PJVK_MOUSE
ID PJVK_MOUSE Reviewed; 352 AA.
AC Q0ZLH2;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 22-AUG-2006, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Pejvakin {ECO:0000303|PubMed:16804542};
DE AltName: Full=Protein sirtaki {ECO:0000303|PubMed:17329413};
GN Name=Pjvk {ECO:0000303|PubMed:16804542, ECO:0000312|MGI:MGI:2685847};
GN Synonyms=Dfnb59 {ECO:0000303|PubMed:16804542},
GN Gm1001 {ECO:0000312|MGI:MGI:2685847};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND MUTAGENESIS OF ARG-183.
RX PubMed=16804542; DOI=10.1038/ng1829;
RA Delmaghani S., Del Castillo F.J., Michel V., Leibovici M., Aghaie A.,
RA Ron U., Van Laer L., Ben-Tal N., Van Camp G., Weil D., Langa F.,
RA Lathrop M., Avan P., Petit C.;
RT "Mutations in the gene encoding pejvakin, a newly identified protein of the
RT afferent auditory pathway, cause DFNB59 auditory neuropathy.";
RL Nat. Genet. 38:770-778(2006).
RN [2]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=17329413; DOI=10.1523/jneurosci.4975-06.2007;
RA Schwander M., Sczaniecka A., Grillet N., Bailey J.S., Avenarius M.,
RA Najmabadi H., Steffy B.M., Federe G.C., Lagler E.A., Banan R., Hice R.,
RA Grabowski-Boase L., Keithley E.M., Ryan A.F., Housley G.D., Wiltshire T.,
RA Smith R.J., Tarantino L.M., Mueller U.;
RT "A forward genetics screen in mice identifies recessive deafness traits and
RT reveals that pejvakin is essential for outer hair cell function.";
RL J. Neurosci. 27:2163-2175(2007).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=26544938; DOI=10.1016/j.cell.2015.10.023;
RA Delmaghani S., Defourny J., Aghaie A., Beurg M., Dulon D., Thelen N.,
RA Perfettini I., Zelles T., Aller M., Meyer A., Emptoz A., Giraudet F.,
RA Leibovici M., Dartevelle S., Soubigou G., Thiry M., Vizi E.S.,
RA Safieddine S., Hardelin J.P., Avan P., Petit C.;
RT "Hypervulnerability to sound exposure through impaired adaptive
RT proliferation of peroxisomes.";
RL Cell 163:894-906(2015).
RN [4]
RP SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND INTERACTION WITH TRIOBP.
RX PubMed=28209736; DOI=10.1523/jneurosci.2711-16.2017;
RA Kazmierczak M., Kazmierczak P., Peng A.W., Harris S.L., Shah P., Puel J.L.,
RA Lenoir M., Franco S.J., Schwander M.;
RT "Pejvakin, a candidate stereociliary rootlet protein, regulates hair cell
RT function in a cell-autonomous manner.";
RL J. Neurosci. 37:3447-3464(2017).
RN [5]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND INTERACTION WITH IQGAP1 AND
RP ROCK2.
RX PubMed=28089576; DOI=10.1016/j.neuroscience.2016.12.055;
RA Harris S.L., Kazmierczak M., Pangrsic T., Shah P., Chuchvara N.,
RA Barrantes-Freer A., Moser T., Schwander M.;
RT "Conditional deletion of pejvakin in adult outer hair cells causes
RT progressive hearing loss in mice.";
RL Neuroscience 344:380-393(2017).
RN [6]
RP FUNCTION, INTERACTION WITH MAP1LC3B, AND MUTAGENESIS OF CYS-309; CYS-312;
RP CYS-325; CYS-328 AND CYS-343.
RX PubMed=30936319; DOI=10.1073/pnas.1821844116;
RA Defourny J., Aghaie A., Perfettini I., Avan P., Delmaghani S., Petit C.;
RT "Pejvakin-mediated pexophagy protects auditory hair cells against noise-
RT induced damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:8010-8017(2019).
CC -!- FUNCTION: Peroxisome-associated protein required to protect auditory
CC hair cells against noise-induced damage (PubMed:26544938,
CC PubMed:30936319). Acts by regulating noise-induced peroxisome
CC proliferation in auditory hair cells and neurons, and promoting
CC autophagic degradation of damaged peroxisomes (pexophagy)
CC (PubMed:26544938, PubMed:30936319). Noise overexposure increases
CC reactive oxygen species (ROS) levels, causing oxidative damage to
CC auditory hair cells and resulting in hearing loss (PubMed:30936319).
CC PJVK acts as a ROS sensor that recruits the autophagy machinery to
CC trigger pexophagy of peroxisomes damaged by oxidative stress
CC (PubMed:30936319). In addition to pexophagy, also required to promote
CC peroxisome proliferation in response to sound overstimulation
CC (PubMed:26544938, PubMed:30936319). {ECO:0000269|PubMed:26544938,
CC ECO:0000269|PubMed:30936319}.
CC -!- SUBUNIT: Interacts with MAP1LC3B; interaction is direct
CC (PubMed:30936319). Interacts with IQGAP1 (PubMed:28089576). Interacts
CC with ROCK2 (PubMed:28089576). Interacts with TRIOBP (PubMed:28209736).
CC {ECO:0000269|PubMed:28089576, ECO:0000269|PubMed:28209736,
CC ECO:0000269|PubMed:30936319}.
CC -!- SUBCELLULAR LOCATION: Peroxisome membrane
CC {ECO:0000269|PubMed:26544938}. Cell projection, cilium
CC {ECO:0000269|PubMed:28209736}. Note=Associates with the peroxisomal
CC membrane; it is unclear whether it is embedded or just associated with
CC the peroxisomal membrane (PubMed:26544938). Localizes to ciliary
CC rootlet (PubMed:28209736). {ECO:0000269|PubMed:26544938,
CC ECO:0000269|PubMed:28209736}.
CC -!- TISSUE SPECIFICITY: In ear, it is detected in the organ of Corti and
CC the spiral ganglion within the cochlea in the sensory areas of the
CC vestibule (cristae ampullares of the semicircular ducts, and maculae of
CC the saccule and utricle) and in the first 3 relays (cochlear nuclei,
CC superior olivary complex and inferior colliculus) of the afferent
CC auditory pathway (PubMed:16804542). Detected in hair cells of the
CC cochlea and vestibule but not in neurons (PubMed:17329413,
CC PubMed:28089576). In the afferent auditory pathway, it is present in
CC the cell bodies of neurons but not in fiber bundles such as the
CC trapezoid body in the brainstem (PubMed:16804542). Also detected in
CC spiral ganglion cells, which form the auditory nerve and project to the
CC cochlear nuclei in the brainstem (PubMed:16804542). Also present in the
CC cochlear nuclei, the superior olive and the inferior colliculus (at
CC protein level) (PubMed:16804542). Expressed in all the adult organs
CC tested: brain, eye, inner ear, heart, lung, kidney, liver, intestine,
CC testis and weakly in skeletal muscle (PubMed:16804542).
CC {ECO:0000269|PubMed:16804542, ECO:0000269|PubMed:17329413,
CC ECO:0000269|PubMed:28089576}.
CC -!- INDUCTION: By noise exposure. {ECO:0000269|PubMed:26544938}.
CC -!- DISRUPTION PHENOTYPE: Mice display progressive hearing loss caused by
CC hypervulnerability to sound exposure (PubMed:17329413,
CC PubMed:26544938). Cochleas display features of marked oxidative stress
CC and impaired antioxidant defenses, and peroxisomes in hair cells show
CC structural abnormalities after the onset of hearing (PubMed:26544938).
CC Mice with conditional deletion in all sensory hair cells show auditory
CC phenotypes with early-onset profound hearing loss and outer hair cell
CC degeneration (PubMed:28089576, PubMed:28209736). Mice with conditional
CC deletion in outer hair cells show auditory phenotypes with early-onset
CC profound hearing loss (PubMed:28089576). Conditional deletion in adult
CC outer hair cells causes a slowly progressive hearing loss associated
CC with outer hair cells degeneration and delayed loss of inner hair cells
CC (PubMed:28089576). {ECO:0000269|PubMed:17329413,
CC ECO:0000269|PubMed:26544938, ECO:0000269|PubMed:28089576,
CC ECO:0000269|PubMed:28209736}.
CC -!- SIMILARITY: Belongs to the gasdermin family. {ECO:0000305}.
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DR EMBL; DQ365828; ABC94895.1; -; mRNA.
DR CCDS; CCDS38153.1; -.
DR RefSeq; NP_001074180.1; NM_001080711.2.
DR AlphaFoldDB; Q0ZLH2; -.
DR STRING; 10090.ENSMUSP00000097566; -.
DR PhosphoSitePlus; Q0ZLH2; -.
DR PaxDb; Q0ZLH2; -.
DR PRIDE; Q0ZLH2; -.
DR Antibodypedia; 33935; 64 antibodies from 16 providers.
DR DNASU; 381375; -.
DR Ensembl; ENSMUST00000099986; ENSMUSP00000097566; ENSMUSG00000075267.
DR GeneID; 381375; -.
DR KEGG; mmu:381375; -.
DR UCSC; uc008kfg.2; mouse.
DR CTD; 494513; -.
DR MGI; MGI:2685847; Pjvk.
DR VEuPathDB; HostDB:ENSMUSG00000075267; -.
DR eggNOG; ENOG502QWBQ; Eukaryota.
DR GeneTree; ENSGT00950000183140; -.
DR InParanoid; Q0ZLH2; -.
DR OMA; RGNQIMN; -.
DR OrthoDB; 1397132at2759; -.
DR PhylomeDB; Q0ZLH2; -.
DR TreeFam; TF352821; -.
DR BioGRID-ORCS; 381375; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q0ZLH2; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q0ZLH2; protein.
DR Bgee; ENSMUSG00000075267; Expressed in proximal tubule and 30 other tissues.
DR ExpressionAtlas; Q0ZLH2; baseline and differential.
DR GO; GO:0035253; C:ciliary rootlet; IDA:MGI.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0005778; C:peroxisomal membrane; IDA:UniProtKB.
DR GO; GO:0120044; C:stereocilium base; IDA:MGI.
DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IMP:MGI.
DR GO; GO:0070997; P:neuron death; IMP:MGI.
DR GO; GO:0000425; P:pexophagy; IMP:UniProtKB.
DR GO; GO:0097468; P:programmed cell death in response to reactive oxygen species; IMP:UniProtKB.
DR GO; GO:1900063; P:regulation of peroxisome organization; IMP:UniProtKB.
DR GO; GO:0000302; P:response to reactive oxygen species; IMP:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR GO; GO:0120045; P:stereocilium maintenance; IMP:MGI.
DR InterPro; IPR007677; Gasdermin.
DR InterPro; IPR040460; Gasdermin_pore.
DR PANTHER; PTHR16399; PTHR16399; 1.
DR Pfam; PF04598; Gasdermin; 1.
PE 1: Evidence at protein level;
KW Cell projection; Hearing; Membrane; Peroxisome; Reference proteome.
FT CHAIN 1..352
FT /note="Pejvakin"
FT /id="PRO_0000249043"
FT MUTAGEN 183
FT /note="R->W: Induces abnormal auditory brainstem responses
FT indicative of neuronal dysfunction along the auditory
FT pathway."
FT /evidence="ECO:0000269|PubMed:16804542"
FT MUTAGEN 309
FT /note="C->S: Does not affect interaction with MAP1LC3B."
FT /evidence="ECO:0000269|PubMed:30936319"
FT MUTAGEN 312
FT /note="C->S: Does not affect interaction with MAP1LC3B."
FT /evidence="ECO:0000269|PubMed:30936319"
FT MUTAGEN 325
FT /note="C->S: Does not affect interaction with MAP1LC3B."
FT /evidence="ECO:0000269|PubMed:30936319"
FT MUTAGEN 328
FT /note="C->S: Abolished interaction with MAP1LC3B and
FT subsequent pexophagy."
FT /evidence="ECO:0000269|PubMed:30936319"
FT MUTAGEN 343
FT /note="C->S: Abolished interaction with MAP1LC3B and
FT subsequent pexophagy."
FT /evidence="ECO:0000269|PubMed:30936319"
SQ SEQUENCE 352 AA; 39858 MW; 394446045A5ECAA7 CRC64;
MFAAATKSFV KQVGDGGRLV PVPSLSEADK YQPLSLVVKK KRCFLFPRCK FTSTPFTLKD
ILLGDREISA GISSYQLLNY EDESDVSLYG RRSNHIVNDV GINVTGSDSI AVKASFGVVT
KHEVEVSTLL KEITARKINF DHSLIRQSRS SRKAVLCVVM ESIRTTRQCS LSVHAGIRGE
AMRFHFMDEQ NPKGREKAIV FPAHTTIAFS VFELFIYLDG AFDICVTSVS KGGFEREETT
TFAMFYRLRN ILFERNRRVM DAISRSQLYL DDLFSDFYDK PLSMTDISLK EGTHIRVNLL
NHNIPKGPCI LCGMGNLKRE TVYGCFQCSV DGVKYVRLHA VPCFDIWHKR MK
