ID MCAT_HUMAN Reviewed; 301 AA. AC O43772; B2R7F4; Q9UIQ2; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 27-MAR-2024, entry version 198. DE RecName: Full=Mitochondrial carnitine/acylcarnitine carrier protein {ECO:0000305}; DE AltName: Full=Carnitine/acylcarnitine translocase {ECO:0000303|PubMed:12892634}; DE Short=CAC {ECO:0000303|PubMed:18307102}; DE Short=CACT {ECO:0000303|PubMed:12892634}; DE AltName: Full=Solute carrier family 25 member 20; GN Name=SLC25A20 {ECO:0000312|HGNC:HGNC:1421}; Synonyms=CAC, CACT; 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], AND DISEASE. RC TISSUE=Liver; RX PubMed=9399886; DOI=10.1086/301628; RA Huizing M., Iacobazzi V., Ijlst L., Savelkoul P., Ruitenbeek W., RA van den Heuvel L., Indiveri C., Smeitink J., Trijbels F., Wanders R., RA Palmieri F.; RT "Cloning of the human carnitine-acylcarnitine carrier cDNA and RT identification of the molecular defect in a patient."; RL Am. J. Hum. Genet. 61:1239-1245(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9837782; DOI=10.1006/bbrc.1998.9738; RA Iacobazzi V., Naglieri M.A., Stanley C.A., Wanders R.J.A., Palmieri F.; RT "The structure and organization of the human carnitine/acylcarnitine RT translocase (CACT) gene."; RL Biochem. Biophys. Res. Commun. 252:770-774(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 MRNA]. RC TISSUE=Skin; 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 [5] RP FUNCTION, AND TRANSPORT ACTIVITY. RX PubMed=12892634; DOI=10.1016/s1087-1845(03)00049-5; RA Perez P., Martinez O., Romero B., Olivas I., Pedregosa A.M., Palmieri F., RA Laborda F., Ramon De Lucas J.; RT "Functional analysis of mutations in the human carnitine/acylcarnitine RT translocase in Aspergillus nidulans."; RL Fungal Genet. Biol. 39:211-220(2003). RN [6] RP FUNCTION, AND TRANSPORT ACTIVITY. RX PubMed=18307102; DOI=10.1080/09687680701697476; RA De Lucas J.R., Indiveri C., Tonazzi A., Perez P., Giangregorio N., RA Iacobazzi V., Palmieri F.; RT "Functional characterization of residues within the carnitine/acylcarnitine RT translocase RX2PANAAXF distinct motif."; RL Mol. Membr. Biol. 25:152-163(2008). RN [7] RP FUNCTION, AND TRANSPORT ACTIVITY. RX PubMed=20347717; DOI=10.1016/j.bbabio.2010.03.017; RA Giangregorio N., Tonazzi A., Console L., Indiveri C., Palmieri F.; RT "Site-directed mutagenesis of charged amino acids of the human RT mitochondrial carnitine/acylcarnitine carrier: insight into the molecular RT mechanism of transport."; RL Biochim. Biophys. Acta 1797:839-845(2010). RN [8] 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 [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). RN [11] RP VARIANT CACTD ARG-238. RX PubMed=12859414; DOI=10.1034/j.1399-0004.2003.00117.x; RA Al-Aqeel A.I., Rashid M.S., Ruiter J.P., Ijlst L., Wanders R.J.A.; RT "A novel molecular defect of the carnitine acylcarnitine translocase gene RT in a Saudi patient."; RL Clin. Genet. 64:163-165(2003). RN [12] RP VARIANT CACTD ARG-238. RX PubMed=15057979; DOI=10.1002/ajmg.a.20573; RA Iacobazzi V., Pasquali M., Singh R., Matern D., Rinaldo P., RA Amat di San Filippo C., Palmieri F., Longo N.; RT "Response to therapy in carnitine/acylcarnitine translocase (CACT) RT deficiency due to a novel missense mutation."; RL Am. J. Med. Genet. A 126:150-155(2004). RN [13] RP VARIANTS CACTD TRP-133 AND HIS-231. RX PubMed=15365988; DOI=10.1002/humu.20085; RA Iacobazzi V., Invernizzi F., Baratta S., Pons R., Chung W., Garavaglia B., RA Dionisi-Vici C., Ribes A., Parini R., Huertas M.D., Roldan S., Lauria G., RA Palmieri F., Taroni F.; RT "Molecular and functional analysis of SLC25A20 mutations causing carnitine- RT acylcarnitine translocase deficiency."; RL Hum. Mutat. 24:312-320(2004). CC -!- FUNCTION: Mediates the electroneutral exchange of acylcarnitines (O- CC acyl-(R)-carnitine or L-acylcarnitine) of different acyl chain lengths CC (ranging from O-acetyl-(R)-carnitine to long-chain O-acyl-(R)- CC carnitines) with free carnitine ((R)-carnitine or L-carnitine) across CC the mitochondrial inner membrane, via a ping-pong mechanism CC (PubMed:12892634, PubMed:18307102) (Probable). Key player in the CC mitochondrial oxidation pathway, it translocates the fatty acids in the CC form of acylcarnitines into the mitochondrial matrix, where the CC carnitine palmitoyltransferase 2 (CPT-2) activates them to undergo CC fatty acid beta-oxidation (Probable). Catalyzes the unidirectional CC transport (uniport) of carnitine at lower rates than the antiport CC (exchange) (PubMed:18307102). {ECO:0000269|PubMed:12892634, CC ECO:0000269|PubMed:18307102, ECO:0000305|PubMed:18307102, CC ECO:0000305|PubMed:20347717}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-carnitine(out) + O-acetyl-(R)-carnitine(in) = (R)- CC carnitine(in) + O-acetyl-(R)-carnitine(out); Xref=Rhea:RHEA:49908, CC ChEBI:CHEBI:16347, ChEBI:CHEBI:57589; CC Evidence={ECO:0000269|PubMed:12892634, ECO:0000269|PubMed:18307102}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-carnitine(out) + O-acyl-(R)-carnitine(in) = (R)- CC carnitine(in) + O-acyl-(R)-carnitine(out); Xref=Rhea:RHEA:49924, CC ChEBI:CHEBI:16347, ChEBI:CHEBI:75659; CC Evidence={ECO:0000305|PubMed:12892634, ECO:0000305|PubMed:18307102, CC ECO:0000305|PubMed:20347717}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-carnitine(out) + O-propanoyl-(R)-carnitine(in) = (R)- CC carnitine(in) + O-propanoyl-(R)-carnitine(out); Xref=Rhea:RHEA:49912, CC ChEBI:CHEBI:16347, ChEBI:CHEBI:53210; CC Evidence={ECO:0000250|UniProtKB:P97521}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-carnitine(out) + O-hexadecanoyl-(R)-carnitine(in) = (R)- CC carnitine(in) + O-hexadecanoyl-(R)-carnitine(out); CC Xref=Rhea:RHEA:49916, ChEBI:CHEBI:16347, ChEBI:CHEBI:17490; CC Evidence={ECO:0000250|UniProtKB:P97521}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-carnitine(out) + O-octanoyl-(R)-carnitine(in) = (R)- CC carnitine(in) + O-octanoyl-(R)-carnitine(out); Xref=Rhea:RHEA:49920, CC ChEBI:CHEBI:16347, ChEBI:CHEBI:18102; CC Evidence={ECO:0000250|UniProtKB:P97521}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-carnitine(in) = (R)-carnitine(out); Xref=Rhea:RHEA:34959, CC ChEBI:CHEBI:16347; Evidence={ECO:0000269|PubMed:18307102}; CC -!- INTERACTION: CC O43772; P13473-2: LAMP2; NbExp=3; IntAct=EBI-727085, EBI-21591415; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane CC protein. CC -!- DISEASE: Carnitine-acylcarnitine translocase deficiency (CACTD) CC [MIM:212138]: A rare long-chain fatty acid oxidation disorder. CC Metabolic consequences include hypoketotic hypoglycemia under fasting CC conditions, hyperammonemia, elevated creatine kinase and transaminases, CC dicarboxylic aciduria, very low free carnitine and abnormal CC acylcarnitine profile with marked elevation of the long-chain CC acylcarnitines. Clinical features include neurologic abnormalities, CC cardiomyopathy, arrhythmias, skeletal muscle damage, liver dysfunction CC and episodes of life-threatening coma, which eventually lead to death. CC Most patients become symptomatic in the neonatal period with a rapidly CC progressive deterioration and a high mortality rate. CC {ECO:0000269|PubMed:12859414, ECO:0000269|PubMed:15057979, CC ECO:0000269|PubMed:15365988}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y10319; CAA71367.1; -; mRNA. DR EMBL; Y17775; CAB55356.1; -; Genomic_DNA. DR EMBL; Y17776; CAB55356.1; JOINED; Genomic_DNA. DR EMBL; Y17777; CAB55356.1; JOINED; Genomic_DNA. DR EMBL; Y17778; CAB55356.1; JOINED; Genomic_DNA. DR EMBL; Y17779; CAB55356.1; JOINED; Genomic_DNA. DR EMBL; AK312962; BAG35801.1; -; mRNA. DR EMBL; BC001689; AAH01689.1; -; mRNA. DR CCDS; CCDS2779.1; -. DR RefSeq; NP_000378.1; NM_000387.5. DR AlphaFoldDB; O43772; -. DR SMR; O43772; -. DR BioGRID; 107241; 65. DR IntAct; O43772; 17. DR STRING; 9606.ENSP00000326305; -. DR BindingDB; O43772; -. DR ChEMBL; CHEMBL2216740; -. DR DrugBank; DB00583; Levocarnitine. DR TCDB; 2.A.29.8.3; the mitochondrial carrier (mc) family. DR iPTMnet; O43772; -. DR PhosphoSitePlus; O43772; -. DR SwissPalm; O43772; -. DR BioMuta; SLC25A20; -. DR EPD; O43772; -. DR jPOST; O43772; -. DR MassIVE; O43772; -. DR MaxQB; O43772; -. DR PaxDb; 9606-ENSP00000326305; -. DR PeptideAtlas; O43772; -. DR ProteomicsDB; 49166; -. DR Pumba; O43772; -. DR TopDownProteomics; O43772; -. DR Antibodypedia; 3111; 257 antibodies from 27 providers. DR DNASU; 788; -. DR Ensembl; ENST00000319017.5; ENSP00000326305.4; ENSG00000178537.10. DR GeneID; 788; -. DR KEGG; hsa:788; -. DR MANE-Select; ENST00000319017.5; ENSP00000326305.4; NM_000387.6; NP_000378.1. DR UCSC; uc003cva.5; human. DR AGR; HGNC:1421; -. DR CTD; 788; -. DR DisGeNET; 788; -. DR GeneCards; SLC25A20; -. DR GeneReviews; SLC25A20; -. DR HGNC; HGNC:1421; SLC25A20. DR HPA; ENSG00000178537; Tissue enhanced (liver). DR MalaCards; SLC25A20; -. DR MIM; 212138; phenotype. DR MIM; 613698; gene. DR neXtProt; NX_O43772; -. DR OpenTargets; ENSG00000178537; -. DR Orphanet; 159; Carnitine-acylcarnitine translocase deficiency. DR PharmGKB; PA35031; -. DR VEuPathDB; HostDB:ENSG00000178537; -. DR eggNOG; KOG0758; Eukaryota. DR GeneTree; ENSGT00940000157863; -. DR HOGENOM; CLU_015166_16_0_1; -. DR InParanoid; O43772; -. DR OMA; QQKCPED; -. DR OrthoDB; 4064096at2759; -. DR PhylomeDB; O43772; -. DR TreeFam; TF300894; -. DR BioCyc; MetaCyc:ENSG00000178537-MONOMER; -. DR PathwayCommons; O43772; -. DR Reactome; R-HSA-200425; Carnitine metabolism. DR SignaLink; O43772; -. DR SIGNOR; O43772; -. DR BioGRID-ORCS; 788; 14 hits in 1159 CRISPR screens. DR ChiTaRS; SLC25A20; human. DR GenomeRNAi; 788; -. DR Pharos; O43772; Tbio. DR PRO; PR:O43772; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; O43772; Protein. DR Bgee; ENSG00000178537; Expressed in right lobe of liver and 196 other cell types or tissues. DR ExpressionAtlas; O43772; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005740; C:mitochondrial envelope; IBA:GO_Central. DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0015227; F:acyl carnitine transmembrane transporter activity; EXP:Reactome. DR GO; GO:0006853; P:carnitine shuttle; TAS:Reactome. DR GO; GO:1902603; P:carnitine transmembrane transport; ISS:UniProtKB. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0006839; P:mitochondrial transport; IBA:GO_Central. DR Gene3D; 1.50.40.10; Mitochondrial carrier domain; 2. DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier. DR InterPro; IPR023395; Mt_carrier_dom_sf. DR PANTHER; PTHR45624; MITOCHONDRIAL BASIC AMINO ACIDS TRANSPORTER-RELATED; 1. DR PANTHER; PTHR45624:SF56; MITOCHONDRIAL CARNITINE_ACYLCARNITINE CARRIER PROTEIN; 1. DR Pfam; PF00153; Mito_carr; 3. DR SUPFAM; SSF103506; Mitochondrial carrier; 1. DR PROSITE; PS50920; SOLCAR; 3. DR Genevisible; O43772; HS. PE 1: Evidence at protein level; KW Acetylation; Disease variant; Lipid transport; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Reference proteome; Repeat; Transmembrane; KW Transmembrane helix; Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:25944712" FT CHAIN 2..301 FT /note="Mitochondrial carnitine/acylcarnitine carrier FT protein" FT /id="PRO_0000090628" FT TOPO_DOM 2..12 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 13..31 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 32..73 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000255" FT TRANSMEM 74..93 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 94..112 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 113..131 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 132..170 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000255" FT TRANSMEM 171..190 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 191..211 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 212..230 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 231..267 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000255" FT TRANSMEM 268..287 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 288..301 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REPEAT 8..99 FT /note="Solcar 1" FT REPEAT 108..196 FT /note="Solcar 2" FT REPEAT 207..293 FT /note="Solcar 3" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:25944712" FT MOD_RES 148 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9Z2Z6" FT MOD_RES 157 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9Z2Z6" FT MOD_RES 170 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9Z2Z6" FT MOD_RES 170 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9Z2Z6" FT VARIANT 133 FT /note="R -> W (in CACTD; dbSNP:rs748394731)" FT /evidence="ECO:0000269|PubMed:15365988" FT /id="VAR_021818" FT VARIANT 231 FT /note="D -> H (in CACTD; dbSNP:rs577331691)" FT /evidence="ECO:0000269|PubMed:15365988" FT /id="VAR_021819" FT VARIANT 238 FT /note="Q -> R (in CACTD; dbSNP:rs28934589)" FT /evidence="ECO:0000269|PubMed:12859414, FT ECO:0000269|PubMed:15057979" FT /id="VAR_021820" FT CONFLICT 203 FT /note="R -> S (in Ref. 2; CAB55356)" FT /evidence="ECO:0000305" FT CONFLICT 240 FT /note="A -> G (in Ref. 2; CAB55356)" FT /evidence="ECO:0000305" SQ SEQUENCE 301 AA; 32944 MW; AEB34E4E335102B0 CRC64; MADQPKPISP LKNLLAGGFG GVCLVFVGHP LDTVKVRLQT QPPSLPGQPP MYSGTFDCFR KTLFREGITG LYRGMAAPII GVTPMFAVCF FGFGLGKKLQ QKHPEDVLSY PQLFAAGMLS GVFTTGIMTP GERIKCLLQI QASSGESKYT GTLDCAKKLY QEFGIRGIYK GTVLTLMRDV PASGMYFMTY EWLKNIFTPE GKRVSELSAP RILVAGGIAG IFNWAVAIPP DVLKSRFQTA PPGKYPNGFR DVLRELIRDE GVTSLYKGFN AVMIRAFPAN AACFLGFEVA MKFLNWATPN L //