Recombinant Human Otoferlin (OTOF), partial

Function

Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion and in the control of neurotransmitter release at these output synapses. Interacts in a calcium-dependent manner to the presynaptic SNARE proteins at ribbon synapses of cochlear inner hair cells (IHCs) to trigger exocytosis of neurotransmitter. Also essential to synaptic exocytosis in immature outer hair cells (OHCs). May also play a role within the recycling of endosomes (By similarity)

Subcellular Location

Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane (Single-pass type IV membrane protein); Basolateral cell membrane (Single-pass type IV membrane protein); Endoplasmic reticulum membrane (Single-pass type IV membrane protein); Golgi apparatus membrane (Single-pass type IV membrane protein); Presynaptic cell membrane (Single-pass type IV membrane protein); Cell membrane (Single-pass type IV membrane protein); Golgi apparatus, trans-Golgi network

Disease Association

Deafness, autosomal recessive, 9 (DFNB9) : A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. [The disease is caused by variants affecting the gene represented in this entry] | Auditory neuropathy, autosomal recessive, 1 (AUNB1) : A form of sensorineural hearing loss with absent or severely abnormal auditory brainstem response, in the presence of normal cochlear outer hair cell function and normal otoacoustic emissions. Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem. In some cases AUNB1 phenotype can be temperature sensitive. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Isoform 1 and isoform 3 are found in adult brain. Isoform 2 is expressed in the fetus and in adult brain, heart, placenta, skeletal muscle and kidney

Subunit

Interacts with SNAP2; the interaction is direct. Interacts with STX1; the interaction is direct. Interacts with RAB8B (By similarity)

• Yasunaga S. et al. A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. — Nat. Genet. (1999)
• Yasunaga S. et al. OTOF encodes multiple long and short isoforms: genetic evidence that the long ones underlie recessive deafness DFNB9. — Am. J. Hum. Genet. (2000)
• Hillier L.W. et al. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. — Nature (2005)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Redpath G.M. et al. Ferlins Show Tissue-Specific Expression and Segregate as Plasma Membrane/Late Endosomal or Trans-Golgi/Recycling Ferlins. — Traffic (2016)
• Migliosi V. et al. Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss. — J. Med. Genet. (2002)
• Mirghomizadeh F. et al. Substitutions in the conserved C2C domain of otoferlin cause DFNB9, a form of nonsyndromic autosomal recessive deafness. — Neurobiol. Dis. (2002)