or differentiation. May be
CC involved in mesoderm development, somite formation and neurogenesis.
CC May enhance HIF1A function by sequestering HIF1AN away from HIF1A (By
CC similarity). Required for the THBS4 function in regulating protective
CC astrogenesis from the subventricular zone (SVZ) niche after injury.
CC Involved in determination of left/right symmetry by modulating the
CC balance between motile and immotile (sensory) cilia at the left-right
CC organiser (LRO) (By similarity). {ECO:0000250|UniProtKB:Q01705}.
CC -!- SUBUNIT: Heterodimer of a C-terminal fragment N(TM) and an N-terminal
CC fragment N(EC) which are probably linked by disulfide bonds. Interacts
CC with DNER, DTX1, DTX2 and RBPJ/RBPSUH. Also interacts with MAML1, MAML2
CC and MAML3 which act as transcriptional coactivators for NOTCH1. Notch 1
CC intracellular domain interacts with SNW1; the interaction involves
CC multimerized NOTCH1 NICD and is implicated in a formation of an
CC intermediate preactivation complex which associates with DNA-bound CBF-
CC 1/RBPJ. The activated membrane-bound form interacts with AAK1 which
CC promotes NOTCH1 stabilization. Forms a trimeric complex with FBXW7 and
CC SGK1. Interacts with HIF1AN. HIF1AN negatively regulates the function
CC of notch intracellular domain (NICD), accelerating myogenic
CC differentiation. Interacts (via NICD) with SNAI1 (via zinc fingers);
CC the interaction induces SNAI1 degradation via MDM2-mediated
CC ubiquitination and inhibits SNAI1-induced cell invasion. Interacts (via
CC NICD) with MDM2A. Interacts (via NICD) with BCL6; the interaction
CC decreases MAML1 recruitment by NOTCH1 NICD on target genes DNA and
CC inhibits NOTCH1 transcractivation activity (By similarity). Interacts
CC with THBS4 (By similarity). Interacts (via the EGF-like repeat region)
CC with CCN3 (via CTCK domain). Interacts (via EGF-like domains) with DLL4
CC (via N-terminal DSL and MNNL domains). Interacts with ZMIZ1. Interacts
CC (via NICD domain) with MEGF10 (via the cytoplasmic domain). Interacts
CC with DLL1 and JAG1 (By similarity). Interacts (via NICD domain) with
CC PRAG1 (By similarity). Forms a complex with PRAG1, N1ICD and MAML1, in
CC a MAML1-dependent manner (By similarity). Interacts (via transmembrane
CC region) with PSEN1; the interaction is direct (By similarity).
CC Interacts with ZFP64 (By similarity). {ECO:0000250|UniProtKB:P46531,
CC ECO:0000250|UniProtKB:Q01705, ECO:0000250|UniProtKB:Q07008}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q01705};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q01705}.
CC -!- SUBCELLULAR LOCATION: [Notch 1 intracellular domain]: Nucleus
CC {ECO:0000250|UniProtKB:Q01705}. Note=Following proteolytical processing
CC NICD is translocated to the nucleus. Nuclear location may require
CC MEGF10. {ECO:0000250|UniProtKB:Q01705}.
CC -!- DOMAIN: Interaction with PSEN1 causes partial unwinding of the
CC transmembrane helix, facilitating access to the scissile peptide bond.
CC {ECO:0000250|UniProtKB:P46531}.
CC -!- PTM: Synthesized in the endoplasmic reticulum as an inactive form which
CC is proteolytically cleaved by a furin-like convertase in the trans-
CC Golgi network before it reaches the plasma membrane to yield an active,
CC ligand-accessible form. Cleavage results in a C-terminal fragment N(TM)
CC and a N-terminal fragment N(EC). Following ligand binding, it is
CC cleaved by ADAM17 to yield a membrane-associated intermediate fragment
CC called notch extracellular truncation (NEXT). Following endocytosis,
CC this fragment is then cleaved by one of the catalytic subunits of
CC gamma-secretase (PSEN1 or PSEN2) to release a Notch-derived peptide
CC containing the intracellular domain (NICD) from the membrane.
CC {ECO:0000250|UniProtKB:Q01705}.
CC -!- PTM: Phosphorylated. {ECO:0000250}.
CC -!- PTM: O-linked glycosylation by GALNT11 is involved in determination of
CC left/right symmetry: glycosylation promotes activation of NOTCH1,
CC possibly by promoting cleavage by ADAM17, modulating the balance
CC between motile and immotile (sensory) cilia at the left-right organiser
CC (LRO) (By similarity). O-glycosylated on the EGF-like domains
CC (PubMed:10734111). O-glucosylated at Ser-451 by KDELC1 and KDELC2 (By
CC similarity). Contains both O-linked fucose and O-linked glucose in the
CC EGF-like domains 11, 12 and 13, which are interacting with the residues
CC on DLL4. MFNG-, RFNG- and LFNG-mediated modification of O-fucose
CC residues at specific EGF-like domains results in inhibition of its
CC activation by JAG1 and enhancement of its activation by DLL1 via an
CC increased binding to DLL1 (By similarity).
CC {ECO:0000250|UniProtKB:P46531, ECO:0000250|UniProtKB:Q01705,
CC ECO:0000250|UniProtKB:Q07008, ECO:0000269|PubMed:10734111}.
CC -!- PTM: Ubiquitinated. Undergoes 'Lys-29'-linked polyubiquitination by
CC ITCH; promotes the lysosomal degradation of non-activated internalized
CC NOTCH1. Monoubiquitination at Lys-1765 is required for activation by
CC gamma-secretase cleavage, it promotes interaction with AAK1, which
CC stabilizes it. Deubiquitination by EIF3F is necessary for nuclear
CC import of activated Notch. {ECO:0000250|UniProtKB:Q01705}.
CC -!- PTM: Hydroxylated at Asn-1961 by HIF1AN. Hydroxylated at Asn-2028 by
CC HIF1AN (By similarity). Hydroxylation reduces affinity for HI1AN and
CC may thus indirectly modulate negative regulation of NICD (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the NOTCH family. {ECO:0000305}.
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DR EMBL; JH001398; EGW12778.1; -; Genomic_DNA.
DR RefSeq; XP_003510910.1; XM_003510862.3.
DR STRING; 10029.XP_007637278.1; -.
DR eggNOG; KOG1217; Eukaryota.
DR InParanoid; G3I6Z6; -.
DR OrthoDB; 7525at2759; -.
DR Proteomes; UP000001075; Unassembled WGS sequence.
DR GO; GO:0005912; C:adherens junction; ISS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0038023; F:signaling receptor activity; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0061314; P:Notch signaling involved in heart development; ISS:UniProtKB.
DR GO; GO:0050793; P:regulation of developmental process; IEA:InterPro.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR013032; EGF-like_CS.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR008297; Notch.
DR InterPro; IPR035993; Notch-like_dom_sf.
DR InterPro; IPR022362; Notch_1.
DR InterPro; IPR024600; Notch_C.
DR InterPro; IPR000800; Notch_dom.
DR InterPro; IPR010660; Notch_NOD_dom.
DR InterPro; IPR011656; Notch_NODP_dom.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF00008; EGF; 20.
DR Pfam; PF07645; EGF_CA; 5.
DR Pfam; PF12661; hEGF; 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; PR01984; NOTCH1.
DR SMART; SM00248; ANK; 6.
DR SMART; SM01334; DUF3454; 1.
DR SMART; SM00181; EGF; 36.
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; 5.
DR SUPFAM; SSF90193; SSF90193; 3.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
DR PROSITE; PS00010; ASX_HYDROXYL; 22.
DR PROSITE; PS00022; EGF_1; 35.
DR PROSITE; PS01186; EGF_2; 28.
DR PROSITE; PS50026; EGF_3; 36.
DR PROSITE; PS01187; EGF_CA; 21.
DR PROSITE; PS50258; LNR; 3.
PE 1: Evidence at protein level;
KW Activator; Angiogenesis; ANK repeat; Calcium; Cell membrane;
KW Developmental protein; Differentiation; Disulfide bond; EGF-like domain;
KW Glycoprotein; Hydroxylation; Isopeptide bond; Membrane; Metal-binding;
KW Notch signaling pathway; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Transcription;
KW Transcription regulation; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT SIGNAL 1..36
FT /evidence="ECO:0000255"
FT CHAIN 37..2527
FT /note="Neurogenic locus notch homolog protein 1"
FT /id="PRO_0000424013"
FT CHAIN 1727..2527
FT /note="Notch 1 extracellular truncation"
FT /evidence="ECO:0000250"
FT /id="PRO_0000424014"
FT CHAIN 1760..2527
FT /note="Notch 1 intracellular domain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000424015"
FT TOPO_DOM 37..1741
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1742..1762
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P46531"
FT TOPO_DOM 1763..2527
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 75..115
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 118..155
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 156..192
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 194..232
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 234..271
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 273..309
FT /note="EGF-like 6; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 311..349
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 351..387
FT /note="EGF-like 8; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 388..426
FT /note="EGF-like 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 428..466
FT /note="EGF-like 10; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 468..504
FT /note="EGF-like 11; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 506..542
FT /note="EGF-like 12; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 544..580
FT /note="EGF-like 13; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 582..617
FT /note="EGF-like 14; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 619..655
FT /note="EGF-like 15; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 657..692
FT /note="EGF-like 16; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 694..730
FT /note="EGF-like 17; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 732..767
FT /note="EGF-like 18; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 769..805
FT /note="EGF-like 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 807..843
FT /note="EGF-like 20; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 845..883
FT /note="EGF-like 21"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 885..921
FT /note="EGF-like 22; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 923..959
FT /note="EGF-like 23"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 961..997
FT /note="EGF-like 24; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 999..1035
FT /note="EGF-like 25"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1037..1073
FT /note="EGF-like 26"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1075..1111
FT /note="EGF-like 27"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1113..1159
FT /note="EGF-like 28"
FT /evidence="ECO:0000305"
FT DOMAIN 1161..1197
FT /note="EGF-like 29"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1199..1235
FT /note="EGF-like 30; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1237..1281
FT /note="EGF-like 31; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1283..1321
FT /note="EGF-like 32"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1323..1362
FT /note="EGF-like 33"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1364..1400
FT /note="EGF-like 34"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1403..1442
FT /note="EGF-like 35"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1465..1505
FT /note="LNR 1"
FT REPEAT 1506..1547
FT /note="LNR 2"
FT REPEAT 1548..1587
FT /note="LNR 3"
FT REPEAT 1933..1962
FT /note="ANK 1"
FT REPEAT 1966..1996
FT /note="ANK 2"
FT REPEAT 2000..2029
FT /note="ANK 3"
FT REPEAT 2033..2062
FT /note="ANK 4"
FT REPEAT 2066..2095
FT /note="ANK 5"
FT REGION 436..437
FT /note="Interaction with DLL4"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT REGION 464..468
FT /note="Interaction with DLL4"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT REGION 1734..1766
FT /note="Interaction with PSEN1"
FT /evidence="ECO:0000250|UniProtKB:P46531"
FT REGION 1786..1818
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1953..1961
FT /note="HIF1AN-binding"
FT /evidence="ECO:0000250"
FT REGION 2020..2028
FT /note="HIF1AN-binding"
FT /evidence="ECO:0000250"
FT REGION 2157..2243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2360..2527
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2176..2193
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2360..2398
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2425..2478
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2486..2520
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 448
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 451
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 468
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 469
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 471
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 485
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 486
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 506
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 507
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 509
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 523
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 524
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 1473
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT BINDING 1476
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT BINDING 1491
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT BINDING 1494
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT SITE 485
FT /note="Interaction with DLL4"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT SITE 1670..1671
FT /note="Cleavage; by furin-like protease"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT SITE 1726..1727
FT /note="Cleavage; by ADAM17"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT MOD_RES 1867
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT MOD_RES 1961
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN; partial"
FT /evidence="ECO:0000250"
FT MOD_RES 2028
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN"
FT /evidence="ECO:0000250"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 81
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 89
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 132
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 162
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 210
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 248
FT /note="O-linked (Fuc...) threonine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 248
FT /note="O-linked (GalNAc...) threonine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 327
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 357
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 365
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 394
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 451
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT CARBOHYD 474
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT CARBOHYD 482
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT CARBOHYD 512
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT CARBOHYD 550
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 625
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 633
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 663
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 708
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 738
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 775
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 783
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 800
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 813
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 821
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 904
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 916
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 937
FT /note="O-linked (Fuc) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 967
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 975
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1013
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1043
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1051
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1081
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1175
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1205
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1213
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1289
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1378
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1395
FT /note="O-linked (GlcNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1418
FT /note="O-linked (Fuc...) threonine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1418
FT /note="O-linked (GalNAc...) threonine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
FT CARBOHYD 1505
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1603
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1731
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P46531"
FT DISULFID 40..53
FT /evidence="ECO:0000250"
FT DISULFID 47..62
FT /evidence="ECO:0000250"
FT DISULFID 64..73
FT /evidence="ECO:0000250"
FT DISULFID 79..90
FT /evidence="ECO:0000250"
FT DISULFID 84..103
FT /evidence="ECO:0000250"
FT DISULFID 105..114
FT /evidence="ECO:0000250"
FT DISULFID 122..133
FT /evidence="ECO:0000250"
FT DISULFID 127..143
FT /evidence="ECO:0000250"
FT DISULFID 145..154
FT /evidence="ECO:0000250"
FT DISULFID 160..171
FT /evidence="ECO:0000250"
FT DISULFID 165..180
FT /evidence="ECO:0000250"
FT DISULFID 182..191
FT /evidence="ECO:0000250"
FT DISULFID 198..211
FT /evidence="ECO:0000250"
FT DISULFID 205..220
FT /evidence="ECO:0000250"
FT DISULFID 222..231
FT /evidence="ECO:0000250"
FT DISULFID 238..249
FT /evidence="ECO:0000250"
FT DISULFID 243..259
FT /evidence="ECO:0000250"
FT DISULFID 261..270
FT /evidence="ECO:0000250"
FT DISULFID 277..288
FT /evidence="ECO:0000250"
FT DISULFID 282..297
FT /evidence="ECO:0000250"
FT DISULFID 299..308
FT /evidence="ECO:0000250"
FT DISULFID 315..328
FT /evidence="ECO:0000250"
FT DISULFID 322..337
FT /evidence="ECO:0000250"
FT DISULFID 339..348
FT /evidence="ECO:0000250"
FT DISULFID 355..366
FT /evidence="ECO:0000250"
FT DISULFID 360..375
FT /evidence="ECO:0000250"
FT DISULFID 377..386
FT /evidence="ECO:0000250"
FT DISULFID 392..403
FT /evidence="ECO:0000250"
FT DISULFID 397..414
FT /evidence="ECO:0000250"
FT DISULFID 416..425
FT /evidence="ECO:0000250"
FT DISULFID 432..445
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT DISULFID 439..454
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT DISULFID 456..465
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT DISULFID 472..483
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT DISULFID 477..492
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT DISULFID 494..503
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT DISULFID 510..521
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT DISULFID 515..530
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT DISULFID 532..541
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT DISULFID 548..559
FT /evidence="ECO:0000250"
FT DISULFID 553..568
FT /evidence="ECO:0000250"
FT DISULFID 570..579
FT /evidence="ECO:0000250"
FT DISULFID 586..596
FT /evidence="ECO:0000250"
FT DISULFID 591..605
FT /evidence="ECO:0000250"
FT DISULFID 607..616
FT /evidence="ECO:0000250"
FT DISULFID 623..634
FT /evidence="ECO:0000250"
FT DISULFID 628..643
FT /evidence="ECO:0000250"
FT DISULFID 645..654
FT /evidence="ECO:0000250"
FT DISULFID 661..671
FT /evidence="ECO:0000250"
FT DISULFID 666..680
FT /evidence="ECO:0000250"
FT DISULFID 682..691
FT /evidence="ECO:0000250"
FT DISULFID 698..709
FT /evidence="ECO:0000250"
FT DISULFID 703..718
FT /evidence="ECO:0000250"
FT DISULFID 720..729
FT /evidence="ECO:0000250"
FT DISULFID 736..746
FT /evidence="ECO:0000250"
FT DISULFID 741..755
FT /evidence="ECO:0000250"
FT DISULFID 757..766
FT /evidence="ECO:0000250"
FT DISULFID 773..784
FT /evidence="ECO:0000250"
FT DISULFID 778..793
FT /evidence="ECO:0000250"
FT DISULFID 795..804
FT /evidence="ECO:0000250"
FT DISULFID 811..822
FT /evidence="ECO:0000250"
FT DISULFID 816..831
FT /evidence="ECO:0000250"
FT DISULFID 833..842
FT /evidence="ECO:0000250"
FT DISULFID 849..860
FT /evidence="ECO:0000250"
FT DISULFID 1117..1138
FT /evidence="ECO:0000305"
FT CROSSLNK 1765
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q01705"
SQ SEQUENCE 2527 AA; 270858 MW; 5E20EC5287850426 CRC64;
MGRSDSRAGA LLEGGCEQNI DPRRAAHCHH PRLATSSLRC SQPSGTCLNG GRCEVANGTE
ACVCSGPFVG QRCQDPNPCL STPCKNAGTC HVVEHGGTVN YACSCPLGFS GPLCLTPLDN
ACLANPCRNG GTCDLLTLTE YKCRCPPGWS GKSCQQADPC ASNPCANGGQ CLPFESSYIC
GCPPGFHGPT CRQDVNECSQ NPGLCRHGGT CHNEIGSYRC VCRATHTGPH CELPYVPCSP
SPCQNGGTCR PTGDTTHECA CLPGFAGQNC EENVDDCPGN NCKNGGACVD GVNTYNCRCP
PEWTGQYCTE DVDECQLMPN ACQNGGTCHN THGGYNCVCV NGWTGEDCSE NIDDCASAAC
FQGATCHDRV ASFYCECPHG RTGLLCHLND ACISNPCNEG SNCDTNPVNG KAICTCPSGY
TGPACSQDVD ECALGANPCE HAGKCLNTLG SFECQCLQGY TGPRCEIDVN ECISNPCQND
ATCLDQIGEF QCICMPGYEG VYCEINTDEC ASSPCLHNGH CMDKINEFLC QCPKGFSGHL
CQYDVDECAS TPCKNGAKCL DGPNTYTCVC TEGYTGTHCE VDIDECDPDP CHYGFCKDGV
ATFTCLCQPG YTGHHCETNI NECHSQPCRH GGTCQDRDNS YLCLCLKGTT GPNCEINLDD
CASNPCDSGT CLDKIDGYEC ACEPGYTGSM CNVNIDECAG SPCHNGGTCE DGIAGFTCRC
PEGYHDPTCL SEVNECNSNP CIHGACRDGL NGYKCDCAPG WSGTNCDINN NECESNPCVN
GGTCKDMTSG YVCTCREGFS GPNCQTNINE CASNPCLNQG TCIDDVAGYK CNCPLPYTGA
TCEVVLAPCA TSPCKNSGVC KESEDYESFS CVCPTGWQGQ TCEIDINECV KSPCRHGASC
QNTNGSYRCL CQAGYTGRNC ESDIDDCRPN PCHNGGSCTD GINMAFCDCL PGFQGAFCEE
DINECASNPC RNGANCTDCV DSYTCTCPAG FNGIHCENNT PDCTESSCFN GGTCVDGINS
FTCLCPPGFT GSYCQYDVNE CDSRPCLHGG TCQDSYGTYK CTCPQGYTGL NCQNLVHWCD
SAPCKNGGKC WQTNTQYHCE CRSGWTGFNC DVLSVSCEVA AQKRGIDVTL LCQHGGLCVD
EEDKHYCHCQ AGYTGSYCED EVDECSPNPC QNGATCTDYL GGFSCKCVAG YHGSNCSEEI
NECLSQPCQN GGTCIDLTNT YKCSCPRGTQ GVHCEINVDD CHPHLDPASR SPKCFNNGTC
VDQVGGYSCT CPPGFVGERC EGDINECLSN PCDPRGTQDC VQRVNDFHCE CRAGHTGRRC
ESVINGCRGK PCKNGGVCAV ASNTARGFIC RCPAGFEGAT CENDARTCGS LRCLNGGTCI
SGPRSPTCLC LGSFTGPECQ FPASSPCVGS NPCYNQGTCE PTSESPFYRC LCPAKFNGLL
CHILDYSFTG GAGRDIPPPQ IEEACELPEC QEDAGNKVCN LQCNNHACGW DGGDCSLNFN
DPWKNCTQSL QCWKYFSDGH CDSQCNSASC LFDGFDCQRT EGQCNPLYDQ YCKDHFSDGH
CDQGCNSAEC DWDGLDCADH VPERLAAGTL VLVVLLPPEQ LRNNSFHFLR ELSHVLHTNV
VFKRDAEGQQ MIFPYYGHEE ELRKHPIKRS AVGWTTSSLL PSTNGGRQRR ELDPMDIRGS
IVYLEIDNRQ CVQSSSQCFQ SATDVAAFLG ALASLGNLNI PYKIEAVKSE TVEPPLPSQL
HLMYLAAAAF VLLFFVGCGV LLSRKRRRQH GQLWFPEGFK VSEASKKKRR EPLGEDSVGL
KPLKNASDGA LMDDNQNEWG DEDLETKKFR FEEPVVVPDL DDQTDHRQWT QQHLDAADLR
MSAMAPTPPQ GEVDADCMDV NVRGPDGFTP LMIASCSGGG LETGNSEEEE DAPAVISDFI
YQGASLHNQT DRTGETALHL AARYSRSDAA KRLLEASADA NIQDNMGRTP LHAAVSADAQ
GVFQILLRNR ATDLDARMHD GTTPLILAAR LAVEGMLEDL INSHADVNAV DDLGKSALHW
AAAVNNVDAA VVLLKNGANK DMQNNKEETP LFLAAREGSY ETAKVLLDHF ANRDITDHMD
RLPRDIAQER MHHDIVRLLD EYNLVRSPQL HGTALGGTPT LSPTLCSPNG YLGNLKSATQ
GKKARKPSTK GLACGSKEAK DLKARRKKSQ DGKGCLLDSS SMLSPVDSLE SPHGYLSDVA
SPPLLPSPFQ QSPSMPLSHL PGMPDTHLGI SHLNVAAKPE MAALAGSSRL AFEPPPPRLP
HLPVASSAST VLSTNGSXGE EEWLAPSQYN PLRPGVASGT LSTQAAGLQH GMMGPLHSSL
STNTLSPMIY QGLPNTRLAT QPHLVQTQQV QPQNLQIQPQ NLQPPSQPHL SVSSAANGHL
GRSFLGGEHS QADVQPLGPS SLPVHTILPQ ESQALPTSLP SSMVPPMTTT QFLTPPSQHS
YSSSPVDNTP SHQLQVPEHP FLTPSPESPD QWSSSSPHSN ISDWSEGISS PPTSMPSQIT
HIPEAFK
