ID S2547_MOUSE Reviewed; 310 AA.
AC Q6IS41; Q3UES2; Q5FW58; Q7TPP3;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 24-JAN-2024, entry version 129.
DE RecName: Full=Solute carrier family 25 member 47;
DE AltName: Full=Hepatocellular carcinoma down-regulated mitochondrial carrier homolog;
DE AltName: Full=Mitochondrial NAD(+) transporter SLC25A47 {ECO:0000303|PubMed:36804859};
GN Name=Slc25a47 {ECO:0000303|PubMed:36804859, ECO:0000312|MGI:MGI:2144766};
GN Synonyms=Hdmcp;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=36804859; DOI=10.1097/hep.0000000000000314;
RA Cheng L., Deepak R.N.V.K., Wang G., Meng Z., Tao L., Xie M., Chi W.,
RA Zhang Y., Yang M., Liao Y., Chen R., Liang Y., Zhang J., Huang Y., Wang W.,
RA Guo Z., Wang Y., Lin J.D., Fan H., Chen L.;
RT "Hepatic mitochondrial NAD + transporter SLC25A47 activates AMPKalpha
RT mediating lipid metabolism and tumorigenesis.";
RL Hepatology 0:0-0(2023).
CC -!- FUNCTION: Mitochondrial NAD(+) transporter that acts as a 'metabolic
CC gate' in hepatic lipogenesis. Provides NAD(+) substrate to
CC mitochondrial SIRT3 deacetylase and enables its NAD(+)-dependent
CC activities in mitochondrial energy metabolism. This triggers downstream
CC activation of PRKAA1/AMPK-alpha signaling cascade that negatively
CC regulates sterol regulatory element-binding protein (SREBP)
CC transcriptional activities and ATP-consuming lipogenesis to restore
CC cellular energy balance. May transport other mitochondrial metabolites
CC having an aromatic nucleotide and phosphate groups, such as acetyl-CoA.
CC Does not transport amino acids. The transport mechanism remains to be
CC elucidated. {ECO:0000269|PubMed:36804859}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+)(in) = NAD(+)(out); Xref=Rhea:RHEA:65408,
CC ChEBI:CHEBI:57540; Evidence={ECO:0000269|PubMed:36804859};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA(in) = acetyl-CoA(out); Xref=Rhea:RHEA:75039,
CC ChEBI:CHEBI:57288; Evidence={ECO:0000269|PubMed:36804859};
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:36804859}; Multi-pass membrane protein
CC {ECO:0000255}. Mitochondrion outer membrane
CC {ECO:0000269|PubMed:36804859}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in liver (at protein level).
CC {ECO:0000269|PubMed:36804859}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice show increased hepatic steatosis upon
CC methionine- and choline-deficient or high-fat diet associated with
CC increased hepatic lipid droplets and triglycerides and cholesterol
CC levels. They spontaneously develop hepatocellular carcinomas.
CC {ECO:0000269|PubMed:36804859}.
CC -!- MISCELLANEOUS: SLC25A47 is transcriptionally up-regulated in response
CC to antihyperglycemic drug metformin. Promotes metformin pharmacological
CC effects. {ECO:0000269|PubMed:36804859}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH55027.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK149369; BAE28839.1; -; mRNA.
DR EMBL; BC055027; AAH55027.1; ALT_INIT; mRNA.
DR EMBL; BC069939; AAH69939.2; -; mRNA.
DR EMBL; BC089616; AAH89616.1; -; mRNA.
DR CCDS; CCDS26165.1; -.
DR RefSeq; NP_001012310.2; NM_001012310.2.
DR AlphaFoldDB; Q6IS41; -.
DR SMR; Q6IS41; -.
DR STRING; 10090.ENSMUSP00000050329; -.
DR iPTMnet; Q6IS41; -.
DR PhosphoSitePlus; Q6IS41; -.
DR PaxDb; 10090-ENSMUSP00000050329; -.
DR Antibodypedia; 27517; 95 antibodies from 23 providers.
DR DNASU; 104910; -.
DR Ensembl; ENSMUST00000057026.10; ENSMUSP00000050329.9; ENSMUSG00000048856.10.
DR GeneID; 104910; -.
DR KEGG; mmu:104910; -.
DR UCSC; uc007pae.1; mouse.
DR AGR; MGI:2144766; -.
DR CTD; 283600; -.
DR MGI; MGI:2144766; Slc25a47.
DR VEuPathDB; HostDB:ENSMUSG00000048856; -.
DR eggNOG; KOG0762; Eukaryota.
DR GeneTree; ENSGT00940000159694; -.
DR HOGENOM; CLU_015166_16_1_1; -.
DR InParanoid; Q6IS41; -.
DR OMA; HICRLRY; -.
DR OrthoDB; 4064096at2759; -.
DR PhylomeDB; Q6IS41; -.
DR TreeFam; TF351739; -.
DR BioGRID-ORCS; 104910; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Slc25a47; mouse.
DR PRO; PR:Q6IS41; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q6IS41; Protein.
DR Bgee; ENSMUSG00000048856; Expressed in left lobe of liver and 161 other cell types or tissues.
DR ExpressionAtlas; Q6IS41; baseline and differential.
DR Genevisible; Q6IS41; MM.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0008521; F:acetyl-CoA transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0051724; F:NAD transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR Gene3D; 1.50.40.10; Mitochondrial carrier domain; 2.
DR InterPro; IPR002067; Mit_carrier.
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:SF3; SOLUTE CARRIER FAMILY 25 MEMBER 47; 1.
DR Pfam; PF00153; Mito_carr; 3.
DR PRINTS; PR00926; MITOCARRIER.
DR SUPFAM; SSF103506; Mitochondrial carrier; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Mitochondrion outer membrane; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..310
FT /note="Solute carrier family 25 member 47"
FT /id="PRO_0000291780"
FT TRANSMEM 3..23
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 55..75
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 98..114
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 194..210
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 219..239
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 280..298
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 1..80
FT /note="Solcar 1"
FT REPEAT 93..208
FT /note="Solcar 2"
FT REPEAT 217..304
FT /note="Solcar 3"
FT CONFLICT 182
FT /note="K -> M (in Ref. 2; AAH89616)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 310 AA; 33646 MW; F5571D9E0D9431F0 CRC64;
MDFVAGAIGG VCGVAVGYPL DTVKVRIQTE AKYAGIWHCI RDTYRQERVW GFYRGLSLPV
CTVSLVSSVS FGTYHHCLAH ICRFRYGSTD AKPTKADITL SGCASGLVRV FLTSPTEVAK
VRLQTQTQAQ TQQRRSSASW TSGAPALCPT PTACLEPRPK YSGPLHCLVT VAREEGLRGL
YKGSSALLLR EGHSFATYFL SYAMLCEWLT PAGHSQPDVL GVLVAGGCAG VLAWAVATPM
DVIKSRLQAD GQGQHRYRGL LHCVVTSVRE EGPRVLFKGL ALNCCRAFPV NMVVFVAYEA
VLRLTQSLLT
//
