PJVK_HUMAN
ID PJVK_HUMAN Reviewed; 352 AA.
AC Q0ZLH3; A0PK14; B9EJE2;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 22-AUG-2006, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Pejvakin {ECO:0000303|PubMed:16804542};
DE AltName: Full=Autosomal recessive deafness type 59 protein;
GN Name=PJVK {ECO:0000303|PubMed:16804542, ECO:0000312|HGNC:HGNC:29502};
GN Synonyms=DFNB59;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN DFNB59, AND VARIANTS DFNB59
RP ILE-54 AND TRP-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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INVOLVEMENT IN DFNB59.
RX PubMed=17301963; DOI=10.1002/humu.20478;
RA Ebermann I., Walger M., Scholl H.P., Charbel Issa P., Lueke C.,
RA Nuernberg G., Lang-Roth R., Becker C., Nuernberg P., Bolz H.J.;
RT "Truncating mutation of the DFNB59 gene causes cochlear hearing impairment
RT and central vestibular dysfunction.";
RL Hum. Mutat. 28:571-577(2007).
RN [4]
RP VARIANTS DFNB59 167-ARG--LYS-352 DEL; TRP-183 AND ARG-244, AND VARIANT
RP ARG-299.
RX PubMed=17373699; DOI=10.1002/humu.20510;
RA Collin R.W., Kalay E., Oostrik J., Caylan R., Wollnik B., Arslan S.,
RA den Hollander A.I., Birinci Y., Lichtner P., Strom T.M., Toraman B.,
RA Hoefsloot L.H., Cremers C.W., Brunner H.G., Cremers F.P., Karaguzel A.,
RA Kremer H.;
RT "Involvement of DFNB59 mutations in autosomal recessive nonsyndromic
RT hearing impairment.";
RL Hum. Mutat. 28:718-723(2007).
RN [5]
RP INVOLVEMENT IN DFNB59.
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 [6]
RP VARIANT DFNB59 SER-343.
RX PubMed=22617256; DOI=10.1016/j.gene.2012.05.013;
RA Mujtaba G., Bukhari I., Fatima A., Naz S.;
RT "A p.C343S missense mutation in PJVK causes progressive hearing loss.";
RL Gene 504:98-101(2012).
RN [7]
RP INVOLVEMENT IN DFNB59.
RX PubMed=25631766; DOI=10.3109/00016489.2014.985799;
RA Zhang Q.J., Lan L., Li N., Qi Y., Zong L., Shi W., Yu L., Wang H., Yang J.,
RA Xie L.Y., Zhao F., Wang D.Y., Han B., Wang Q.J.;
RT "Identification of a novel mutation of PJVK in the Chinese non-syndromic
RT hearing loss population with low prevalence of the PJVK mutations.";
RL Acta Oto-Laryngol. 135:211-216(2015).
RN [8]
RP CHARACTERIZATION OF VARIANT DFNB59 ILE-54.
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).
CC -!- FUNCTION: Peroxisome-associated protein required to protect auditory
CC hair cells against noise-induced damage. Acts by regulating noise-
CC induced peroxisome proliferation in auditory hair cells and neurons,
CC and promoting autophagic degradation of damaged peroxisomes
CC (pexophagy). Noise overexposure increases reactive oxygen species (ROS)
CC levels, causing oxidative damage to auditory hair cells and resulting
CC in hearing loss. PJVK acts as a ROS sensor that recruits the autophagy
CC machinery to trigger pexophagy of peroxisomes damaged by oxidative
CC stress. In addition to pexophagy, also required to promote peroxisome
CC proliferation in response to sound overstimulation.
CC {ECO:0000250|UniProtKB:Q0ZLH2}.
CC -!- SUBUNIT: Interacts with MAP1LC3B; interaction is direct. Interacts with
CC IQGAP1. Interacts with ROCK2. Interacts with TRIOBP.
CC {ECO:0000250|UniProtKB:Q0ZLH2}.
CC -!- SUBCELLULAR LOCATION: Peroxisome membrane
CC {ECO:0000250|UniProtKB:Q0ZLH2}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q0ZLH2}. Note=Associates with the peroxisomal
CC membrane; it is unclear whether it is embedded or just associated with
CC the peroxisomal membrane. Localizes to ciliary rootlet.
CC {ECO:0000250|UniProtKB:Q0ZLH2}.
CC -!- DISEASE: Deafness, autosomal recessive, 59 (DFNB59) [MIM:610220]: A
CC form of sensorineural hearing impairment with absent or severely
CC abnormal auditory brainstem response but normal otoacoustic emissions
CC (auditory neuropathy or auditory dys-synchrony). Auditory neuropathies
CC result from a lesion in the area including the inner hair cells,
CC connections between the inner hair cells and the cochlear branch of the
CC auditory nerve, the auditory nerve itself and auditory pathways of the
CC brainstem. {ECO:0000269|PubMed:16804542, ECO:0000269|PubMed:17301963,
CC ECO:0000269|PubMed:17329413, ECO:0000269|PubMed:17373699,
CC ECO:0000269|PubMed:22617256, ECO:0000269|PubMed:25631766,
CC ECO:0000269|PubMed:26544938}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: 'Pejvakin' means 'echo' in Persian.
CC {ECO:0000305|PubMed:16804542}.
CC -!- SIMILARITY: Belongs to the gasdermin family. {ECO:0000305}.
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DR EMBL; DQ365827; ABC94894.1; -; mRNA.
DR EMBL; BC127902; AAI27903.1; -; mRNA.
DR EMBL; BC146938; AAI46939.1; -; mRNA.
DR CCDS; CCDS42787.1; -.
DR RefSeq; NP_001036167.1; NM_001042702.3.
DR AlphaFoldDB; Q0ZLH3; -.
DR BioGRID; 138969; 1.
DR STRING; 9606.ENSP00000386647; -.
DR TCDB; 1.C.123.1.7; the pore-forming gasdermin (gasdermin) family.
DR iPTMnet; Q0ZLH3; -.
DR PhosphoSitePlus; Q0ZLH3; -.
DR BioMuta; PJVK; -.
DR DMDM; 114152117; -.
DR EPD; Q0ZLH3; -.
DR MassIVE; Q0ZLH3; -.
DR PaxDb; Q0ZLH3; -.
DR PeptideAtlas; Q0ZLH3; -.
DR PRIDE; Q0ZLH3; -.
DR Antibodypedia; 33935; 64 antibodies from 16 providers.
DR DNASU; 494513; -.
DR Ensembl; ENST00000375129.8; ENSP00000364271.4; ENSG00000204311.15.
DR Ensembl; ENST00000644580.2; ENSP00000495855.2; ENSG00000204311.15.
DR GeneID; 494513; -.
DR KEGG; hsa:494513; -.
DR MANE-Select; ENST00000644580.2; ENSP00000495855.2; NM_001042702.5; NP_001036167.1.
DR UCSC; uc002umi.5; human.
DR CTD; 494513; -.
DR DisGeNET; 494513; -.
DR GeneCards; PJVK; -.
DR GeneReviews; PJVK; -.
DR HGNC; HGNC:29502; PJVK.
DR HPA; ENSG00000204311; Tissue enhanced (testis).
DR MalaCards; PJVK; -.
DR MIM; 610219; gene.
DR MIM; 610220; phenotype.
DR neXtProt; NX_Q0ZLH3; -.
DR OpenTargets; ENSG00000204311; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR PharmGKB; PA134927047; -.
DR VEuPathDB; HostDB:ENSG00000204311; -.
DR eggNOG; ENOG502QWBQ; Eukaryota.
DR GeneTree; ENSGT00950000183140; -.
DR HOGENOM; CLU_068267_0_0_1; -.
DR InParanoid; Q0ZLH3; -.
DR OMA; RGNQIMN; -.
DR OrthoDB; 1397132at2759; -.
DR PhylomeDB; Q0ZLH3; -.
DR TreeFam; TF352821; -.
DR PathwayCommons; Q0ZLH3; -.
DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR Reactome; R-HSA-9662361; Sensory processing of sound by outer hair cells of the cochlea.
DR BioGRID-ORCS; 494513; 6 hits in 1062 CRISPR screens.
DR ChiTaRS; DFNB59; human.
DR GenomeRNAi; 494513; -.
DR Pharos; Q0ZLH3; Tbio.
DR PRO; PR:Q0ZLH3; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q0ZLH3; protein.
DR Bgee; ENSG00000204311; Expressed in sperm and 117 other tissues.
DR ExpressionAtlas; Q0ZLH3; baseline and differential.
DR Genevisible; Q0ZLH3; HS.
DR GO; GO:0035253; C:ciliary rootlet; IEA:Ensembl.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR GO; GO:0005778; C:peroxisomal membrane; ISS:UniProtKB.
DR GO; GO:0120044; C:stereocilium base; IEA:Ensembl.
DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IEA:Ensembl.
DR GO; GO:0070997; P:neuron death; IEA:Ensembl.
DR GO; GO:0000425; P:pexophagy; ISS:UniProtKB.
DR GO; GO:0097468; P:programmed cell death in response to reactive oxygen species; ISS:UniProtKB.
DR GO; GO:1900063; P:regulation of peroxisome organization; ISS:UniProtKB.
DR GO; GO:0000302; P:response to reactive oxygen species; ISS:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; ISS:UniProtKB.
DR GO; GO:0120045; P:stereocilium maintenance; IEA:Ensembl.
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; Deafness; Disease variant; Hearing; Membrane;
KW Non-syndromic deafness; Peroxisome; Reference proteome.
FT CHAIN 1..352
FT /note="Pejvakin"
FT /id="PRO_0000249042"
FT VARIANT 54
FT /note="T -> I (in DFNB59; causes hypervulnerability to
FT sound; dbSNP:rs118203988)"
FT /evidence="ECO:0000269|PubMed:16804542,
FT ECO:0000269|PubMed:26544938"
FT /id="VAR_027387"
FT VARIANT 167..352
FT /note="Missing (in DFNB59)"
FT /evidence="ECO:0000269|PubMed:17373699"
FT /id="VAR_083912"
FT VARIANT 183
FT /note="R -> W (in DFNB59; dbSNP:rs111706634)"
FT /evidence="ECO:0000269|PubMed:16804542,
FT ECO:0000269|PubMed:17373699"
FT /id="VAR_027388"
FT VARIANT 244
FT /note="L -> R (in DFNB59; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:17373699"
FT /id="VAR_083913"
FT VARIANT 265
FT /note="R -> C (in dbSNP:rs17304212)"
FT /id="VAR_053103"
FT VARIANT 299
FT /note="L -> R"
FT /evidence="ECO:0000269|PubMed:17373699"
FT /id="VAR_083914"
FT VARIANT 343
FT /note="C -> S (in DFNB59; dbSNP:rs569088856)"
FT /evidence="ECO:0000269|PubMed:22617256"
FT /id="VAR_068891"
SQ SEQUENCE 352 AA; 39913 MW; 7DEBA07E73A3C92E CRC64;
MFAAATKSFV KQVGDGGRLV PVPSLSEADK YQPLSLVVKK KRCFLFPRYK FTSTPFTLKD
ILLGDREISA GISSYQLLNY EDESDVSLYG RRGNHIVNDV GINVAGSDSI AVKASFGIVT
KHEVEVSTLL KEITTRKINF DHSLIRQSRS SRKAVLCVVM ESIRTTRQCS LSVHAGIRGE
AMRFHFMDEQ NPKGRDKAIV FPAHTTIAFS VFELFIYLDG AFDLCVTSVS KGGFEREETA
TFALLYRLRN ILFERNRRVM DVISRSQLYL DDLFSDYYDK PLSMTDISLK EGTHIRVNLL
NHNIPKGPCI LCGMGNFKRE TVYGCFQCSV DGQKYVRLHA VPCFDIWHKR MK
