NGN3_HUMAN
ID NGN3_HUMAN Reviewed; 214 AA.
AC Q9Y4Z2; Q5VVI0; Q6DJX6; Q9BY24;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Neurogenin-3;
DE Short=NGN-3;
DE AltName: Full=Class A basic helix-loop-helix protein 7;
DE Short=bHLHa7;
DE AltName: Full=Protein atonal homolog 5;
GN Name=NEUROG3; Synonyms=ATOH5, BHLHA7, NGN3;
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 SER-199.
RA Ravassard P., Icard-Liepkalns C., Wiard L., Julien J.P., Mallet J.;
RT "The human neurogenin 3 homolog maps to chromosome 10q21.3 and its
RT expression pattern is identical to that of its murine counterparts.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-199.
RA del Bosque-Plata L., Lin J., Horikawa Y., Schwarz P.E.H., Cox N.J.,
RA Iwasaki N., Iwamoto Y., German M., Bell G.;
RT "Beta-cell transcription factors and diabetes: no evidence for diabetes-
RT associated mutations in the coding region of the proendocrine neurogenin 3
RT gene (NEUROG3) in Japanese patients with MODY.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Rectum;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-199.
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 [7]
RP VARIANTS DIAR4 LEU-93 AND SER-107, AND CHARACTERIZATION OF VARIANTS DIAR4
RP LEU-93 AND SER-107.
RX PubMed=16855267; DOI=10.1056/nejmoa054288;
RA Wang J., Cortina G., Wu S.V., Tran R., Cho J.-H., Tsai M.-J., Bailey T.J.,
RA Jamrich M., Ament M.E., Treem W.R., Hill I.D., Vargas J.H., Gershman G.,
RA Farmer D.G., Reyen L., Martin M.G.;
RT "Mutant neurogenin-3 in congenital malabsorptive diarrhea.";
RL N. Engl. J. Med. 355:270-280(2006).
CC -!- FUNCTION: Acts as a transcriptional regulator. Together with NKX2-2,
CC initiates transcriptional activation of NEUROD1. Involved in
CC neurogenesis. Also required for the specification of a common precursor
CC of the 4 pancreatic endocrine cell types (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Interacts with ATOH8. {ECO:0000250,
CC ECO:0000250|UniProtKB:P70661}.
CC -!- INTERACTION:
CC Q9Y4Z2; P78424: POU6F2; NbExp=3; IntAct=EBI-10328570, EBI-12029004;
CC Q9Y4Z2; Q04864: REL; NbExp=3; IntAct=EBI-10328570, EBI-307352;
CC Q9Y4Z2; Q99081: TCF12; NbExp=4; IntAct=EBI-10328570, EBI-722877;
CC Q9Y4Z2; Q99081-3: TCF12; NbExp=7; IntAct=EBI-10328570, EBI-11952764;
CC Q9Y4Z2; P15884-3: TCF4; NbExp=4; IntAct=EBI-10328570, EBI-13636688;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- DISEASE: Diarrhea 4, malabsorptive, congenital (DIAR4) [MIM:610370]: A
CC disease characterized by severe, life-threatening watery diarrhea
CC associated with generalized malabsorption and a paucity of
CC enteroendocrine cells. {ECO:0000269|PubMed:16855267}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
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DR EMBL; AJ133776; CAB45384.1; -; Genomic_DNA.
DR EMBL; AF234829; AAK15022.1; -; Genomic_DNA.
DR EMBL; AK313952; BAG36669.1; -; mRNA.
DR EMBL; AL450311; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54328.1; -; Genomic_DNA.
DR EMBL; BC074938; AAH74938.1; -; mRNA.
DR EMBL; BC074939; AAH74939.1; -; mRNA.
DR EMBL; BC117488; AAI17489.1; -; mRNA.
DR EMBL; BC126468; AAI26469.1; -; mRNA.
DR CCDS; CCDS31212.1; -.
DR RefSeq; NP_066279.2; NM_020999.3.
DR RefSeq; XP_016871769.1; XM_017016280.1.
DR AlphaFoldDB; Q9Y4Z2; -.
DR SMR; Q9Y4Z2; -.
DR BioGRID; 119118; 113.
DR IntAct; Q9Y4Z2; 44.
DR STRING; 9606.ENSP00000242462; -.
DR iPTMnet; Q9Y4Z2; -.
DR PhosphoSitePlus; Q9Y4Z2; -.
DR BioMuta; NEUROG3; -.
DR DMDM; 229462908; -.
DR PaxDb; Q9Y4Z2; -.
DR PeptideAtlas; Q9Y4Z2; -.
DR PRIDE; Q9Y4Z2; -.
DR Antibodypedia; 28907; 558 antibodies from 33 providers.
DR DNASU; 50674; -.
DR Ensembl; ENST00000242462.5; ENSP00000242462.4; ENSG00000122859.5.
DR GeneID; 50674; -.
DR KEGG; hsa:50674; -.
DR MANE-Select; ENST00000242462.5; ENSP00000242462.4; NM_020999.4; NP_066279.2.
DR UCSC; uc001jpp.4; human.
DR CTD; 50674; -.
DR DisGeNET; 50674; -.
DR GeneCards; NEUROG3; -.
DR HGNC; HGNC:13806; NEUROG3.
DR HPA; ENSG00000122859; Group enriched (brain, intestine).
DR MalaCards; NEUROG3; -.
DR MIM; 604882; gene.
DR MIM; 610370; phenotype.
DR neXtProt; NX_Q9Y4Z2; -.
DR OpenTargets; ENSG00000122859; -.
DR Orphanet; 83620; Enteric anendocrinosis.
DR PharmGKB; PA31571; -.
DR VEuPathDB; HostDB:ENSG00000122859; -.
DR eggNOG; KOG3898; Eukaryota.
DR GeneTree; ENSGT00940000163077; -.
DR HOGENOM; CLU_097959_1_0_1; -.
DR InParanoid; Q9Y4Z2; -.
DR OMA; ADHSFYG; -.
DR OrthoDB; 1524429at2759; -.
DR PhylomeDB; Q9Y4Z2; -.
DR TreeFam; TF315153; -.
DR PathwayCommons; Q9Y4Z2; -.
DR Reactome; R-HSA-210744; Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.
DR Reactome; R-HSA-210746; Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells.
DR SignaLink; Q9Y4Z2; -.
DR SIGNOR; Q9Y4Z2; -.
DR BioGRID-ORCS; 50674; 26 hits in 1087 CRISPR screens.
DR GeneWiki; NEUROG3; -.
DR GenomeRNAi; 50674; -.
DR Pharos; Q9Y4Z2; Tbio.
DR PRO; PR:Q9Y4Z2; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9Y4Z2; protein.
DR Bgee; ENSG00000122859; Expressed in mucosa of transverse colon and 27 other tissues.
DR Genevisible; Q9Y4Z2; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0031018; P:endocrine pancreas development; IEA:InterPro.
DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0030902; P:hindbrain development; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0007422; P:peripheral nervous system development; TAS:ProtInc.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0021510; P:spinal cord development; IEA:Ensembl.
DR GO; GO:0060290; P:transdifferentiation; ISS:UniProtKB.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR032656; Ngn3.
DR PANTHER; PTHR19290:SF94; PTHR19290:SF94; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Activator; Developmental protein; Differentiation; Disease variant;
KW DNA-binding; Neurogenesis; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..214
FT /note="Neurogenin-3"
FT /id="PRO_0000127402"
FT DOMAIN 83..135
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..98
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..18
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 93
FT /note="R -> L (in DIAR4; attenuated NEUROG3 function in
FT vivo; dbSNP:rs121917838)"
FT /evidence="ECO:0000269|PubMed:16855267"
FT /id="VAR_029003"
FT VARIANT 107
FT /note="R -> S (in DIAR4; attenuated NEUROG3 function in
FT vivo; dbSNP:rs121917837)"
FT /evidence="ECO:0000269|PubMed:16855267"
FT /id="VAR_029004"
FT VARIANT 199
FT /note="F -> S (in dbSNP:rs4536103)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.1,
FT ECO:0000269|Ref.2"
FT /id="VAR_055316"
FT CONFLICT 43
FT /note="R -> P (in Ref. 1; CAB45384)"
FT /evidence="ECO:0000305"
FT CONFLICT 98
FT /note="N -> D (in Ref. 1; CAB45384)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="S -> P (in Ref. 1; CAB45384)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 214 AA; 23077 MW; 2E80623E46F88B83 CRC64;
MTPQPSGAPT VQVTRETERS FPRASEDEVT CPTSAPPSPT RTRGNCAEAE EGGCRGAPRK
LRARRGGRSR PKSELALSKQ RRSRRKKAND RERNRMHNLN SALDALRGVL PTFPDDAKLT
KIETLRFAHN YIWALTQTLR IADHSLYALE PPAPHCGELG SPGGSPGDWG SLYSPVSQAG
SLSPAASLEE RPGLLGATFS ACLSPGSLAF SDFL
