MPCP_HUMAN
ID MPCP_HUMAN Reviewed; 362 AA.
AC Q00325; B3KS34; Q7Z7N7; Q96A03;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 2.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Phosphate carrier protein, mitochondrial;
DE AltName: Full=Phosphate transport protein;
DE Short=PTP;
DE AltName: Full=Solute carrier family 25 member 3;
DE Flags: Precursor;
GN Name=SLC25A3; Synonyms=PHC; ORFNames=OK/SW-cl.48;
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 [GENOMIC DNA] (ISOFORMS A AND B).
RC TISSUE=Placenta;
RX PubMed=8144629; DOI=10.1016/s0021-9258(17)34081-4;
RA Dolce V., Iacobazzi V., Palmieri F., Walker J.E.;
RT "The sequences of human and bovine genes of the phosphate carrier from
RT mitochondria contain evidence of alternatively spliced forms.";
RL J. Biol. Chem. 269:10451-10460(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC TISSUE=Heart;
RX PubMed=1777677; DOI=10.3109/10425179109039683;
RA Dolce V., Fiermonte G., Messina A., Palmieri F.;
RT "Nucleotide sequence of a human heart cDNA encoding the mitochondrial
RT phosphate carrier.";
RL DNA Seq. 2:133-135(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-reactive
RT CTL generated from TIL of colon cancer patients.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC TISSUE=Skeletal muscle;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC TISSUE=Brain, Cervix, Lung, Ovary, Placenta, and Prostate;
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-196, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-99, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-112, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [14]
RP VARIANT MPCD GLU-72.
RX PubMed=17273968; DOI=10.1086/511788;
RA Mayr J.A., Merkel O., Kohlwein S.D., Gebhardt B.R., Boehles H.,
RA Foetschl U., Koch J., Jaksch M., Lochmueller H., Horvath R., Freisinger P.,
RA Sperl W.;
RT "Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative
RT phosphorylation.";
RL Am. J. Hum. Genet. 80:478-484(2007).
CC -!- FUNCTION: Transport of phosphate groups from the cytosol to the
CC mitochondrial matrix. Phosphate is cotransported with H(+). May play a
CC role regulation of the mitochondrial permeability transition pore
CC (mPTP).
CC -!- SUBUNIT: Interacts with PPIF; the interaction is impaired by CsA.
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q00325-2; P42858: HTT; NbExp=3; IntAct=EBI-5456178, EBI-466029;
CC Q00325-2; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-5456178, EBI-17589229;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=Q00325-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q00325-2; Sequence=VSP_003269;
CC -!- DISEASE: Mitochondrial phosphate carrier deficiency (MPCD)
CC [MIM:610773]: An autosomal recessive disorder of oxidative
CC phosphorylation. Patients have lactic acidosis, hypertrophic
CC cardiomyopathy and muscular hypotonia and die within the first year of
CC life. {ECO:0000269|PubMed:17273968}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; X77337; CAB56611.1; -; Genomic_DNA.
DR EMBL; X77337; CAB56612.1; -; Genomic_DNA.
DR EMBL; X60036; CAA42641.1; -; mRNA.
DR EMBL; AB064666; BAB93517.1; -; mRNA.
DR EMBL; AK092689; BAG52596.1; -; mRNA.
DR EMBL; CH471054; EAW97595.1; -; Genomic_DNA.
DR EMBL; CH471054; EAW97597.1; -; Genomic_DNA.
DR EMBL; BC000998; AAH00998.1; -; mRNA.
DR EMBL; BC001328; AAH01328.1; -; mRNA.
DR EMBL; BC003504; AAH03504.1; -; mRNA.
DR EMBL; BC004345; AAH04345.1; -; mRNA.
DR EMBL; BC006455; AAH06455.1; -; mRNA.
DR EMBL; BC011574; AAH11574.1; -; mRNA.
DR EMBL; BC011641; AAH11641.1; -; mRNA.
DR EMBL; BC014019; AAH14019.1; -; mRNA.
DR EMBL; BC015379; AAH15379.2; -; mRNA.
DR EMBL; BC051367; AAH51367.2; -; mRNA.
DR CCDS; CCDS9065.1; -. [Q00325-2]
DR CCDS; CCDS9066.1; -. [Q00325-1]
DR PIR; A53737; A53737.
DR PIR; B53737; B53737.
DR RefSeq; NP_002626.1; NM_002635.3. [Q00325-2]
DR RefSeq; NP_005879.1; NM_005888.3. [Q00325-1]
DR RefSeq; NP_998776.1; NM_213611.2. [Q00325-2]
DR AlphaFoldDB; Q00325; -.
DR SMR; Q00325; -.
DR BioGRID; 111269; 333.
DR CORUM; Q00325; -.
DR IntAct; Q00325; 129.
DR MINT; Q00325; -.
DR STRING; 9606.ENSP00000228318; -.
DR ChEMBL; CHEMBL4295795; -.
DR TCDB; 2.A.29.4.2; the mitochondrial carrier (mc) family.
DR GlyGen; Q00325; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q00325; -.
DR MetOSite; Q00325; -.
DR PhosphoSitePlus; Q00325; -.
DR SwissPalm; Q00325; -.
DR BioMuta; SLC25A3; -.
DR DMDM; 730052; -.
DR EPD; Q00325; -.
DR jPOST; Q00325; -.
DR MassIVE; Q00325; -.
DR MaxQB; Q00325; -.
DR PaxDb; Q00325; -.
DR PeptideAtlas; Q00325; -.
DR PRIDE; Q00325; -.
DR ProteomicsDB; 57843; -. [Q00325-1]
DR ProteomicsDB; 57844; -. [Q00325-2]
DR TopDownProteomics; Q00325-1; -. [Q00325-1]
DR TopDownProteomics; Q00325-2; -. [Q00325-2]
DR Antibodypedia; 30219; 57 antibodies from 17 providers.
DR DNASU; 5250; -.
DR Ensembl; ENST00000188376.9; ENSP00000188376.5; ENSG00000075415.15. [Q00325-2]
DR Ensembl; ENST00000228318.8; ENSP00000228318.3; ENSG00000075415.15. [Q00325-1]
DR Ensembl; ENST00000401722.7; ENSP00000383898.3; ENSG00000075415.15. [Q00325-2]
DR Ensembl; ENST00000549338.5; ENSP00000447740.1; ENSG00000075415.15. [Q00325-2]
DR Ensembl; ENST00000551917.5; ENSP00000447310.1; ENSG00000075415.15. [Q00325-1]
DR Ensembl; ENST00000552981.6; ENSP00000448708.2; ENSG00000075415.15. [Q00325-2]
DR GeneID; 5250; -.
DR KEGG; hsa:5250; -.
DR MANE-Select; ENST00000552981.6; ENSP00000448708.2; NM_002635.4; NP_002626.1. [Q00325-2]
DR UCSC; uc001tfm.4; human. [Q00325-1]
DR CTD; 5250; -.
DR DisGeNET; 5250; -.
DR GeneCards; SLC25A3; -.
DR HGNC; HGNC:10989; SLC25A3.
DR HPA; ENSG00000075415; Tissue enhanced (skeletal).
DR MalaCards; SLC25A3; -.
DR MIM; 600370; gene.
DR MIM; 610773; phenotype.
DR neXtProt; NX_Q00325; -.
DR OpenTargets; ENSG00000075415; -.
DR Orphanet; 91130; Cardiomyopathy-hypotonia-lactic acidosis syndrome.
DR PharmGKB; PA35865; -.
DR VEuPathDB; HostDB:ENSG00000075415; -.
DR eggNOG; KOG0767; Eukaryota.
DR GeneTree; ENSGT00390000008708; -.
DR InParanoid; Q00325; -.
DR OMA; KFFFFEY; -.
DR PhylomeDB; Q00325; -.
DR TreeFam; TF314119; -.
DR PathwayCommons; Q00325; -.
DR SignaLink; Q00325; -.
DR BioGRID-ORCS; 5250; 536 hits in 1085 CRISPR screens.
DR ChiTaRS; SLC25A3; human.
DR GeneWiki; SLC25A3; -.
DR GenomeRNAi; 5250; -.
DR Pharos; Q00325; Tbio.
DR PRO; PR:Q00325; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q00325; protein.
DR Bgee; ENSG00000075415; Expressed in left ventricle myocardium and 204 other tissues.
DR ExpressionAtlas; Q00325; baseline and differential.
DR Genevisible; Q00325; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:ProtInc.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005315; F:inorganic phosphate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015317; F:phosphate:proton symporter activity; TAS:ProtInc.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:MGI.
DR GO; GO:1990547; P:mitochondrial phosphate ion transmembrane transport; IEA:InterPro.
DR GO; GO:0035435; P:phosphate ion transmembrane transport; IBA:GO_Central.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR InterPro; IPR044677; Pic2/Mir1-like.
DR PANTHER; PTHR45671; PTHR45671; 1.
DR Pfam; PF00153; Mito_carr; 3.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Disease variant; Membrane; Methylation;
KW Mitochondrion; Mitochondrion inner membrane; Phosphoprotein;
KW Primary mitochondrial disease; Reference proteome; Repeat; Symport;
KW Transit peptide; Transmembrane; Transmembrane helix; Transport.
FT TRANSIT 1..49
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 50..362
FT /note="Phosphate carrier protein, mitochondrial"
FT /id="PRO_0000019256"
FT TOPO_DOM 50..63
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 64..86
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 87..121
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..141
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 142..161
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 162..183
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 184..218
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 219..238
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 239..261
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..284
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 285..314
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 315..333
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 334..362
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT REPEAT 63..147
FT /note="Solcar 1"
FT REPEAT 160..244
FT /note="Solcar 2"
FT REPEAT 261..339
FT /note="Solcar 3"
FT MOD_RES 99
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 112
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 196
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 209
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8VEM8"
FT VAR_SEQ 54..83
FT /note="QYSCDYGSGRFFILCGLGGIISCGTTHTAL -> YSCEFGSAKYYALCGFGG
FT VLSCGLTHTAV (in isoform B)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1777677, ECO:0000303|Ref.3"
FT /id="VSP_003269"
FT VARIANT 72
FT /note="G -> E (in MPCD; dbSNP:rs104894375)"
FT /evidence="ECO:0000269|PubMed:17273968"
FT /id="VAR_032850"
SQ SEQUENCE 362 AA; 40095 MW; 78714C85931B22D5 CRC64;
MFSSVAHLAR ANPFNTPHLQ LVHDGLGDLR SSSPGPTGQP RRPRNLAAAA VEEQYSCDYG
SGRFFILCGL GGIISCGTTH TALVPLDLVK CRMQVDPQKY KGIFNGFSVT LKEDGVRGLA
KGWAPTFLGY SMQGLCKFGF YEVFKVLYSN MLGEENTYLW RTSLYLAASA SAEFFADIAL
APMEAAKVRI QTQPGYANTL RDAAPKMYKE EGLKAFYKGV APLWMRQIPY TMMKFACFER
TVEALYKFVV PKPRSECSKP EQLVVTFVAG YIAGVFCAIV SHPADSVVSV LNKEKGSSAS
LVLKRLGFKG VWKGLFARII MIGTLTALQW FIYDSVKVYF RLPRPPPPEM PESLKKKLGL
TQ
