MOT11_HUMAN
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 03-AUG-2022, entry version 135.
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 NIDDM,
RP AND 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 NIDDM, 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: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]:
CC A multifactorial disorder of glucose homeostasis caused by a lack of
CC sensitivity to the body's own insulin. Affected individuals usually
CC have an obese body habitus and manifestations of a metabolic syndrome
CC characterized by diabetes, insulin resistance, hypertension and
CC hypertriglyceridemia. The disease results in long-term complications
CC that affect the eyes, kidneys, nerves, and blood vessels.
CC {ECO:0000269|PubMed:24390345}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC A risk haplotype spanning SLC16A11 is associated with a 20% increased
CC risk for NIDDM. The haplotype includes 5 SLC16A11 variants in strong
CC linkage disequilibrium: variants Ile-113, Gly-127, Ser-340, Thr-443 and
CC a silent variant. This risk haplotype probably derives from H.sapiens
CC neanderthalensis (Neanderthal) introgression and is present at 50%
CC frequency in Native-American samples, 10% in east Asian, while it is
CC rare in European and African samples populations. The risk haplotype
CC contains a cis-eQTL that is responsible for reduced SLC16A11 expression
CC in liver (PubMed:28666119). {ECO:0000269|PubMed:24390345,
CC 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; 556.
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; Q8NCK7; -.
DR PeptideAtlas; Q8NCK7; -.
DR PRIDE; Q8NCK7; -.
DR Antibodypedia; 53202; 116 antibodies from 21 providers.
DR DNASU; 162515; -.
DR GeneID; 162515; -.
DR KEGG; hsa:162515; -.
DR UCSC; uc002gei.1; human.
DR CTD; 162515; -.
DR DisGeNET; 162515; -.
DR GeneCards; SLC16A11; -.
DR HGNC; HGNC:23093; SLC16A11.
DR HPA; ENSG00000174326; Tissue enhanced (fallopian tube, thyroid gland).
DR MIM; 125853; phenotype.
DR neXtProt; NX_Q8NCK7; -.
DR PharmGKB; PA134976903; -.
DR VEuPathDB; HostDB:ENSG00000174326; -.
DR eggNOG; KOG2504; Eukaryota.
DR InParanoid; Q8NCK7; -.
DR OrthoDB; 916876at2759; -.
DR PhylomeDB; Q8NCK7; -.
DR TreeFam; TF313792; -.
DR PathwayCommons; Q8NCK7; -.
DR SignaLink; Q8NCK7; -.
DR BioGRID-ORCS; 162515; 24 hits in 1067 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 tissues.
DR ExpressionAtlas; Q8NCK7; baseline and differential.
DR Genevisible; Q8NCK7; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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; -; 1.
DR InterPro; IPR030769; MCT11.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR PANTHER; PTHR11360:SF80; PTHR11360:SF80; 1.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
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 NIDDM 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 NIDDM 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 NIDDM 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 NIDDM 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
