MOT5_HUMAN
ID MOT5_HUMAN Reviewed; 487 AA.
AC O15374; A8K3V5; B2R9C9; B4DJ67; B4DPX7; E7EPY8; G3V175; Q5T612; Q8WU09;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Monocarboxylate transporter 5;
DE Short=MCT 5;
DE AltName: Full=Monocarboxylate transporter 4;
DE Short=MCT 4;
DE AltName: Full=Solute carrier family 16 member 4;
GN Name=SLC16A4; Synonyms=MCT4, MCT5;
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] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=9425115; DOI=10.1042/bj3290321;
RA Price N.T., Jackson V.N., Halestrap A.P.;
RT "Cloning and sequencing of four new mammalian monocarboxylate transporter
RT (MCT) homologues confirms the existence of a transporter family with an
RT ancient past.";
RL Biochem. J. 329:321-328(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 4 AND 5), AND
RP VARIANT HIS-264.
RC TISSUE=Lung, Mesangial cell, Placenta, and Substantia nigra;
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 [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 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
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).
CC -!- FUNCTION: Proton-linked monocarboxylate transporter. Catalyzes the
CC rapid transport across the plasma membrane of many monocarboxylates
CC such as lactate, pyruvate, branched-chain oxo acids derived from
CC leucine, valine and isoleucine, and the ketone bodies acetoacetate,
CC beta-hydroxybutyrate and acetate (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC O15374-3; Q9BRK0: REEP2; NbExp=3; IntAct=EBI-12889748, EBI-11337973;
CC O15374-3; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-12889748, EBI-10982110;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=O15374-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O15374-2; Sequence=VSP_046242, VSP_046243;
CC Name=3;
CC IsoId=O15374-3; Sequence=VSP_046244;
CC Name=4;
CC IsoId=O15374-4; Sequence=VSP_046456, VSP_046458;
CC Name=5;
CC IsoId=O15374-5; Sequence=VSP_046457;
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC Monocarboxylate porter (TC 2.A.1.13) family. {ECO:0000305}.
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DR EMBL; U59185; AAB72035.1; -; mRNA.
DR EMBL; AK290720; BAF83409.1; -; mRNA.
DR EMBL; AK295946; BAG58729.1; -; mRNA.
DR EMBL; AK298539; BAG60739.1; -; mRNA.
DR EMBL; AK313735; BAG36476.1; -; mRNA.
DR EMBL; AL355488; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56443.1; -; Genomic_DNA.
DR EMBL; CH471122; EAW56445.1; -; Genomic_DNA.
DR EMBL; CH471122; EAW56446.1; -; Genomic_DNA.
DR EMBL; BC021664; AAH21664.1; -; mRNA.
DR CCDS; CCDS55621.1; -. [O15374-4]
DR CCDS; CCDS55622.1; -. [O15374-2]
DR CCDS; CCDS55623.1; -. [O15374-5]
DR CCDS; CCDS55624.1; -. [O15374-3]
DR CCDS; CCDS823.1; -. [O15374-1]
DR RefSeq; NP_001188475.1; NM_001201546.1. [O15374-5]
DR RefSeq; NP_001188476.1; NM_001201547.1. [O15374-2]
DR RefSeq; NP_001188477.1; NM_001201548.1. [O15374-4]
DR RefSeq; NP_001188478.1; NM_001201549.1. [O15374-3]
DR RefSeq; NP_004687.1; NM_004696.2. [O15374-1]
DR RefSeq; XP_005271374.1; XM_005271317.4. [O15374-1]
DR AlphaFoldDB; O15374; -.
DR SMR; O15374; -.
DR BioGRID; 114570; 12.
DR IntAct; O15374; 4.
DR MINT; O15374; -.
DR STRING; 9606.ENSP00000358794; -.
DR DrugBank; DB00119; Pyruvic acid.
DR TCDB; 2.A.1.13.7; the major facilitator superfamily (mfs).
DR iPTMnet; O15374; -.
DR PhosphoSitePlus; O15374; -.
DR BioMuta; SLC16A4; -.
DR jPOST; O15374; -.
DR MassIVE; O15374; -.
DR MaxQB; O15374; -.
DR PaxDb; O15374; -.
DR PeptideAtlas; O15374; -.
DR PRIDE; O15374; -.
DR ProteomicsDB; 17467; -.
DR ProteomicsDB; 32280; -.
DR ProteomicsDB; 4352; -.
DR ProteomicsDB; 48616; -. [O15374-1]
DR ProteomicsDB; 74621; -.
DR Antibodypedia; 20096; 127 antibodies from 23 providers.
DR DNASU; 9122; -.
DR Ensembl; ENST00000369779.9; ENSP00000358794.4; ENSG00000168679.18. [O15374-1]
DR Ensembl; ENST00000369781.8; ENSP00000358796.4; ENSG00000168679.18. [O15374-3]
DR Ensembl; ENST00000437429.6; ENSP00000394790.2; ENSG00000168679.18. [O15374-4]
DR Ensembl; ENST00000472422.6; ENSP00000432495.1; ENSG00000168679.18. [O15374-5]
DR Ensembl; ENST00000541986.5; ENSP00000446087.1; ENSG00000168679.18. [O15374-2]
DR GeneID; 9122; -.
DR KEGG; hsa:9122; -.
DR MANE-Select; ENST00000369779.9; ENSP00000358794.4; NM_004696.3; NP_004687.1.
DR UCSC; uc001dzo.3; human. [O15374-1]
DR CTD; 9122; -.
DR DisGeNET; 9122; -.
DR GeneCards; SLC16A4; -.
DR HGNC; HGNC:10925; SLC16A4.
DR HPA; ENSG00000168679; Tissue enriched (kidney).
DR MIM; 603878; gene.
DR neXtProt; NX_O15374; -.
DR OpenTargets; ENSG00000168679; -.
DR PharmGKB; PA35816; -.
DR VEuPathDB; HostDB:ENSG00000168679; -.
DR eggNOG; KOG2504; Eukaryota.
DR GeneTree; ENSGT00940000158411; -.
DR HOGENOM; CLU_001265_59_2_1; -.
DR InParanoid; O15374; -.
DR OMA; CKTNGCF; -.
DR OrthoDB; 916876at2759; -.
DR PhylomeDB; O15374; -.
DR TreeFam; TF313792; -.
DR PathwayCommons; O15374; -.
DR SignaLink; O15374; -.
DR SIGNOR; O15374; -.
DR BioGRID-ORCS; 9122; 5 hits in 1078 CRISPR screens.
DR ChiTaRS; SLC16A4; human.
DR GeneWiki; SLC16A4; -.
DR GenomeRNAi; 9122; -.
DR Pharos; O15374; Tbio.
DR PRO; PR:O15374; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O15374; protein.
DR Bgee; ENSG00000168679; Expressed in palpebral conjunctiva and 144 other tissues.
DR ExpressionAtlas; O15374; baseline and differential.
DR Genevisible; O15374; HS.
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:0016020; C:membrane; TAS:ProtInc.
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:0015718; P:monocarboxylic acid transport; IBA:GO_Central.
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 Alternative splicing; Cell membrane; Membrane; Reference proteome; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..487
FT /note="Monocarboxylate transporter 5"
FT /id="PRO_0000211398"
FT TOPO_DOM 1..16
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..59
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 81..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 109
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 110..129
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 130..143
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..174
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 175..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 196..299
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 300..320
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 321..337
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..372
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 373..393
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 394
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 395..415
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 416..425
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 426..446
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 447..458
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 459..479
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 480..487
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 206..250
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 223..238
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..120
FT /note="MLKREGKVQPYTKTLDGGWGWMIVIHFFLVNVFVMGMTKTFAIFFVVFQEEF
FT EGTSEQIGWIGSIMSSLRFCAGPLVAIICDILGEKTTSILGAFVVTGGYLISSWATSIP
FT FLCVTMGLL -> MGMDDCDSFF (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046456"
FT VAR_SEQ 1..34
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046242"
FT VAR_SEQ 38..73
FT /note="TKTFAIFFVVFQEEFEGTSEQIGWIGSIMSSLRFCA -> DDCDSFFP (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046243"
FT VAR_SEQ 74..121
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046457"
FT VAR_SEQ 176..343
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046244"
FT VAR_SEQ 446..487
FT /note="GWLYDYTQTYNGSFYFSGICYLLSSVSFFFVPLAERWKNSLT -> EIIPSF
FT QAGYMIIPRHTMALSTSLAYAISSLQFPFFLYHWPKDGKTV (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046458"
FT VARIANT 185
FT /note="A -> T (in dbSNP:rs35157487)"
FT /id="VAR_053655"
FT VARIANT 264
FT /note="N -> H (in dbSNP:rs2271885)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_020309"
FT CONFLICT 25
FT /note="I -> V (in Ref. 2; BAF83409)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 487 AA; 54022 MW; 3CF236C69CC29631 CRC64;
MLKREGKVQP YTKTLDGGWG WMIVIHFFLV NVFVMGMTKT FAIFFVVFQE EFEGTSEQIG
WIGSIMSSLR FCAGPLVAII CDILGEKTTS ILGAFVVTGG YLISSWATSI PFLCVTMGLL
PGLGSAFLYQ VAAVVTTKYF KKRLALSTAI ARSGMGLTFL LAPFTKFLID LYDWTGALIL
FGAIALNLVP SSMLLRPIHI KSENNSGIKD KGSSLSAHGP EAHATETHCH ETEESTIKDS
TTQKAGLPSK NLTVSQNQSE EFYNGPNRNR LLLKSDEESD KVISWSCKQL FDISLFRNPF
FYIFTWSFLL SQLAYFIPTF HLVARAKTLG IDIMDASYLV SVAGILETVS QIISGWVADQ
NWIKKYHYHK SYLILCGITN LLAPLATTFP LLMTYTICFA IFAGGYLALI LPVLVDLCRN
STVNRFLGLA SFFAGMAVLS GPPIAGWLYD YTQTYNGSFY FSGICYLLSS VSFFFVPLAE
RWKNSLT
