ID NT2NC_HUMAN Reviewed; 236 AA. AC P0DPK4; DT 12-SEP-2018, integrated into UniProtKB/Swiss-Prot. DT 12-SEP-2018, sequence version 1. DT 22-APR-2020, entry version 11. DE RecName: Full=Notch homolog 2 N-terminal-like protein C {ECO:0000303|PubMed:29856954, ECO:0000303|PubMed:29856955}; GN Name=NOTCH2NLC {ECO:0000303|PubMed:29856954, ECO:0000303|PubMed:29856955, GN ECO:0000312|HGNC:HGNC:53924}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [2] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NOTCH2, TISSUE RP SPECIFICITY, AND INVOLVEMENT IN CHROMOSOME 1Q21.1 DELETION/DUPLICATION RP SYNDROME. RX PubMed=29856954; DOI=10.1016/j.cell.2018.03.051; RA Fiddes I.T., Lodewijk G.A., Mooring M., Bosworth C.M., Ewing A.D., RA Mantalas G.L., Novak A.M., van den Bout A., Bishara A., Rosenkrantz J.L., RA Lorig-Roach R., Field A.R., Haeussler M., Russo L., Bhaduri A., RA Nowakowski T.J., Pollen A.A., Dougherty M.L., Nuttle X., Addor M.C., RA Zwolinski S., Katzman S., Kriegstein A., Eichler E.E., Salama S.R., RA Jacobs F.M.J., Haussler D.; RT "Human-specific NOTCH2NL genes affect Notch signaling and cortical RT neurogenesis."; RL Cell 173:1356-1369(2018). RN [3] RP FUNCTION, AND DEVELOPMENTAL STAGE. RX PubMed=29856955; DOI=10.1016/j.cell.2018.03.067; RA Suzuki I.K., Gacquer D., Van Heurck R., Kumar D., Wojno M., Bilheu A., RA Herpoel A., Lambert N., Cheron J., Polleux F., Detours V., RA Vanderhaeghen P.; RT "Human-specific NOTCH2NL genes expand cortical neurogenesis through RT Delta/Notch regulation."; RL Cell 173:1370-1384(2018). RN [4] RP FUNCTION. RX PubMed=29561261; DOI=10.7554/elife.32332; RA Florio M., Heide M., Pinson A., Brandl H., Albert M., Winkler S., RA Wimberger P., Huttner W.B., Hiller M.; RT "Evolution and cell-type specificity of human-specific genes preferentially RT expressed in progenitors of fetal neocortex."; RL Elife 7:0-0(2018). RN [5] RP INVOLVEMENT IN NIID. RX PubMed=31178126; DOI=10.1016/j.ajhg.2019.05.013; RA Tian Y., Wang J.L., Huang W., Zeng S., Jiao B., Liu Z., Chen Z., Li Y., RA Wang Y., Min H.X., Wang X.J., You Y., Zhang R.X., Chen X.Y., Yi F., RA Zhou Y.F., Long H.Y., Zhou C.J., Hou X., Wang J.P., Xie B., Liang F., RA Yang Z.Y., Sun Q.Y., Allen E.G., Shafik A.M., Kong H.E., Guo J.F., RA Yan X.X., Hu Z.M., Xia K., Jiang H., Xu H.W., Duan R.H., Jin P., Tang B.S., RA Shen L.; RT "Expansion of human-specific GGC repeat in neuronal intranuclear inclusion RT disease-related disorders."; RL Am. J. Hum. Genet. 105:166-176(2019). RN [6] RP INVOLVEMENT IN NIID. RX PubMed=31332381; DOI=10.1038/s41588-019-0459-y; RA Sone J., Mitsuhashi S., Fujita A., Mizuguchi T., Hamanaka K., Mori K., RA Koike H., Hashiguchi A., Takashima H., Sugiyama H., Kohno Y., Takiyama Y., RA Maeda K., Doi H., Koyano S., Takeuchi H., Kawamoto M., Kohara N., Ando T., RA Ieda T., Kita Y., Kokubun N., Tsuboi Y., Katoh K., Kino Y., Katsuno M., RA Iwasaki Y., Yoshida M., Tanaka F., Suzuki I.K., Frith M.C., Matsumoto N., RA Sobue G.; RT "Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC RT associated with neuronal intranuclear inclusion disease."; RL Nat. Genet. 51:1215-1221(2019). RN [7] RP INVOLVEMENT IN NIID. RX PubMed=31332380; DOI=10.1038/s41588-019-0458-z; RA Ishiura H., Shibata S., Yoshimura J., Suzuki Y., Qu W., Doi K., RA Almansour M.A., Kikuchi J.K., Taira M., Mitsui J., Takahashi Y., RA Ichikawa Y., Mano T., Iwata A., Harigaya Y., Matsukawa M.K., Matsukawa T., RA Tanaka M., Shirota Y., Ohtomo R., Kowa H., Date H., Mitsue A., Hatsuta H., RA Morimoto S., Murayama S., Shiio Y., Saito Y., Mitsutake A., Kawai M., RA Sasaki T., Sugiyama Y., Hamada M., Ohtomo G., Terao Y., Nakazato Y., RA Takeda A., Sakiyama Y., Umeda-Kameyama Y., Shinmi J., Ogata K., Kohno Y., RA Lim S.Y., Tan A.H., Shimizu J., Goto J., Nishino I., Toda T., Morishita S., RA Tsuji S.; RT "Noncoding CGG repeat expansions in neuronal intranuclear inclusion RT disease, oculopharyngodistal myopathy and an overlapping disease."; RL Nat. Genet. 51:1222-1232(2019). CC -!- FUNCTION: Human-specific protein that promotes neural progenitor CC proliferation and evolutionary expansion of the brain neocortex by CC regulating the Notch signaling pathway (PubMed:29856954, CC PubMed:29856955, PubMed:29561261). Able to promote neural progenitor CC self-renewal, possibly by down-regulating neuronal differentiation CC genes, thereby delaying the differentiation of neuronal progenitors and CC leading to an overall final increase in neuronal production CC (PubMed:29856954). Acts by enhancing the Notch signaling pathway via CC two different mechanisms that probably work in parallel to reach the CC same effect (PubMed:29856954). Enhances Notch signaling pathway in a CC non-cell-autonomous manner via direct interaction with NOTCH2 CC (PubMed:29856954). Also promotes Notch signaling pathway in a cell- CC autonomous manner through inhibition of cis DLL1-NOTCH2 interactions, CC which promotes neuronal differentiation (By similarity). CC {ECO:0000250|UniProtKB:P0DPK3, ECO:0000269|PubMed:29561261, CC ECO:0000269|PubMed:29856954, ECO:0000269|PubMed:29856955}. CC -!- SUBUNIT: Interacts with NOTCH2 (PubMed:29856954). Interacts with DLL1; CC the interaction is direct (By similarity). CC {ECO:0000250|UniProtKB:P0DPK3, ECO:0000269|PubMed:29856954}. CC -!- INTERACTION: CC P0DPK4; O43184-4: ADAM12; NbExp=3; IntAct=EBI-22310682, EBI-12006944; CC P0DPK4; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-22310682, EBI-10173507; CC P0DPK4; P21549: AGXT; NbExp=3; IntAct=EBI-22310682, EBI-727098; CC P0DPK4; Q8IZ83: ALDH16A1; NbExp=3; IntAct=EBI-22310682, EBI-1044483; CC P0DPK4; P05187: ALPP; NbExp=3; IntAct=EBI-22310682, EBI-1211484; CC P0DPK4; Q49AR9: ANKS1A; NbExp=3; IntAct=EBI-22310682, EBI-11954519; CC P0DPK4; P29972: AQP1; NbExp=3; IntAct=EBI-22310682, EBI-745213; CC P0DPK4; Q7Z3C6-3: ATG9A; NbExp=3; IntAct=EBI-22310682, EBI-12006308; CC P0DPK4; P30049: ATP5F1D; NbExp=3; IntAct=EBI-22310682, EBI-1049505; CC P0DPK4; P50895: BCAM; NbExp=3; IntAct=EBI-22310682, EBI-10212133; CC P0DPK4; P18075: BMP7; NbExp=3; IntAct=EBI-22310682, EBI-1035195; CC P0DPK4; Q0VDD7-2: C19orf57; NbExp=3; IntAct=EBI-22310682, EBI-12040255; CC P0DPK4; Q9Y2V2: CARHSP1; NbExp=3; IntAct=EBI-22310682, EBI-718719; CC P0DPK4; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-22310682, EBI-744545; CC P0DPK4; Q8TC90: CCER1; NbExp=3; IntAct=EBI-22310682, EBI-746041; CC P0DPK4; Q04900: CD164; NbExp=3; IntAct=EBI-22310682, EBI-2115896; CC P0DPK4; Q8N6W0: CELF5; NbExp=3; IntAct=EBI-22310682, EBI-12139335; CC P0DPK4; Q8TCT0: CERK; NbExp=3; IntAct=EBI-22310682, EBI-10274247; CC P0DPK4; Q9NX63: CHCHD3; NbExp=3; IntAct=EBI-22310682, EBI-743375; CC P0DPK4; Q9UKJ5: CHIC2; NbExp=3; IntAct=EBI-22310682, EBI-741528; CC P0DPK4; Q9H2X0: CHRD; NbExp=3; IntAct=EBI-22310682, EBI-947551; CC P0DPK4; P07510-2: CHRNG; NbExp=3; IntAct=EBI-22310682, EBI-11979451; CC P0DPK4; Q8NE01: CNNM3; NbExp=3; IntAct=EBI-22310682, EBI-741032; CC P0DPK4; P27658: COL8A1; NbExp=5; IntAct=EBI-22310682, EBI-747133; CC P0DPK4; Q02930-3: CREB5; NbExp=3; IntAct=EBI-22310682, EBI-10192698; CC P0DPK4; P06850: CRH; NbExp=3; IntAct=EBI-22310682, EBI-3870390; CC P0DPK4; Q49AN0: CRY2; NbExp=3; IntAct=EBI-22310682, EBI-2212355; CC P0DPK4; P09228: CST2; NbExp=3; IntAct=EBI-22310682, EBI-8832659; CC P0DPK4; Q9H4G1: CST9L; NbExp=3; IntAct=EBI-22310682, EBI-3923092; CC P0DPK4; Q9NSA3: CTNNBIP1; NbExp=3; IntAct=EBI-22310682, EBI-747082; CC P0DPK4; Q9UBR2: CTSZ; NbExp=3; IntAct=EBI-22310682, EBI-8636823; CC P0DPK4; Q6ZMK1-3: CYHR1; NbExp=3; IntAct=EBI-22310682, EBI-11997340; CC P0DPK4; Q08AG9: CYP21A2; NbExp=3; IntAct=EBI-22310682, EBI-14156412; CC P0DPK4; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-22310682, EBI-3867333; CC P0DPK4; Q8NCG7: DAGLB; NbExp=3; IntAct=EBI-22310682, EBI-721948; CC P0DPK4; Q5D0E6-2: DALRD3; NbExp=3; IntAct=EBI-22310682, EBI-9090939; CC P0DPK4; P09172: DBH; NbExp=3; IntAct=EBI-22310682, EBI-8589586; CC P0DPK4; P52824: DGKQ; NbExp=3; IntAct=EBI-22310682, EBI-4401238; CC P0DPK4; Q96LJ7: DHRS1; NbExp=3; IntAct=EBI-22310682, EBI-746300; CC P0DPK4; Q9NQL9: DMRT3; NbExp=3; IntAct=EBI-22310682, EBI-9679045; CC P0DPK4; Q92608: DOCK2; NbExp=3; IntAct=EBI-22310682, EBI-448771; CC P0DPK4; P21918: DRD5; NbExp=3; IntAct=EBI-22310682, EBI-12139313; CC P0DPK4; Q9NPA0: EMC7; NbExp=3; IntAct=EBI-22310682, EBI-6309137; CC P0DPK4; P00742: F10; NbExp=3; IntAct=EBI-22310682, EBI-719750; CC P0DPK4; O95864-3: FADS2; NbExp=3; IntAct=EBI-22310682, EBI-12057609; CC P0DPK4; A4D161: FAM221A; NbExp=3; IntAct=EBI-22310682, EBI-11960181; CC P0DPK4; Q8NEG0: FAM71C; NbExp=3; IntAct=EBI-22310682, EBI-752049; CC P0DPK4; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-22310682, EBI-6658203; CC P0DPK4; Q969U6: FBXW5; NbExp=3; IntAct=EBI-22310682, EBI-741068; CC P0DPK4; O43559: FRS3; NbExp=3; IntAct=EBI-22310682, EBI-725515; CC P0DPK4; Q9BXU8: FTHL17; NbExp=3; IntAct=EBI-22310682, EBI-12156897; CC P0DPK4; Q9ULW2: FZD10; NbExp=3; IntAct=EBI-22310682, EBI-8803802; CC P0DPK4; P43220: GLP1R; NbExp=3; IntAct=EBI-22310682, EBI-7466542; CC P0DPK4; Q6IB77-2: GLYAT; NbExp=3; IntAct=EBI-22310682, EBI-12142423; CC P0DPK4; Q9Y223-2: GNE; NbExp=3; IntAct=EBI-22310682, EBI-11975289; CC P0DPK4; P09211: GSTP1; NbExp=3; IntAct=EBI-22310682, EBI-353467; CC P0DPK4; Q9GZV7: HAPLN2; NbExp=3; IntAct=EBI-22310682, EBI-11956675; CC P0DPK4; P69905: HBA2; NbExp=3; IntAct=EBI-22310682, EBI-714680; CC P0DPK4; P02008: HBZ; NbExp=3; IntAct=EBI-22310682, EBI-719843; CC P0DPK4; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-22310682, EBI-14103818; CC P0DPK4; P08631-2: HCK; NbExp=3; IntAct=EBI-22310682, EBI-9834454; CC P0DPK4; Q03014: HHEX; NbExp=3; IntAct=EBI-22310682, EBI-747421; CC P0DPK4; P49639: HOXA1; NbExp=3; IntAct=EBI-22310682, EBI-740785; CC P0DPK4; P17482: HOXB9; NbExp=3; IntAct=EBI-22310682, EBI-745290; CC P0DPK4; P31273: HOXC8; NbExp=3; IntAct=EBI-22310682, EBI-1752118; CC P0DPK4; P37235: HPCAL1; NbExp=3; IntAct=EBI-22310682, EBI-749311; CC P0DPK4; Q96MM6: HSPA12B; NbExp=3; IntAct=EBI-22310682, EBI-10291310; CC P0DPK4; Q14773-3: ICAM4; NbExp=3; IntAct=EBI-22310682, EBI-10233928; CC P0DPK4; P22301: IL10; NbExp=3; IntAct=EBI-22310682, EBI-1031632; CC P0DPK4; Q9C086: INO80B; NbExp=3; IntAct=EBI-22310682, EBI-715611; CC P0DPK4; P01308: INS; NbExp=3; IntAct=EBI-22310682, EBI-7090529; CC P0DPK4; P05107: ITGB2; NbExp=3; IntAct=EBI-22310682, EBI-300173; CC P0DPK4; P16144-2: ITGB4; NbExp=3; IntAct=EBI-22310682, EBI-11051601; CC P0DPK4; P18084: ITGB5; NbExp=3; IntAct=EBI-22310682, EBI-1223434; CC P0DPK4; Q15040: JOSD1; NbExp=3; IntAct=EBI-22310682, EBI-2510602; CC P0DPK4; Q9ULS6: KCNS2; NbExp=3; IntAct=EBI-22310682, EBI-10323864; CC P0DPK4; Q96SI1-2: KCTD15; NbExp=3; IntAct=EBI-22310682, EBI-12382297; CC P0DPK4; Q2WGJ6: KLHL38; NbExp=3; IntAct=EBI-22310682, EBI-6426443; CC P0DPK4; O60259: KLK8; NbExp=3; IntAct=EBI-22310682, EBI-3915857; CC P0DPK4; Q5T749: KPRP; NbExp=3; IntAct=EBI-22310682, EBI-10981970; CC P0DPK4; P78385: KRT83; NbExp=3; IntAct=EBI-22310682, EBI-10221390; CC P0DPK4; P60014: KRTAP10-10; NbExp=3; IntAct=EBI-22310682, EBI-11955579; CC P0DPK4; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-22310682, EBI-10172150; CC P0DPK4; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-22310682, EBI-10171774; CC P0DPK4; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-22310682, EBI-10172052; CC P0DPK4; P59990: KRTAP12-1; NbExp=3; IntAct=EBI-22310682, EBI-10210845; CC P0DPK4; P59991: KRTAP12-2; NbExp=3; IntAct=EBI-22310682, EBI-10176379; CC P0DPK4; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-22310682, EBI-11953334; CC P0DPK4; P60329: KRTAP12-4; NbExp=3; IntAct=EBI-22310682, EBI-10176396; CC P0DPK4; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-22310682, EBI-11953846; CC P0DPK4; Q3SY46: KRTAP13-3; NbExp=3; IntAct=EBI-22310682, EBI-10241252; CC P0DPK4; Q3LI77: KRTAP13-4; NbExp=3; IntAct=EBI-22310682, EBI-11953996; CC P0DPK4; Q9BYR9: KRTAP2-4; NbExp=3; IntAct=EBI-22310682, EBI-14065470; CC P0DPK4; Q6PEX3: KRTAP26-1; NbExp=3; IntAct=EBI-22310682, EBI-3957672; CC P0DPK4; Q9BYQ6: KRTAP4-11; NbExp=3; IntAct=EBI-22310682, EBI-10302392; CC P0DPK4; Q9BYR5: KRTAP4-2; NbExp=3; IntAct=EBI-22310682, EBI-10172511; CC P0DPK4; Q9BYR3: KRTAP4-4; NbExp=4; IntAct=EBI-22310682, EBI-11958132; CC P0DPK4; Q9BYR2: KRTAP4-5; NbExp=3; IntAct=EBI-22310682, EBI-11993254; CC P0DPK4; Q6L8G4: KRTAP5-11; NbExp=3; IntAct=EBI-22310682, EBI-11993296; CC P0DPK4; Q6L8H2: KRTAP5-3; NbExp=3; IntAct=EBI-22310682, EBI-11974251; CC P0DPK4; Q6L8H1: KRTAP5-4; NbExp=3; IntAct=EBI-22310682, EBI-11963072; CC P0DPK4; Q6L8G9: KRTAP5-6; NbExp=3; IntAct=EBI-22310682, EBI-10250562; CC P0DPK4; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-22310682, EBI-3958099; CC P0DPK4; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-22310682, EBI-1044640; CC P0DPK4; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-22310682, EBI-1043191; CC P0DPK4; Q9BYQ0: KRTAP9-8; NbExp=3; IntAct=EBI-22310682, EBI-11958364; CC P0DPK4; Q5T7P2: LCE1A; NbExp=3; IntAct=EBI-22310682, EBI-11962058; CC P0DPK4; Q5T7P3: LCE1B; NbExp=3; IntAct=EBI-22310682, EBI-10245913; CC P0DPK4; Q5T752: LCE1D; NbExp=3; IntAct=EBI-22310682, EBI-11741311; CC P0DPK4; Q5T753: LCE1E; NbExp=3; IntAct=EBI-22310682, EBI-11955335; CC P0DPK4; Q5T754: LCE1F; NbExp=3; IntAct=EBI-22310682, EBI-11958008; CC P0DPK4; O14633: LCE2B; NbExp=4; IntAct=EBI-22310682, EBI-11478468; CC P0DPK4; Q5TA81: LCE2C; NbExp=3; IntAct=EBI-22310682, EBI-11973993; CC P0DPK4; Q5TA82: LCE2D; NbExp=3; IntAct=EBI-22310682, EBI-10246750; CC P0DPK4; Q5TA76: LCE3A; NbExp=3; IntAct=EBI-22310682, EBI-9394625; CC P0DPK4; Q5T5A8: LCE3C; NbExp=3; IntAct=EBI-22310682, EBI-10245291; CC P0DPK4; Q9BYE3: LCE3D; NbExp=3; IntAct=EBI-22310682, EBI-6658837; CC P0DPK4; Q5T5B0: LCE3E; NbExp=3; IntAct=EBI-22310682, EBI-10245456; CC P0DPK4; Q5TA78: LCE4A; NbExp=3; IntAct=EBI-22310682, EBI-10246358; CC P0DPK4; Q5TCM9: LCE5A; NbExp=3; IntAct=EBI-22310682, EBI-11955689; CC P0DPK4; Q8IXW0: LMNTD2; NbExp=3; IntAct=EBI-22310682, EBI-12028858; CC P0DPK4; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-22310682, EBI-739832; CC P0DPK4; Q6PJG9: LRFN4; NbExp=3; IntAct=EBI-22310682, EBI-7910762; CC P0DPK4; Q9Y5Y7: LYVE1; NbExp=3; IntAct=EBI-22310682, EBI-10329546; CC P0DPK4; Q8N5G2: MACO1; NbExp=3; IntAct=EBI-22310682, EBI-2683507; CC P0DPK4; Q8WVR3: MAP11; NbExp=3; IntAct=EBI-22310682, EBI-719893; CC P0DPK4; O60336: MAPKBP1; NbExp=3; IntAct=EBI-22310682, EBI-947402; CC P0DPK4; P08582-2: MELTF; NbExp=3; IntAct=EBI-22310682, EBI-10195914; CC P0DPK4; Q14CX5: MFSD13A; NbExp=3; IntAct=EBI-22310682, EBI-12120958; CC P0DPK4; P00540: MOS; NbExp=3; IntAct=EBI-22310682, EBI-1757866; CC P0DPK4; Q9NV56: MRGBP; NbExp=3; IntAct=EBI-22310682, EBI-399076; CC P0DPK4; Q9NQ50: MRPL40; NbExp=3; IntAct=EBI-22310682, EBI-1053902; CC P0DPK4; Q13330: MTA1; NbExp=3; IntAct=EBI-22310682, EBI-714236; CC P0DPK4; Q9BW11: MXD3; NbExp=3; IntAct=EBI-22310682, EBI-741574; CC P0DPK4; P50539-3: MXI1; NbExp=3; IntAct=EBI-22310682, EBI-10211940; CC P0DPK4; Q86VE0: MYPOP; NbExp=3; IntAct=EBI-22310682, EBI-2858213; CC P0DPK4; Q92692-2: NECTIN2; NbExp=3; IntAct=EBI-22310682, EBI-6979889; CC P0DPK4; Q9NQS3-2: NECTIN3; NbExp=3; IntAct=EBI-22310682, EBI-12106440; CC P0DPK4; Q14511-2: NEDD9; NbExp=3; IntAct=EBI-22310682, EBI-11746523; CC P0DPK4; P48645: NMU; NbExp=3; IntAct=EBI-22310682, EBI-10210351; CC P0DPK4; Q9NQX5: NPDC1; NbExp=3; IntAct=EBI-22310682, EBI-748927; CC P0DPK4; Q6NSM0: NR1D2; NbExp=3; IntAct=EBI-22310682, EBI-10250949; CC P0DPK4; Q9P121-3: NTM; NbExp=3; IntAct=EBI-22310682, EBI-12027160; CC P0DPK4; Q9HB63: NTN4; NbExp=3; IntAct=EBI-22310682, EBI-743459; CC P0DPK4; O95897: OLFM2; NbExp=3; IntAct=EBI-22310682, EBI-721741; CC P0DPK4; P32242: OTX1; NbExp=3; IntAct=EBI-22310682, EBI-740446; CC P0DPK4; Q99571: P2RX4; NbExp=3; IntAct=EBI-22310682, EBI-2828248; CC P0DPK4; Q99572: P2RX7; NbExp=3; IntAct=EBI-22310682, EBI-1753251; CC P0DPK4; Q15077: P2RY6; NbExp=3; IntAct=EBI-22310682, EBI-10235794; CC P0DPK4; Q92824-2: PCSK5; NbExp=3; IntAct=EBI-22310682, EBI-11956269; CC P0DPK4; A2BDE7: PHLDA1; NbExp=3; IntAct=EBI-22310682, EBI-14084211; CC P0DPK4; Q96S52: PIGS; NbExp=3; IntAct=EBI-22310682, EBI-2908273; CC P0DPK4; Q494U1-3: PLEKHN1; NbExp=3; IntAct=EBI-22310682, EBI-12014286; CC P0DPK4; P14222: PRF1; NbExp=3; IntAct=EBI-22310682, EBI-724466; CC P0DPK4; P0CG20: PRR35; NbExp=3; IntAct=EBI-22310682, EBI-11986293; CC P0DPK4; P25786: PSMA1; NbExp=3; IntAct=EBI-22310682, EBI-359352; CC P0DPK4; Q13308: PTK7; NbExp=3; IntAct=EBI-22310682, EBI-2803245; CC P0DPK4; Q8WUK0: PTPMT1; NbExp=3; IntAct=EBI-22310682, EBI-7199479; CC P0DPK4; P15151: PVR; NbExp=3; IntAct=EBI-22310682, EBI-3919694; CC P0DPK4; Q9Y2K5: R3HDM2; NbExp=3; IntAct=EBI-22310682, EBI-948428; CC P0DPK4; Q8TBN0: RAB3IL1; NbExp=3; IntAct=EBI-22310682, EBI-743796; CC P0DPK4; O60896: RAMP3; NbExp=3; IntAct=EBI-22310682, EBI-720447; CC P0DPK4; Q9Y272: RASD1; NbExp=3; IntAct=EBI-22310682, EBI-740818; CC P0DPK4; Q6P9E2: RECK; NbExp=3; IntAct=EBI-22310682, EBI-10253121; CC P0DPK4; Q86WX3: RPS19BP1; NbExp=3; IntAct=EBI-22310682, EBI-4479407; CC P0DPK4; Q86UN2: RTN4RL1; NbExp=3; IntAct=EBI-22310682, EBI-10258951; CC P0DPK4; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-22310682, EBI-748391; CC P0DPK4; Q13214-2: SEMA3B; NbExp=3; IntAct=EBI-22310682, EBI-11017428; CC P0DPK4; Q9C0C4: SEMA4C; NbExp=3; IntAct=EBI-22310682, EBI-10303490; CC P0DPK4; Q9NUL5-4: SHFL; NbExp=3; IntAct=EBI-22310682, EBI-11955083; CC P0DPK4; O76082: SLC22A5; NbExp=3; IntAct=EBI-22310682, EBI-9846338; CC P0DPK4; Q9UHI7-3: SLC23A1; NbExp=3; IntAct=EBI-22310682, EBI-11998660; CC P0DPK4; Q8N370: SLC43A2; NbExp=3; IntAct=EBI-22310682, EBI-10265149; CC P0DPK4; Q92911: SLC5A5; NbExp=3; IntAct=EBI-22310682, EBI-12313867; CC P0DPK4; Q9NP91: SLC6A20; NbExp=3; IntAct=EBI-22310682, EBI-10311198; CC P0DPK4; P49901: SMCP; NbExp=3; IntAct=EBI-22310682, EBI-750494; CC P0DPK4; Q86W54-2: SPATA24; NbExp=3; IntAct=EBI-22310682, EBI-12041693; CC P0DPK4; Q6RVD6: SPATA8; NbExp=3; IntAct=EBI-22310682, EBI-8635958; CC P0DPK4; Q9UQ90: SPG7; NbExp=3; IntAct=EBI-22310682, EBI-717201; CC P0DPK4; Q8IUH8: SPPL2C; NbExp=3; IntAct=EBI-22310682, EBI-14064968; CC P0DPK4; O43609: SPRY1; NbExp=3; IntAct=EBI-22310682, EBI-3866665; CC P0DPK4; Q99469: STAC; NbExp=3; IntAct=EBI-22310682, EBI-2652799; CC P0DPK4; O75716: STK16; NbExp=3; IntAct=EBI-22310682, EBI-749295; CC P0DPK4; Q9BX59: TAPBPL; NbExp=3; IntAct=EBI-22310682, EBI-12017416; CC P0DPK4; Q9Y4C2-2: TCAF1; NbExp=3; IntAct=EBI-22310682, EBI-11974855; CC P0DPK4; Q9BT49: THAP7; NbExp=3; IntAct=EBI-22310682, EBI-741350; CC P0DPK4; Q08117-2: TLE5; NbExp=3; IntAct=EBI-22310682, EBI-11741437; CC P0DPK4; Q9UIK5: TMEFF2; NbExp=3; IntAct=EBI-22310682, EBI-11423693; CC P0DPK4; Q86TG1: TMEM150A; NbExp=3; IntAct=EBI-22310682, EBI-2799342; CC P0DPK4; Q9HCN3: TMEM8A; NbExp=3; IntAct=EBI-22310682, EBI-10310808; CC P0DPK4; Q96KP6: TNIP3; NbExp=3; IntAct=EBI-22310682, EBI-2509913; CC P0DPK4; Q63HR2: TNS2; NbExp=3; IntAct=EBI-22310682, EBI-949753; CC P0DPK4; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-22310682, EBI-5235829; CC P0DPK4; Q12815: TROAP; NbExp=3; IntAct=EBI-22310682, EBI-2349743; CC P0DPK4; O14817: TSPAN4; NbExp=3; IntAct=EBI-22310682, EBI-8652667; CC P0DPK4; P49638: TTPA; NbExp=3; IntAct=EBI-22310682, EBI-10210710; CC P0DPK4; Q9BRU9: UTP23; NbExp=3; IntAct=EBI-22310682, EBI-5457544; CC P0DPK4; Q9UBK9: UXT; NbExp=3; IntAct=EBI-22310682, EBI-357355; CC P0DPK4; Q6EMK4: VASN; NbExp=3; IntAct=EBI-22310682, EBI-10249550; CC P0DPK4; Q64LD2-2: WDR25; NbExp=3; IntAct=EBI-22310682, EBI-12032042; CC P0DPK4; Q8WTX9: ZDHHC1; NbExp=3; IntAct=EBI-22310682, EBI-2818796; CC P0DPK4; Q15973: ZNF124; NbExp=3; IntAct=EBI-22310682, EBI-2555767; CC P0DPK4; Q9P2F9: ZNF319; NbExp=3; IntAct=EBI-22310682, EBI-11993110; CC P0DPK4; Q9Y3S2: ZNF330; NbExp=3; IntAct=EBI-22310682, EBI-373456; CC P0DPK4; Q9H9D4: ZNF408; NbExp=3; IntAct=EBI-22310682, EBI-347633; CC P0DPK4; Q96IQ9: ZNF414; NbExp=3; IntAct=EBI-22310682, EBI-744257; CC P0DPK4; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-22310682, EBI-740727; CC P0DPK4; Q8IYI8: ZNF440; NbExp=3; IntAct=EBI-22310682, EBI-726439; CC P0DPK4; Q9NWS9-2: ZNF446; NbExp=3; IntAct=EBI-22310682, EBI-740232; CC P0DPK4; Q6ZNH5: ZNF497; NbExp=3; IntAct=EBI-22310682, EBI-10486136; CC P0DPK4; Q9UK33: ZNF580; NbExp=3; IntAct=EBI-22310682, EBI-746277; CC P0DPK4; Q9P0T4: ZNF581; NbExp=3; IntAct=EBI-22310682, EBI-745520; CC P0DPK4; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-22310682, EBI-6427977; CC P0DPK4; Q5T619: ZNF648; NbExp=3; IntAct=EBI-22310682, EBI-11985915; CC P0DPK4; Q499Z4: ZNF672; NbExp=3; IntAct=EBI-22310682, EBI-12146251; CC P0DPK4; Q8N393: ZNF786; NbExp=3; IntAct=EBI-22310682, EBI-10265203; CC P0DPK4; Q96EG3: ZNF837; NbExp=3; IntAct=EBI-22310682, EBI-11962574; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:29856954}. CC -!- TISSUE SPECIFICITY: Expressed in radial glia neural stem cells during CC cortical development. {ECO:0000269|PubMed:29856954}. CC -!- DEVELOPMENTAL STAGE: Expressed at very low level during corticogenesis. CC {ECO:0000269|PubMed:29856955}. CC -!- DISEASE: Neuronal intranuclear inclusion disease (NIID) [MIM:603472]: CC An autosomal dominant, slowly progressive, neurodegenerative disease CC characterized by eosinophilic hyaline intranuclear inclusions in the CC central and peripheral nervous system, and also in the visceral organs. CC Clinical manifestations are variable and include pyramidal and CC extrapyramidal symptoms, cerebellar ataxia, cognitive decline and CC dementia, peripheral neuropathy, and autonomic dysfunction. CC {ECO:0000269|PubMed:31178126, ECO:0000269|PubMed:31332380, CC ECO:0000269|PubMed:31332381}. Note=The disease is caused by mutations CC affecting the gene represented in this entry. The molecular defect in CC NOTCH2NLC is a CGG repeat expansion in the 5-prime untranslated region CC of the gene. The expansion can be greater than one hundred repeat units CC in patients, while healthy individuals have 5 to 43 repeats. CC {ECO:0000269|PubMed:31178126, ECO:0000269|PubMed:31332380, CC ECO:0000269|PubMed:31332381}. CC -!- DISEASE: Note=Defects in NOTCH2NLC may be a cause of chromosome 1q21.1 CC deletion/duplication syndrome (PubMed:29856954). Deletions of NOTCH2NL CC (NOTCH2NLA, NOTCH2NLB and/or NOTCH2NLC) are present in patients CC affected by microcephaly, whereas macrocephaly is observed in patients CC with NOTCH2NL duplications (PubMed:29856954). CC {ECO:0000269|PubMed:29856954}. CC -!- MISCELLANEOUS: NOTCH2NLA, NOTCH2NLB and NOTCH2NLC paralogs arose CC between 4 and 3 million years ago, after the separation of hominids CC from the chimpanzee and during the early stages of the expansion of the CC human cortex. {ECO:0000269|PubMed:29856954}. CC -!- SIMILARITY: Belongs to the NOTCH family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AC239799; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS86015.1; -. DR RefSeq; NP_982283.2; NM_203458.4. DR RefSeq; XP_016855384.1; XM_016999895.1. DR RefSeq; XP_016855385.1; XM_016999896.1. DR RefSeq; XP_016855386.1; XM_016999897.1. DR RefSeq; XP_016855387.1; XM_016999898.1. DR RefSeq; XP_016858537.1; XM_017003048.1. DR RefSeq; XP_016858538.1; XM_017003049.1. DR RefSeq; XP_016858539.1; XM_017003050.1. DR RefSeq; XP_016858540.1; XM_017003051.1. DR SMR; P0DPK4; -. DR IntAct; P0DPK4; 217. DR MassIVE; P0DPK4; -. DR PeptideAtlas; P0DPK4; -. DR Antibodypedia; 72493; 61 antibodies. DR Ensembl; ENST00000578189; ENSP00000462298; ENSG00000286219. DR Ensembl; ENST00000652191; ENSP00000498514; ENSG00000286219. DR GeneID; 388677; -. DR KEGG; hsa:388677; -. DR CTD; 388677; -. DR GeneCards; NOTCH2NLC; -. DR HGNC; HGNC:53924; NOTCH2NLC. DR MIM; 603472; phenotype. DR MIM; 618025; gene. DR neXtProt; NX_P0DPK4; -. DR OpenTargets; ENSG00000264343; -. DR Orphanet; 2289; Neuronal intranuclear inclusion disease. DR OMA; HNCSIET; -. DR PRO; PR:P0DPK4; -. DR Proteomes; UP000005640; Chromosome 1. DR ExpressionAtlas; P0DPK4; baseline and differential. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0021987; P:cerebral cortex development; IDA:UniProtKB. DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW. DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:UniProtKB. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR013032; EGF-like_CS. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR Pfam; PF00008; EGF; 3. DR Pfam; PF07645; EGF_CA; 1. DR SMART; SM00181; EGF; 5. DR SMART; SM00179; EGF_CA; 4. DR PROSITE; PS00010; ASX_HYDROXYL; 1. DR PROSITE; PS00022; EGF_1; 5. DR PROSITE; PS01186; EGF_2; 5. DR PROSITE; PS50026; EGF_3; 6. PE 1: Evidence at protein level; KW Calcium; Disulfide bond; EGF-like domain; Glycoprotein; Neurodegeneration; KW Notch signaling pathway; Reference proteome; Repeat; Secreted. FT CHAIN 1..236 FT /note="Notch homolog 2 N-terminal-like protein C" FT /id="PRO_0000445071" FT DOMAIN 1..24 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 25..63 FT /note="EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 66..104 FT /note="EGF-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 105..141 FT /note="EGF-like 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 143..180 FT /note="EGF-like 5; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 182..219 FT /note="EGF-like 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT CARBOHYD 7 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 116 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 14..23 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 29..40 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 34..51 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 53..62 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 70..82 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 76..92 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 94..103 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 109..120 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 114..129 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 131..140 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 147..159 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 153..168 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 170..179 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 186..197 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 191..207 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" SQ SEQUENCE 236 AA; 25835 MW; 2DF01880A22814C9 CRC64; MCVTYHNGTG YCKCPEGFLG EYCQHRDPCE KNRCQNGGTC VAQAMLGKAT CRCASGFTGE DCQYSTSHPC FVSRPCLNGG TCHMLSRDTY ECTCQVGFTG KECQWTDACL SHPCANGSTC TTVANQFSCK CLTGFTGQKC ETDVNECDIP GHCQHGGTCL NLPGSYQCQC LQGFTGQYCD SLYVPCAPSP CVNGGTCRQT GDFTFECNCL PETVRRGTEL WERDREVWNG KEHDEN //