Q02577 · HEN2_HUMAN
- ProteinHelix-loop-helix protein 2
- GeneNHLH2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids135 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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
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 annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameHelix-loop-helix protein 2
- Short namesHEN-2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ02577
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Hypogonadotropic hypogonadism 27 without anosmia (HH27)
- Note
- DescriptionA 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 alsoMIM:619755
Natural variants in HH27
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_086935 | 31 | V>M | in HH27; uncertain significance; the patient also carries KISS1 and PROKR2 variants | |
VAR_086936 | 79 | R>C | in HH27; uncertain significance; severely reduced binding to MC4R promoter; reduced transactivation activity on KISS1 promoter |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_086934 | 9 | found 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 | |||
Sequence: A → L | ||||||
Natural variant | VAR_086935 | 31 | in HH27; uncertain significance; the patient also carries KISS1 and PROKR2 variants | |||
Sequence: V → M | ||||||
Natural variant | VAR_086936 | 79 | in HH27; uncertain significance; severely reduced binding to MC4R promoter; reduced transactivation activity on KISS1 promoter | |||
Sequence: R → C |
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.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000127199 | 1-135 | Helix-loop-helix protein 2 | |||
Sequence: MMLSPDQAADSDHPSSAHSDPESLGGTDTKVLGSVSDLEPVEEAEGDGKGGSRAALYPHPQQLSREEKRRRRRATAKYRSAHATRERIRVEAFNLAFAELRKLLPTLPPDKKLSKIEILRLAICYISYLNHVLDV |
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Homodimer. Interacts and may form heterodimers with STAT3.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q02577 | KCNIP1 Q9NZI2-2 | 3 | EBI-5378683, EBI-22452746 | |
BINARY | Q02577 | MYF5 P13349 | 3 | EBI-5378683, EBI-17491620 | |
BINARY | Q02577 | SIRT1 Q96EB6 | 2 | EBI-5378683, EBI-1802965 | |
BINARY | Q02577 | TAF1D Q9H5J8 | 3 | EBI-5378683, EBI-716128 | |
BINARY | Q02577 | TCF12 Q99081-3 | 3 | EBI-5378683, EBI-11952764 | |
BINARY | Q02577 | TCF4 P15884-3 | 3 | EBI-5378683, EBI-13636688 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-80 | Disordered | ||||
Sequence: MMLSPDQAADSDHPSSAHSDPESLGGTDTKVLGSVSDLEPVEEAEGDGKGGSRAALYPHPQQLSREEKRRRRRATAKYRS | ||||||
Compositional bias | 9-23 | Polar residues | ||||
Sequence: ADSDHPSSAHSDPES | ||||||
Domain | 77-129 | bHLH | ||||
Sequence: KYRSAHATRERIRVEAFNLAFAELRKLLPTLPPDKKLSKIEILRLAICYISYL |
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length135
- Mass (Da)15,018
- Last updated1993-07-01 v1
- Checksum083730499F610AAE
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A6PVY9 | A6PVY9_HUMAN | NHLH2 | 107 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 9-23 | Polar residues | ||||
Sequence: ADSDHPSSAHSDPES |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |