HERC1

Probable E3 ubiquitin-protein ligase HERC1 is an enzyme that in humans is encoded by the HERC1 gene.[5][6][7]

HERC1
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 4O2W, 4QT6
Identifiers
Aliases	HERC1, p532, p619, HECT and RLD domain containing E3 ubiquitin protein ligase family member 1, MDFPMR
External IDs	OMIM: 605109 MGI: 2384589 HomoloGene: 31207 GeneCards: HERC1
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q22.31 Start 63,608,618 bp[1] End 63,833,948 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 C Start 66,257,732 bp[2] End 66,416,057 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in middle temporal gyrus Brodmann area 23 ganglionic eminence prefrontal cortex Achilles tendon Brodmann area 9 cancellous bone sural nerve gastrocnemius muscle superior frontal gyrus Top expressed in cingulate gyrus entorhinal cortex medial dorsal nucleus primary motor cortex cerebellar vermis medullary collecting duct habenula superior colliculus inferior colliculus renal corpuscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function ubiquitin-protein transferase activity guanyl-nucleotide exchange factor activity transferase activity Cellular component cytoplasm cytosol Golgi apparatus membrane Biological process cerebellar Purkinje cell differentiation negative regulation of autophagy neuron projection development protein ubiquitination neuromuscular process controlling balance Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8925 235439 Ensembl ENSG00000103657 ENSMUSG00000038664 UniProt Q15751 n/a RefSeq (mRNA) NM_003922 NM_145617 RefSeq (protein) NP_003913 n/a Location (UCSC) Chr 15: 63.61 – 63.83 Mb Chr 9: 66.26 – 66.42 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The protein encoded by this gene stimulates guanine nucleotide exchange on ARF1 and Rab proteins. This protein is thought to be involved in membrane transport processes[7]

Knowledge of the gene is facilitated by the discovery of a mouse mutation. The tambaleante (tbl) mutation arose spontaneously on the DW/J-Pas genetic background,[8] a recessive mutation of the Herc1 gene located on mouse chromosome 9 that increases Herc1 protein levels.[9] This protein is largely expressed in many tissues (Sanchez-Tena et al., 2016; https://www.proteinatlas.org/ENSG00000103657-HERC1/tissue) and multiple brain regions including the cerebellum (https://www.proteinatlas.org/ENSG00000103657-HERC1/brain).

Herc1-tbl (tambaleante) mutant mice are characterized by Purkinje cell loss.[8] In addition to the cerebellum, Herc1tbl mutants had lower dendritic spine widths in CA1 pyramidal neurons.[10] Herc1-tbl mutant mice are also characterized by cerebellar ataxia, an unstable gait, and a limb-flexion reflex triggered by tail lifting[9] seen in other cerebellar mutants, the reverse of the normal limb extensor reflex.[11]

Relative to wild-type mice, Herc1-tbl mutant mice fell sooner and more often from a rotarod,[12][13] fell sooner from a vertical pole,[14][9] slipped more often and took more time to reach the end of a stationary beam</ref>,[13] and had weaker forelimb grip strength measured by a grip strength meter.[12] The rotarod deficit was rescued when Herc1tbl mutants were bred with transgenic mice expressing normal human HERC1.[9] Herc1tbl mutants were also less adept at landing correctly on all four legs when released in the air.[14]

Biallelic HERC1 mutations were reported in two siblings with facial dysmorphism, macrocephaly, motor development delay, ataxic gait, hypotonia, and intellectual disability.[15] Likewise, a nonsense HERC1 variant was reported in one subject with an autosomal recessive condition consisting of facial dysmorphism, macrocephaly, epilepsy, motor development delay, cerebellar atrophy, and intellectual disability.[16] Facial dysmorphism, macrocephaly, and intellectual disability but without cerebellar ataxia were also reported in two siblings with a HERC1 splice variant mutation.[17] The lack of cerebellar involvement was ascribed either to the nature of the mutation or the influence of modifier genes. Another patient with a frameshift HERC1 mutation predicted to truncate the protein displayed facial dysmorphism, macrocephaly, epileptiform discharges, hypotonia, intellectual disability, and autistic features.[18]