MPC1_HUMAN
ID MPC1_HUMAN Reviewed; 109 AA.
AC Q9Y5U8; B2R5I7; Q5TI66; Q9HB67; Q9UQN4;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Mitochondrial pyruvate carrier 1;
DE AltName: Full=Brain protein 44-like protein;
GN Name=MPC1; Synonyms=BRP44L; ORFNames=CGI-129, HSPC040, PNAS-115;
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 [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 53-109.
RC TISSUE=Promyelocytic leukemia;
RA Yu W.-Q., Chai Y.-B., Sun B.-Z., Zhu F., Liu X.-S., Li Z., Lu F., Yan W.,
RA Yang H., Zhao Z.-L.;
RT "Human acute promyelocytic leukemia cell line NB4's apoptosis related
RT genes.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [7]
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 [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND VARIANTS MPYCD HIS-79 AND TRP-97.
RX PubMed=22628558; DOI=10.1126/science.1218099;
RA Bricker D.K., Taylor E.B., Schell J.C., Orsak T., Boutron A., Chen Y.C.,
RA Cox J.E., Cardon C.M., Van Vranken J.G., Dephoure N., Redin C., Boudina S.,
RA Gygi S.P., Brivet M., Thummel C.S., Rutter J.;
RT "A mitochondrial pyruvate carrier required for pyruvate uptake in yeast,
RT Drosophila, and humans.";
RL Science 337:96-100(2012).
RN [9]
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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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).
CC -!- FUNCTION: Mediates the uptake of pyruvate into mitochondria.
CC {ECO:0000269|PubMed:22628558}.
CC -!- SUBUNIT: The functional 150 kDa pyruvate import complex is a heteromer
CC of MPC1 and MPC2. {ECO:0000250|UniProtKB:P63030}.
CC -!- INTERACTION:
CC Q9Y5U8; O95563: MPC2; NbExp=3; IntAct=EBI-721137, EBI-719403;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:22628558}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:22628558}.
CC -!- DISEASE: Mitochondrial pyruvate carrier deficiency (MPYCD)
CC [MIM:614741]: An autosomal recessive metabolic disorder characterized
CC by severely delayed psychomotor development, mild dysmorphic features,
CC hepatomegaly, marked metabolic acidosis, hyperlactacidemia with normal
CC lactate/pyruvate, and encephalopathy. Some patients have epilepsy and
CC peripheral neuropathy. {ECO:0000269|PubMed:22628558}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the mitochondrial pyruvate carrier (MPC) (TC
CC 2.A.105) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG23822.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF125101; AAD39918.1; -; mRNA.
DR EMBL; AF151887; AAD34124.1; -; mRNA.
DR EMBL; AK312201; BAG35134.1; -; mRNA.
DR EMBL; AL022069; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000810; AAH00810.1; -; mRNA.
DR EMBL; AF275811; AAG23822.1; ALT_INIT; mRNA.
DR CCDS; CCDS5293.1; -.
DR RefSeq; NP_057182.1; NM_016098.3.
DR AlphaFoldDB; Q9Y5U8; -.
DR SMR; Q9Y5U8; -.
DR BioGRID; 119665; 5.
DR ComplexPortal; CPX-6154; Mitochondrial pyruvate carrier complex.
DR IntAct; Q9Y5U8; 4.
DR STRING; 9606.ENSP00000354223; -.
DR TCDB; 2.A.105.1.2; the mitochondrial pyruvate carrier (mpc) family.
DR iPTMnet; Q9Y5U8; -.
DR PhosphoSitePlus; Q9Y5U8; -.
DR SwissPalm; Q9Y5U8; -.
DR BioMuta; MPC1; -.
DR EPD; Q9Y5U8; -.
DR jPOST; Q9Y5U8; -.
DR MassIVE; Q9Y5U8; -.
DR MaxQB; Q9Y5U8; -.
DR PaxDb; Q9Y5U8; -.
DR PeptideAtlas; Q9Y5U8; -.
DR PRIDE; Q9Y5U8; -.
DR ProteomicsDB; 86511; -.
DR TopDownProteomics; Q9Y5U8; -.
DR Antibodypedia; 49022; 146 antibodies from 25 providers.
DR DNASU; 51660; -.
DR Ensembl; ENST00000360961.11; ENSP00000354223.6; ENSG00000060762.19.
DR GeneID; 51660; -.
DR KEGG; hsa:51660; -.
DR MANE-Select; ENST00000360961.11; ENSP00000354223.6; NM_016098.4; NP_057182.1.
DR UCSC; uc063svb.1; human.
DR CTD; 51660; -.
DR DisGeNET; 51660; -.
DR GeneCards; MPC1; -.
DR HGNC; HGNC:21606; MPC1.
DR HPA; ENSG00000060762; Tissue enhanced (heart muscle, tongue).
DR MalaCards; MPC1; -.
DR MIM; 614738; gene.
DR MIM; 614741; phenotype.
DR neXtProt; NX_Q9Y5U8; -.
DR OpenTargets; ENSG00000060762; -.
DR Orphanet; 447784; Mitochondrial pyruvate carrier deficiency.
DR PharmGKB; PA134940737; -.
DR VEuPathDB; HostDB:ENSG00000060762; -.
DR eggNOG; KOG1590; Eukaryota.
DR GeneTree; ENSGT00510000046988; -.
DR HOGENOM; CLU_099502_3_2_1; -.
DR InParanoid; Q9Y5U8; -.
DR OrthoDB; 1584711at2759; -.
DR PhylomeDB; Q9Y5U8; -.
DR TreeFam; TF314444; -.
DR PathwayCommons; Q9Y5U8; -.
DR Reactome; R-HSA-70268; Pyruvate metabolism.
DR SignaLink; Q9Y5U8; -.
DR BioGRID-ORCS; 51660; 11 hits in 1078 CRISPR screens.
DR ChiTaRS; MPC1; human.
DR GenomeRNAi; 51660; -.
DR Pharos; Q9Y5U8; Tbio.
DR PRO; PR:Q9Y5U8; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9Y5U8; protein.
DR Bgee; ENSG00000060762; Expressed in heart right ventricle and 199 other tissues.
DR ExpressionAtlas; Q9Y5U8; baseline and differential.
DR Genevisible; Q9Y5U8; HS.
DR GO; GO:0098800; C:inner mitochondrial membrane protein complex; IC:ComplexPortal.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0050833; F:pyruvate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0006850; P:mitochondrial pyruvate transmembrane transport; IBA:GO_Central.
DR InterPro; IPR005336; MPC.
DR Pfam; PF03650; MPC; 1.
PE 1: Evidence at protein level;
KW Acetylation; Disease variant; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:25944712"
FT CHAIN 2..109
FT /note="Mitochondrial pyruvate carrier 1"
FT /id="PRO_0000212797"
FT TRANSMEM 21..41
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 53..71
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:25944712"
FT MOD_RES 72
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P63030"
FT VARIANT 36
FT /note="L -> I (in dbSNP:rs11557064)"
FT /id="VAR_052486"
FT VARIANT 79
FT /note="L -> H (in MPYCD; dbSNP:rs387907238)"
FT /evidence="ECO:0000269|PubMed:22628558"
FT /id="VAR_068099"
FT VARIANT 97
FT /note="R -> W (in MPYCD; inactive; dbSNP:rs387907237)"
FT /evidence="ECO:0000269|PubMed:22628558"
FT /id="VAR_068100"
FT CONFLICT 14
FT /note="R -> Q (in Ref. 2; AAD34124)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 109 AA; 12347 MW; E33344CD1AA29124 CRC64;
MAGALVRKAA DYVRSKDFRD YLMSTHFWGP VANWGLPIAA INDMKKSPEI ISGRMTFALC
CYSLTFMRFA YKVQPRNWLL FACHATNEVA QLIQGGRLIK HEMTKTASA
