S2536_HUMAN
ID S2536_HUMAN Reviewed; 311 AA.
AC Q96CQ1; A8MYF7; Q05CY1; Q9H0G8; Q9NVN5;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Solute carrier family 25 member 36;
GN Name=SLC25A36;
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] (ISOFORM 3).
RC TISSUE=Teratocarcinoma;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney, and 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-129.
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [6]
RP IDENTIFICATION, AND TISSUE SPECIFICITY.
RX PubMed=17210862; DOI=10.1001/archopht.125.1.117;
RA Rozsa F.W., Scott K.M., Pawar H., Samples J.R., Wirtz M.K., Richards J.E.;
RT "Differential expression profile prioritization of positional candidate
RT glaucoma genes: the GLC1C locus.";
RL Arch. Ophthalmol. 125:117-127(2007).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, 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. Transports preferentially
CC cytosine and uracil (deoxy)nucleoside mono-, di-, and triphosphates by
CC uniport and antiport mechanism. Also transports guanine but not adenine
CC (deoxy)nucleotides. 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). Participates in
CC mitochondrial genome maintenance, regulation of mitochondrial membrane
CC potential and mitochondrial respiration. {ECO:0000269|PubMed:25320081}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.19 mM for UTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC KM=0.21 mM for CTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC KM=2.5 mM for TTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC KM=0.23 mM for GTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC Vmax=30.7 umol/min/g enzyme toward UTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC Vmax=51.2 umol/min/g enzyme toward CTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC Vmax=8 umol/min/g enzyme toward TTP (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:25320081};
CC Vmax=23.6 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 1.3 um
CC (UTP), 224 um (CTP), 276 um (GTP), and 181 um (ITP). CTP is the best
CC substrate. {ECO:0000269|PubMed:25320081};
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000305|PubMed:25320081}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q96CQ1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96CQ1-2; Sequence=VSP_026240, VSP_026241;
CC Name=3;
CC IsoId=Q96CQ1-3; Sequence=VSP_026242;
CC Name=4;
CC IsoId=Q96CQ1-4; Sequence=VSP_035517;
CC -!- TISSUE SPECIFICITY: Expressed at moderate level.
CC {ECO:0000269|PubMed:17210862}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; AK001480; BAA91715.1; -; mRNA.
DR EMBL; AC108727; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC132032; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW79012.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79013.1; -; Genomic_DNA.
DR EMBL; BC014064; AAH14064.1; -; mRNA.
DR EMBL; BC019859; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL136803; CAB66737.2; -; mRNA.
DR CCDS; CCDS3114.1; -. [Q96CQ1-3]
DR CCDS; CCDS46927.1; -. [Q96CQ1-1]
DR RefSeq; NP_001098117.1; NM_001104647.1. [Q96CQ1-1]
DR RefSeq; NP_060625.2; NM_018155.2. [Q96CQ1-3]
DR AlphaFoldDB; Q96CQ1; -.
DR SMR; Q96CQ1; -.
DR BioGRID; 120484; 8.
DR IntAct; Q96CQ1; 4.
DR STRING; 9606.ENSP00000320688; -.
DR TCDB; 2.A.29.10.6; the mitochondrial carrier (mc) family.
DR iPTMnet; Q96CQ1; -.
DR PhosphoSitePlus; Q96CQ1; -.
DR BioMuta; SLC25A36; -.
DR DMDM; 74760768; -.
DR EPD; Q96CQ1; -.
DR jPOST; Q96CQ1; -.
DR MassIVE; Q96CQ1; -.
DR MaxQB; Q96CQ1; -.
DR PaxDb; Q96CQ1; -.
DR PeptideAtlas; Q96CQ1; -.
DR PRIDE; Q96CQ1; -.
DR ProteomicsDB; 76207; -. [Q96CQ1-1]
DR ProteomicsDB; 76208; -. [Q96CQ1-2]
DR ProteomicsDB; 76209; -. [Q96CQ1-3]
DR ProteomicsDB; 76210; -. [Q96CQ1-4]
DR Antibodypedia; 18006; 75 antibodies from 16 providers.
DR DNASU; 55186; -.
DR Ensembl; ENST00000324194.12; ENSP00000320688.6; ENSG00000114120.14. [Q96CQ1-1]
DR Ensembl; ENST00000446041.6; ENSP00000401938.2; ENSG00000114120.14. [Q96CQ1-3]
DR Ensembl; ENST00000502594.5; ENSP00000423319.1; ENSG00000114120.14. [Q96CQ1-2]
DR Ensembl; ENST00000631654.1; ENSP00000487839.1; ENSG00000114120.14. [Q96CQ1-2]
DR GeneID; 55186; -.
DR KEGG; hsa:55186; -.
DR MANE-Select; ENST00000324194.12; ENSP00000320688.6; NM_001104647.3; NP_001098117.1.
DR UCSC; uc003etr.3; human. [Q96CQ1-1]
DR CTD; 55186; -.
DR DisGeNET; 55186; -.
DR GeneCards; SLC25A36; -.
DR HGNC; HGNC:25554; SLC25A36.
DR HPA; ENSG00000114120; Low tissue specificity.
DR MIM; 616149; gene.
DR neXtProt; NX_Q96CQ1; -.
DR OpenTargets; ENSG00000114120; -.
DR PharmGKB; PA142670908; -.
DR VEuPathDB; HostDB:ENSG00000114120; -.
DR eggNOG; KOG0757; Eukaryota.
DR GeneTree; ENSGT00940000154369; -.
DR HOGENOM; CLU_015166_6_0_1; -.
DR InParanoid; Q96CQ1; -.
DR OMA; HVHEGWR; -.
DR OrthoDB; 1372287at2759; -.
DR PhylomeDB; Q96CQ1; -.
DR TreeFam; TF314220; -.
DR PathwayCommons; Q96CQ1; -.
DR SignaLink; Q96CQ1; -.
DR BioGRID-ORCS; 55186; 16 hits in 1077 CRISPR screens.
DR ChiTaRS; SLC25A36; human.
DR GenomeRNAi; 55186; -.
DR Pharos; Q96CQ1; Tbio.
DR PRO; PR:Q96CQ1; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q96CQ1; protein.
DR Bgee; ENSG00000114120; Expressed in caput epididymis and 216 other tissues.
DR ExpressionAtlas; Q96CQ1; baseline and differential.
DR Genevisible; Q96CQ1; 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:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0015218; F:pyrimidine nucleotide transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0000002; P:mitochondrial genome maintenance; IDA:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; IDA:UniProtKB.
DR GO; GO:1990519; P:pyrimidine nucleotide import into mitochondrion; IBA:GO_Central.
DR GO; GO:0006864; P:pyrimidine nucleotide transport; IDA:UniProtKB.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IDA:UniProtKB.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR002067; Mit_carrier.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR Pfam; PF00153; Mito_carr; 3.
DR PRINTS; PR00926; MITOCARRIER.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..311
FT /note="Solute carrier family 25 member 36"
FT /id="PRO_0000291797"
FT TRANSMEM 7..27
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 41..57
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..131
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 180..200
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 226..246
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 291..311
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT REPEAT 4..108
FT /note="Solcar 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 116..203
FT /note="Solcar 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT REPEAT 224..308
FT /note="Solcar 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00282"
FT VAR_SEQ 1..157
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_035517"
FT VAR_SEQ 130..132
FT /note="FTA -> HFL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026240"
FT VAR_SEQ 133..311
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026241"
FT VAR_SEQ 248
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_026242"
FT CONFLICT 216
FT /note="D -> G (in Ref. 1; BAA91715)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 311 AA; 34283 MW; D87DFDF7BC992D83 CRC64;
MSQRDTLVHL FAGGCGGTVG AILTCPLEVV KTRLQSSSVT LYISEVQLNT MAGASVNRVV
SPGPLHCLKV ILEKEGPRSL FRGLGPNLVG VAPSRAIYFA AYSNCKEKLN DVFDPDSTQV
HMISAAMAGF TAITATNPIW LIKTRLQLDA RNRGERRMGA FECVRKVYQT DGLKGFYRGM
SASYAGISET VIHFVIYESI KQKLLEYKTA STMENDEESV KEASDFVGMM LAAATSKTCA
TTIAYPHEVV RTRLREEGTK YRSFFQTLSL LVQEEGYGSL YRGLTTHLVR QIPNTAIMMA
TYELVVYLLN G