ID NDF1_HUMAN Reviewed; 356 AA. AC Q13562; B2R9I8; F1T0E1; O00343; Q13340; Q5U095; Q96TH0; Q99455; Q9UEC8; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 02-NOV-2010, sequence version 3. DT 24-JAN-2024, entry version 211. DE RecName: Full=Neurogenic differentiation factor 1; DE Short=NeuroD; DE Short=NeuroD1; DE AltName: Full=Class A basic helix-loop-helix protein 3; DE Short=bHLHa3; GN Name=NEUROD1; Synonyms=BHLHA3, NEUROD; 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 [GENOMIC DNA], AND VARIANT ALA-45. RX PubMed=8786144; DOI=10.1006/geno.1996.0306; RA Tamimi R., Steingrimsson E., Copeland N.G., Dyer-Montgomery K., Lee J.E., RA Hernandez R., Jenkins N.A., Tapscott S.J.; RT "The NEUROD gene maps to human chromosome 2q32 and mouse chromosome 2."; RL Genomics 34:418-421(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-45. RX PubMed=8915591; DOI=10.1016/s0169-328x(96)00154-4; RA Yokoyama M., Nishi Y., Miyamoto Y., Nakamura M., Akiyama K., Matsubara K., RA Okubo K.; RT "Molecular cloning of a human neuroD from a neuroblastoma cell line RT specifically expressed in the fetal brain and adult cerebellum."; RL Brain Res. Mol. Brain Res. 42:135-139(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-45. RA Furuta H., Horikawa Y., Iwasaki N., Hara M., Sussel L., le Beau M.M., RA Davis E.M., Ogata M., Iwamoto Y., German M.S., Bell G.I.; RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-45. RX PubMed=10366743; DOI=10.1016/s0169-328x(99)00112-6; RA Miyachi T., Maruyama H., Kitamura T., Nakamura S., Kawakami H.; RT "Structure and regulation of the human NeuroD (BETA2/BHF1) gene."; RL Brain Res. Mol. Brain Res. 69:223-231(1999). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-45. RA Noma T.; RL Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-45. RA Kuroe A., Yamada Y., Kubota A., Someya Y., Iwakura T., Watanabe R., RA Inada A., Miyawaki K., Ban N., Ihara Y., Seino Y.; RT "Ala45Thr mutation of the human BETA2 gene."; RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-45. RC TISSUE=Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-45. RX PubMed=21697133; DOI=10.1167/iovs.11-7479; RA Oshikawa M., Tsutsui C., Ikegami T., Fuchida Y., Matsubara M., Toyama S., RA Usami R., Ohtoko K., Kato S.; RT "Full-length transcriptome analysis of human retina-derived cell lines RT ARPE-19 and Y79 using the vector-capping method."; RL Invest. Ophthalmol. Vis. Sci. 52:6662-6670(2011). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-45. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-45. RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 88-200. RC TISSUE=Retina; RX PubMed=9144558; DOI=10.1006/bbrc.1997.6483; RA Acharya H.R., Dooley C.M., Thoreson W.B., Ahmad I.; RT "cDNA cloning and expression analysis of NeuroD mRNA in human retina."; RL Biochem. Biophys. Res. Commun. 233:459-463(1997). RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 147-198. RC TISSUE=Rhabdomyosarcoma; RA Shum C.H., Triche T.J.; RL Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases. RN [15] RP INTERACTION WITH RREB1. RX PubMed=12482979; DOI=10.1128/mcb.23.1.259-271.2003; RA Ray S.K., Nishitani J., Petry M.W., Fessing M.Y., Leiter A.B.; RT "Novel transcriptional potentiation of BETA2/NeuroD on the secretin gene RT promoter by the DNA-binding protein Finb/RREB-1."; RL Mol. Cell. Biol. 23:259-271(2003). RN [16] RP INTERACTION WITH NR0B2; EP300 AND TCF3, HETERODIMERIZATION, TISSUE RP SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=14752053; DOI=10.1210/me.2003-0311; RA Kim J.Y., Chu K., Kim H.J., Seong H.A., Park K.C., Sanyal S., Takeda J., RA Ha H., Shong M., Tsai M.J., Choi H.S.; RT "Orphan nuclear receptor small heterodimer partner, a novel corepressor for RT a basic helix-loop-helix transcription factor BETA2/neuroD."; RL Mol. Endocrinol. 18:776-790(2004). RN [17] RP INVOLVEMENT IN MODY6 AND T2D, AND VARIANT T2D LEU-111. RX PubMed=10545951; DOI=10.1038/15500; RA Malecki M.T., Jhala U.S., Antonellis A., Fields L., Doria A., Orban T., RA Saad M., Warram J.H., Montminy M., Krolewski A.S.; RT "Mutations in NEUROD1 are associated with the development of type 2 RT diabetes mellitus."; RL Nat. Genet. 23:323-328(1999). RN [18] RP VARIANT MODY6 LYS-110. RX PubMed=11719843; DOI=10.1007/s001250100016; RA Kristinsson S.Y., Thorolfsdottir E.T., Talseth B., Steingrimsson E., RA Thorsson A.V., Helgason T., Hreidarsson A.B., Arngrimsson R.; RT "MODY in Iceland is associated with mutations in HNF-1alpha and a novel RT mutation in NeuroD1."; RL Diabetologia 44:2098-2103(2001). RN [19] RP VARIANT ILE-242. RX PubMed=25477324; DOI=10.1167/iovs.14-15382; RA Wang F., Li H., Xu M., Li H., Zhao L., Yang L., Zaneveld J.E., Wang K., RA Li Y., Sui R., Chen R.; RT "A homozygous missense mutation in NEUROD1 is associated with nonsyndromic RT autosomal recessive retinitis pigmentosa."; RL Invest. Ophthalmol. Vis. Sci. 56:150-155(2015). RN [20] RP VARIANT MODY6 PRO-103. RX PubMed=26773576; DOI=10.1016/j.ejmg.2016.01.002; RA Szopa M., Ludwig-Galezowska A.H., Radkowski P., Skupien J., Machlowska J., RA Klupa T., Wolkow P., Borowiec M., Mlynarski W., Malecki M.T.; RT "A family with the Arg103Pro mutation in the NEUROD1 gene detected by next- RT generation sequencing - Clinical characteristics of mutation carriers."; RL Eur. J. Med. Genet. 59:75-79(2016). CC -!- FUNCTION: Acts as a transcriptional activator: mediates transcriptional CC activation by binding to E box-containing promoter consensus core CC sequences 5'-CANNTG-3'. Associates with the p300/CBP transcription CC coactivator complex to stimulate transcription of the secretin gene as CC well as the gene encoding the cyclin-dependent kinase inhibitor CDKN1A. CC Contributes to the regulation of several cell differentiation pathways, CC like those that promote the formation of early retinal ganglion cells, CC inner ear sensory neurons, granule cells forming either the cerebellum CC or the dentate gyrus cell layer of the hippocampus, endocrine islet CC cells of the pancreas and enteroendocrine cells of the small intestine. CC Together with PAX6 or SIX3, is required for the regulation of amacrine CC cell fate specification. Also required for dendrite morphogenesis and CC maintenance in the cerebellar cortex. Associates with chromatin to CC enhancer regulatory elements in genes encoding key transcriptional CC regulators of neurogenesis (By similarity). CC {ECO:0000250|UniProtKB:Q60867}. CC -!- SUBUNIT: Efficient DNA-binding requires dimerization with another bHLH CC protein (By similarity). Heterodimer with TCF3/E47; the heterodimer is CC inhibited in presence of ID2, but not NR0B2, to E-box element CC (PubMed:14752053). Interacts with EP300; the interaction is inhibited CC by NR0B2 (PubMed:14752053). Interacts with RREB1 (PubMed:12482979). CC Interacts with ATOH8 (By similarity). {ECO:0000250|UniProtKB:Q60867, CC ECO:0000269|PubMed:12482979, ECO:0000269|PubMed:14752053}. CC -!- INTERACTION: CC Q13562; Q0VDC6: FKBP1A; NbExp=3; IntAct=EBI-3908303, EBI-10226858; CC Q13562; P54652: HSPA2; NbExp=3; IntAct=EBI-3908303, EBI-356991; CC Q13562; O43464: HTRA2; NbExp=3; IntAct=EBI-3908303, EBI-517086; CC Q13562; P42858: HTT; NbExp=6; IntAct=EBI-3908303, EBI-466029; CC Q13562; O14901: KLF11; NbExp=3; IntAct=EBI-3908303, EBI-948266; CC Q13562; P28331-2: NDUFS1; NbExp=3; IntAct=EBI-3908303, EBI-6190702; CC Q13562; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-3908303, EBI-2811583; CC Q13562; P41219: PRPH; NbExp=3; IntAct=EBI-3908303, EBI-752074; CC Q13562; Q99081-3: TCF12; NbExp=4; IntAct=EBI-3908303, EBI-11952764; CC Q13562; P15884-3: TCF4; NbExp=3; IntAct=EBI-3908303, EBI-13636688; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus CC {ECO:0000255|PROSITE-ProRule:PRU00981, ECO:0000269|PubMed:14752053}. CC Note=In pancreatic islet cells, shuttles to the nucleus in response to CC glucose stimulation (By similarity). Colocalizes with NR0B2 in the CC nucleus. {ECO:0000250}. CC -!- PTM: Phosphorylated. In islet cells, phosphorylated on Ser-274 upon CC glucose stimulation; which may be required for nuclear localization. In CC activated neurons, phosphorylated on Ser-335; which promotes dendritic CC growth. Phosphorylated by MAPK1; phosphorylation regulates CC heterodimerization and DNA-binding activities. Phosphorylation on Ser- CC 266 and Ser-274 increases transactivation on the insulin promoter in CC glucose-stimulated insulinoma cells (By similarity). {ECO:0000250}. CC -!- DISEASE: Maturity-onset diabetes of the young 6 (MODY6) [MIM:606394]: A CC form of diabetes that is characterized by an autosomal dominant mode of CC inheritance, onset in childhood or early adulthood (usually before 25 CC years of age), a primary defect in insulin secretion and frequent CC insulin-independence at the beginning of the disease. CC {ECO:0000269|PubMed:10545951, ECO:0000269|PubMed:11719843, CC ECO:0000269|PubMed:26773576}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Type 2 diabetes mellitus (T2D) [MIM:125853]: A multifactorial CC disorder of glucose homeostasis caused by a lack of sensitivity to the CC body's own insulin. Affected individuals usually have an obese body CC habitus and manifestations of a metabolic syndrome characterized by CC diabetes, insulin resistance, hypertension and hypertriglyceridemia. CC The disease results in long-term complications that affect the eyes, CC kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:10545951}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. 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; U50822; AAA93480.1; -; Genomic_DNA. DR EMBL; D82347; BAA11558.1; -; mRNA. DR EMBL; AF045152; AAC83145.1; -; Genomic_DNA. DR EMBL; AB018693; BAA76603.1; -; Genomic_DNA. DR EMBL; AB009997; BAA87605.1; -; Genomic_DNA. DR EMBL; AB016079; BAA36519.1; -; Genomic_DNA. DR EMBL; BT019731; AAV38536.1; -; mRNA. DR EMBL; AK313799; BAG36535.1; -; mRNA. DR EMBL; AB593068; BAJ84015.1; -; mRNA. DR EMBL; AB593069; BAJ84016.1; -; mRNA. DR EMBL; AB593070; BAJ84017.1; -; mRNA. DR EMBL; AB593071; BAJ84018.1; -; mRNA. DR EMBL; AC013733; AAY24267.1; -; Genomic_DNA. DR EMBL; CH471058; EAX10983.1; -; Genomic_DNA. DR EMBL; BC009046; AAH09046.1; -; mRNA. DR EMBL; U80578; AAC51318.1; -; mRNA. DR EMBL; U36472; AAA79702.1; -; mRNA. DR CCDS; CCDS2283.1; -. DR RefSeq; NP_002491.2; NM_002500.4. DR AlphaFoldDB; Q13562; -. DR SMR; Q13562; -. DR BioGRID; 110833; 20. DR CORUM; Q13562; -. DR IntAct; Q13562; 14. DR STRING; 9606.ENSP00000295108; -. DR CarbonylDB; Q13562; -. DR iPTMnet; Q13562; -. DR PhosphoSitePlus; Q13562; -. DR BioMuta; NEUROD1; -. DR DMDM; 311033428; -. DR MassIVE; Q13562; -. DR PaxDb; 9606-ENSP00000295108; -. DR PeptideAtlas; Q13562; -. DR Antibodypedia; 922; 614 antibodies from 38 providers. DR DNASU; 4760; -. DR Ensembl; ENST00000295108.4; ENSP00000295108.3; ENSG00000162992.5. DR Ensembl; ENST00000683430.1; ENSP00000506907.1; ENSG00000162992.5. DR Ensembl; ENST00000684079.1; ENSP00000507492.1; ENSG00000162992.5. DR GeneID; 4760; -. DR KEGG; hsa:4760; -. DR MANE-Select; ENST00000295108.4; ENSP00000295108.3; NM_002500.5; NP_002491.3. DR UCSC; uc002uof.5; human. DR AGR; HGNC:7762; -. DR CTD; 4760; -. DR DisGeNET; 4760; -. DR GeneCards; NEUROD1; -. DR GeneReviews; NEUROD1; -. DR HGNC; HGNC:7762; NEUROD1. DR HPA; ENSG00000162992; Group enriched (brain, retina). DR MalaCards; NEUROD1; -. DR MIM; 125853; phenotype. DR MIM; 601724; gene. DR MIM; 606394; phenotype. DR neXtProt; NX_Q13562; -. DR OpenTargets; ENSG00000162992; -. DR Orphanet; 552; MODY. DR PharmGKB; PA31564; -. DR VEuPathDB; HostDB:ENSG00000162992; -. DR eggNOG; KOG3898; Eukaryota. DR GeneTree; ENSGT00940000160478; -. DR HOGENOM; CLU_055134_0_0_1; -. DR InParanoid; Q13562; -. DR OMA; SFKHEPA; -. DR OrthoDB; 2915590at2759; -. DR PhylomeDB; Q13562; -. DR TreeFam; TF315153; -. DR PathwayCommons; Q13562; -. DR Reactome; R-HSA-210745; Regulation of gene expression in beta cells. DR Reactome; R-HSA-210746; Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells. DR SignaLink; Q13562; -. DR SIGNOR; Q13562; -. DR BioGRID-ORCS; 4760; 9 hits in 1175 CRISPR screens. DR GeneWiki; NEUROD1; -. DR GenomeRNAi; 4760; -. DR Pharos; Q13562; Tbio. DR PRO; PR:Q13562; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q13562; Protein. DR Bgee; ENSG00000162992; Expressed in paraflocculus and 79 other cell types or tissues. DR ExpressionAtlas; Q13562; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:BHF-UCL. DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:GO_Central. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:BHF-UCL. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:BHF-UCL. DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0035881; P:amacrine cell differentiation; ISS:UniProtKB. DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl. DR GO; GO:0061564; P:axon development; IBA:GO_Central. DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl. DR GO; GO:0021549; P:cerebellum development; ISS:UniProtKB. DR GO; GO:0021542; P:dentate gyrus development; ISS:UniProtKB. DR GO; GO:0048562; P:embryonic organ morphogenesis; ISS:BHF-UCL. DR GO; GO:0031018; P:endocrine pancreas development; ISS:UniProtKB. DR GO; GO:0035883; P:enteroendocrine cell differentiation; ISS:UniProtKB. DR GO; GO:0042593; P:glucose homeostasis; ISS:BHF-UCL. DR GO; GO:0048839; P:inner ear development; ISS:UniProtKB. DR GO; GO:0030073; P:insulin secretion; IDA:BHF-UCL. DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; IEA:Ensembl. DR GO; GO:2000675; P:negative regulation of type B pancreatic cell apoptotic process; ISS:BHF-UCL. DR GO; GO:0022008; P:neurogenesis; TAS:BHF-UCL. DR GO; GO:0007263; P:nitric oxide mediated signal transduction; IDA:BHF-UCL. DR GO; GO:0006913; P:nucleocytoplasmic transport; IEA:Ensembl. DR GO; GO:0003326; P:pancreatic A cell fate commitment; IEA:Ensembl. DR GO; GO:0003329; P:pancreatic PP cell fate commitment; IEA:Ensembl. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0045597; P:positive regulation of cell differentiation; ISS:UniProtKB. DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:2000679; P:positive regulation of transcription regulatory region DNA binding; IDA:BHF-UCL. DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IEA:Ensembl. DR GO; GO:0050796; P:regulation of insulin secretion; IC:BHF-UCL. DR GO; GO:0060730; P:regulation of intestinal epithelial structure maintenance; ISS:UniProtKB. DR GO; GO:0009749; P:response to glucose; IMP:BHF-UCL. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0007423; P:sensory organ development; IBA:GO_Central. DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR CDD; cd19719; bHLH_TS_NeuroD1; 1. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR InterPro; IPR022575; NeuroD_DUF. DR InterPro; IPR016637; TF_bHLH_NeuroD. DR PANTHER; PTHR19290; BASIC HELIX-LOOP-HELIX PROTEIN NEUROGENIN-RELATED; 1. DR PANTHER; PTHR19290:SF88; NEUROGENIC DIFFERENTIATION FACTOR 1; 1. DR Pfam; PF00010; HLH; 1. DR Pfam; PF12533; Neuro_bHLH; 1. DR PIRSF; PIRSF015618; bHLH_NeuroD; 1. DR SMART; SM00353; HLH; 1. DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1. DR PROSITE; PS50888; BHLH; 1. DR Genevisible; Q13562; HS. PE 1: Evidence at protein level; KW Activator; Cytoplasm; Developmental protein; Diabetes mellitus; KW Differentiation; Disease variant; DNA-binding; Neurogenesis; Nucleus; KW Phosphoprotein; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1..356 FT /note="Neurogenic differentiation factor 1" FT /id="PRO_0000127381" FT DOMAIN 101..153 FT /note="bHLH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981" FT REGION 1..94 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 87..93 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 27..53 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 54..76 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 162 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q60867" FT MOD_RES 259 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q60867" FT MOD_RES 266 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q60867" FT MOD_RES 274 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q60867" FT MOD_RES 335 FT /note="Phosphoserine; by CaMK2" FT /evidence="ECO:0000250|UniProtKB:Q64289" FT VARIANT 45 FT /note="T -> A (in dbSNP:rs1801262)" FT /evidence="ECO:0000269|PubMed:10366743, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:21697133, ECO:0000269|PubMed:8786144, FT ECO:0000269|PubMed:8915591, ECO:0000269|Ref.11, FT ECO:0000269|Ref.3, ECO:0000269|Ref.5, ECO:0000269|Ref.6" FT /id="VAR_014820" FT VARIANT 103 FT /note="R -> P (in MODY6)" FT /evidence="ECO:0000269|PubMed:26773576" FT /id="VAR_076552" FT VARIANT 110 FT /note="E -> K (in MODY6; uncertain significance; FT dbSNP:rs763092306)" FT /evidence="ECO:0000269|PubMed:11719843" FT /id="VAR_076553" FT VARIANT 111 FT /note="R -> L (in T2D; dbSNP:rs104893649)" FT /evidence="ECO:0000269|PubMed:10545951" FT /id="VAR_012487" FT VARIANT 197 FT /note="P -> H (in dbSNP:rs8192556)" FT /id="VAR_031260" FT VARIANT 242 FT /note="V -> I (found in one consanguineous family with FT non-syndromic autosomal recessive retinitis pigmentosa; FT uncertain significance; dbSNP:rs786205158)" FT /evidence="ECO:0000269|PubMed:25477324" FT /id="VAR_076554" FT CONFLICT 157 FT /note="L -> S (in Ref. 1; AAA93480)" FT /evidence="ECO:0000305" FT CONFLICT 185 FT /note="A -> G (in Ref. 2; BAA11558 and 5; BAA87605)" FT /evidence="ECO:0000305" FT CONFLICT 232 FT /note="G -> D (in Ref. 6; BAA36519)" FT /evidence="ECO:0000305" SQ SEQUENCE 356 AA; 39920 MW; B78075D1CF66E943 CRC64; MTKSYSESGL MGEPQPQGPP SWTDECLSSQ DEEHEADKKE DDLETMNAEE DSLRNGGEEE DEDEDLEEEE EEEEEDDDQK PKRRGPKKKK MTKARLERFK LRRMKANARE RNRMHGLNAA LDNLRKVVPC YSKTQKLSKI ETLRLAKNYI WALSEILRSG KSPDLVSFVQ TLCKGLSQPT TNLVAGCLQL NPRTFLPEQN QDMPPHLPTA SASFPVHPYS YQSPGLPSPP YGTMDSSHVF HVKPPPHAYS AALEPFFESP LTDCTSPSFD GPLSPPLSIN GNFSFKHEPS AEFEKNYAFT MHYPAATLAG AQSHGSIFSG TAAPRCEIPI DNIMSFDSHS HHERVMSAQL NAIFHD //