ID   BHE22_HUMAN             Reviewed;         381 AA.
AC   Q8NFJ8;
DT   06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   24-JAN-2024, entry version 144.
DE   RecName: Full=Class E basic helix-loop-helix protein 22;
DE            Short=bHLHe22;
DE   AltName: Full=Class B basic helix-loop-helix protein 5;
DE            Short=bHLHb5;
DE   AltName: Full=Trinucleotide repeat-containing gene 20 protein;
GN   Name=BHLHE22; Synonyms=BHLHB5, TNRC20;
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 TISSUE SPECIFICITY.
RX   PubMed=12213201; DOI=10.1006/geno.2002.6833;
RA   Xu Z.-P., Dutra A., Stellrecht C.M., Wu C., Piatigorsky J., Saunders G.F.;
RT   "Functional and structural characterization of the human gene BHLHB5,
RT   encoding a basic helix-loop-helix transcription factor.";
RL   Genomics 80:311-318(2002).
RN   [2]
RP   IDENTIFICATION.
RX   PubMed=14516699; DOI=10.1016/s0925-4773(03)00130-8;
RA   McLellan A.S., Langlands K., Kealey T.;
RT   "Exhaustive identification of human class II basic helix-loop-helix
RT   proteins by virtual library screening.";
RL   Mech. Dev. 119:S285-S291(2002).
CC   -!- FUNCTION: Inhibits DNA binding of TCF3/E47 homodimers and TCF3
CC       (E47)/NEUROD1 heterodimers and acts as a strong repressor of Neurod1
CC       and Myod-responsive genes, probably by heterodimerization with class a
CC       basic helix-loop-helix factors. Despite the presence of an intact basic
CC       domain, does not bind to DNA (By similarity). In the brain, may
CC       function as an area-specific transcription factor that regulates the
CC       postmitotic acquisition of area identities and elucidate the genetic
CC       hierarchy between progenitors and postmitotic neurons driving
CC       neocortical arealization. May be required for the survival of a
CC       specific population of inhibitory neurons in the superficial laminae of
CC       the spinal cord dorsal horn that may regulate pruritis. Seems to play a
CC       crucial role in the retinogenesis, in the specification of amacrine and
CC       bipolar subtypes. Forms with PRDM8 a transcriptional repressor complex
CC       controlling genes involved in neural development and neuronal
CC       differentiation. {ECO:0000250|UniProtKB:Q8C6A8}.
CC   -!- SUBUNIT: Interacts with PRDM8. {ECO:0000250|UniProtKB:Q8C6A8}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Brain-specific, with the highest expression in the
CC       cerebellum. {ECO:0000269|PubMed:12213201}.
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DR   EMBL; AF504925; AAM28881.1; -; Genomic_DNA.
DR   EMBL; BK000273; DAA01053.1; -; mRNA.
DR   CCDS; CCDS6179.1; -.
DR   RefSeq; NP_689627.1; NM_152414.4.
DR   AlphaFoldDB; Q8NFJ8; -.
DR   SMR; Q8NFJ8; -.
DR   BioGRID; 118136; 2.
DR   STRING; 9606.ENSP00000318799; -.
DR   iPTMnet; Q8NFJ8; -.
DR   PhosphoSitePlus; Q8NFJ8; -.
DR   BioMuta; BHLHE22; -.
DR   DMDM; 74751284; -.
DR   MassIVE; Q8NFJ8; -.
DR   PaxDb; 9606-ENSP00000318799; -.
DR   PeptideAtlas; Q8NFJ8; -.
DR   ProteomicsDB; 73318; -.
DR   Antibodypedia; 11910; 167 antibodies from 26 providers.
DR   DNASU; 27319; -.
DR   Ensembl; ENST00000321870.3; ENSP00000318799.1; ENSG00000180828.3.
DR   GeneID; 27319; -.
DR   KEGG; hsa:27319; -.
DR   MANE-Select; ENST00000321870.3; ENSP00000318799.1; NM_152414.5; NP_689627.1.
DR   UCSC; uc003xvi.4; human.
DR   AGR; HGNC:11963; -.
DR   CTD; 27319; -.
DR   DisGeNET; 27319; -.
DR   GeneCards; BHLHE22; -.
DR   HGNC; HGNC:11963; BHLHE22.
DR   HPA; ENSG00000180828; Tissue enriched (brain).
DR   MIM; 613483; gene.
DR   neXtProt; NX_Q8NFJ8; -.
DR   OpenTargets; ENSG00000180828; -.
DR   PharmGKB; PA36650; -.
DR   VEuPathDB; HostDB:ENSG00000180828; -.
DR   eggNOG; KOG3898; Eukaryota.
DR   GeneTree; ENSGT00940000162962; -.
DR   HOGENOM; CLU_070971_0_0_1; -.
DR   InParanoid; Q8NFJ8; -.
DR   OMA; KKMDPFR; -.
DR   OrthoDB; 5324482at2759; -.
DR   PhylomeDB; Q8NFJ8; -.
DR   TreeFam; TF322733; -.
DR   PathwayCommons; Q8NFJ8; -.
DR   Reactome; R-HSA-9762293; Regulation of CDH11 gene transcription.
DR   SignaLink; Q8NFJ8; -.
DR   BioGRID-ORCS; 27319; 19 hits in 1158 CRISPR screens.
DR   GenomeRNAi; 27319; -.
DR   Pharos; Q8NFJ8; Tbio.
DR   PRO; PR:Q8NFJ8; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; Q8NFJ8; Protein.
DR   Bgee; ENSG00000180828; Expressed in secondary oocyte and 145 other cell types or tissues.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR   GO; GO:0070888; F:E-box binding; IBA:GO_Central.
DR   GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR   GO; GO:0061564; P:axon development; IBA:GO_Central.
DR   GO; GO:0048663; P:neuron fate commitment; IBA:GO_Central.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0007423; P:sensory organ development; IBA:GO_Central.
DR   CDD; cd18954; bHLH_TS_bHLHe22_bHLHb5; 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   PANTHER; PTHR19290; BASIC HELIX-LOOP-HELIX PROTEIN NEUROGENIN-RELATED; 1.
DR   PANTHER; PTHR19290:SF52; CLASS E BASIC HELIX-LOOP-HELIX PROTEIN 22; 1.
DR   Pfam; PF00010; HLH; 1.
DR   SMART; SM00353; HLH; 1.
DR   SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1.
DR   PROSITE; PS50888; BHLH; 1.
DR   Genevisible; Q8NFJ8; HS.
PE   2: Evidence at transcript level;
KW   Neurogenesis; Nucleus; Reference proteome; Repressor; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..381
FT                   /note="Class E basic helix-loop-helix protein 22"
FT                   /id="PRO_0000274285"
FT   DOMAIN          242..296
FT                   /note="bHLH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT   REGION          30..94
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          135..154
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          188..242
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        206..236
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         28
FT                   /note="S -> A (in dbSNP:rs7016250)"
FT                   /id="VAR_061255"
SQ   SEQUENCE   381 AA;  36997 MW;  7B17A9BD5C7F8569 CRC64;
     MERGMHLGAA AAGEDDLFLH KSLSASTSKR LEAAFRSTPP GMDLSLAPPP RERPASSSSS
     PLGCFEPADP EGAGLLLPPP GGGGGGSAGS GGGGGGGVGV PGLLVGSAGV GGDPSLSSLP
     AGAALCLKYG ESASRGSVAE SSGGEQSPDD DSDGRCELVL RAGVADPRAS PGAGGGGAKA
     AEGCSNAHLH GGASVPPGGL GGGGGGGSSS GSSGGGGGSG SGSGGSSSSS SSSSKKSKEQ
     KALRLNINAR ERRRMHDLND ALDELRAVIP YAHSPSVRKL SKIATLLLAK NYILMQAQAL
     EEMRRLVAYL NQGQAISAAS LPSSAAAAAA AAALHPALGA YEQAAGYPFS AGLPPAASCP
     EKCALFNSVS SSLCKQCTEK P
//