HERC1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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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; OMA: HERC1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Probable E3 ubiquitin-protein ligase HERC1 is an enzyme that in humans is encoded by the HERC1 gene. [5] [6] [7]
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, [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]
The 2022 version of this article was updated by an external expert under a dual publication model. The corresponding
academic peer reviewed article was published in Gene and can be cited as: Robert Lalonde; Catherine Strazielle (10 March 2022). "The Herc1 gene in neurobiology". Gene. Gene Wiki Review Series. 814. doi: 10.1016/J.GENE.2021.146144. ISSN 0378-1119. PMID 34990797. Wikidata Q110874820. |
HERC1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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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; OMA: HERC1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Probable E3 ubiquitin-protein ligase HERC1 is an enzyme that in humans is encoded by the HERC1 gene. [5] [6] [7]
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, [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]
The 2022 version of this article was updated by an external expert under a dual publication model. The corresponding
academic peer reviewed article was published in Gene and can be cited as: Robert Lalonde; Catherine Strazielle (10 March 2022). "The Herc1 gene in neurobiology". Gene. Gene Wiki Review Series. 814. doi: 10.1016/J.GENE.2021.146144. ISSN 0378-1119. PMID 34990797. Wikidata Q110874820. |