HERC1

Protein-coding gene in the species Homo sapiens

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; OMA:HERC1 - orthologs

Gene location (Human)

Chr.	Chromosome 15 (human)^[1]

Band	15q22.31	Start	63,608,618 bp^[1]
Band	15q22.31	End	63,833,948 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 9 (mouse)^[2]

Band	9\|9 C	Start	66,257,732 bp^[2]
Band	9\|9 C	End	66,416,057 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

middle temporal gyrus

Brodmann area 23

ganglionic eminence

right hemisphere of cerebellum

primary visual cortex

prefrontal cortex

Achilles tendon

Skeletal muscle tissue of biceps brachii

muscle of thigh

right frontal lobe

Top expressed in

perirhinal cortex

CA3 field

cingulate gyrus

entorhinal cortex

medial dorsal nucleus

primary motor cortex

cerebellar vermis

medullary collecting duct

lobe of cerebellum

habenula

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

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]

Notes

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.

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000103657 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000038664 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Rosa JL, Casaroli-Marano RP, Buckler AJ, Vilaro S, Barbacid M (Dec 1996). "p619, a giant protein related to the chromosome condensation regulator RCC1, stimulates guanine nucleotide exchange on ARF1 and Rab proteins". EMBO J. 15 (16): 4262–73. doi:10.1002/j.1460-2075.1996.tb00801.x. PMC 452152. PMID 8861955.
^ Rosa JL, Barbacid M (Aug 1997). "A giant protein that stimulates guanine nucleotide exchange on ARF1 and Rab proteins forms a cytosolic ternary complex with clathrin and Hsp70". Oncogene. 15 (1): 1–6. doi:10.1038/sj.onc.1201170. PMID 9233772.
^ ^a ^b "Entrez Gene: HERC1 hect (homologous to the E6-AP (UBE3A) carboxyl terminus) domain and RCC1 (CHC1)-like domain (RLD) 1".
^ ^a ^b Wassef M, Sotelo C, Cholley B, Brehier A, Thomasset M (Dec 1996). "Cerebellar mutations affecting the postnatal survival of Purkinje cells in the mouse disclose a longitudinal pattern of differentially sensitive cells". Dev Biol. 124 (2): 379–89. doi:10.1016/0012-1606(87)90490-8. PMID 3678603.
^ ^a ^b ^c ^d Mashimo T, Hadjebi O, Amair-Pinedo F, Tsurumi T, Langa F, Serikawa T, Sotelo C, Guénet JL, Rosa JL (2009). "Progressive Purkinje cell degeneration in tambaleante mutant mice is a consequence of a missense mutation in HERC1 E3 ubiquitin ligase". PLOS Genet. 5 (2): e1000784. doi:10.1371/journal.pgen.1000784. PMC 2791161. PMID 20041218.
^ Pérez-Villegas EM, Pérez-Rodríguez M, Negrete-Díaz JV, Ruiz R, Rosa JL, de Toledo GA, Rodríguez-Moreno A, Armengol JA (2020). "HERC1 Ubiquitin ligase is required for hippocampal learning and memory". Front Neuroanat. 14: 592797. doi:10.3389/fnana.2020.592797. PMC 7710975. PMID 33328904.
^ Lalonde R, Strazielle C (2011). "Brain regions and genes affecting limb-clasping responses". Brain Res Rev. 67 (1–2): 252–9. doi:10.1016/j.brainresrev.2011.02.005. PMID 21356243. S2CID 206345554.
^ ^a ^b Bachiller S, Rybkina T, Porras-García E, Pérez-Villegas E, Tabares L, Armengol JA, Carrión AM, Ruiz R (2015). "The HERC1 E3 Ubiquitin Ligase is essential for normal development and for neurotransmission at the mouse neuromuscular junction". Life Sci. 72 (15): 2961–71. doi:10.1007/s00018-015-1878-2. PMC 11113414. PMID 25746226. S2CID 1976227.
^ ^a ^b Fuca E, Guglielmotto M, Boda E, Rossi F, Leto K, Buffo A (2017). "Preventive motor training but not progenitor grafting ameliorates cerebellar ataxia and deregulated autophagy in tambaleante mice". Neurobiol Dis. 102: 49–59. doi:10.1016/j.nbd.2017.02.005. PMC 452152. PMID 28237314.
^ ^a ^b Porras-Garcia ME, Ruiz R, Pérez-Villegas EM, Armengol JÁ (2013). "Motor learning of mice lacking cerebellar Purkinje cells". Front Neuroanat. 7: 4. doi:10.3389/fnana.2013.00004. PMC 452152. PMID 23630472.
^ Ortega-Recalde O, Beltrán OI, Gálvez JM, Palma-Montero A, Restrepo CM, Mateus HE, Laissue P (2015). "Biallelic HERC1 mutations in a syndromic form of overgrowth and intellectual disability". Clin Genet. 88 (4): e1-3. doi:10.1111/cge.12634. PMID 26138117. S2CID 5725254.
^ Nguyen LS, Schneider T, Rio M, Moutton S, Siquier-Pernet K, Verny F, Boddaert N, Desguerre I, Munich A, Rosa JL, Cormier-Daire V, Colleaux L (2016). "A nonsense variant in HERC1 is associated with intellectual disability, megalencephaly, thick corpus callosum and cerebellar atrophy". Eur J Hum Genet. 24 (3): 455–8. doi:10.1038/ejhg.2015.140. PMC 4755376. PMID 26153217.
^ Aggarwal S, Bhowmik AD, Ramprasad, VL, Murugan S, Dalal A (2016). "A splice site mutation in HERC1 leads to syndromic intellectual disability with macrocephaly and facial dysmorphism: Further delineation of the phenotypic spectrum". Am J Med Genet A. 15 (16): 4262–73. doi:10.1002/ajmg.a.37654. PMID 27108999. S2CID 44849688.
^ Utine GE, Taşkıran EZ, Koşukcu C, Karaosmanoğlu B, Güleray N, Doğan ÖA, Kiper PÖ, Boduroğlu K, Alikaşifoğlu M (2017). "HERC1 mutations in idiopathic intellectual disability". Eur J Med Genet. 60 (5): 279–83. doi:10.1016/j.ejmg.2017.03.007. PMID 28323226.