NOTC1_HUMAN » Neurogenic locus notch homolog protein 1

NOTC1_HUMAN » Neurogenic locus notch homolog protein 1
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
NOTC1_HUMAN » Neurogenic locus notch homolog protein 1 » Notch 1; hN1; Translocation-associated notch protein TAN-1;
Hydrophobic Thickness 33.2 ± 2.2 Å
Tilt Angle 0 ± 0°
ΔGtransfer -39.5 kcal/mol
ΔGfold -21.8 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 1732-1756 (1731-1761)
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)

Prion diseases (KEGG)

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

Signal Transduction (Reactome)

PDB 1pb5 (1446-1480), 3eto (1446-1733), 1yyh (1872-2114), 2f8x (1872-2126), 3nbn (1872-2126), 3v79 (1872-2126, R=1759-1777), 2f8y (1905-2126), 1toz (411-526), 2vj3 (411-526), 4d0e (411-526), 4cuf (411-526), 2he0 (A/B=1872-2114), 3i08 (A/C=1446-1664, B/D=1665-1733), 4cue (A=411-526), 4cud (A=411-526), 4d0f (A=411-526), 3l95 (X/Y=1448-1728)
OPM none
Complexes

NOTC1:NOTC1_HUMAN

Interactions

A4, Complex: NOTC1:A4, PubMed

ADA17, Complex: ADA17:NOTC1, PubMed

DLL1, Complex: NOTC1:DLL1, PubMed

DLL3, Complex: DLL3:NOTC1, PubMed

DLL4, Complex: DLL4:NOTC1, PubMed

FURIN, Complex: NOTC1:FURIN, PubMed

JAG1, Complex: NOTC1:JAG1, PubMed

JAG2, Complex: NOTC1:JAG2, PubMed

LFNG, Complex: LFNG:NOTC1, PubMed

LRBA, Complex: LRBA:NOTC1, PubMed

MFNG, Complex: MFNG:NOTC1, PubMed

NICA, Complex: NICA:NOTC1, PubMed

NOTC1, Complex: Homodimer of neurogenic locus notch homolog protein 1, PDBID: 2HE0

NOTC2, Complex: NOTC1:NOTC2, PubMed

NOTC3, Complex: NOTC1:NOTC3, PubMed

TGFR1, Complex: TGFR1:NOTC1

WDR11, Complex: NOTC1:WDR11, PubMed

Domains

AA: 63-97, PDBID: 3POY, Subunit A, Seq Identity:45%, EGF-like domain

AA: 106-137, PDBID: 4XBM, Subunit B, Seq Identity:51%, EGF-like domain

AA: 144-174, PDBID: 1BF9, Subunit A, Seq Identity:55%, EGF-like domain

AA: 178-219, PDBID: 1TOZ, Subunit A, Seq Identity:44%, Calcium-binding EGF domain

AA: 222-253, PDBID: 1CVU, Subunit B, Seq Identity:48%, EGF-like domain

AA: 261-291, PDBID: 4XBM, Subunit B, Seq Identity:52%, EGF-like domain

AA: 295-335, PDBID: 1TOZ, Subunit A, Seq Identity:50%, Calcium-binding EGF domain

AA: 339-369, PDBID: 1TOZ, Subunit A, Seq Identity:57%, EGF-like domain

AA: 412-450, PDBID: 1TOZ, Subunit A, Seq Identity:100%, Calcium-binding EGF domain

AA: 456-486, PDBID: 1TOZ, Subunit A, Seq Identity:100%, EGF-like domain

AA: 494-524, PDBID: 1TOZ, Subunit A, Seq Identity:100%, EGF-like domain

AA: 532-562, PDBID: 1TOZ, Subunit A, Seq Identity:52%, EGF-like domain

AA: 570-599, PDBID: 3H5C, Subunit B, Seq Identity:51%, EGF-like domain

AA: 607-637, PDBID: 3H5C, Subunit B, Seq Identity:54%, EGF-like domain

AA: 645-673, PDBID: 1TOZ, Subunit A, Seq Identity:54%, EGF-like domain

AA: 682-712, PDBID: 4XBM, Subunit B, Seq Identity:52%, EGF-like domain

AA: 720-749, PDBID: 1BF9, Subunit A, Seq Identity:50%, EGF-like domain

AA: 757-787, PDBID: 1EDM, Subunit B, Seq Identity:63%, EGF-like domain

AA: 795-825, PDBID: 1EDM, Subunit B, Seq Identity:51%, EGF-like domain

AA: 833-865, PDBID: 4XBM, Subunit B, Seq Identity:54%, EGF-like domain

AA: 869-906, PDBID: 1LMJ, Subunit A, Seq Identity:44%, Calcium-binding EGF domain

AA: 911-941, PDBID: 4XBM, Subunit B, Seq Identity:60%, EGF-like domain

AA: 992-1013, PDBID: 2YGQ, Subunit A, Seq Identity:56%, Human growth factor-like EGF

AA: 1025-1055, PDBID: 3H5C, Subunit B, Seq Identity:63%, EGF-like domain

AA: 1063-1093, PDBID: 4XBM, Subunit B, Seq Identity:55%, EGF-like domain

AA: 1111-1141, PDBID: 4XBM, Subunit B, Seq Identity:39%, EGF-like domain

AA: 1149-1179, PDBID: 1TOZ, Subunit A, Seq Identity:55%, EGF-like domain

AA: 1187-1217, PDBID: 1TOZ, Subunit A, Seq Identity:55%, EGF-like domain

AA: 1225-1263, PDBID: 4XBM, Subunit B, Seq Identity:40%, EGF-like domain

AA: 1311-1344, PDBID: 2VJ2, Subunit A, Seq Identity:45%, EGF-like domain

AA: 1357-1375, PDBID: 4D90, Subunit A, Seq Identity:47%, Human growth factor-like EGF

AA: 1446-1480, PDBID: 1PB5, Subunit A, Seq Identity:100%, LNR domain

AA: 1487-1522, PDBID: 3ETO, Subunit A, Seq Identity:100%, LNR domain

AA: 1525-1562, PDBID: 3ETO, Subunit A, Seq Identity:100%, LNR domain

AA: 1566-1621, PDBID: 3ETO, Subunit A, Seq Identity:100%, NOTCH protein

AA: 1671-1729, PDBID: 3ETO, Subunit A, Seq Identity:100%, NOTCH protein

AA: 1880-1926, PDBID: 1YYH, Subunit A, Seq Identity:100%, Ankyrin repeat

AA: 1928-1981, PDBID: 1YYH, Subunit B, Seq Identity:100%, Ankyrin repeats (many copies)

AA: 1973-2058, PDBID: 1YYH, Subunit B, Seq Identity:100%, Ankyrin repeats (3 copies)

AA: 1999-2093, PDBID: 1YYH, Subunit B, Seq Identity:100%, Ankyrin repeats (3 copies)

AA: 2479-2540, Domain of unknown function (DUF3454)

UniProt annotation for NOTC1_HUMAN » Neurogenic locus notch homolog protein 1
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. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4+ and CD8+ cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO).

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 DNER, DTX1, DTX2 and RBPJ/RBPSUH. Also interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH1. Notch 1 intracellular domain interacts with SNW1; the interaction involves multimerized NOTCH1 NICD and is implicated in a formation of an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ. The activated membrane-bound form interacts with AAK1 which promotes NOTCH1 stabilization. Forms a trimeric complex with FBXW7 and SGK1. Interacts with HIF1AN. HIF1AN negatively regulates the function of notch intracellular domain (NICD), accelerating myogenic differentiation. Interacts (via NICD) with SNAI1 (via zinc fingers); the interaction induces SNAI1 degradation via MDM2- mediated ubiquitination and inhibits SNAI1-induced cell invasion. Interacts (via NICD) with MDM2A. Interacts (via NICD) with BCL6; the interaction decreases MAML1 recruitment by NOTCH1 NICD on target genes DNA and inhibits NOTCH1 transcractivation activity. Interacts with THBS4 (By similarity).

TISSUE SPECIFICITY: In fetal tissues most abundant in spleen, brain stem and lung. Also present in most adult tissues where it is found mainly in lymphoid tissues.

DISEASE: Aortic valve disease 1 (AOVD1) OMIM: A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification, stenosis and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome. mutations affecting the gene represented in this entry.

DISEASE: Adams-Oliver syndrome 5 (AOS5) OMIM: A form of Adams-Oliver syndrome, a disorder characterized by the congenital absence of skin (aplasia cutis congenita) in combination with transverse limb defects. Aplasia cutis congenita can be located anywhere on the body, but in the vast majority of the cases, it is present on the posterior parietal region where it is often associated with an underlying defect of the parietal bones. Limb abnormalities are typically limb truncation defects affecting the distal phalanges or entire digits (true ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal limb structures are also affected. Apart from transverse limb defects, syndactyly, most commonly of second and third toes, can also be observed. The clinical features are highly variable and can also include cardiovascular malformations, brain abnormalities and vascular defects such as cutis marmorata and dilated scalp veins. mutations affecting the gene represented in this entry.

Amino Acid Sequence for NOTC1_HUMAN » Neurogenic locus notch homolog protein 1
MPPLLAPLLC LALLPALAAR GPRCSQPGET CLNGGKCEAA NGTEACVCGG AFVGPRCQDP NPCLSTPCKN AGTCHVVDRR GVADYACSCA LGFSGPLCLT PLDNACLTNP CRNGGTCDLL TLTEYKCRCP PGWSGKSCQQ ADPCASNPCA NGGQCLPFEA SYICHCPPSF HGPTCRQDVN ECGQKPGLCR HGGTCHNEVG SYRCVCRATH TGPNCERPYV PCSPSPCQNG GTCRPTGDVT HECACLPGFT GQNCEENIDD CPGNNCKNGG ACVDGVNTYN CRCPPEWTGQ YCTEDVDECQ LMPNACQNGG TCHNTHGGYN CVCVNGWTGE DCSENIDDCA SAACFHGATC HDRVASFYCE CPHGRTGLLC HLNDACISNP CNEGSNCDTN PVNGKAICTC PSGYTGPACS QDVDECSLGA NPCEHAGKCI NTLGSFECQC LQGYTGPRCE IDVNECVSNP CQNDATCLDQ IGEFQCICMP GYEGVHCEVN TDECASSPCL HNGRCLDKIN EFQCECPTGF TGHLCQYDVD ECASTPCKNG AKCLDGPNTY TCVCTEGYTG THCEVDIDEC DPDPCHYGSC KDGVATFTCL CRPGYTGHHC ETNINECSSQ PCRHGGTCQD RDNAYLCFCL KGTTGPNCEI NLDDCASSPC DSGTCLDKID GYECACEPGY TGSMCNINID ECAGNPCHNG GTCEDGINGF TCRCPEGYHD PTCLSEVNEC NSNPCVHGAC RDSLNGYKCD CDPGWSGTNC DINNNECESN PCVNGGTCKD MTSGYVCTCR EGFSGPNCQT NINECASNPC LNQGTCIDDV AGYKCNCLLP YTGATCEVVL APCAPSPCRN GGECRQSEDY ESFSCVCPTG WQGQTCEVDI NECVLSPCRH GASCQNTHGG YRCHCQAGYS GRNCETDIDD CRPNPCHNGG SCTDGINTAF CDCLPGFRGT FCEEDINECA SDPCRNGANC TDCVDSYTCT CPAGFSGIHC ENNTPDCTES SCFNGGTCVD GINSFTCLCP PGFTGSYCQH DVNECDSQPC LHGGTCQDGC GSYRCTCPQG YTGPNCQNLV HWCDSSPCKN GGKCWQTHTQ YRCECPSGWT GLYCDVPSVS CEVAAQRQGV DVARLCQHGG LCVDAGNTHH CRCQAGYTGS YCEDLVDECS PSPCQNGATC TDYLGGYSCK CVAGYHGVNC SEEIDECLSH PCQNGGTCLD LPNTYKCSCP RGTQGVHCEI NVDDCNPPVD PVSRSPKCFN NGTCVDQVGG YSCTCPPGFV GERCEGDVNE CLSNPCDARG TQNCVQRVND FHCECRAGHT GRRCESVING CKGKPCKNGG TCAVASNTAR GFICKCPAGF EGATCENDAR TCGSLRCLNG GTCISGPRSP TCLCLGPFTG PECQFPASSP CLGGNPCYNQ GTCEPTSESP FYRCLCPAKF NGLLCHILDY SFGGGAGRDI PPPLIEEACE LPECQEDAGN KVCSLQCNNH ACGWDGGDCS LNFNDPWKNC TQSLQCWKYF SDGHCDSQCN SAGCLFDGFD CQRAEGQCNP LYDQYCKDHF SDGHCDQGCN SAECEWDGLD CAEHVPERLA AGTLVVVVLM PPEQLRNSSF HFLRELSRVL HTNVVFKRDA HGQQMIFPYY GREEELRKHP IKRAAEGWAA PDALLGQVKA SLLPGGSEGG RRRRELDPMD VRGSIVYLEI DNRQCVQASS QCFQSATDVA AFLGALASLG SLNIPYKIEA VQSETVEPPP PAQLHFMYVA AAAFVLLFFV GCGVLLSRKR RRQHGQLWFP EGFKVSEASK KKRREPLGED SVGLKPLKNA SDGALMDDNQ NEWGDEDLET KKFRFEEPVV LPDLDDQTDH RQWTQQHLDA ADLRMSAMAP TPPQGEVDAD CMDVNVRGPD GFTPLMIASC SGGGLETGNS EEEEDAPAVI SDFIYQGASL HNQTDRTGET ALHLAARYSR SDAAKRLLEA SADANIQDNM GRTPLHAAVS ADAQGVFQIL IRNRATDLDA RMHDGTTPLI LAARLAVEGM LEDLINSHAD VNAVDDLGKS ALHWAAAVNN VDAAVVLLKN GANKDMQNNR EETPLFLAAR EGSYETAKVL LDHFANRDIT DHMDRLPRDI AQERMHHDIV RLLDEYNLVR SPQLHGAPLG GTPTLSPPLC SPNGYLGSLK PGVQGKKVRK PSSKGLACGS KEAKDLKARR KKSQDGKGCL LDSSGMLSPV DSLESPHGYL SDVASPPLLP SPFQQSPSVP LNHLPGMPDT HLGIGHLNVA AKPEMAALGG GGRLAFETGP PRLSHLPVAS GTSTVLGSSS GGALNFTVGG STSLNGQCEW LSRLQSGMVP NQYNPLRGSV APGPLSTQAP SLQHGMVGPL HSSLAASALS QMMSYQGLPS TRLATQPHLV QTQQVQPQNL QMQQQNLQPA NIQQQQSLQP PPPPPQPHLG VSSAASGHLG RSFLSGEPSQ ADVQPLGPSS LAVHTILPQE SPALPTSLPS SLVPPVTAAQ FLTPPSQHSY SSPVDNTPSH QLQVPEHPFL TPSPESPDQW SSSSPHSNVS DWSEGVSSPP TSMQSQIARI PEAFK