NOTCH2
entrez
4853
canonical
uniprot
Q04721
canonical
ensembl
ENSG00000134250
resolver
ensp
ENSP00000256646
resolver
enst
ENST00000256646
resolver
genesymbol
NOTCH2
resolver
hgnc
HGNC:7882
resolver
uniprot
Q5T3X7
resolver
uniprot
Q6IQ50
resolver
uniprot
Q99734
resolver
uniprot
Q9H240
resolver
uniprot_entry
NOTC2_HUMAN
resolver
uniprot_entry
Q6IQ50_HUMAN
resolver
uniprot_sec
Q5T3X7
resolver
uniprot_sec
Q99734
resolver
uniprot_sec
Q9H240
resolver
amino_acid_sequence
MPALRPALLWALLALWLCCAAPAHALQCRDGYEPCVNEGMCVTYHNGTGYCKCPEGFLGEYCQHRDPCEKNRCQNGGTCVAQAMLGKATCRCASGFTGEDCQYSTSHPCFVSRPCLNGGTCHMLSRDTYECTCQVGFTGKECQWTDACLSHPCANGSTCTTVANQFSCKCLTGFTGQKCETDVNECDIPGHCQHGGTCLNLPGSYQCQCPQGFTGQYCDSLYVPCAPSPCVNGGTCRQTGDFTFECNCLPGFEGSTCERNIDDCPNHRCQNGGVCVDGVNTYNCRCPPQWTGQFCTEDVDECLLQPNACQNGGTCANRNGGYGCVCVNGWSGDDCSENIDDCAFASCTPGSTCIDRVASFSCMCPEGKAGLLCHLDDACISNPCHKGALCDTNPLNGQYICTCPQGYKGADCTEDVDECAMANSNPCEHAGKCVNTDGAFHCECLKGYAGPRCEMDINECHSDPCQNDATCLDKIGGFTCLCMPGFKGVHCELEINECQSNPCVNNGQCVDKVNRFQCLCPPGFTGPVCQIDIDDCSSTPCLNGAKCIDHPNGYECQCATGFTGVLCEENIDNCDPDPCHHGQCQDGIDSYTCICNPGYMGAICSDQIDECYSSPCLNDGRCIDLVNGYQCNCQPGTSGVNCEINFDDCASNPCIHGICMDGINRYSCVCSPGFTGQRCNIDIDECASNPCRKGATCINGVNGFRCICPEGPHHPSCYSQVNECLSNPCIHGNCTGGLSGYKCLCDAGWVGINCEVDKNECLSNPCQNGGTCDNLVNGYRCTCKKGFKGYNCQVNIDECASNPCLNQGTCFDDISGYTCHCVLPYTGKNCQTVLAPCSPNPCENAAVCKESPNFESYTCLCAPGWQGQRCTIDIDECISKPCMNHGLCHNTQGSYMCECPPGFSGMDCEEDIDDCLANPCQNGGSCMDGVNTFSCLCLPGFTGDKCQTDMNECLSEPCKNGGTCSDYVNSYTCKCQAGFDGVHCENNINECTESSCFNGGTCVDGINSFSCLCPVGFTGSFCLHEINECSSHPCLNEGTCVDGLGTYRCSCPLGYTGKNCQTLVNLCSRSPCKNKGTCVQKKAESQCLCPSGWAGAYCDVPNVSCDIAASRRGVLVEHLCQHSGVCINAGNTHYCQCPLGYTGSYCEEQLDECASNPCQHGATCSDFIGGYRCECVPGYQGVNCEYEVDECQNQPCQNGGTCIDLVNHFKCSCPPGTRGLLCEENIDDCARGPHCLNGGQCMDRIGGYSCRCLPGFAGERCEGDINECLSNPCSSEGSLDCIQLTNDYLCVCRSAFTGRHCETFVDVCPQMPCLNGGTCAVASNMPDGFICRCPPGFSGARCQSSCGQVKCRKGEQCVHTASGPRCFCPSPRDCESGCASSPCQHGGSCHPQRQPPYYSCQCAPPFSGSRCELYTAPPSTPPATCLSQYCADKARDGVCDEACNSHACQWDGGDCSLTMENPWANCSSPLPCWDYINNQCDELCNTVECLFDNFECQGNSKTCKYDKYCADHFKDNHCDQGCNSEECGWDGLDCAADQPENLAEGTLVIVVLMPPEQLLQDARSFLRALGTLLHTNLRIKRDSQGELMVYPYYGEKSAAMKKQRMTRRSLPGEQEQEVAGSKVFLEIDNRQCVQDSDHCFKNTDAAAALLASHAIQGTLSYPLVSVVSESLTPERTQLLYLLAVAVVIILFIILLGVIMAKRKRKHGSLWLPEGFTLRRDASNHKRREPVGQDAVGLKNLSVQVSEANLIGTGTSEHWVDDEGPQPKKVKAEDEALLSEEDDPIDRRPWTQQHLEAADIRRTPSLALTPPQAEQEVDVLDVNVRGPDGCTPLMLASLRGGSSDLSDEDEDAEDSSANIITDLVYQGASLQAQTDRTGEMALHLAARYSRADAAKRLLDAGADANAQDNMGRCPLHAAVAADAQGVFQILIRNRVTDLDARMNDGTTPLILAARLAVEGMVAELINCQADVNAVDDHGKSALHWAAAVNNVEATLLLLKNGANRDMQDNKEETPLFLAAREGSYEAAKILLDHFANRDITDHMDRLPRDVARDRMHHDIVRLLDEYNVTPSPPGTVLTSALSPVICGPNRSFLSLKHTPMGKKSRRPSAKSTMPTSLPNLAKEAKDAKGSRRKKSLSEKVQLSESSVTLSPVDSLESPHTYVSDTTSSPMITSPGILQASPNPMLATAAPPAPVHAQHALSFSNLHEMQPLAHGASTVLPSVSQLLSHHHIVSPGSGSAGSLSRLHPVPVPADWMNRMEVNETQYNEMFGMVLAPAEGTHPGIAPQSRPPEGKHITTPREPLPPIVTFQLIPKGSIAQPAGAPQPQSTCPPAVAGPLPTMYQIPEMARLPSVAFPTAMMPQQDGQVAQTILPAYHPFPASVGKYPTPPSQHSYASSNAAERTPSHSGHLQGEHPYLTPSPESPDQWSSSSPHSASDWSDVTTSPTPGGAGGGQRGPGTHMSEPPHNNMQVYA
uniprot
proteins
disease_involvement
DISEASE: Alagille syndrome 2 (ALGS2) [MIM:610205]: A form of Alagille syndrome, an autosomal dominant multisystem disorder. It is clinically defined by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical involvement of the renal and vascular systems. {ECO:0000269|PubMed:16773578}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hajdu-Cheney syndrome (HJCYS) [MIM:102500]: A rare, autosomal dominant skeletal disorder characterized by the association of facial anomalies, acro-osteolysis, general osteoporosis, insufficient ossification of the skull, and periodontal disease (premature loss of permanent teeth). Other features include cleft palate, congenital heart defects, polycystic kidneys, orthopedic problems and anomalies of the genitalia, intestines and eyes. {ECO:0000269|PubMed:21378985, ECO:0000269|PubMed:21378989, ECO:0000269|PubMed:21681853, ECO:0000269|PubMed:21712856, ECO:0000269|PubMed:21793104, ECO:0000269|PubMed:23389697, ECO:0000269|PubMed:29149593}. Note=The disease is caused by variants affecting the gene represented in this entry. NOTCH2 nonsense and frameshift mutations associated with Hajdu-Cheney syndrome cluster to the last coding exon of the gene. Mutant mRNA products escape nonsense-mediated decay and the resulting truncated NOTCH2 proteins act in a gain-of-function manner (PubMed:21378989). The pathological mechanism at cellular level involves disruption of a high affinity degron recognized by FBXW7 at the C-terminus, loss of interaction with FBXW7, reduced ubiquitination and degradation, and increased NOTCH2 levels. Bone marrow cells derived from HJCYS patients have an enhanced capacity of osteoclastogenesis due to sustained NOTCH2 activity (PubMed:29149593). {ECO:0000269|PubMed:21378989, ECO:0000269|PubMed:29149593}.
uniprot
proteins
function
FUNCTION: 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). {ECO:0000250|UniProtKB:O35516, ECO:0000269|PubMed:21378985, ECO:0000269|PubMed:21378989, ECO:0000269|PubMed:25985737, ECO:0000269|PubMed:29149593}.
uniprot
proteins
mass_dalton
265405
uniprot
proteins
mutagenesis
MUTAGEN 2416; /note="T->A: Loss of interaction with FBW7. Results in decreased ubiquitination and degradation."; /evidence="ECO:0000269|PubMed:29149593
uniprot
proteins
post_translational_modification
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 (By similarity). Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC) (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:O35516, ECO:0000250|UniProtKB:Q01705}.; PTM: Hydroxylated by HIF1AN. {ECO:0000269|PubMed:18299578}.; PTM: Can be either O-glucosylated or O-xylosylated at Ser-613 by POGLUT1. {ECO:0000250|UniProtKB:O35516}.; PTM: Phosphorylated by GSK3. GSK3-mediated phosphorylation is necessary for NOTCH2 recognition by FBXW7, ubiquitination and degradation via the ubiquitin proteasome pathway. {ECO:0000269|PubMed:29149593}.
uniprot
proteins
protein_family
NOTCH family
uniprot
proteins
pubmed
10079256
uniprot
proteins
pubmed
11101851
uniprot
proteins
pubmed
12370315
uniprot
proteins
pubmed
1303260
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
16773578
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17401372
uniprot
proteins
pubmed
17573339
uniprot
proteins
pubmed
18299578
uniprot
proteins
pubmed
18469519
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21378985
uniprot
proteins
pubmed
21378989
uniprot
proteins
pubmed
21681853
uniprot
proteins
pubmed
21712856
uniprot
proteins
pubmed
21793104
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23389697
uniprot
proteins
pubmed
25985737
uniprot
proteins
pubmed
29149593
uniprot
proteins
pubmed
29329397
uniprot
proteins
pubmed
29856954
uniprot
proteins
pubmed
32954300
uniprot
proteins
pubmed
9244302
uniprot
proteins
sequence_length
2471
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Notch 2 extracellular truncation]: Cell membrane {ECO:0000269|PubMed:29329397, ECO:0000269|PubMed:9244302}; Single-pass type I membrane protein {ECO:0000269|PubMed:9244302}.; SUBCELLULAR LOCATION: [Notch 2 intracellular domain]: Nucleus {ECO:0000269|PubMed:25985737}. Cytoplasm {ECO:0000269|PubMed:25985737}. Note=Following proteolytical processing NICD is translocated to the nucleus. Retained at the cytoplasm by TCIM (PubMed:25985737). {ECO:0000269|PubMed:25985737}.
uniprot
proteins
transmembrane_region
TRANSMEM 1678..1698; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins