HEN2_HUMAN
ID HEN2_HUMAN Reviewed; 135 AA.
AC Q02577; Q5T1P6;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Helix-loop-helix protein 2;
DE Short=HEN-2;
DE AltName: Full=Class A basic helix-loop-helix protein 34;
DE Short=bHLHa34;
DE AltName: Full=Nescient helix loop helix 2;
DE Short=NSCL-2;
GN Name=NHLH2; Synonyms=BHLHA34, HEN2, KIAA0490;
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].
RC TISSUE=Brain;
RX PubMed=1528853; DOI=10.1073/pnas.89.18.8492;
RA Brown L., Espinosa R. III, le Beau M.M., Siciliano M.J., Baer R.;
RT "HEN1 and HEN2: a subgroup of basic helix-loop-helix genes that are
RT coexpressed in a human neuroblastoma.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8492-8496(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Brain;
RX PubMed=1328219; DOI=10.1016/s0021-9258(19)36798-5;
RA Lipkowitz S., Gobel V., Varterasian M.L., Nakahara K., Tchorz K.,
RA Kirsch I.R.;
RT "A comparative structural characterization of the human NSCL-1 and NSCL-2
RT genes. Two basic helix-loop-helix genes expressed in the developing nervous
RT system.";
RL J. Biol. Chem. 267:21065-21071(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=9455484; DOI=10.1093/dnares/4.5.345;
RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D.,
RA Nomura N., Ohara O.;
RT "Characterization of cDNA clones in size-fractionated cDNA libraries from
RT human brain.";
RL DNA Res. 4:345-349(1997).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
CC -!- FUNCTION: Transcription factor which binds the E box motif 5'-
CC CA[TC][AG]TG-3'. Involved in regulating energy expenditure, body mass,
CC voluntary physical activity, mating behavior and reproductive
CC longevity, acting through the hypothalamic-pituitary-gonadal axis. Acts
CC as a transcriptional activator of target genes, including NDN and
CC PCSK1. May act centrally to regulate function of both white and brown
CC adipose tissue. Together with NHLH1, required to maintain migration and
CC survival of cells in the anterior extramural migration stream (aes),
CC which forms the precerebellar nuclei. Also, in concert with NHLH1, may
CC determine fate of gonadotropin releasing hormone-1 (GnRH-1) neurons.
CC {ECO:0000250|UniProtKB:Q64221}.
CC -!- SUBUNIT: Homodimer. Interacts and may form heterodimers with STAT3.
CC {ECO:0000250|UniProtKB:Q64221}.
CC -!- INTERACTION:
CC Q02577; Q9NZI2-2: KCNIP1; NbExp=3; IntAct=EBI-5378683, EBI-22452746;
CC Q02577; P13349: MYF5; NbExp=3; IntAct=EBI-5378683, EBI-17491620;
CC Q02577; Q96EB6: SIRT1; NbExp=2; IntAct=EBI-5378683, EBI-1802965;
CC Q02577; Q9H5J8: TAF1D; NbExp=3; IntAct=EBI-5378683, EBI-716128;
CC Q02577; Q99081-3: TCF12; NbExp=3; IntAct=EBI-5378683, EBI-11952764;
CC Q02577; P15884-3: TCF4; NbExp=3; IntAct=EBI-5378683, EBI-13636688;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
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; M97508; AAA58635.1; -; Genomic_DNA.
DR EMBL; AB007959; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL449264; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096359; AAH96359.1; -; mRNA.
DR EMBL; BC096360; AAH96360.1; -; mRNA.
DR CCDS; CCDS885.1; -.
DR PIR; B45075; B45075.
DR RefSeq; NP_001104531.1; NM_001111061.1.
DR RefSeq; NP_005590.1; NM_005599.3.
DR AlphaFoldDB; Q02577; -.
DR SMR; Q02577; -.
DR BioGRID; 110873; 25.
DR CORUM; Q02577; -.
DR IntAct; Q02577; 6.
DR STRING; 9606.ENSP00000358519; -.
DR iPTMnet; Q02577; -.
DR PhosphoSitePlus; Q02577; -.
DR BioMuta; NHLH2; -.
DR DMDM; 399887; -.
DR MassIVE; Q02577; -.
DR PaxDb; Q02577; -.
DR PeptideAtlas; Q02577; -.
DR PRIDE; Q02577; -.
DR Antibodypedia; 33870; 195 antibodies from 24 providers.
DR DNASU; 4808; -.
DR Ensembl; ENST00000320238.3; ENSP00000322087.3; ENSG00000177551.5.
DR Ensembl; ENST00000369506.1; ENSP00000358519.1; ENSG00000177551.5.
DR GeneID; 4808; -.
DR KEGG; hsa:4808; -.
DR MANE-Select; ENST00000320238.3; ENSP00000322087.3; NM_005599.3; NP_005590.1.
DR UCSC; uc001efy.4; human.
DR CTD; 4808; -.
DR DisGeNET; 4808; -.
DR GeneCards; NHLH2; -.
DR HGNC; HGNC:7818; NHLH2.
DR HPA; ENSG00000177551; Group enriched (brain, esophagus, retina, skin).
DR MIM; 162361; gene.
DR neXtProt; NX_Q02577; -.
DR OpenTargets; ENSG00000177551; -.
DR PharmGKB; PA31620; -.
DR VEuPathDB; HostDB:ENSG00000177551; -.
DR eggNOG; KOG4029; Eukaryota.
DR GeneTree; ENSGT00940000162602; -.
DR HOGENOM; CLU_148882_1_0_1; -.
DR InParanoid; Q02577; -.
DR OMA; RSCCASD; -.
DR PhylomeDB; Q02577; -.
DR PathwayCommons; Q02577; -.
DR SignaLink; Q02577; -.
DR SIGNOR; Q02577; -.
DR BioGRID-ORCS; 4808; 17 hits in 1092 CRISPR screens.
DR GenomeRNAi; 4808; -.
DR Pharos; Q02577; Tbio.
DR PRO; PR:Q02577; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q02577; protein.
DR Bgee; ENSG00000177551; Expressed in buccal mucosa cell and 78 other tissues.
DR ExpressionAtlas; Q02577; baseline and differential.
DR Genevisible; Q02577; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005667; C:transcription regulator complex; TAS:BHF-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
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: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:0006915; P:apoptotic process; IEA:Ensembl.
DR GO; GO:0021535; P:cell migration in hindbrain; IEA:Ensembl.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0021888; P:hypothalamus gonadotrophin-releasing hormone neuron development; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0060179; P:male mating behavior; IEA:Ensembl.
DR GO; GO:0042698; P:ovulation cycle; IEA:Ensembl.
DR GO; GO:0007422; P:peripheral nervous system development; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; TAS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; TAS:BHF-UCL.
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; IPR040238; TAL-like.
DR PANTHER; PTHR13864; PTHR13864; 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; DNA-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..135
FT /note="Helix-loop-helix protein 2"
FT /id="PRO_0000127199"
FT DOMAIN 77..129
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 COMPBIAS 9..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 135 AA; 15018 MW; 083730499F610AAE CRC64;
MMLSPDQAAD SDHPSSAHSD PESLGGTDTK VLGSVSDLEP VEEAEGDGKG GSRAALYPHP
QQLSREEKRR RRRATAKYRS AHATRERIRV EAFNLAFAEL RKLLPTLPPD KKLSKIEILR
LAICYISYLN HVLDV
