S2533_HUMAN
ID S2533_HUMAN Reviewed; 321 AA.
AC Q9BSK2;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Solute carrier family 25 member 33;
DE AltName: Full=Bone marrow stromal cell mitochondrial carrier protein;
DE Short=BMSC-MCP;
DE Short=HuBMSC-MCP;
DE AltName: Full=Protein PNC1;
GN Name=SLC25A33;
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], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=14715278; DOI=10.1016/j.bbrc.2003.12.071;
RA Wang B., Li N., Sui L., Wu Y., Wang X., Wang Q., Xia D., Wan T., Cao X.;
RT "HuBMSC-MCP, a novel member of mitochondrial carrier superfamily, enhances
RT dendritic cell endocytosis.";
RL Biochem. Biophys. Res. Commun. 314:292-300(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, AND FUNCTION.
RC TISSUE=Testis;
RX PubMed=17596519; DOI=10.1091/mbc.e06-12-1109;
RA Floyd S., Favre C., Lasorsa F.M., Leahy M., Trigiante G., Stroebel P.,
RA Marx A., Loughran G., O'Callaghan K., Marobbio C.M., Slotboom D.J.,
RA Kunji E.R., Palmieri F., O'Connor R.;
RT "The insulin-like growth factor-I-mTOR signaling pathway induces the
RT mitochondrial pyrimidine nucleotide carrier to promote cell growth.";
RL Mol. Biol. Cell 18:3545-3555(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, and 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 IDENTIFICATION.
RX PubMed=16949250; DOI=10.1016/j.ygeno.2006.06.016;
RA Haitina T., Lindblom J., Renstroem T., Fredriksson R.;
RT "Fourteen novel human members of mitochondrial solute carrier family 25
RT (SLC25) widely expressed in the central nervous system.";
RL Genomics 88:779-790(2006).
RN [6]
RP FUNCTION.
RX PubMed=20453889; DOI=10.1038/onc.2010.146;
RA Favre C., Zhdanov A., Leahy M., Papkovsky D., O'Connor R.;
RT "Mitochondrial pyrimidine nucleotide carrier (PNC1) regulates mitochondrial
RT biogenesis and the invasive phenotype of cancer cells.";
RL Oncogene 29:3964-3976(2010).
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, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=25320081; DOI=10.1074/jbc.m114.610808;
RA Di Noia M.A., Todisco S., Cirigliano A., Rinaldi T., Agrimi G.,
RA Iacobazzi V., Palmieri F.;
RT "The human SLC25A33 and SLC25A36 genes of solute carrier family 25 encode
RT two mitochondrial pyrimidine nucleotide transporters.";
RL J. Biol. Chem. 289:33137-33148(2014).
CC -!- FUNCTION: Mitochondrial transporter that imports/exports pyrimidine
CC nucleotides into and from mitochondria (PubMed:25320081). Transports
CC preferentially uracil, thymine, and cytosine (deoxy)nucleoside di- and
CC triphosphates by an antiport mechanism (PubMed:25320081). Also
CC transports guanine but not adenine (deoxy)nucleotides
CC (PubMed:25320081). Is inhibited strongly by pyridoxal 5'-phosphate,
CC 4,7-diphenyl-1,10-phenanthroline, tannic acid, and mercurials (mercury
CC dichloride, mersalyl acid, p-hydroxymercuribenzoate) (PubMed:25320081).
CC Participates in mitochondrial genome maintenance, regulation of
CC mitochondrial membrane potential and mitochondrial respiration
CC (PubMed:20453889). Upon INS or IGF1 stimulation regulates cell growth
CC and proliferation by controlling mitochondrial DNA replication and
CC transcription, the ratio of mitochondria-to nuclear-encoded components
CC of the electron transport chain resulting in control of mitochondrial
CC ROS production (PubMed:20453889, PubMed:17596519). Participates in
CC dendritic cell endocytosis and may associate with mitochondrial
CC oxidative phosphorylation (PubMed:14715278).
CC {ECO:0000269|PubMed:14715278, ECO:0000269|PubMed:17596519,
CC ECO:0000269|PubMed:20453889, ECO:0000269|PubMed:25320081}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.16 mM for UTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC KM=0.18 mM for CTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC KM=0.08 mM for TTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC KM=0.30 mM for GTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC Vmax=98.5 umol/min/g enzyme toward UTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC Vmax=22.5 umol/min/g enzyme toward CTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC Vmax=50.8 umol/min/g enzyme toward TTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC Vmax=15.7 umol/min/g enzyme toward GTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC Note=The inhibitory constants (Ki) of these compounds are 174 um
CC (UTP), 195 um (CTP), 318 um (GTP), and 333 um (ITP). UTP is the best
CC substrate. {ECO:0000269|PubMed:25320081};
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000305|PubMed:14715278}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in the central nervous system. Also
CC expressed in testis and skeletal muscle. Weakly expressed in heart,
CC liver, kidney, prostate, colon and peripheral blood leukocytes.
CC {ECO:0000269|PubMed:14715278}.
CC -!- INDUCTION: By INS or IGF1 through the PI-3 kinase/mTOR pathway.
CC {ECO:0000269|PubMed:17596519}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; AF495714; AAM18051.1; -; mRNA.
DR EMBL; AJ880283; CAI54244.1; -; mRNA.
DR EMBL; AL954705; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL928921; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004991; AAH04991.1; -; mRNA.
DR EMBL; BC073135; AAH73135.1; -; mRNA.
DR CCDS; CCDS103.1; -.
DR RefSeq; NP_115691.1; NM_032315.2.
DR AlphaFoldDB; Q9BSK2; -.
DR SMR; Q9BSK2; -.
DR BioGRID; 124002; 43.
DR IntAct; Q9BSK2; 5.
DR MINT; Q9BSK2; -.
DR STRING; 9606.ENSP00000306328; -.
DR TCDB; 2.A.29.10.7; the mitochondrial carrier (mc) family.
DR iPTMnet; Q9BSK2; -.
DR PhosphoSitePlus; Q9BSK2; -.
DR BioMuta; SLC25A33; -.
DR DMDM; 74752304; -.
DR EPD; Q9BSK2; -.
DR jPOST; Q9BSK2; -.
DR MassIVE; Q9BSK2; -.
DR MaxQB; Q9BSK2; -.
DR PaxDb; Q9BSK2; -.
DR PeptideAtlas; Q9BSK2; -.
DR PRIDE; Q9BSK2; -.
DR ProteomicsDB; 78911; -.
DR Antibodypedia; 53479; 76 antibodies from 18 providers.
DR DNASU; 84275; -.
DR Ensembl; ENST00000302692.7; ENSP00000306328.5; ENSG00000171612.7.
DR GeneID; 84275; -.
DR KEGG; hsa:84275; -.
DR MANE-Select; ENST00000302692.7; ENSP00000306328.5; NM_032315.3; NP_115691.1.
DR UCSC; uc001apw.4; human.
DR CTD; 84275; -.
DR DisGeNET; 84275; -.
DR GeneCards; SLC25A33; -.
DR HGNC; HGNC:29681; SLC25A33.
DR HPA; ENSG00000171612; Tissue enhanced (tongue).
DR MIM; 610816; gene.
DR neXtProt; NX_Q9BSK2; -.
DR OpenTargets; ENSG00000171612; -.
DR PharmGKB; PA162403588; -.
DR VEuPathDB; HostDB:ENSG00000171612; -.
DR eggNOG; KOG0757; Eukaryota.
DR GeneTree; ENSGT00940000158954; -.
DR HOGENOM; CLU_015166_6_0_1; -.
DR InParanoid; Q9BSK2; -.
DR OMA; PTWAVYM; -.
DR OrthoDB; 1372287at2759; -.
DR PhylomeDB; Q9BSK2; -.
DR TreeFam; TF314220; -.
DR PathwayCommons; Q9BSK2; -.
DR SignaLink; Q9BSK2; -.
DR BioGRID-ORCS; 84275; 50 hits in 1074 CRISPR screens.
DR ChiTaRS; SLC25A33; human.
DR GenomeRNAi; 84275; -.
DR Pharos; Q9BSK2; Tbio.
DR PRO; PR:Q9BSK2; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9BSK2; protein.
DR Bgee; ENSG00000171612; Expressed in putamen and 98 other tissues.
DR Genevisible; Q9BSK2; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0015218; F:pyrimidine nucleotide transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProtKB.
DR GO; GO:1990314; P:cellular response to insulin-like growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0031930; P:mitochondria-nucleus signaling pathway; ISS:UniProtKB.
DR GO; GO:0000002; P:mitochondrial genome maintenance; IDA:UniProtKB.
DR GO; GO:0034551; P:mitochondrial respiratory chain complex III assembly; IMP:UniProtKB.
DR GO; GO:0006390; P:mitochondrial transcription; IMP:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; IDA:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:1990519; P:pyrimidine nucleotide import into mitochondrion; IMP:UniProtKB.
DR GO; GO:0006864; P:pyrimidine nucleotide transport; IDA:UniProtKB.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IDA:UniProtKB.
DR GO; GO:0002082; P:regulation of oxidative phosphorylation; IMP:UniProtKB.
DR GO; GO:1903426; P:regulation of reactive oxygen species biosynthetic process; IMP:UniProtKB.
DR Gene3D; 1.50.40.10; -; 2.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR Pfam; PF00153; Mito_carr; 3.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW Membrane; Mitochondrion; Mitochondrion inner membrane; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..321
FT /note="Solute carrier family 25 member 33"
FT /id="PRO_0000291785"
FT TRANSMEM 12..32
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 49..65
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 121..141
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 190..210
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 298..318
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 9..118
FT /note="Solcar 1"
FT REPEAT 126..213
FT /note="Solcar 2"
FT REPEAT 231..315
FT /note="Solcar 3"
FT VARIANT 242
FT /note="L -> I (in dbSNP:rs35819756)"
FT /id="VAR_032861"
SQ SEQUENCE 321 AA; 35375 MW; A8B636704937A020 CRC64;
MATGGQQKEN TLLHLFAGGC GGTVGAIFTC PLEVIKTRLQ SSRLALRTVY YPQVHLGTIS
GAGMVRPTSV TPGLFQVLKS ILEKEGPKSL FRGLGPNLVG VAPSRAVYFA CYSKAKEQFN
GIFVPNSNIV HIFSAGSAAF ITNSLMNPIW MVKTRMQLEQ KVRGSKQMNT LQCARYVYQT
EGIRGFYRGL TASYAGISET IICFAIYESL KKYLKEAPLA SSANGTEKNS TSFFGLMAAA
ALSKGCASCI AYPHEVIRTR LREEGTKYKS FVQTARLVFR EEGYLAFYRG LFAQLIRQIP
NTAIVLSTYE LIVYLLEDRT Q
