NOTC2_HUMAN » Neurogenic locus notch homolog protein 2

NOTC2_HUMAN » Neurogenic locus notch homolog protein 2
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
NOTC2_HUMAN » Neurogenic locus notch homolog protein 2 » Notch 2; hN2;
Hydrophobic Thickness 34.4 ± 5.0 Å
Tilt Angle 23 ± 16°
ΔGtransfer -31.8 kcal/mol
ΔGfold -30.5 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 1677-1701 (1673-1704)
Pathways

A third proteolytic cleavage releases NICD (Reactome)

Dorso-ventral axis formation (KEGG)

Gene Expression (Reactome)

NICD traffics to nucleus (Reactome)

Notch signaling pathway (KEGG)

Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor (Reactome)

Signal Transduction (Reactome)

PDB 2oo4 (1423-1677)
OPM none
Complexes none
Interactions

DLL1, Complex: NOTC2:DLL1, PubMed

I13R2, Complex: I13R2:NOTC2, PubMed

JAG1, Complex: JAG1:NOTC2, PubMed

JAG2, Complex: JAG2:NOTC2, PubMed

LFNG, Complex: NOTC2:LFNG, PubMed

MFNG, Complex: MFNG:NOTC2, PubMed

NOTC1, Complex: NOTC1:NOTC2, PubMed

ST14, Complex: ST14:NOTC2, PubMed

Domains

AA: 68-100, PDBID: 1APO, Subunit A, Seq Identity:42%, EGF-like domain

AA: 109-141, PDBID: 1PFX, Subunit L, Seq Identity:47%, EGF-like domain

AA: 148-178, PDBID: 4XBM, Subunit B, Seq Identity:50%, EGF-like domain

AA: 182-221, PDBID: 4XL1, Subunit A, Seq Identity:58%, Calcium-binding EGF domain

AA: 230-252, PDBID: 2YGQ, Subunit A, Seq Identity:45%, Human growth factor-like EGF

AA: 264-294, PDBID: 4XBM, Subunit B, Seq Identity:50%, EGF-like domain

AA: 298-338, PDBID: 1TOZ, Subunit A, Seq Identity:48%, Calcium-binding EGF domain

AA: 347-367, PDBID: 4D90, Subunit A, Seq Identity:52%, Human growth factor-like EGF

AA: 379-411, PDBID: 4BDW, Subunit A, Seq Identity:45%, EGF-like domain

AA: 415-454, PDBID: 4XL1, Subunit A, Seq Identity:77%, Calcium-binding EGF domain

AA: 460-490, PDBID: 1TOZ, Subunit A, Seq Identity:76%, EGF-like domain

AA: 498-528, PDBID: 1TOZ, Subunit A, Seq Identity:62%, EGF-like domain

AA: 536-566, PDBID: 1TOZ, Subunit A, Seq Identity:57%, EGF-like domain

AA: 579-599, PDBID: 2YGQ, Subunit A, Seq Identity:39%, Human growth factor-like EGF

AA: 611-641, PDBID: 4XBM, Subunit B, Seq Identity:55%, EGF-like domain

AA: 649-678, PDBID: 1EDM, Subunit B, Seq Identity:54%, EGF-like domain

AA: 686-721, PDBID: 3POY, Subunit A, Seq Identity:38%, EGF-like domain

AA: 729-749, PDBID: 2YGQ, Subunit A, Seq Identity:39%, Human growth factor-like EGF

AA: 761-791, PDBID: 4XBM, Subunit B, Seq Identity:54%, EGF-like domain

AA: 799-829, PDBID: 1EDM, Subunit B, Seq Identity:60%, EGF-like domain

AA: 837-869, PDBID: 1PFX, Subunit L, Seq Identity:44%, EGF-like domain

AA: 873-910, PDBID: 1TOZ, Subunit A, Seq Identity:53%, Calcium-binding EGF domain

AA: 915-945, PDBID: 4XBM, Subunit B, Seq Identity:58%, EGF-like domain

AA: 953-983, PDBID: 4XBM, Subunit B, Seq Identity:58%, EGF-like domain

AA: 988-1021, PDBID: 4XBM, Subunit B, Seq Identity:54%, EGF-like domain

AA: 1029-1059, PDBID: 1APO, Subunit A, Seq Identity:60%, EGF-like domain

AA: 1067-1097, PDBID: 1TOZ, Subunit A, Seq Identity:45%, EGF-like domain

AA: 1116-1145, PDBID: 1IVO, Subunit D, Seq Identity:35%, EGF-like domain

AA: 1153-1183, PDBID: 1TOZ, Subunit A, Seq Identity:64%, EGF-like domain

AA: 1191-1221, PDBID: 4XBM, Subunit B, Seq Identity:54%, EGF-like domain

AA: 1229-1260, PDBID: 4XBM, Subunit B, Seq Identity:58%, EGF-like domain

AA: 1308-1341, PDBID: 2VJ2, Subunit A, Seq Identity:51%, EGF-like domain

AA: 1422-1456, PDBID: 2OO4, Subunit A, Seq Identity:100%, LNR domain

AA: 1463-1497, PDBID: 2OO4, Subunit A, Seq Identity:100%, LNR domain

AA: 1500-1535, PDBID: 2OO4, Subunit A, Seq Identity:100%, LNR domain

AA: 1539-1594, PDBID: 2OO4, Subunit A, Seq Identity:100%, NOTCH protein

AA: 1618-1674, PDBID: 2OO4, Subunit A, Seq Identity:100%, NOTCH protein

AA: 1850-1943, PDBID: 1YMP, Subunit B, Seq Identity:71%, Ankyrin repeats (3 copies)

AA: 1881-1974, PDBID: 1OT8, Subunit C, Seq Identity:35%, Ankyrin repeats (3 copies)

AA: 1948-2041, PDBID: 1YYH, Subunit B, Seq Identity:78%, Ankyrin repeats (3 copies)

AA: 2381-2444, Domain of unknown function (DUF3454)

UniProt annotation for NOTC2_HUMAN » Neurogenic locus notch homolog protein 2
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.

SUBUNIT: 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.

TISSUE SPECIFICITY: Expressed in the brain, heart, kidney, lung, skeletal muscle and liver. Ubiquitously expressed in the embryo.

DISEASE: Alagille syndrome 2 (ALGS2) OMIM: 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. mutations affecting the gene represented in this entry.

DISEASE: Hajdu-Cheney syndrome (HJCYS) OMIM: A rare 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 mutations associated with Hajdu- Cheney syndrome cluster to the last coding exon of the gene. This suggests that the mutant mRNA products may escape nonsense- mediated decay and the resulting truncated NOTCH2 proteins act in a gain-of-function manner.

Amino Acid Sequence for NOTC2_HUMAN » Neurogenic locus notch homolog protein 2
MPALRPALLW ALLALWLCCA APAHALQCRD GYEPCVNEGM CVTYHNGTGY CKCPEGFLGE YCQHRDPCEK NRCQNGGTCV AQAMLGKATC RCASGFTGED CQYSTSHPCF VSRPCLNGGT CHMLSRDTYE CTCQVGFTGK ECQWTDACLS HPCANGSTCT TVANQFSCKC LTGFTGQKCE TDVNECDIPG HCQHGGTCLN LPGSYQCQCP QGFTGQYCDS LYVPCAPSPC VNGGTCRQTG DFTFECNCLP GFEGSTCERN IDDCPNHRCQ NGGVCVDGVN TYNCRCPPQW TGQFCTEDVD ECLLQPNACQ NGGTCANRNG GYGCVCVNGW SGDDCSENID DCAFASCTPG STCIDRVASF SCMCPEGKAG LLCHLDDACI SNPCHKGALC DTNPLNGQYI CTCPQGYKGA DCTEDVDECA MANSNPCEHA GKCVNTDGAF HCECLKGYAG PRCEMDINEC HSDPCQNDAT CLDKIGGFTC LCMPGFKGVH CELEINECQS NPCVNNGQCV DKVNRFQCLC PPGFTGPVCQ IDIDDCSSTP CLNGAKCIDH PNGYECQCAT GFTGVLCEEN IDNCDPDPCH HGQCQDGIDS YTCICNPGYM GAICSDQIDE CYSSPCLNDG RCIDLVNGYQ CNCQPGTSGV NCEINFDDCA SNPCIHGICM DGINRYSCVC SPGFTGQRCN IDIDECASNP CRKGATCING VNGFRCICPE GPHHPSCYSQ VNECLSNPCI HGNCTGGLSG YKCLCDAGWV GINCEVDKNE CLSNPCQNGG TCDNLVNGYR CTCKKGFKGY NCQVNIDECA SNPCLNQGTC FDDISGYTCH CVLPYTGKNC QTVLAPCSPN PCENAAVCKE SPNFESYTCL CAPGWQGQRC TIDIDECISK PCMNHGLCHN TQGSYMCECP PGFSGMDCEE DIDDCLANPC QNGGSCMDGV NTFSCLCLPG FTGDKCQTDM NECLSEPCKN GGTCSDYVNS YTCKCQAGFD GVHCENNINE CTESSCFNGG TCVDGINSFS CLCPVGFTGS FCLHEINECS SHPCLNEGTC VDGLGTYRCS CPLGYTGKNC QTLVNLCSRS PCKNKGTCVQ KKAESQCLCP SGWAGAYCDV PNVSCDIAAS RRGVLVEHLC QHSGVCINAG NTHYCQCPLG YTGSYCEEQL DECASNPCQH GATCSDFIGG YRCECVPGYQ GVNCEYEVDE CQNQPCQNGG TCIDLVNHFK CSCPPGTRGL LCEENIDDCA RGPHCLNGGQ CMDRIGGYSC RCLPGFAGER CEGDINECLS NPCSSEGSLD CIQLTNDYLC VCRSAFTGRH CETFVDVCPQ MPCLNGGTCA VASNMPDGFI CRCPPGFSGA RCQSSCGQVK CRKGEQCVHT ASGPRCFCPS PRDCESGCAS SPCQHGGSCH PQRQPPYYSC QCAPPFSGSR CELYTAPPST PPATCLSQYC ADKARDGVCD EACNSHACQW DGGDCSLTME NPWANCSSPL PCWDYINNQC DELCNTVECL FDNFECQGNS KTCKYDKYCA DHFKDNHCDQ GCNSEECGWD GLDCAADQPE NLAEGTLVIV VLMPPEQLLQ DARSFLRALG TLLHTNLRIK RDSQGELMVY PYYGEKSAAM KKQRMTRRSL PGEQEQEVAG SKVFLEIDNR QCVQDSDHCF KNTDAAAALL ASHAIQGTLS YPLVSVVSES LTPERTQLLY LLAVAVVIIL FIILLGVIMA KRKRKHGSLW LPEGFTLRRD ASNHKRREPV GQDAVGLKNL SVQVSEANLI GTGTSEHWVD DEGPQPKKVK AEDEALLSEE DDPIDRRPWT QQHLEAADIR RTPSLALTPP QAEQEVDVLD VNVRGPDGCT PLMLASLRGG SSDLSDEDED AEDSSANIIT DLVYQGASLQ AQTDRTGEMA LHLAARYSRA DAAKRLLDAG ADANAQDNMG RCPLHAAVAA DAQGVFQILI RNRVTDLDAR MNDGTTPLIL AARLAVEGMV AELINCQADV NAVDDHGKSA LHWAAAVNNV EATLLLLKNG ANRDMQDNKE ETPLFLAARE GSYEAAKILL DHFANRDITD HMDRLPRDVA RDRMHHDIVR LLDEYNVTPS PPGTVLTSAL SPVICGPNRS FLSLKHTPMG KKSRRPSAKS TMPTSLPNLA KEAKDAKGSR RKKSLSEKVQ LSESSVTLSP VDSLESPHTY VSDTTSSPMI TSPGILQASP NPMLATAAPP APVHAQHALS FSNLHEMQPL AHGASTVLPS VSQLLSHHHI VSPGSGSAGS LSRLHPVPVP ADWMNRMEVN ETQYNEMFGM VLAPAEGTHP GIAPQSRPPE GKHITTPREP LPPIVTFQLI PKGSIAQPAG APQPQSTCPP AVAGPLPTMY QIPEMARLPS VAFPTAMMPQ QDGQVAQTIL PAYHPFPASV GKYPTPPSQH SYASSNAAER TPSHSGHLQG EHPYLTPSPE SPDQWSSSSP HSASDWSDVT TSPTPGGAGG GQRGPGTHMS EPPHNNMQVY A