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Q04721 Proteins EGF-like domain Repeats
Uniprot ID:Q04721
Protein name: Neurogenic locus notch homolog protein 2
Gene : NOTCH2
Protein Family:NOTCH family
Squence Length : 2471
Sequnce
>Q04721 2472 MPALRPALLWALLALWLCCAAPAHALQCRDGYEPCVNEGMCVTYHNGTGYCKCPEGFLGEYCQHRDPCEKNRCQNGGTCVAQAMLGKATCRCASGFTGEDCQYSTSHPCFVSRPCLNGGTCHMLSRDTYECTCQVGFTGKECQWTDACLSHPCANGSTCTTVANQFSCKCLTGFTGQKCETDVNECDIPGHCQHGGTCLNLPGSYQCQCPQGFTGQYCDSLYVPCAPSPCVNGGTCRQTGDFTFECNCLPGFEGSTCERNIDDCPNHRCQNGGVCVDGVNTYNCRCPPQWTGQFCTEDVDECLLQPNACQNGGTCANRNGGYGCVCVNGWSGDDCSENIDDCAFASCTPGSTCIDRVASFSCMCPEGKAGLLCHLDDACISNPCHKGALCDTNPLNGQYICTCPQGYKGADCTEDVDECAMANSNPCEHAGKCVNTDGAFHCECLKGYAGPRCEMDINECHSDPCQNDATCLDKIGGFTCLCMPGFKGVHCELEINECQSNPCVNNGQCVDKVNRFQCLCPPGFTGPVCQIDIDDCSSTPCLNGAKCIDHPNGYECQCATGFTGVLCEENIDNCDPDPCHHGQCQDGIDSYTCICNPGYMGAICSDQIDECYSSPCLNDGRCIDLVNGYQCNCQPGTSGVNCEINFDDCASNPCIHGICMDGINRYSCVCSPGFTGQRCNIDIDECASNPCRKGATCINGVNGFRCICPEGPHHPSCYSQVNECLSNPCIHGNCTGGLSGYKCLCDAGWVGINCEVDKNECLSNPCQNGGTCDNLVNGYRCTCKKGFKGYNCQVNIDECASNPCLNQGTCFDDISGYTCHCVLPYTGKNCQTVLAPCSPNPCENAAVCKESPNFESYTCLCAPGWQGQRCTIDIDECISKPCMNHGLCHNTQGSYMCECPPGFSGMDCEEDIDDCLANPCQNGGSCMDGVNTFSCLCLPGFTGDKCQTDMNECLSEPCKNGGTCSDYVNSYTCKCQAGFDGVHCENNINECTESSCFNGGTCVDGINSFSCLCPVGFTGSFCLHEINECSSHPCLNEGTCVDGLGTYRCSCPLGYTGKNCQTLVNLCSRSPCKNKGTCVQKKAESQCLCPSGWAGAYCDVPNVSCDIAASRRGVLVEHLCQHSGVCINAGNTHYCQCPLGYTGSYCEEQLDECASNPCQHGATCSDFIGGYRCECVPGYQGVNCEYEVDECQNQPCQNGGTCIDLVNHFKCSCPPGTRGLLCEENIDDCARGPHCLNGGQCMDRIGGYSCRCLPGFAGERCEGDINECLSNPCSSEGSLDCIQLTNDYLCVCRSAFTGRHCETFVDVCPQMPCLNGGTCAVASNMPDGFICRCPPGFSGARCQSSCGQVKCRKGEQCVHTASGPRCFCPSPRDCESGCASSPCQHGGSCHPQRQPPYYSCQCAPPFSGSRCELYTAPPSTPPATCLSQYCADKARDGVCDEACNSHACQWDGGDCSLTMENPWANCSSPLPCWDYINNQCDELCNTVECLFDNFECQGNSKTCKYDKYCADHFKDNHCDQGCNSEECGWDGLDCAADQPENLAEGTLVIVVLMPPEQLLQDARSFLRALGTLLHTNLRIKRDSQGELMVYPYYGEKSAAMKKQRMTRRSLPGEQEQEVAGSKVFLEIDNRQCVQDSDHCFKNTDAAAALLASHAIQGTLSYPLVSVVSESLTPERTQLLYLLAVAVVIILFIILLGVIMAKRKRKHGSLWLPEGFTLRRDASNHKRREPVGQDAVGLKNLSVQVSEANLIGTGTSEHWVDDEGPQPKKVKAEDEALLSEEDDPIDRRPWTQQHLEAADIRRTPSLALTPPQAEQEVDVLDVNVRGPDGCTPLMLASLRGGSSDLSDEDEDAEDSSANIITDLVYQGASLQAQTDRTGEMALHLAARYSRADAAKRLLDAGADANAQDNMGRCPLHAAVAADAQGVFQILIRNRVTDLDARMNDGTTPLILAARLAVEGMVAELINCQADVNAVDDHGKSALHWAAAVNNVEATLLLLKNGANRDMQDNKEETPLFLAAREGSYEAAKILLDHFANRDITDHMDRLPRDVARDRMHHDIVRLLDEYNVTPSPPGTVLTSALSPVICGPNRSFLSLKHTPMGKKSRRPSAKSTMPTSLPNLAKEAKDAKGSRRKKSLSEKVQLSESSVTLSPVDSLESPHTYVSDTTSSPMITSPGILQASPNPMLATAAPPAPVHAQHALSFSNLHEMQPLAHGASTVLPSVSQLLSHHHIVSPGSGSAGSLSRLHPVPVPADWMNRMEVNETQYNEMFGMVLAPAEGTHPGIAPQSRPPEGKHITTPREPLPPIVTFQLIPKGSIAQPAGAPQPQSTCPPAVAGPLPTMYQIPEMARLPSVAFPTAMMPQQDGQVAQTILPAYHPFPASVGKYPTPPSQHSYASSNAAERTPSHSGHLQGEHPYLTPSPESPDQWSSSSPHSASDWSDVTTSPTPGGAGGGQRGPGTHMSEPPHNNMQVYA
Domains
DOMAIN 26 63 EGF-like 1 DOMAIN 64 102 EGF-like 2 DOMAIN 105 143 EGF-like 3 DOMAIN 144 180 EGF-like 4 DOMAIN 182 219 EGF-like 5 calcium-binding DOMAIN 221 258 EGF-like 6 DOMAIN 260 296 EGF-like 7 calcium-binding DOMAIN 298 336 EGF-like 8 calcium-binding DOMAIN 338 374 EGF-like 9 calcium-binding DOMAIN 375 413 EGF-like 10 DOMAIN 415 454 EGF-like 11 calcium-binding DOMAIN 456 492 EGF-like 12 calcium-binding DOMAIN 494 530 EGF-like 13 calcium-binding DOMAIN 532 568 EGF-like 14 calcium-binding DOMAIN 570 605 EGF-like 15 calcium-binding DOMAIN 607 643 EGF-like 16 calcium-binding DOMAIN 645 680 EGF-like 17 calcium-binding DOMAIN 682 718 EGF-like 18 calcium-binding DOMAIN 720 755 EGF-like 19 DOMAIN 757 793 EGF-like 20 calcium-binding DOMAIN 795 831 EGF-like 21 calcium-binding DOMAIN 833 871 EGF-like 22 DOMAIN 873 909 EGF-like 23 calcium-binding DOMAIN 911 947 EGF-like 24 calcium-binding DOMAIN 949 985 EGF-like 25 calcium-binding DOMAIN 987 1023 EGF-like 26 calcium-binding DOMAIN 1025 1061 EGF-like 27 calcium-binding DOMAIN 1063 1099 EGF-like 28 DOMAIN 1101 1147 EGF-like 29 DOMAIN 1149 1185 EGF-like 30 calcium-binding DOMAIN 1187 1223 EGF-like 31 calcium-binding DOMAIN 1225 1262 EGF-like 32 calcium-binding DOMAIN 1264 1302 EGF-like 33 DOMAIN 1304 1343 EGF-like 34 DOMAIN 1374 1412 EGF-like 35
EGF-like sequence regions
26 - 63 CRDGYEPCVNEGMCVTYHNGTGYCKCPEGFLGEYCQHR 64 - 102 DPCEKNRCQNGGTCVAQAMLGKATCRCASGFTGEDCQYS 105 - 143 HPCFVSRPCLNGGTCHMLSRDTYECTCQVGFTGKECQWT 144 - 180 DACLSHPCANGSTCTTVANQFSCKCLTGFTGQKCETD 182 - 219 NECDIPGHCQHGGTCLNLPGSYQCQCPQGFTGQYCDSL 221 - 258 VPCAPSPCVNGGTCRQTGDFTFECNCLPGFEGSTCERN 260 - 296 DDCPNHRCQNGGVCVDGVNTYNCRCPPQWTGQFCTED 298 - 336 DECLLQPNACQNGGTCANRNGGYGCVCVNGWSGDDCSEN 338 - 374 DDCAFASCTPGSTCIDRVASFSCMCPEGKAGLLCHLD 375 - 413 DACISNPCHKGALCDTNPLNGQYICTCPQGYKGADCTED 415 - 454 DECAMANSNPCEHAGKCVNTDGAFHCECLKGYAGPRCEMD 456 - 492 NECHSDPCQNDATCLDKIGGFTCLCMPGFKGVHCELE 494 - 530 NECQSNPCVNNGQCVDKVNRFQCLCPPGFTGPVCQID 532 - 568 DDCSSTPCLNGAKCIDHPNGYECQCATGFTGVLCEEN 570 - 605 DNCDPDPCHHGQCQDGIDSYTCICNPGYMGAICSDQ 607 - 643 DECYSSPCLNDGRCIDLVNGYQCNCQPGTSGVNCEIN 645 - 680 DDCASNPCIHGICMDGINRYSCVCSPGFTGQRCNID 682 - 718 DECASNPCRKGATCINGVNGFRCICPEGPHHPSCYSQ 720 - 755 NECLSNPCIHGNCTGGLSGYKCLCDAGWVGINCEVD 757 - 793 NECLSNPCQNGGTCDNLVNGYRCTCKKGFKGYNCQVN 795 - 831 DECASNPCLNQGTCFDDISGYTCHCVLPYTGKNCQTV 833 - 871 APCSPNPCENAAVCKESPNFESYTCLCAPGWQGQRCTID 873 - 909 DECISKPCMNHGLCHNTQGSYMCECPPGFSGMDCEED 911 - 947 DDCLANPCQNGGSCMDGVNTFSCLCLPGFTGDKCQTD 949 - 985 NECLSEPCKNGGTCSDYVNSYTCKCQAGFDGVHCENN 987 - 1023 NECTESSCFNGGTCVDGINSFSCLCPVGFTGSFCLHE 1025 - 1061 NECSSHPCLNEGTCVDGLGTYRCSCPLGYTGKNCQTL 1063 - 1099 NLCSRSPCKNKGTCVQKKAESQCLCPSGWAGAYCDVP 1101 - 1147 VSCDIAASRRGVLVEHLCQHSGVCINAGNTHYCQCPLGYTGSYCEEQ 1149 - 1185 DECASNPCQHGATCSDFIGGYRCECVPGYQGVNCEYE 1187 - 1223 DECQNQPCQNGGTCIDLVNHFKCSCPPGTRGLLCEEN 1225 - 1262 DDCARGPHCLNGGQCMDRIGGYSCRCLPGFAGERCEGD 1264 - 1302 NECLSNPCSSEGSLDCIQLTNDYLCVCRSAFTGRHCETF 1304 - 1343 DVCPQMPCLNGGTCAVASNMPDGFICRCPPGFSGARCQSS 1374 - 1412 SGCASSPCQHGGSCHPQRQPPYYSCQCAPPFSGSRCELY
Function
"Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 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. 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)"
Mutation
2416 2416 T->A: Loss of interaction with FBW7
Disease
"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 Note=The disease is caused by mutations 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 Note=The disease is caused by mutations 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)"