{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q04721","secondaryAccessions":["Q5T3X7","Q99734","Q9H240"],"uniProtkbId":"NOTC2_HUMAN","entryAudit":{"firstPublicDate":"2002-03-27","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2007-04-03","entryVersion":260,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Neurogenic locus notch homolog protein 2"},"shortNames":[{"value":"Notch 2"},{"value":"hN2"}]},"contains":[{"recommendedName":{"fullName":{"value":"Notch 2 extracellular truncation"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"25985737"}],"value":"N2ECD"}]}},{"recommendedName":{"fullName":{"value":"Notch 2 intracellular domain"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"25985737"}],"value":"N2ICD"}]}}],"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:7882"}],"value":"NOTCH2"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O35516"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21378985"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21378989"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25985737"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29149593"}],"value":"Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. 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:21378985, PubMed:21378989). Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation (PubMed:29149593). Positively regulates self-renewal of liver cancer cells (PubMed:25985737)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11101851"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12370315"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17573339"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18469519"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25985737"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29149593"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29329397"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29856954"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32954300"}],"value":"Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by disulfide bonds (By similarity). Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH2. Interacts with RELA/p65 (By similarity). Interacts with HIF1AN. Interacts (via ANK repeats) with TCIM, the interaction inhibits the nuclear translocation of NOTCH2 N2ICD (PubMed:25985737). Interacts with CUL1, RBX1, SKP1 and FBXW7 that are SCF(FBXW7) E3 ubiquitin-protein ligase complex components (PubMed:29149593). Interacts with MINAR1; this interaction increases MINAR1 stability and function (PubMed:29329397). Interacts with NOTCH2NL (NOTCH2NLA, NOTCH2NLB and/or NOTCH2NLC); leading to enhance Notch signaling pathway in a non-cell-autonomous manner (PubMed:29856954). Interacts with MDK; this interaction mediates a nuclear accumulation of NOTCH2 and therefore activation of NOTCH2 signaling leading to interaction between HES1 and STAT3 (PubMed:18469519). 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