Full text data of SLC25A3
SLC25A3
(PHC)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Phosphate carrier protein, mitochondrial (Phosphate transport protein; PTP; Solute carrier family 25 member 3; Flags: Precursor)
Phosphate carrier protein, mitochondrial (Phosphate transport protein; PTP; Solute carrier family 25 member 3; Flags: Precursor)
Comments
Isoform Q00325-2 was detected.
Isoform Q00325-2 was detected.
UniProt
Q00325
ID MPCP_HUMAN Reviewed; 362 AA.
AC Q00325; B3KS34; Q7Z7N7; Q96A03;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 2.
DT 22-JAN-2014, entry version 139.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A AND B).
RC TISSUE=Placenta;
RX PubMed=8144629;
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;
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-
RT reactive 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-196, AND MASS
RP SPECTROMETRY.
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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-99, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [9]
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.,
RA Buerckstuemmer T., 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 [10]
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.,
RA Freisinger P., Sperl W.;
RT "Mitochondrial phosphate-carrier deficiency: a novel disorder of
RT oxidative 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
CC play a role regulation of the mitochondrial permeability
CC transition pore (mPTP).
CC -!- SUBUNIT: Interacts with PPIF; the interaction is impaired by CsA
CC (By similarity).
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass
CC membrane 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]: Fatal disorder of oxidative phosphorylation.
CC Patients have lactic acidosis, hypertrophic cardiomyopathy and
CC muscular hypotonia and die within the first year of life. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29)
CC family.
CC -!- SIMILARITY: Contains 3 Solcar repeats.
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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 PIR; A53737; A53737.
DR PIR; B53737; B53737.
DR RefSeq; NP_002626.1; NM_002635.3.
DR RefSeq; NP_005879.1; NM_005888.3.
DR RefSeq; NP_998776.1; NM_213611.2.
DR RefSeq; XP_005269038.1; XM_005268981.1.
DR RefSeq; XP_005269039.1; XM_005268982.1.
DR UniGene; Hs.290404; -.
DR ProteinModelPortal; Q00325; -.
DR SMR; Q00325; 69-337.
DR IntAct; Q00325; 29.
DR MINT; MINT-1156379; -.
DR STRING; 9606.ENSP00000228318; -.
DR TCDB; 2.A.29.4.2; the mitochondrial carrier (mc) family.
DR PhosphoSite; Q00325; -.
DR DMDM; 730052; -.
DR PaxDb; Q00325; -.
DR PRIDE; Q00325; -.
DR DNASU; 5250; -.
DR Ensembl; ENST00000188376; ENSP00000188376; ENSG00000075415.
DR Ensembl; ENST00000228318; ENSP00000228318; ENSG00000075415.
DR Ensembl; ENST00000401722; ENSP00000383898; ENSG00000075415.
DR Ensembl; ENST00000549338; ENSP00000447740; ENSG00000075415.
DR Ensembl; ENST00000551917; ENSP00000447310; ENSG00000075415.
DR Ensembl; ENST00000552981; ENSP00000448708; ENSG00000075415.
DR GeneID; 5250; -.
DR KEGG; hsa:5250; -.
DR UCSC; uc001tfo.3; human.
DR CTD; 5250; -.
DR GeneCards; GC12P098920; -.
DR HGNC; HGNC:10989; SLC25A3.
DR HPA; HPA045709; -.
DR MIM; 600370; gene.
DR MIM; 610773; phenotype.
DR neXtProt; NX_Q00325; -.
DR Orphanet; 91130; Cardiomyopathy - hypotonia - lactic acidosis.
DR PharmGKB; PA35865; -.
DR eggNOG; NOG265500; -.
DR HOGENOM; HOG000164438; -.
DR HOVERGEN; HBG024440; -.
DR InParanoid; Q00325; -.
DR KO; K15102; -.
DR OMA; KERQLPF; -.
DR OrthoDB; EOG7KQ228; -.
DR PhylomeDB; Q00325; -.
DR ChiTaRS; slc25a3; human.
DR GeneWiki; SLC25A3; -.
DR GenomeRNAi; 5250; -.
DR NextBio; 20278; -.
DR PRO; PR:Q00325; -.
DR ArrayExpress; Q00325; -.
DR Bgee; Q00325; -.
DR CleanEx; HS_SLC25A3; -.
DR Genevestigator; Q00325; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:ProtInc.
DR GO; GO:0015320; F:phosphate ion carrier activity; TAS:ProtInc.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom.
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; Complete proteome;
KW Disease mutation; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Phosphoprotein; Reference proteome;
KW Repeat; Symport; Transit peptide; Transmembrane; Transmembrane helix;
KW Transport.
FT TRANSIT 1 49 Mitochondrion (By similarity).
FT CHAIN 50 362 Phosphate carrier protein, mitochondrial.
FT /FTId=PRO_0000019256.
FT TOPO_DOM 50 63 Mitochondrial intermembrane (Potential).
FT TRANSMEM 64 86 Helical; Name=1; (Potential).
FT TOPO_DOM 87 121 Mitochondrial matrix (Potential).
FT TRANSMEM 122 141 Helical; Name=2; (Potential).
FT TOPO_DOM 142 161 Mitochondrial intermembrane (Potential).
FT TRANSMEM 162 183 Helical; Name=3; (Potential).
FT TOPO_DOM 184 218 Mitochondrial matrix (Potential).
FT TRANSMEM 219 238 Helical; Name=4; (Potential).
FT TOPO_DOM 239 261 Mitochondrial intermembrane (Potential).
FT TRANSMEM 262 284 Helical; Name=5; (Potential).
FT TOPO_DOM 285 314 Mitochondrial matrix (Potential).
FT TRANSMEM 315 333 Helical; Name=6; (Potential).
FT TOPO_DOM 334 362 Mitochondrial intermembrane (Potential).
FT REPEAT 63 147 Solcar 1.
FT REPEAT 160 244 Solcar 2.
FT REPEAT 261 339 Solcar 3.
FT MOD_RES 99 99 N6-acetyllysine.
FT MOD_RES 196 196 Phosphotyrosine.
FT MOD_RES 209 209 N6-acetyllysine (By similarity).
FT VAR_SEQ 54 83 QYSCDYGSGRFFILCGLGGIISCGTTHTAL -> YSCEFGS
FT AKYYALCGFGGVLSCGLTHTAV (in isoform B).
FT /FTId=VSP_003269.
FT VARIANT 72 72 G -> E (in MPCD).
FT /FTId=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
//
ID MPCP_HUMAN Reviewed; 362 AA.
AC Q00325; B3KS34; Q7Z7N7; Q96A03;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 2.
DT 22-JAN-2014, entry version 139.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A AND B).
RC TISSUE=Placenta;
RX PubMed=8144629;
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;
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-
RT reactive 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-196, AND MASS
RP SPECTROMETRY.
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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-99, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [9]
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.,
RA Buerckstuemmer T., 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 [10]
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.,
RA Freisinger P., Sperl W.;
RT "Mitochondrial phosphate-carrier deficiency: a novel disorder of
RT oxidative 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
CC play a role regulation of the mitochondrial permeability
CC transition pore (mPTP).
CC -!- SUBUNIT: Interacts with PPIF; the interaction is impaired by CsA
CC (By similarity).
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass
CC membrane 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]: Fatal disorder of oxidative phosphorylation.
CC Patients have lactic acidosis, hypertrophic cardiomyopathy and
CC muscular hypotonia and die within the first year of life. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29)
CC family.
CC -!- SIMILARITY: Contains 3 Solcar repeats.
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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 PIR; A53737; A53737.
DR PIR; B53737; B53737.
DR RefSeq; NP_002626.1; NM_002635.3.
DR RefSeq; NP_005879.1; NM_005888.3.
DR RefSeq; NP_998776.1; NM_213611.2.
DR RefSeq; XP_005269038.1; XM_005268981.1.
DR RefSeq; XP_005269039.1; XM_005268982.1.
DR UniGene; Hs.290404; -.
DR ProteinModelPortal; Q00325; -.
DR SMR; Q00325; 69-337.
DR IntAct; Q00325; 29.
DR MINT; MINT-1156379; -.
DR STRING; 9606.ENSP00000228318; -.
DR TCDB; 2.A.29.4.2; the mitochondrial carrier (mc) family.
DR PhosphoSite; Q00325; -.
DR DMDM; 730052; -.
DR PaxDb; Q00325; -.
DR PRIDE; Q00325; -.
DR DNASU; 5250; -.
DR Ensembl; ENST00000188376; ENSP00000188376; ENSG00000075415.
DR Ensembl; ENST00000228318; ENSP00000228318; ENSG00000075415.
DR Ensembl; ENST00000401722; ENSP00000383898; ENSG00000075415.
DR Ensembl; ENST00000549338; ENSP00000447740; ENSG00000075415.
DR Ensembl; ENST00000551917; ENSP00000447310; ENSG00000075415.
DR Ensembl; ENST00000552981; ENSP00000448708; ENSG00000075415.
DR GeneID; 5250; -.
DR KEGG; hsa:5250; -.
DR UCSC; uc001tfo.3; human.
DR CTD; 5250; -.
DR GeneCards; GC12P098920; -.
DR HGNC; HGNC:10989; SLC25A3.
DR HPA; HPA045709; -.
DR MIM; 600370; gene.
DR MIM; 610773; phenotype.
DR neXtProt; NX_Q00325; -.
DR Orphanet; 91130; Cardiomyopathy - hypotonia - lactic acidosis.
DR PharmGKB; PA35865; -.
DR eggNOG; NOG265500; -.
DR HOGENOM; HOG000164438; -.
DR HOVERGEN; HBG024440; -.
DR InParanoid; Q00325; -.
DR KO; K15102; -.
DR OMA; KERQLPF; -.
DR OrthoDB; EOG7KQ228; -.
DR PhylomeDB; Q00325; -.
DR ChiTaRS; slc25a3; human.
DR GeneWiki; SLC25A3; -.
DR GenomeRNAi; 5250; -.
DR NextBio; 20278; -.
DR PRO; PR:Q00325; -.
DR ArrayExpress; Q00325; -.
DR Bgee; Q00325; -.
DR CleanEx; HS_SLC25A3; -.
DR Genevestigator; Q00325; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:ProtInc.
DR GO; GO:0015320; F:phosphate ion carrier activity; TAS:ProtInc.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom.
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; Complete proteome;
KW Disease mutation; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Phosphoprotein; Reference proteome;
KW Repeat; Symport; Transit peptide; Transmembrane; Transmembrane helix;
KW Transport.
FT TRANSIT 1 49 Mitochondrion (By similarity).
FT CHAIN 50 362 Phosphate carrier protein, mitochondrial.
FT /FTId=PRO_0000019256.
FT TOPO_DOM 50 63 Mitochondrial intermembrane (Potential).
FT TRANSMEM 64 86 Helical; Name=1; (Potential).
FT TOPO_DOM 87 121 Mitochondrial matrix (Potential).
FT TRANSMEM 122 141 Helical; Name=2; (Potential).
FT TOPO_DOM 142 161 Mitochondrial intermembrane (Potential).
FT TRANSMEM 162 183 Helical; Name=3; (Potential).
FT TOPO_DOM 184 218 Mitochondrial matrix (Potential).
FT TRANSMEM 219 238 Helical; Name=4; (Potential).
FT TOPO_DOM 239 261 Mitochondrial intermembrane (Potential).
FT TRANSMEM 262 284 Helical; Name=5; (Potential).
FT TOPO_DOM 285 314 Mitochondrial matrix (Potential).
FT TRANSMEM 315 333 Helical; Name=6; (Potential).
FT TOPO_DOM 334 362 Mitochondrial intermembrane (Potential).
FT REPEAT 63 147 Solcar 1.
FT REPEAT 160 244 Solcar 2.
FT REPEAT 261 339 Solcar 3.
FT MOD_RES 99 99 N6-acetyllysine.
FT MOD_RES 196 196 Phosphotyrosine.
FT MOD_RES 209 209 N6-acetyllysine (By similarity).
FT VAR_SEQ 54 83 QYSCDYGSGRFFILCGLGGIISCGTTHTAL -> YSCEFGS
FT AKYYALCGFGGVLSCGLTHTAV (in isoform B).
FT /FTId=VSP_003269.
FT VARIANT 72 72 G -> E (in MPCD).
FT /FTId=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
//
MIM
600370
*RECORD*
*FIELD* NO
600370
*FIELD* TI
*600370 SOLUTE CARRIER FAMILY 25 (MITOCHONDRIAL CARRIER), MEMBER 3; SLC25A3
;;PHOSPHATE CARRIER, MITOCHONDRIAL; PHC
read more*FIELD* TX
CLONING
In the terminal steps of oxidative phosphorylation, the phosphate
carrier (PHC) catalyzes the uptake across the mitochondrial inner
membrane of the oxidative phosphorylation substrate phosphate in symport
(cotransport) with a proton. The phosphorylation of ADP, which enters
the matrix on adenine nucleotide translocase (ANT; 103220), is catalyzed
by the ATP synthase complex. The ATP synthase enzyme of higher
eukaryotic cells is a complex oligomer containing at least 13 different
peptides in an asymmetric stoichiometry. These polypeptides include the
alpha, beta (ATP5B; 102910), delta, and gamma (ATP5C1; 108729) subunits.
Dolce et al. (1994) identified 2 alternatively spliced mRNAs for PHC,
designated PHC-A and PHC-B, which differ by 13 amino acids.
Huizing et al. (1998) studied the human tissue distribution of
mitochondrial transmembrane metabolite carriers by Northern and Western
blot analyses. They found that PHC-A mRNA is expressed in heart,
skeletal muscle, and pancreas in high amounts, whereas PHC-B mRNA is
poorly expressed in all tissues. Isoforms A and B contain 42 and 41
amino acids, respectively. In vitro, the 2 isoforms display different
substrate affinities and transport rates.
GENE STRUCTURE
Dolce et al. (1994) determined that the PHC gene contains 9 exons.
MAPPING
Using a rat liver cDNA as a probe in the analysis of somatic cell hybrid
DNAs, Jabs et al. (1994) demonstrated that the PHC gene is located on
chromosome 12. Marsh et al. (1995) mapped the PHC gene to 12q23 by
fluorescence in situ hybridization.
MOLECULAR GENETICS
Mayr et al. (2007) described the first patients with mitochondrial
phosphate carrier deficiency (610773) caused by a mutation in the
SLC25A3 gene. Two sibs showed lactic acidosis, hypertrophic
cardiomyopathy, and muscular hypotonia and died within the first year of
life. Functional investigation of intact mitochondria showed a
deficiency of ATP synthetase in muscle but not in fibroblasts, which
correlated with the tissue-specific expression of exon 3A in muscle
versus exon 3B in fibroblasts. The 2 sibs carried a homozygous mutation
in the alternatively spliced exon 3A of the SLC25A3 gene (600370.0001).
*FIELD* AV
.0001
MITOCHONDRIAL PHOSPHATE CARRIER DEFICIENCY
SLC25A3, GLY72GLU
In 2 sibs with deficiency of mitochondrial phosphate carrier protein
(610773), Mayr et al. (2007) identified homozygosity for a 215G-A
transition in exon 3A of the SLC25A3 gene, resulting in a gly72-to-glu
(G72E) amino acid substitution. Both patients presented with lactic
acidosis, hypertrophic cardiomyopathy, and muscular hypotonia, and died
within the first year of life.
*FIELD* RF
1. Dolce, V.; Iacobazzi, V.; Palmieri, F.; Walker, J. E.: The sequences
of human and bovine genes of the phosphate carrier from mitochondria
contain evidence of alternatively spliced forms. J. Biol. Chem. 269:
10451-10460, 1994.
2. Huizing, M.; Ruitenbeek, W.; van den Heuvel, L. P.; Dolce, V.;
Iacobazzi, V.; Smeitink, J. A. M.; Palmieri, F.; Trijbels, J. M. F.
: Human mitochondrial transmembrane metabolite carriers: tissue distribution
and its implication for mitochondrial disorders. J. Bioenerg. Biomembr. 30:
277-284, 1998.
3. Jabs, E. W.; Thomas, P. J.; Bernstein, M.; Coss, C.; Ferreira,
G. C.; Pedersen, P. L.: Chromosomal localization of genes required
for the terminal steps of oxidative metabolism: alpha and gamma subunits
of ATP synthase and the phosphate carrier. Hum. Genet. 93: 600-602,
1994.
4. Marsh, S.; Carter, N. P.; Dolce, V.; Iacobazzi, V.; Palmieri, F.
: Chromosomal localization of the mitochondrial phosphate carrier
gene PHC to 12q23. Genomics 29: 814-815, 1995.
5. Mayr, J. A.; Merkel, O.; Kohlwein, S. D.; Gebhardt, B. R.; Bohles,
H.; Fotschl, U.; Koch, J.; Jaksch, M.; Lochmuller, H.; Horvath, R.;
Freisinger, P.; Sperl, W.: Mitochondrial phosphate-carrier deficiency:
a novel disorder of oxidative phosphorylation. Am. J. Hum. Genet. 80:
478-484, 2007.
*FIELD* CN
Victor A. McKusick - updated: 2/15/2007
Wilson H. Y. Lo - updated: 8/10/1999
Alan F. Scott - updated: 11/8/1995
*FIELD* CD
Victor A. McKusick: 2/3/1995
*FIELD* ED
alopez: 02/19/2007
carol: 2/15/2007
terry: 3/28/2002
carol: 3/13/2000
carol: 8/10/1999
joanna: 5/8/1998
mark: 11/8/1995
carol: 2/3/1995
*RECORD*
*FIELD* NO
600370
*FIELD* TI
*600370 SOLUTE CARRIER FAMILY 25 (MITOCHONDRIAL CARRIER), MEMBER 3; SLC25A3
;;PHOSPHATE CARRIER, MITOCHONDRIAL; PHC
read more*FIELD* TX
CLONING
In the terminal steps of oxidative phosphorylation, the phosphate
carrier (PHC) catalyzes the uptake across the mitochondrial inner
membrane of the oxidative phosphorylation substrate phosphate in symport
(cotransport) with a proton. The phosphorylation of ADP, which enters
the matrix on adenine nucleotide translocase (ANT; 103220), is catalyzed
by the ATP synthase complex. The ATP synthase enzyme of higher
eukaryotic cells is a complex oligomer containing at least 13 different
peptides in an asymmetric stoichiometry. These polypeptides include the
alpha, beta (ATP5B; 102910), delta, and gamma (ATP5C1; 108729) subunits.
Dolce et al. (1994) identified 2 alternatively spliced mRNAs for PHC,
designated PHC-A and PHC-B, which differ by 13 amino acids.
Huizing et al. (1998) studied the human tissue distribution of
mitochondrial transmembrane metabolite carriers by Northern and Western
blot analyses. They found that PHC-A mRNA is expressed in heart,
skeletal muscle, and pancreas in high amounts, whereas PHC-B mRNA is
poorly expressed in all tissues. Isoforms A and B contain 42 and 41
amino acids, respectively. In vitro, the 2 isoforms display different
substrate affinities and transport rates.
GENE STRUCTURE
Dolce et al. (1994) determined that the PHC gene contains 9 exons.
MAPPING
Using a rat liver cDNA as a probe in the analysis of somatic cell hybrid
DNAs, Jabs et al. (1994) demonstrated that the PHC gene is located on
chromosome 12. Marsh et al. (1995) mapped the PHC gene to 12q23 by
fluorescence in situ hybridization.
MOLECULAR GENETICS
Mayr et al. (2007) described the first patients with mitochondrial
phosphate carrier deficiency (610773) caused by a mutation in the
SLC25A3 gene. Two sibs showed lactic acidosis, hypertrophic
cardiomyopathy, and muscular hypotonia and died within the first year of
life. Functional investigation of intact mitochondria showed a
deficiency of ATP synthetase in muscle but not in fibroblasts, which
correlated with the tissue-specific expression of exon 3A in muscle
versus exon 3B in fibroblasts. The 2 sibs carried a homozygous mutation
in the alternatively spliced exon 3A of the SLC25A3 gene (600370.0001).
*FIELD* AV
.0001
MITOCHONDRIAL PHOSPHATE CARRIER DEFICIENCY
SLC25A3, GLY72GLU
In 2 sibs with deficiency of mitochondrial phosphate carrier protein
(610773), Mayr et al. (2007) identified homozygosity for a 215G-A
transition in exon 3A of the SLC25A3 gene, resulting in a gly72-to-glu
(G72E) amino acid substitution. Both patients presented with lactic
acidosis, hypertrophic cardiomyopathy, and muscular hypotonia, and died
within the first year of life.
*FIELD* RF
1. Dolce, V.; Iacobazzi, V.; Palmieri, F.; Walker, J. E.: The sequences
of human and bovine genes of the phosphate carrier from mitochondria
contain evidence of alternatively spliced forms. J. Biol. Chem. 269:
10451-10460, 1994.
2. Huizing, M.; Ruitenbeek, W.; van den Heuvel, L. P.; Dolce, V.;
Iacobazzi, V.; Smeitink, J. A. M.; Palmieri, F.; Trijbels, J. M. F.
: Human mitochondrial transmembrane metabolite carriers: tissue distribution
and its implication for mitochondrial disorders. J. Bioenerg. Biomembr. 30:
277-284, 1998.
3. Jabs, E. W.; Thomas, P. J.; Bernstein, M.; Coss, C.; Ferreira,
G. C.; Pedersen, P. L.: Chromosomal localization of genes required
for the terminal steps of oxidative metabolism: alpha and gamma subunits
of ATP synthase and the phosphate carrier. Hum. Genet. 93: 600-602,
1994.
4. Marsh, S.; Carter, N. P.; Dolce, V.; Iacobazzi, V.; Palmieri, F.
: Chromosomal localization of the mitochondrial phosphate carrier
gene PHC to 12q23. Genomics 29: 814-815, 1995.
5. Mayr, J. A.; Merkel, O.; Kohlwein, S. D.; Gebhardt, B. R.; Bohles,
H.; Fotschl, U.; Koch, J.; Jaksch, M.; Lochmuller, H.; Horvath, R.;
Freisinger, P.; Sperl, W.: Mitochondrial phosphate-carrier deficiency:
a novel disorder of oxidative phosphorylation. Am. J. Hum. Genet. 80:
478-484, 2007.
*FIELD* CN
Victor A. McKusick - updated: 2/15/2007
Wilson H. Y. Lo - updated: 8/10/1999
Alan F. Scott - updated: 11/8/1995
*FIELD* CD
Victor A. McKusick: 2/3/1995
*FIELD* ED
alopez: 02/19/2007
carol: 2/15/2007
terry: 3/28/2002
carol: 3/13/2000
carol: 8/10/1999
joanna: 5/8/1998
mark: 11/8/1995
carol: 2/3/1995
MIM
610773
*RECORD*
*FIELD* NO
610773
*FIELD* TI
#610773 MITOCHONDRIAL PHOSPHATE CARRIER DEFICIENCY
;;MPCD
*FIELD* TX
A number sign (#) is used with this entry because mitochondrial
read morephosphate carrier deficiency can be caused by mutation in the SLC25A3
gene (600370).
CLINICAL FEATURES
Mayr et al. (2007) described 2 sisters, offspring of nonconsanguineous
Turkish parents, with mitochondrial phosphate carrier deficiency. The
younger sister presented at age 12 hours with cyanosis and muscular
hypotonia that necessitated intensive care treatment. Echocardiography
revealed hypertrophic cardiomyopathy with low cardiac output. Lactate
was constantly elevated in plasma. Cardiac hypertrophy was progressive.
Severe muscular hypotonia and failure to thrive persisted. At age 4
months, she died from heart failure. Histologic examination of a muscle
biopsy showed lipid myopathy with lipid accumulation in both fiber
types, prominent in type I fibers. The elder sister presented at age 10
hours with muscular hypotonia, respiratory distress, metabolic acidosis
(pH 6.9), and lactic acidosis that necessitated intensive care
treatment. Artificial ventilation was necessary for 3 months. She
developed increasing hypertrophic cardiomyopathy. Metabolic workup
revealed constantly elevated plasma lactate and an increased
lactate:pyruvate ratio of 62. At age 9 months, she died from intractable
low-output hypertrophic heart failure.
MOLECULAR GENETICS
In 2 sibs with mitochondrial phosphate carrier deficiency, Mayr et al.
(2007) identified homozygosity for a mutation in the alternatively
spliced exon 3A of the SLC25A3 gene (600370.0001), which produces the
heart/muscle-specific isoform of mitochondrial phosphate carrier
protein. In both patients, functional investigation of intact
mitochondria showed a deficiency of ATP synthetase in muscle but not in
fibroblasts, which correlated with the tissue-specific expression of
exon 3A in muscle versus exon 3B in fibroblasts.
*FIELD* RF
1. Mayr, J. A.; Merkel, O.; Kohlwein, S. D.; Gebhardt, B. R.; Bohles,
H.; Fotschl, U.; Koch, J.; Jaksch, M.; Lochmuller, H.; Horvath, R.;
Freisinger, P.; Sperl, W.: Mitochondrial phosphate-carrier deficiency:
a novel disorder of oxidative phosphorylation. Am. J. Hum. Genet. 80:
478-484, 2007.
*FIELD* CD
Victor A. McKusick: 2/19/2007
*FIELD* ED
alopez: 02/19/2007
*RECORD*
*FIELD* NO
610773
*FIELD* TI
#610773 MITOCHONDRIAL PHOSPHATE CARRIER DEFICIENCY
;;MPCD
*FIELD* TX
A number sign (#) is used with this entry because mitochondrial
read morephosphate carrier deficiency can be caused by mutation in the SLC25A3
gene (600370).
CLINICAL FEATURES
Mayr et al. (2007) described 2 sisters, offspring of nonconsanguineous
Turkish parents, with mitochondrial phosphate carrier deficiency. The
younger sister presented at age 12 hours with cyanosis and muscular
hypotonia that necessitated intensive care treatment. Echocardiography
revealed hypertrophic cardiomyopathy with low cardiac output. Lactate
was constantly elevated in plasma. Cardiac hypertrophy was progressive.
Severe muscular hypotonia and failure to thrive persisted. At age 4
months, she died from heart failure. Histologic examination of a muscle
biopsy showed lipid myopathy with lipid accumulation in both fiber
types, prominent in type I fibers. The elder sister presented at age 10
hours with muscular hypotonia, respiratory distress, metabolic acidosis
(pH 6.9), and lactic acidosis that necessitated intensive care
treatment. Artificial ventilation was necessary for 3 months. She
developed increasing hypertrophic cardiomyopathy. Metabolic workup
revealed constantly elevated plasma lactate and an increased
lactate:pyruvate ratio of 62. At age 9 months, she died from intractable
low-output hypertrophic heart failure.
MOLECULAR GENETICS
In 2 sibs with mitochondrial phosphate carrier deficiency, Mayr et al.
(2007) identified homozygosity for a mutation in the alternatively
spliced exon 3A of the SLC25A3 gene (600370.0001), which produces the
heart/muscle-specific isoform of mitochondrial phosphate carrier
protein. In both patients, functional investigation of intact
mitochondria showed a deficiency of ATP synthetase in muscle but not in
fibroblasts, which correlated with the tissue-specific expression of
exon 3A in muscle versus exon 3B in fibroblasts.
*FIELD* RF
1. Mayr, J. A.; Merkel, O.; Kohlwein, S. D.; Gebhardt, B. R.; Bohles,
H.; Fotschl, U.; Koch, J.; Jaksch, M.; Lochmuller, H.; Horvath, R.;
Freisinger, P.; Sperl, W.: Mitochondrial phosphate-carrier deficiency:
a novel disorder of oxidative phosphorylation. Am. J. Hum. Genet. 80:
478-484, 2007.
*FIELD* CD
Victor A. McKusick: 2/19/2007
*FIELD* ED
alopez: 02/19/2007