NDF4_HUMAN
ID NDF4_HUMAN Reviewed; 331 AA.
AC Q9HD90; B2RAC9;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Neurogenic differentiation factor 4;
DE Short=NeuroD4;
DE AltName: Full=Class A basic helix-loop-helix protein 4;
DE Short=bHLHa4;
DE AltName: Full=Protein atonal homolog 3;
DE Short=ATH-3;
DE Short=Atoh3;
GN Name=NEUROD4; Synonyms=ATH3, ATOH3, BHLHA4;
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 THR-68.
RX PubMed=11078465; DOI=10.2337/diabetes.49.11.1955;
RA Horikawa Y., Horikawa Y., Cox N.J., Iwasaki N., Ogata M., Iwamoto Y.,
RA Schwitzgebel V., German M.S., Bell G.I.;
RT "Beta-cell transcription factors and diabetes: no evidence for diabetes-
RT associated mutations in the gene encoding the basic helix-loop-helix
RT transcription factor neurogenic differentiation 4 (NEUROD4) in Japanese
RT patients with MODY.";
RL Diabetes 49:1955-1957(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thalamus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
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.
CC -!- FUNCTION: Probably acts as a transcriptional activator. Mediates
CC neuronal differentiation. Required for the regulation of amacrine cell
CC fate specification in the retina (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. {ECO:0000250}.
CC -!- INTERACTION:
CC Q9HD90; O15481: MAGEB4; NbExp=5; IntAct=EBI-3917781, EBI-751857;
CC Q9HD90; Q13526: PIN1; NbExp=3; IntAct=EBI-3917781, EBI-714158;
CC Q9HD90; P15884-3: TCF4; NbExp=3; IntAct=EBI-3917781, EBI-13636688;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- PTM: Serine or threonine phosphorylation within the basic region may
CC regulate neurogenic activity. {ECO:0000250}.
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; AF203901; AAF99097.1; -; Genomic_DNA.
DR EMBL; AK314136; BAG36826.1; -; mRNA.
DR EMBL; AC027287; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW96803.1; -; Genomic_DNA.
DR CCDS; CCDS8886.1; -.
DR RefSeq; NP_067014.2; NM_021191.2.
DR AlphaFoldDB; Q9HD90; -.
DR SMR; Q9HD90; -.
DR BioGRID; 121799; 23.
DR IntAct; Q9HD90; 5.
DR STRING; 9606.ENSP00000242994; -.
DR iPTMnet; Q9HD90; -.
DR PhosphoSitePlus; Q9HD90; -.
DR BioMuta; NEUROD4; -.
DR DMDM; 296439241; -.
DR MassIVE; Q9HD90; -.
DR PaxDb; Q9HD90; -.
DR PeptideAtlas; Q9HD90; -.
DR PRIDE; Q9HD90; -.
DR ProteomicsDB; 81843; -.
DR Antibodypedia; 15429; 79 antibodies from 22 providers.
DR DNASU; 58158; -.
DR Ensembl; ENST00000242994.4; ENSP00000242994.3; ENSG00000123307.4.
DR GeneID; 58158; -.
DR KEGG; hsa:58158; -.
DR MANE-Select; ENST00000242994.4; ENSP00000242994.3; NM_021191.3; NP_067014.2.
DR UCSC; uc001sgp.5; human.
DR CTD; 58158; -.
DR DisGeNET; 58158; -.
DR GeneCards; NEUROD4; -.
DR HGNC; HGNC:13802; NEUROD4.
DR HPA; ENSG00000123307; Group enriched (pituitary gland, retina).
DR MIM; 611635; gene.
DR neXtProt; NX_Q9HD90; -.
DR OpenTargets; ENSG00000123307; -.
DR PharmGKB; PA31566; -.
DR VEuPathDB; HostDB:ENSG00000123307; -.
DR eggNOG; KOG3898; Eukaryota.
DR GeneTree; ENSGT00940000160217; -.
DR HOGENOM; CLU_055134_0_0_1; -.
DR InParanoid; Q9HD90; -.
DR OMA; MAHYPSV; -.
DR OrthoDB; 1096531at2759; -.
DR PhylomeDB; Q9HD90; -.
DR TreeFam; TF315153; -.
DR PathwayCommons; Q9HD90; -.
DR SignaLink; Q9HD90; -.
DR SIGNOR; Q9HD90; -.
DR BioGRID-ORCS; 58158; 7 hits in 1083 CRISPR screens.
DR GenomeRNAi; 58158; -.
DR Pharos; Q9HD90; Tbio.
DR PRO; PR:Q9HD90; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9HD90; protein.
DR Bgee; ENSG00000123307; Expressed in ganglionic eminence and 15 other tissues.
DR Genevisible; Q9HD90; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA: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; IBA:GO_Central.
DR GO; GO:0035881; P:amacrine cell differentiation; ISS:UniProtKB.
DR GO; GO:0045165; P:cell fate commitment; IEA:Ensembl.
DR GO; GO:0097475; P:motor neuron migration; IEA:Ensembl.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0048666; P:neuron development; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR032651; Neurod4.
DR InterPro; IPR022575; Neurogenic_DUF.
DR InterPro; IPR016637; TF_bHLH_NeuroD.
DR PANTHER; PTHR19290:SF86; PTHR19290:SF86; 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; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Activator; Developmental protein; Differentiation; DNA-binding;
KW Neurogenesis; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..331
FT /note="Neurogenic differentiation factor 4"
FT /id="PRO_0000127390"
FT DOMAIN 87..139
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 246..265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 68
FT /note="K -> T (in dbSNP:rs76064726)"
FT /evidence="ECO:0000269|PubMed:11078465"
FT /id="VAR_012979"
FT CONFLICT 194
FT /note="D -> G (in Ref. 1; AAF99097)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 331 AA; 37041 MW; EBA3DC61B70ABF28 CRC64;
MSKTFVKSKE MGELVNTPSW MDKGLGSQNE VKEEESRPGT YGMLSSLTEE HDSIEEEEEE
EEDGEKPKRR GPKKKKMTKA RLERFRARRV KANARERTRM HGLNDALDNL RRVMPCYSKT
QKLSKIETLR LARNYIWALS EVLETGQTPE GKGFVEMLCK GLSQPTSNLV AGCLQLGPQS
VLLEKHEDKS PICDSAISVH NFNYQSPGLP SPPYGHMETH LLHLKPQVFK SLGESSFGSH
LPDCSTPPYE GPLTPPLSIS GNFSLKQDGS PDLEKSYSFM PHYPSSSLSS GHVHSTPFQA
GTPRYDVPID MSYDSYPHHG IGTQLNTVFT E
