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Details on Person UniProt:O35516 Notch2

Class:IdReferenceGeneProduct:96669
_chainChangeLogsignal peptide:1-25 added on Fri February 6 2015;chain:26-2470 added on Fri February 6 2015;chain:1666-2470 added on Fri February 6 2015;chain:1697-2470 added on Fri February 6 2015;chain:26-2470 for 96669 removed on Thu May 2 2019;chain:1666-2470 for 96669 removed on Thu May 2 2019;chain:1697-2470 for 96669 removed on Thu May 2 2019;chain:26-2473 for 96669 added on Thu May 2 2019;chain:1668-2473 for 96669 added on Thu May 2 2019;chain:1699-2473 for 96669 added on Thu May 2 2019
_displayNameUniProt:O35516 Notch2
_timestamp2026-02-20 23:08:25
chainsignal peptide:1-25
chain:26-2473
chain:1668-2473
chain:1699-2473
checksum3A9067BBE3B1F480
commentFUNCTION Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination (PubMed:10393120). Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus (PubMed:10393120, PubMed:18710934). Affects the implementation of differentiation, proliferation and apoptotic programs (PubMed:10393120, PubMed:18710934). May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation (By similarity). In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation (PubMed:18710934). Positively regulates self-renewal of liver cancer cells (By similarity).SUBUNIT Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by disulfide bonds. Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH2. Interacts with RELA/p65. Interacts with HIF1AN. Interacts (via ANK repeats) with TCIM, the interaction inhibits the nuclear translocation of NOTCH2 N2ICD (By similarity). Interacts with CUL1, RBX1, SKP1 and FBXW7 that are SCF(FBXW7) E3 ubiquitin-protein ligase complex components. Interacts with MINAR1; this interaction increases MINAR1 stability and function (By similarity). Interacts with MDK; this interaction mediates a nuclear accumulation of NOTCH2 and therefore activation of NOTCH2 signaling leading to interaction between HES1 and STAT3 (By similarity). Interacts with MINAR2 (By similarity).SUBCELLULAR LOCATION Following proteolytical processing NICD is translocated to the nucleus. Retained at the cytoplasm by TCIM.ALTERNATIVE PRODUCTS Expressed in the brain, liver, kidney, neuroepithelia, somites, optic vesicles and branchial arches, but not heart.DEVELOPMENTAL STAGE Expressed in the embryonic ventricular zone, the postnatal ependymal cells, and the choroid plexus throughout embryonic and postnatal development.PTM Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form (PubMed:11459941, PubMed:11518718). Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC) (PubMed:11459941, PubMed:11518718). Following ligand binding, it is cleaved by TNF converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT) (By similarity). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (PubMed:11459941, PubMed:11518718).PTM Hydroxylated by HIF1AN.PTM Can be either O-glucosylated or O-xylosylated at Ser-613 by POGLUT1.PTM Phosphorylated by GSK3. GSK3-mediated phosphorylation is necessary for NOTCH2 recognition by FBXW7, ubiquitination and degradation via the ubiquitin proteasome pathway.SIMILARITY Belongs to the NOTCH family.
descriptionrecommendedName: fullName evidence="3"Neurogenic locus notch homolog protein 2 shortName: Notch 2 alternativeName: fullName evidence="17"Motch B component recommendedName: Notch 2 extracellular truncation /component component recommendedName: Notch 2 intracellular domain /component
geneNameNotch2
identifierO35516
isSequenceChangedFALSE
keywordActivator
Alternative splicing
ANK repeat
Cell membrane
Cytoplasm
Developmental protein
Differentiation
Disulfide bond
EGF-like domain
Glycoprotein
Membrane
Notch signaling pathway
Nucleus
Phosphoprotein
Receptor
Reference proteome
Repeat
Signal
Transcription
Transcription regulation
Transmembrane
Transmembrane helix
Ubl conjugation
modified[InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10
[InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
[InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12
[InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39
[InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18
[InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35
[InstanceEdit:423310] Kanapin, AA
[InstanceEdit:435478] Kanapin, AA
[InstanceEdit:435871] Kanapin, AA
[InstanceEdit:447347] Kanapin, AA
[InstanceEdit:525883] Kanapin, AA
[InstanceEdit:613449] Kanapin, AA
[InstanceEdit:797602] Kanapin, AA
[InstanceEdit:937368] Yung, CK
[InstanceEdit:1042053] Yung, CK
[InstanceEdit:1220657] Yung, CK
[InstanceEdit:1300696] Yung, CK
[InstanceEdit:1301627] Yung, CK
[InstanceEdit:1551960] Weiser, JD
[InstanceEdit:1995863] Weiser, JD
[InstanceEdit:2132304] Weiser, JD
[InstanceEdit:2265580] Weiser, JD
[InstanceEdit:5433710] Weiser, JD
[InstanceEdit:5618415] Weiser, JD
[InstanceEdit:5634237] Weiser, JD
[InstanceEdit:5673015] Weiser, JD
[InstanceEdit:6807888] Weiser, JD
[InstanceEdit:9037114] Weiser, JD
[InstanceEdit:9607352] Weiser, JD
[InstanceEdit:9616384] Weiser, JD
[InstanceEdit:9627708] Weiser, JD
[InstanceEdit:9637257] Weiser, JD
[InstanceEdit:9645038] Weiser, JD
[InstanceEdit:9645058] Weiser, JD
[InstanceEdit:9645290] Weiser, JD, 2019-05-08
[InstanceEdit:9657908] Weiser, JD
[InstanceEdit:9676415] Weiser, JD
[InstanceEdit:9730071] Weiser, JD
[InstanceEdit:9750299] Weiser, JD
[InstanceEdit:9834092] Weiser, Joel
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
nameNotch2
referenceDatabase[ReferenceDatabase:2] UniProt
secondaryIdentifierNOTC2_MOUSE
G5E8J0
Q06008
Q60941
sequenceLength2473
species[Species:48892] Mus musculus
(isoformParent)[ReferenceIsoform:151359] UniProt:O35516-2 Notch2 [Mus musculus]
[ReferenceIsoform:401414] UniProt:O35516-1 Notch2 [Mus musculus]
(referenceEntity)[EntityWithAccessionedSequence:1984029] Pre-Notch2 [endoplasmic reticulum membrane] [Mus musculus]
[EntityWithAccessionedSequence:1986542] Fuc-Pre-Notch2 [endoplasmic reticulum membrane] [Mus musculus]
[EntityWithAccessionedSequence:2023153] Glc,Fuc-Pre-Notch2 [Golgi membrane] [Mus musculus]
[EntityWithAccessionedSequence:2023164] Glc,GlcNAc-Fuc-Pre-Notch2 [Golgi membrane] [Mus musculus]
[EntityWithAccessionedSequence:2023168] Glc,Fuc-Pre-Notch2 [endoplasmic reticulum membrane] [Mus musculus]
[EntityWithAccessionedSequence:2032288] Notch2 Extracellular Domain (NECD2) [extracellular region] [Mus musculus]
[EntityWithAccessionedSequence:2032293] Notch2 Transmembrane and Intracellular Domain (NTMID2) [plasma membrane] [Mus musculus]
[EntityWithAccessionedSequence:2193064] mNEXT2 [plasma membrane] [Mus musculus]
[EntityWithAccessionedSequence:2193071] Notch2 ligand bound fragment [extracellular region] [Mus musculus]
[EntityWithAccessionedSequence:2197553] mNICD2 [cytosol] [Mus musculus]
List all 11 refering instances
(referenceSequence)[ModifiedResidue:1986522] O-fucosyl-L-threonine at 1199
[ModifiedResidue:1986523] O-fucosyl-L-threonine at 999
[ModifiedResidue:1986524] O-fucosyl-L-threonine at 769
[ModifiedResidue:1986526] O-fucosyl-L-serine at 923
[ModifiedResidue:1986527] O-fucosyl-L-threonine at 78
[ModifiedResidue:1986528] O-fucosyl-L-threonine at 233
[ModifiedResidue:1986529] O-fucosyl-L-threonine at 158
[ModifiedResidue:1986530] O-fucosyl-L-threonine at 312
[ModifiedResidue:1986531] O-fucosyl-L-threonine at 694
[ModifiedResidue:1986532] O-fucosyl-L-threonine at 961
List all 36 refering instances
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No pathways have been reviewed or authored by UniProt:O35516 Notch2 (96669)