MPV17_MOUSE
ID MPV17_MOUSE Reviewed; 176 AA.
AC P19258;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Protein Mpv17;
DE Short=Mpv-17;
GN Name=Mpv17;
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].
RX PubMed=1696177; DOI=10.1016/0092-8674(90)90008-3;
RA Weiher H., Noda T., Gray D.A., Sharpe A.H., Jaenisch R.;
RT "Transgenic mouse model of kidney disease: insertional inactivation of
RT ubiquitously expressed gene leads to nephrotic syndrome.";
RL Cell 62:425-434(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
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 PRELIMINARY SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=7957077; DOI=10.1002/j.1460-2075.1994.tb06842.x;
RA Zwacka R.M., Reuter A., Pfaff E., Moll J., Gorgas K., Karasawa M.,
RA Weiher H.;
RT "The glomerulosclerosis gene Mpv17 encodes a peroxisomal protein producing
RT reactive oxygen species.";
RL EMBO J. 13:5129-5134(1994).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=9447939; DOI=10.1016/s0378-5955(97)00175-5;
RA Muller M., Smolders J.W.T., Meyer zum Gottesberge A.M., Reuter A.,
RA Zwacka R.M., Weiher H., Klinke R.;
RT "Loss of auditory function in transgenic Mpv17-deficient mice.";
RL Hear. Res. 114:259-263(1997).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=11377883; DOI=10.1016/s0378-5955(01)00268-4;
RA Meyer zum Gottesberge A.M., Felix H., Reuter A., Weiher H.;
RT "Ultrastructural and physiological defects in the cochlea of the Mpv17
RT mouse strain. A comparison between young and old adult animals.";
RL Hear. Res. 156:69-80(2001).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION.
RX PubMed=26760297; DOI=10.1371/journal.pgen.1005779;
RA Dalla Rosa I., Camara Y., Durigon R., Moss C.F., Vidoni S., Akman G.,
RA Hunt L., Johnson M.A., Grocott S., Wang L., Thorburn D.R., Hirano M.,
RA Poulton J., Taylor R.W., Elgar G., Marti R., Voshol P., Holt I.J.,
RA Spinazzola A.;
RT "MPV17 loss causes deoxynucleotide insufficiency and slow DNA replication
RT in mitochondria.";
RL PLoS Genet. 12:E1005779-E1005779(2016).
CC -!- FUNCTION: Non-selective channel that modulates the membrane potential
CC under normal conditions and oxidative stress, and is involved in
CC mitochondrial homeostasis (By similarity). Involved in mitochondrial
CC deoxynucleoside triphosphates (dNTP) pool homeostasis and mitochondrial
CC DNA (mtDNA) maintenance (PubMed:26760297). May be involved in the
CC regulation of reactive oxygen species metabolism and the control of
CC oxidative phosphorylation (Probable). {ECO:0000250|UniProtKB:P39210,
CC ECO:0000269|PubMed:26760297, ECO:0000305|PubMed:7957077}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P39210}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P39210}.
CC -!- TISSUE SPECIFICITY: High levels in heart, kidney, and brain,
CC intermediate levels in testis, and low levels in liver and spleen.
CC -!- DISRUPTION PHENOTYPE: Mice lack expression of this protein resulting in
CC the development of adult onset nephrotic syndrome and chronic renal
CC failure. They also develop severe morphological degeneration of the
CC inner ear. In the inner ear, mice lacking Mpv17 display degenerative
CC changes of the cochlear structures already at the age of 2 months. The
CC degenerative changes are patchy arranged throughout the entire length
CC of the cochlea and involved the organ of Corti as well as the stria
CC vascularis epithelia with alterations of the basement membrane of the
CC capillaries. {ECO:0000269|PubMed:11377883, ECO:0000269|PubMed:9447939}.
CC -!- SIMILARITY: Belongs to the peroxisomal membrane protein PXMP2/4 family.
CC {ECO:0000305}.
CC -!- CAUTION: Was initially thought to be a peroxisomal protein
CC (PubMed:7957077). However, it was later shown in human that it is a
CC mitochondrial protein (PubMed:16582907 and PubMed:16582910).
CC {ECO:0000305|PubMed:7957077}.
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DR EMBL; M36411; AAA39736.1; -; mRNA.
DR EMBL; BC013452; AAH13452.1; -; mRNA.
DR CCDS; CCDS19175.1; -.
DR PIR; S29031; S29031.
DR RefSeq; NP_001281253.1; NM_001294324.1.
DR RefSeq; NP_001297456.1; NM_001310527.1.
DR RefSeq; NP_032648.1; NM_008622.6.
DR AlphaFoldDB; P19258; -.
DR STRING; 10090.ENSMUSP00000115292; -.
DR TCDB; 1.A.126.1.5; the mpv17/pmp22 4 tms putative channel (mpv17) family.
DR PhosphoSitePlus; P19258; -.
DR jPOST; P19258; -.
DR MaxQB; P19258; -.
DR PaxDb; P19258; -.
DR PRIDE; P19258; -.
DR ProteomicsDB; 291502; -.
DR Antibodypedia; 28381; 182 antibodies from 28 providers.
DR DNASU; 17527; -.
DR Ensembl; ENSMUST00000154241; ENSMUSP00000115292; ENSMUSG00000107283.
DR Ensembl; ENSMUST00000200864; ENSMUSP00000144331; ENSMUSG00000107283.
DR Ensembl; ENSMUST00000201353; ENSMUSP00000144198; ENSMUSG00000107283.
DR GeneID; 17527; -.
DR KEGG; mmu:17527; -.
DR UCSC; uc008wxf.3; mouse.
DR CTD; 4358; -.
DR MGI; MGI:97138; Mpv17.
DR VEuPathDB; HostDB:ENSMUSG00000107283; -.
DR eggNOG; KOG1944; Eukaryota.
DR GeneTree; ENSGT00940000160891; -.
DR InParanoid; P19258; -.
DR OMA; TYLSWKT; -.
DR TreeFam; TF324070; -.
DR Reactome; R-MMU-9033241; Peroxisomal protein import.
DR BioGRID-ORCS; 17527; 1 hit in 40 CRISPR screens.
DR ChiTaRS; Mpv17; mouse.
DR PRO; PR:P19258; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P19258; protein.
DR Bgee; ENSMUSG00000107283; Expressed in right kidney and 253 other tissues.
DR ExpressionAtlas; P19258; baseline and differential.
DR Genevisible; P19258; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IMP:MGI.
DR GO; GO:0005777; C:peroxisome; IDA:MGI.
DR GO; GO:0015267; F:channel activity; ISS:UniProtKB.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:UniProtKB.
DR GO; GO:0032836; P:glomerular basement membrane development; IMP:UniProtKB.
DR GO; GO:0042592; P:homeostatic process; ISO:MGI.
DR GO; GO:0048839; P:inner ear development; IMP:UniProtKB.
DR GO; GO:0000002; P:mitochondrial genome maintenance; ISO:MGI.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IDA:MGI.
DR GO; GO:1901858; P:regulation of mitochondrial DNA metabolic process; IMP:UniProtKB.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:UniProtKB.
DR InterPro; IPR007248; Mpv17_PMP22.
DR PANTHER; PTHR11266; PTHR11266; 1.
DR Pfam; PF04117; Mpv17_PMP22; 1.
PE 1: Evidence at protein level;
KW Deafness; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..176
FT /note="Protein Mpv17"
FT /id="PRO_0000218928"
FT TRANSMEM 18..38
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 53..73
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 94..114
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 131..151
FT /note="Helical"
FT /evidence="ECO:0000255"
FT SITE 92
FT /note="Determines ion selectivity"
FT /evidence="ECO:0000250|UniProtKB:P39210"
SQ SEQUENCE 176 AA; 19686 MW; 7060A7B122F77DB1 CRC64;
MALWRAYQRA LAAHPWKVQV LTAGSLMGVG DMISQQLVER RGLQQHQAGR TLTMVSLGCG
FVGPVVGGWY KVLDHLIPGT TKVHALKKML LDQGGFAPCF LGCFLPLVGI LNGMSAQDNW
AKLKRDYPDA LITNYYLWPA VQLANFYLVP LHYRLAVVQC VAIVWNSYLS WKAHQF
