Q02577 · HEN2_HUMAN

  • Protein
    Helix-loop-helix protein 2
  • Gene
    NHLH2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Transcription factor which binds the E box motif 5'-CA[TC][AG]TG-3'. Involved in regulating energy expenditure, body mass, voluntary physical activity, mating behavior and reproductive longevity, acting through the hypothalamic-pituitary-gonadal axis. Acts as a transcriptional activator of target genes, including NDN, PCSK1, MC4R (By similarity).
Is also a transcriptional activator of KISS1 (PubMed:35066646).
May act centrally to regulate function of both white and brown adipose tissue. Together with NHLH1, required to maintain migration and survival of cells in the anterior extramural migration stream (aes), which forms the precerebellar nuclei. Also, in concert with NHLH1, may determine fate of gonadotropin releasing hormone-1 (GnRH-1) neurons

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentchromatin
Cellular Componentnucleus
Cellular Componenttranscription regulator complex
Molecular FunctionDNA-binding transcription activator activity, RNA polymerase II-specific
Molecular FunctionDNA-binding transcription factor activity, RNA polymerase II-specific
Molecular Functionprotein dimerization activity
Molecular FunctionRNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular FunctionRNA polymerase II-specific DNA-binding transcription factor binding
Molecular Functionsequence-specific double-stranded DNA binding
Biological Processapoptotic process
Biological Processcell migration in hindbrain
Biological Processcentral nervous system development
Biological Processhypothalamus gonadotrophin-releasing hormone neuron development
Biological Processmale gonad development
Biological Processmale mating behavior
Biological Processovulation cycle
Biological Processperipheral nervous system development
Biological Processpositive regulation of DNA-binding transcription factor activity
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processregulation of transcription by RNA polymerase II

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Helix-loop-helix protein 2
  • Short names
    HEN-2
  • Alternative names
    • Class A basic helix-loop-helix protein 34 (bHLHa34)
    • Nescient helix loop helix 2 (NSCL-2)

Gene names

    • Name
      NHLH2
    • Synonyms
      BHLHA34, HEN2, KIAA0490

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q02577
  • Secondary accessions
    • Q5T1P6

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Disease & Variants

Involvement in disease

Hypogonadotropic hypogonadism 27 without anosmia (HH27)

  • Note
    • The disease may be caused by variants affecting the gene represented in this entry
  • Description
    A form of hypogonadotropic hypogonadism, a group of disorders characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone, and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). HH27 is an autosomal recessive normosmic form characterized by lack of pubertal development associated with onset of obesity in early adolescence.
  • See also
    MIM:619755
Natural variants in HH27
Variant IDPosition(s)ChangeDescription
VAR_08693531V>Min HH27; uncertain significance; the patient also carries KISS1 and PROKR2 variants
VAR_08693679R>Cin HH27; uncertain significance; severely reduced binding to MC4R promoter; reduced transactivation activity on KISS1 promoter

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variantVAR_0869349found in a patient with features of hypogonadotropic hypogonadism and Kabuki syndrome also carrying a KMT2D variant; uncertain significance; reduced transactivation activity on KISS1 promoter; requires 2 nucleotide substitutions
Natural variantVAR_08693531in HH27; uncertain significance; the patient also carries KISS1 and PROKR2 variants
Natural variantVAR_08693679in HH27; uncertain significance; severely reduced binding to MC4R promoter; reduced transactivation activity on KISS1 promoter

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 175 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00001271991-135Helix-loop-helix protein 2

Proteomic databases

PTM databases

Expression

Gene expression databases

Organism-specific databases

Interaction

Subunit

Homodimer. Interacts and may form heterodimers with STAT3.

Binary interactions

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, compositional bias, domain.

TypeIDPosition(s)Description
Region1-80Disordered
Compositional bias9-23Polar residues
Domain77-129bHLH

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    135
  • Mass (Da)
    15,018
  • Last updated
    1993-07-01 v1
  • Checksum
    083730499F610AAE
MMLSPDQAADSDHPSSAHSDPESLGGTDTKVLGSVSDLEPVEEAEGDGKGGSRAALYPHPQQLSREEKRRRRRATAKYRSAHATRERIRVEAFNLAFAELRKLLPTLPPDKKLSKIEILRLAICYISYLNHVLDV

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A6PVY9A6PVY9_HUMANNHLH2107

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias9-23Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M97508
EMBL· GenBank· DDBJ
AAA58635.1
EMBL· GenBank· DDBJ
Genomic DNA
AB007959
EMBL· GenBank· DDBJ
-mRNA No translation available.
AL449264
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC096359
EMBL· GenBank· DDBJ
AAH96359.1
EMBL· GenBank· DDBJ
mRNA
BC096360
EMBL· GenBank· DDBJ
AAH96360.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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