ID   MOT11_HUMAN             Reviewed;         471 AA.
AC   Q8NCK7;
DT   15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   24-JAN-2024, entry version 143.
DE   RecName: Full=Monocarboxylate transporter 11;
DE            Short=MCT 11;
DE   AltName: Full=Solute carrier family 16 member 11;
GN   Name=SLC16A11; Synonyms=MCT11;
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=Mammary gland;
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 MRNA].
RC   TISSUE=Heart, and Lung;
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, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INVOLVEMENT IN T2D, AND
RP   VARIANTS ILE-113; GLY-127; SER-340 AND THR-443.
RX   PubMed=24390345; DOI=10.1038/nature12828;
RG   The SIGMA Type 2 Diabetes Consortium;
RT   "Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes
RT   in Mexico.";
RL   Nature 506:97-101(2014).
RN   [4]
RP   FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH BSG,
RP   INVOLVEMENT IN T2D, AND CHARACTERIZATION OF VARIANTS ILE-113; GLY-127;
RP   SER-340 AND THR-443.
RX   PubMed=28666119; DOI=10.1016/j.cell.2017.06.011;
RG   MEDIA Consortium;
RG   SIGMA T2D Consortium;
RA   Rusu V., Hoch E., Mercader J.M., Tenen D.E., Gymrek M., Hartigan C.R.,
RA   DeRan M., von Grotthuss M., Fontanillas P., Spooner A., Guzman G.,
RA   Deik A.A., Pierce K.A., Dennis C., Clish C.B., Carr S.A., Wagner B.K.,
RA   Schenone M., Ng M.C.Y., Chen B.H., Centeno-Cruz F., Zerrweck C., Orozco L.,
RA   Altshuler D.M., Schreiber S.L., Florez J.C., Jacobs S.B.R., Lander E.S.;
RT   "Type 2 diabetes variants disrupt function of SLC16A11 through two distinct
RT   mechanisms.";
RL   Cell 170:199-212(2017).
CC   -!- FUNCTION: Proton-linked monocarboxylate transporter. It catalyzes the
CC       transport of pyruvate across the plasma membrane (PubMed:28666119).
CC       Probably involved in hepatic lipid metabolism: overexpression results
CC       in an increase of triacylglycerol(TAG) levels, small increases in
CC       intracellular diacylglycerols and decreases in lysophosphatidylcholine,
CC       cholesterol ester and sphingomyelin lipids (PubMed:24390345).
CC       {ECO:0000269|PubMed:24390345, ECO:0000269|PubMed:28666119}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H(+)(out) + pyruvate(out) = H(+)(in) + pyruvate(in);
CC         Xref=Rhea:RHEA:64720, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378;
CC         Evidence={ECO:0000269|PubMed:28666119};
CC   -!- SUBUNIT: Interacts with isoform 2 of BSG.
CC       {ECO:0000269|PubMed:28666119}.
CC   -!- INTERACTION:
CC       Q8NCK7; P35613: BSG; NbExp=5; IntAct=EBI-21840241, EBI-750709;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:24390345}; Multi-pass membrane protein
CC       {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:28666119}; Multi-pass
CC       membrane protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Expressed in liver, salivary gland and thyroid.
CC       {ECO:0000269|PubMed:24390345}.
CC   -!- DISEASE: Type 2 diabetes mellitus (T2D) [MIM:125853]: A multifactorial
CC       disorder of glucose homeostasis caused by a lack of sensitivity to the
CC       body's own insulin. Affected individuals usually have an obese body
CC       habitus and manifestations of a metabolic syndrome characterized by
CC       diabetes, insulin resistance, hypertension and hypertriglyceridemia.
CC       The disease results in long-term complications that affect the eyes,
CC       kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:24390345}.
CC       Note=Disease susceptibility is associated with variants affecting the
CC       gene represented in this entry. A risk haplotype spanning SLC16A11 is
CC       associated with a 20% increased risk for T2D. The haplotype includes 5
CC       SLC16A11 variants in strong linkage disequilibrium: variants Ile-113,
CC       Gly-127, Ser-340, Thr-443 and a silent variant. This risk haplotype
CC       probably derives from H.sapiens neanderthalensis (Neanderthal)
CC       introgression and is present at 50% frequency in Native-American
CC       samples, 10% in east Asian, while it is rare in European and African
CC       samples populations. The risk haplotype contains a cis-eQTL that is
CC       responsible for reduced SLC16A11 expression in liver (PubMed:28666119).
CC       {ECO:0000269|PubMed:24390345, ECO:0000269|PubMed:28666119}.
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-25 is the initiator.
CC       {ECO:0000305}.
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DR   EMBL; AK074674; BAC11128.1; -; mRNA.
DR   EMBL; BC093860; AAH93860.1; -; mRNA.
DR   EMBL; BC093886; AAH93886.1; -; mRNA.
DR   RefSeq; NP_699188.1; NM_153357.1.
DR   AlphaFoldDB; Q8NCK7; -.
DR   SMR; Q8NCK7; -.
DR   BioGRID; 127822; 7.
DR   IntAct; Q8NCK7; 555.
DR   STRING; 9606.ENSP00000310490; -.
DR   TCDB; 2.A.1.13.13; the major facilitator superfamily (mfs).
DR   iPTMnet; Q8NCK7; -.
DR   PhosphoSitePlus; Q8NCK7; -.
DR   BioMuta; SLC16A11; -.
DR   DMDM; 74730153; -.
DR   MassIVE; Q8NCK7; -.
DR   PaxDb; 9606-ENSP00000310490; -.
DR   PeptideAtlas; Q8NCK7; -.
DR   Antibodypedia; 53202; 148 antibodies from 21 providers.
DR   DNASU; 162515; -.
DR   GeneID; 162515; -.
DR   KEGG; hsa:162515; -.
DR   UCSC; uc002gei.1; human.
DR   AGR; HGNC:23093; -.
DR   CTD; 162515; -.
DR   DisGeNET; 162515; -.
DR   GeneCards; SLC16A11; -.
DR   HGNC; HGNC:23093; SLC16A11.
DR   MIM; 125853; phenotype.
DR   neXtProt; NX_Q8NCK7; -.
DR   PharmGKB; PA134976903; -.
DR   VEuPathDB; HostDB:ENSG00000174326; -.
DR   eggNOG; KOG2504; Eukaryota.
DR   InParanoid; Q8NCK7; -.
DR   OrthoDB; 4741584at2759; -.
DR   PhylomeDB; Q8NCK7; -.
DR   TreeFam; TF313792; -.
DR   PathwayCommons; Q8NCK7; -.
DR   SignaLink; Q8NCK7; -.
DR   BioGRID-ORCS; 162515; 25 hits in 1145 CRISPR screens.
DR   GenomeRNAi; 162515; -.
DR   Pharos; Q8NCK7; Tbio.
DR   PRO; PR:Q8NCK7; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q8NCK7; Protein.
DR   Bgee; ENSG00000174326; Expressed in right uterine tube and 92 other cell types or tissues.
DR   ExpressionAtlas; Q8NCK7; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; IBA:GO_Central.
DR   GO; GO:0050833; F:pyruvate transmembrane transporter activity; IDA:UniProtKB.
DR   GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR   GO; GO:0006629; P:lipid metabolic process; IDA:UniProtKB.
DR   GO; GO:0015718; P:monocarboxylic acid transport; IBA:GO_Central.
DR   Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1.
DR   InterPro; IPR011701; MFS.
DR   InterPro; IPR020846; MFS_dom.
DR   InterPro; IPR036259; MFS_trans_sf.
DR   PANTHER; PTHR11360; MONOCARBOXYLATE TRANSPORTER; 1.
DR   PANTHER; PTHR11360:SF80; MONOCARBOXYLATE TRANSPORTER 11; 1.
DR   Pfam; PF07690; MFS_1; 1.
DR   SUPFAM; SSF103473; MFS general substrate transporter; 1.
DR   PROSITE; PS50850; MFS; 1.
DR   Genevisible; Q8NCK7; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; Diabetes mellitus; Endoplasmic reticulum; Lipid metabolism;
KW   Membrane; Reference proteome; Symport; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..471
FT                   /note="Monocarboxylate transporter 11"
FT                   /id="PRO_0000286673"
FT   TOPO_DOM        1..35
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:24390345"
FT   TRANSMEM        36..56
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        78..98
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        106..126
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        131..151
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        163..183
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        198..218
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        243..263
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        273..293
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        312..332
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        333..353
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        367..389
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        407..427
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        428..471
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:24390345"
FT   REGION          1..31
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         113
FT                   /note="V -> I (risk factor for T2D when associated with
FT                   G-127, S-340 and T-443; reduced pyruvate transmembrane
FT                   transporter activity, loss of interaction with BSG and
FT                   decreased localization to plasma membrane when associated
FT                   with G-127, S-340 and T-443; dbSNP:rs117767867)"
FT                   /evidence="ECO:0000269|PubMed:24390345,
FT                   ECO:0000269|PubMed:28666119"
FT                   /id="VAR_070544"
FT   VARIANT         127
FT                   /note="D -> G (risk factor for T2D when associated with
FT                   I-113, S-340 and T-443; reduced pyruvate transmembrane
FT                   transporter activity, loss of interaction with BSG and
FT                   decreased localization to plasma membrane when associated
FT                   with I-113, S-340 and T-443; dbSNP:rs13342692)"
FT                   /evidence="ECO:0000269|PubMed:24390345,
FT                   ECO:0000269|PubMed:28666119"
FT                   /id="VAR_032157"
FT   VARIANT         340
FT                   /note="G -> S (risk factor for T2D when associated with
FT                   I-113, G-127 and T-443; reduced pyruvate transmembrane
FT                   transporter activity, loss of interaction with BSG and
FT                   decreased localization to plasma membrane when associated
FT                   with I-113, G-127 and T-443; dbSNP:rs75418188)"
FT                   /evidence="ECO:0000269|PubMed:24390345,
FT                   ECO:0000269|PubMed:28666119"
FT                   /id="VAR_070545"
FT   VARIANT         443
FT                   /note="P -> T (risk factor for T2D when associated with
FT                   I-113, G-127 and S-340; reduced pyruvate transmembrane
FT                   transporter activity, loss of interaction with BSG and
FT                   decreased localization to plasma membrane when associated
FT                   with I-113, G-127 and S-340; dbSNP:rs75493593)"
FT                   /evidence="ECO:0000269|PubMed:24390345,
FT                   ECO:0000269|PubMed:28666119"
FT                   /id="VAR_070546"
SQ   SEQUENCE   471 AA;  47791 MW;  C586C4FE7A00B626 CRC64;
     MPAPQRKHRR GGFSHRCFPT PQTAMTPQPA GPPDGGWGWV VAAAAFAING LSYGLLRSLG
     LAFPDLAEHF DRSAQDTAWI SALALAVQQA ASPVGSALST RWGARPVVMV GGVLASLGFV
     FSAFASDLLH LYLGLGLLAG FGWALVFAPA LGTLSRYFSR RRVLAVGLAL TGNGASSLLL
     APALQLLLDT FGWRGALLLL GAITLHLTPC GALLLPLVLP GDPPAPPRSP LAALGLSLFT
     RRAFSIFALG TALVGGGYFV PYVHLAPHAL DRGLGGYGAA LVVAVAAMGD AGARLVCGWL
     ADQGWVPLPR LLAVFGALTG LGLWVVGLVP VVGGEESWGG PLLAAAVAYG LSAGSYAPLV
     FGVLPGLVGV GGVVQATGLV MMLMSLGGLL GPPLSGFLRD ETGDFTASFL LSGSLILSGS
     FIYIGLPRAL PSCGPASPPA TPPPETGELL PAPQAVLLSP GGPGSTLDTT C
//