MOT12_HUMAN
ID MOT12_HUMAN Reviewed; 516 AA.
AC Q6ZSM3; E9PSF9; Q5M9M9; Q5T7J2; Q6ZV76;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2018, sequence version 3.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Monocarboxylate transporter 12 {ECO:0000305};
DE Short=MCT 12 {ECO:0000305};
DE AltName: Full=Creatine transporter 2 {ECO:0000303|PubMed:23578822};
DE Short=CRT2 {ECO:0000303|PubMed:23578822};
DE AltName: Full=Solute carrier family 16 member 12 {ECO:0000312|HGNC:HGNC:23094};
GN Name=SLC16A12 {ECO:0000312|HGNC:HGNC:23094};
GN Synonyms=MCT12 {ECO:0000303|PubMed:21778275};
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=Hippocampus;
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=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 250-516.
RC TISSUE=Cardiac myocyte, and Skeletal muscle;
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 [4]
RP INVOLVEMENT IN CTRCT47, VARIANT CTRCT47 245-GLN--THR-516 DEL, AND TISSUE
RP SPECIFICITY.
RX PubMed=18304496; DOI=10.1016/j.ajhg.2007.12.013;
RA Kloeckener-Gruissem B., Vandekerckhove K., Nuernberg G., Neidhardt J.,
RA Zeitz C., Nuernberg P., Schipper I., Berger W.;
RT "Mutation of solute carrier SLC16A12 associates with a syndrome combining
RT juvenile cataract with microcornea and renal glucosuria.";
RL Am. J. Hum. Genet. 82:772-779(2008).
RN [5]
RP CHARACTERIZATION OF VARIANT CTRCT47 245-GLN--THR-516 DEL, INTERACTION WITH
RP BSG, AND SUBCELLULAR LOCATION.
RX PubMed=21778275; DOI=10.1167/iovs.10-6579;
RA Castorino J.J., Gallagher-Colombo S.M., Levin A.V., Fitzgerald P.G.,
RA Polishook J., Kloeckener-Gruissem B., Ostertag E., Philp N.J.;
RT "Juvenile cataract-associated mutation of solute carrier SLC16A12 impairs
RT trafficking of the protein to the plasma membrane.";
RL Invest. Ophthalmol. Vis. Sci. 52:6774-6784(2011).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, VARIANT SER-437, CHARACTERIZATION OF
RP VARIANT SER-437, AND TISSUE SPECIFICITY.
RX PubMed=23578822; DOI=10.1093/hmg/ddt175;
RA Abplanalp J., Laczko E., Philp N.J., Neidhardt J., Zuercher J., Braun P.,
RA Schorderet D.F., Munier F.L., Verrey F., Berger W., Camargo S.M.,
RA Kloeckener-Gruissem B.;
RT "The cataract and glucosuria associated monocarboxylate transporter MCT12
RT is a new creatine transporter.";
RL Hum. Mol. Genet. 22:3218-3226(2013).
CC -!- FUNCTION: Proton-linked monocarboxylate transporter that mediates
CC creatine transport across the plasma membrane.
CC {ECO:0000269|PubMed:23578822}.
CC -!- SUBUNIT: Interacts with isoform 2 of BSG.
CC {ECO:0000269|PubMed:21778275}.
CC -!- INTERACTION:
CC Q6ZSM3; Q13520: AQP6; NbExp=3; IntAct=EBI-17460560, EBI-13059134;
CC Q6ZSM3; P11912: CD79A; NbExp=3; IntAct=EBI-17460560, EBI-7797864;
CC Q6ZSM3; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-17460560, EBI-12175685;
CC Q6ZSM3; P48165: GJA8; NbExp=3; IntAct=EBI-17460560, EBI-17458373;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21778275,
CC ECO:0000269|PubMed:23578822}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Most highly expressed in kidney, followed by
CC retina, lung, heart and testis. Very weakly expressed in brain and
CC liver. Also detected in lens. {ECO:0000269|PubMed:18304496,
CC ECO:0000269|PubMed:23578822}.
CC -!- DISEASE: Cataract 47 (CTRCT47) [MIM:612018]: A form of cataract, an
CC opacification of the crystalline lens of the eye that frequently
CC results in visual impairment or blindness. Opacities vary in
CC morphology, are often confined to a portion of the lens, and may be
CC static or progressive. In general, the more posteriorly located and
CC dense an opacity, the greater the impact on visual function. CTRCT47 is
CC characterized by the association of cataract with microcornea and renal
CC glucosuria. Microcornea is defined by a corneal diameter inferior to 10
CC mm in both meridians in an otherwise normal eye. Renal glucosuria is
CC defined by elevated glucose level in the urine without hyperglycemia
CC and without evidence of morphological renal anomalies.
CC {ECO:0000269|PubMed:18304496, ECO:0000269|PubMed:21778275}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC Monocarboxylate porter (TC 2.A.1.13) family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-31 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC85987.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC86925.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK124901; BAC85987.1; ALT_INIT; mRNA.
DR EMBL; AK127303; BAC86925.1; ALT_FRAME; mRNA.
DR EMBL; AL353146; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC086873; AAH86873.1; -; mRNA.
DR CCDS; CCDS7404.2; -.
DR RefSeq; NP_998771.3; NM_213606.3.
DR RefSeq; XP_016871726.1; XM_017016237.1.
DR RefSeq; XP_016871727.1; XM_017016238.1.
DR RefSeq; XP_016871728.1; XM_017016239.1.
DR AlphaFoldDB; Q6ZSM3; -.
DR SMR; Q6ZSM3; -.
DR BioGRID; 132399; 4.
DR IntAct; Q6ZSM3; 4.
DR STRING; 9606.ENSP00000360855; -.
DR TCDB; 2.A.1.13.14; the major facilitator superfamily (mfs).
DR iPTMnet; Q6ZSM3; -.
DR PhosphoSitePlus; Q6ZSM3; -.
DR BioMuta; SLC16A12; -.
DR DMDM; 147704293; -.
DR MassIVE; Q6ZSM3; -.
DR PaxDb; Q6ZSM3; -.
DR PeptideAtlas; Q6ZSM3; -.
DR PRIDE; Q6ZSM3; -.
DR Antibodypedia; 16234; 119 antibodies from 24 providers.
DR DNASU; 387700; -.
DR Ensembl; ENST00000371790.5; ENSP00000360855.4; ENSG00000152779.14.
DR GeneID; 387700; -.
DR KEGG; hsa:387700; -.
DR MANE-Select; ENST00000371790.5; ENSP00000360855.4; NM_213606.4; NP_998771.3.
DR CTD; 387700; -.
DR DisGeNET; 387700; -.
DR GeneCards; SLC16A12; -.
DR HGNC; HGNC:23094; SLC16A12.
DR HPA; ENSG00000152779; Group enriched (choroid plexus, epididymis, kidney, pancreas).
DR MalaCards; SLC16A12; -.
DR MIM; 611910; gene.
DR MIM; 612018; phenotype.
DR neXtProt; NX_Q6ZSM3; -.
DR OpenTargets; ENSG00000152779; -.
DR Orphanet; 247794; Juvenile cataract-microcornea-renal glucosuria syndrome.
DR PharmGKB; PA134969386; -.
DR VEuPathDB; HostDB:ENSG00000152779; -.
DR eggNOG; KOG2504; Eukaryota.
DR GeneTree; ENSGT00940000156169; -.
DR HOGENOM; CLU_001265_59_1_1; -.
DR InParanoid; Q6ZSM3; -.
DR OMA; WVLASHQ; -.
DR OrthoDB; 916876at2759; -.
DR PhylomeDB; Q6ZSM3; -.
DR TreeFam; TF313792; -.
DR PathwayCommons; Q6ZSM3; -.
DR SignaLink; Q6ZSM3; -.
DR BioGRID-ORCS; 387700; 8 hits in 1058 CRISPR screens.
DR ChiTaRS; SLC16A12; human.
DR GenomeRNAi; 387700; -.
DR Pharos; Q6ZSM3; Tbio.
DR PRO; PR:Q6ZSM3; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q6ZSM3; protein.
DR Bgee; ENSG00000152779; Expressed in body of pancreas and 92 other tissues.
DR ExpressionAtlas; Q6ZSM3; baseline and differential.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005308; F:creatine transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0015881; P:creatine transmembrane transport; IDA:UniProtKB.
DR GO; GO:0015718; P:monocarboxylic acid transport; IBA:GO_Central.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR Gene3D; 1.20.1250.20; -; 2.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Cataract; Cell membrane; Membrane; Reference proteome; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..516
FT /note="Monocarboxylate transporter 12"
FT /id="PRO_0000286675"
FT TOPO_DOM 1..50
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 51..73
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 116..136
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 145..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..227
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 283..303
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 319..339
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 350..370
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 377..397
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 410..430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 440..460
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 461..516
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT VARIANT 245..516
FT /note="Missing (in CTRCT47; loss of localization to the
FT plasma membrane; retained in the endoplasmic reticulum
FT where it undergoes degradation by the proteasome; has no
FT dominant effect on wild-type protein expression and
FT localization)"
FT /evidence="ECO:0000269|PubMed:18304496"
FT /id="VAR_080957"
FT VARIANT 437
FT /note="G -> S (found in a patient with age-related
FT cataract; unknown pathological significance; decreases
FT creatine transport; dbSNP:rs759863805)"
FT /evidence="ECO:0000269|PubMed:23578822"
FT /id="VAR_071890"
FT CONFLICT 334
FT /note="I -> T (in Ref. 1; BAC86925)"
FT /evidence="ECO:0000305"
FT CONFLICT 363
FT /note="C -> S (in Ref. 1; BAC85987)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 516 AA; 56498 MW; 467BF0C95C98052A CRC64;
MPSGSHWTAN SSKIITWLLE QPGKEEKRKT MAKVNRARST SPPDGGWGWM IVAGCFLVTI
CTRAVTRCIS IFFVEFQTYF TQDYAQTAWI HSIVDCVTML CAPLGSVVSN HLSCQVGIML
GGLLASTGLI LSSFATSLKH LYLTLGVLTG LGFALCYSPA IAMVGKYFSR RKALAYGIAM
SGSGIGTFIL APVVQLLIEQ FSWRGALLIL GGFVLNLCVC GALMRPITLK EDHTTPEQNH
VCRTQKEDIK RVSPYSSLTK EWAQTCLCCC LQQEYSFLLM SDFVVLAVSV LFMAYGCSPL
FVYLVPYALS VGVSHQQAAF LMSILGVIDI IGNITFGWLT DRRCLKNYQY VCYLFAVGMD
GLCYLCLPML QSLPLLVPFS CTFGYFDGAY VTLIPVVTTE IVGTTSLSSA LGVVYFLHAV
PYLVSPPIAG RLVDTTGSYT AAFLLCGFSM IFSSVLLGFA RLIKRMRKTQ LQFIAKESDP
KLQLWTNGSV AYSVARELDQ KHGEPVATAV PGYSLT
