Otoferlin

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OTOF
Identifiers
AliasesOTOF, AUNB1, DFNB6, DFNB9, FER1L2, NSRD9, otoferlin
External IDsMGI: 1891247 HomoloGene: 12892 GeneCards: OTOF
Gene location (Human)
Chromosome 2 (human)
Chr.Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for OTOF
Genomic location for OTOF
Band2p23.3Start26,457,203 bp[1]
End26,558,698 bp[1]
RNA expression pattern
PBB GE OTOF 220492 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001287489
NM_004802
NM_194248
NM_194322
NM_194323

NM_001100395
NM_001286421
NM_031875
NM_001313767

RefSeq (protein)

NP_001274418
NP_004793
NP_919224
NP_919303
NP_919304

NP_001093865
NP_001273350
NP_001300696
NP_114081

Location (UCSC)Chr 2: 26.46 – 26.56 MbChr 5: 30.37 – 30.46 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Otoferlin is a protein that in humans is encoded by the OTOF gene.[5][6][7]

Function[edit]

Mutations in this gene are a cause of neurosensory nonsyndromic recessive deafness, DFNB9. The short form of the encoded protein has three C2 domains, a single carboxy-terminal transmembrane domain found also in the C. elegans spermatogenesis factor FER-1 and human dysferlin, while the long form has six C2 domains. Otoferlin homologous proteins in humans that have been shown to be associated with human diseases are dysferlin and myoferlin. Both dysferlin and myoferlin have seven C2 domains. C2A in otoferlin's longer form with six C2 domains is structurally similar to dysferlin C2A. However, the loop 1 in calcium binding site of otoferlin C2A is significantly shorter than the homologous loop in dysferlin and myoferlin C2A domains. Therefore, it is unable to bind to calcium. Otoferlin C2A is also unable to bind to phospholipids and hence it is structurally and functionally different from other C2 domains.[8] The homology suggests that this protein may be involved in vesicle membrane fusion. Similar to dysferlin and myoferlin, otoferlin has a FerA domain and its FerA domain has been shown to interact with zwitterionic lipids in a calcium-dependent manner and with negatively charged lipids in a calcium-independent manner.[9] The estimated charge of FerA domain among ferlin proteins varies significantly. At pH 7, the estimated charge of dysferlin is -8.4 while otoferlin FerA is +8.5.[9] Several transcript variants encoding multiple isoforms have been found for this gene.[7]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115155 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000062372 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Yasunaga S, Grati M, Cohen-Salmon M, El-Amraoui A, Mustapha M, Salem N, El-Zir E, Loiselet J, Petit C (April 1999). "A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness". Nature Genetics. 21 (4): 363–9. doi:10.1038/7693. PMC 305826. PMID 10192385.
  6. ^ Rodríguez-Ballesteros M, Reynoso R, Olarte M, Villamar M, Morera C, Santarelli R, Arslan E, Medá C, Curet C, Völter C, Sainz-Quevedo M, Castorina P, Ambrosetti U, Berrettini S, Frei K, Tedín S, Smith J, Cruz Tapia M, Cavallé L, Gelvez N, Primignani P, Gómez-Rosas E, Martín M, Moreno-Pelayo MA, Tamayo M, Moreno-Barral J, Moreno F, del Castillo I (June 2008). "A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy". Human Mutation. 29 (6): 823–31. doi:10.1002/humu.20708. PMID 18381613.
  7. ^ a b "Entrez Gene: OTOF otoferlin".
  8. ^ Helfmann S, Neumann P, Tittmann K, Moser T, Ficner R, Reisinger E (February 2011). "The crystal structure of the C₂A domain of otoferlin reveals an unconventional top loop region". Journal of Molecular Biology. 406 (3): 479–90. doi:10.1016/j.jmb.2010.12.031. PMID 21216247.
  9. ^ a b Harsini FM, Chebrolu S, Fuson KL, White MA, Rice AM, Sutton RB (July 2018). "FerA is a Membrane-Associating Four-Helix Bundle Domain in the Ferlin Family of Membrane-Fusion Proteins". Scientific Reports. 8 (1): 10949. doi:10.1038/s41598-018-29184-1. PMID 30026467.

External links[edit]

Further reading[edit]