P53985 (MOT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Monocarboxylate transporter 1
Short name=MCT 1

Alternative name(s):
Solute carrier family 16 member 1

Gene names

Name:	SLC16A1
Synonyms:	MCT1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	500 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Widely expressed in normal and in cancer cells.
Involvement in disease	Defects in SLC16A1 are the cause of symptomatic deficiency in lactate transport (SDLT) [MIM:245340]; also known as erythrocyte lactate transporter defect. Deficiency of lactate transporter may result in an acidic intracellular environment created by muscle activity with consequent degeneration of muscle and release of myoglobin and creatine kinase. This defect might compromise extreme performance in otherwise healthy individuals. Ref.14 Defects in SLC16A1 are the cause of familial hyperinsulinemic hypoglycemia type 7 (HHF7) [MIM:610021]; also known as exercise-induced hyperinsulinemic hypoglycemia. HHF7 is a dominantly inherited hypoglycemic disorder characterized by inappropriate insulin secretion during anaerobic exercise or on pyruvate load. Ref.15
Sequence similarities	Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family. [View classification]

Ontologies

Keywords
Biological process	Symport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	blood coagulation Traceable author statement. Source: Reactome leukocyte migration Traceable author statement. Source: Reactome organic anion transport Inferred from electronic annotation. Source: InterPro pyruvate metabolic process Traceable author statement. Source: Reactome
Cellular component	integral to membrane Traceable author statement. Source: ProtInc membrane fraction Traceable author statement. Source: ProtInc plasma membrane Inferred from direct assay. Source: HPA
Molecular function	mevalonate transmembrane transporter activity Traceable author statement. Source: ProtInc secondary active monocarboxylate transmembrane transporter activity Inferred from electronic annotation. Source: InterPro symporter activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AP1S1	P61966	1	EBI-1054708,EBI-516199
DEGS1	O15121	1	EBI-1054708,EBI-1052713
SERINC3	Q13530	1	EBI-1054708,EBI-1045571

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 500	500	Monocarboxylate transporter 1		PRO_0000211381
Regions
	Topological domain	1 – 15	15	Cytoplasmic Potential
	Transmembrane	16 – 36	21	Helical; Potential
	Topological domain	37 – 59	23	Extracellular Potential
	Transmembrane	60 – 80	21	Helical; Potential
	Topological domain	81 – 86	6	Cytoplasmic Potential
	Transmembrane	87 – 107	21	Helical; Potential
	Topological domain	108 – 111	4	Extracellular Potential
	Transmembrane	112 – 132	21	Helical; Potential
	Topological domain	133 – 143	11	Cytoplasmic Potential
	Transmembrane	144 – 164	21	Helical; Potential
	Topological domain	165 – 166	2	Extracellular Potential
	Transmembrane	167 – 187	21	Helical; Potential
	Topological domain	188 – 262	75	Cytoplasmic Potential
	Transmembrane	263 – 283	21	Helical; Potential
	Topological domain	284 – 298	15	Extracellular Potential
	Transmembrane	299 – 319	21	Helical; Potential
	Topological domain	320 – 328	9	Cytoplasmic Potential
	Transmembrane	329 – 349	21	Helical; Potential
	Topological domain	350 – 353	4	Extracellular Potential
	Transmembrane	354 – 374	21	Helical; Potential
	Topological domain	375 – 389	15	Cytoplasmic Potential
	Transmembrane	390 – 410	21	Helical; Potential
	Topological domain	411 – 422	12	Extracellular Potential
	Transmembrane	423 – 443	21	Helical; Potential
	Topological domain	444 – 500	57	Cytoplasmic Potential
Amino acid modifications
	Modified residue	210	1	Phosphoserine By similarity
	Modified residue	213	1	Phosphoserine Ref.7
	Modified residue	461	1	Phosphoserine Ref.9 Ref.10 Ref.11 Ref.12
	Modified residue	466	1	Phosphothreonine Ref.7 Ref.10 Ref.11 Ref.12
	Modified residue	467	1	Phosphoserine Ref.7 Ref.9 Ref.10 Ref.11
	Modified residue	483	1	Phosphoserine Ref.9 Ref.10
	Modified residue	498	1	Phosphoserine Ref.7 Ref.8 Ref.9 Ref.10 Ref.12
Natural variations
	Natural variant	85	1	S → G. Corresponds to variant rs11551867 [ dbSNP | Ensembl ].		VAR_054804
	Natural variant	204	1	K → E in SDLT. Ref.14		VAR_010434
	Natural variant	472	1	G → R in SDLT. Ref.14		VAR_010435
	Natural variant	490	1	D → E. Ref.1 Ref.3 Ref.14 Corresponds to variant rs1049434 [ dbSNP | Ensembl ].		VAR_010436
Experimental info
	Sequence conflict	480	1	A → T in AAC41707. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P53985 [UniParc]. Last modified November 30, 2010. Version 3. Checksum: 3F5B048CB962ECC8	FASTA	500	53,944
	10 20 30 40 50 60 MPPAVGGPVG YTPPDGGWGW AVVIGAFISI GFSYAFPKSI TVFFKEIEGI FHATTSEVSW 70 80 90 100 110 120 ISSIMLAVMY GGGPISSILV NKYGSRIVMI VGGCLSGCGL IAASFCNTVQ QLYVCIGVIG 130 140 150 160 170 180 GLGLAFNLNP ALTMIGKYFY KRRPLANGLA MAGSPVFLCT LAPLNQVFFG IFGWRGSFLI 190 200 210 220 230 240 LGGLLLNCCV AGALMRPIGP KPTKAGKDKS KASLEKAGKS GVKKDLHDAN TDLIGRHPKQ 250 260 270 280 290 300 EKRSVFQTIN QFLDLTLFTH RGFLLYLSGN VIMFFGLFAP LVFLSSYGKS QHYSSEKSAF 310 320 330 340 350 360 LLSILAFVDM VARPSMGLVA NTKPIRPRIQ YFFAASVVAN GVCHMLAPLS TTYVGFCVYA 370 380 390 400 410 420 GFFGFAFGWL SSVLFETLMD LVGPQRFSSA VGLVTIVECC PVLLGPPLLG RLNDMYGDYK 430 440 450 460 470 480 YTYWACGVVL IISGIYLFIG MGINYRLLAK EQKANEQKKE SKEEETSIDV AGKPNEVTKA 490 500 AESPDQKDTD GGPKEEESPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12." Garcia C.K., Li X., Luna J., Francke U. Genomics 23:500-503(1994) [PubMed: 7835905] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLU-490. Tissue: Heart.
[2]	"The human monocarboxylate transporter, MCT1: genomic organization and promoter analysis." Cuff M.A., Shirazi-Beechey S.P. Biochem. Biophys. Res. Commun. 292:1048-1056(2002) [PubMed: 11944921] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Colon.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLU-490. Tissue: Melanoma.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213; THR-466; SER-467 AND SER-498, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-498, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-461; SER-467; SER-483 AND SER-498, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-461; THR-466; SER-467; SER-483 AND SER-498, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-461; THR-466 AND SER-467, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[12]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-461; THR-466 AND SER-498, MASS SPECTROMETRY.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport." Merezhinskaya N., Fishbein W.N., Davis J.I., Foellmer J.W. Muscle Nerve 23:90-97(2000) [PubMed: 10590411] [Abstract] Cited for: VARIANTS SDLT GLU-204 AND ARG-472, VARIANT GLU-490.
[15]	"Physical exercise-induced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic beta cells." Otonkoski T., Jiao H., Kaminen-Ahola N., Tapia-Paez I., Ullah M.S., Parton L.E., Schuit F., Quintens R., Sipilae I., Mayatepek E., Meissner T., Halestrap A.P., Rutter G.A., Kere J. Am. J. Hum. Genet. 81:467-474(2007) [PubMed: 17701893] [Abstract] Cited for: INVOLVEMENT IN HHF7.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L31801 mRNA. Translation: AAC41707.1. AJ438945 Genomic DNA. Translation: CAD27707.1. AL162079 mRNA. Translation: CAB82412.1. AL158844 Genomic DNA. Translation: CAI21872.1. CH471122 Genomic DNA. Translation: EAW56552.1. BC026317 mRNA. Translation: AAH26317.1.
IPI	IPI00024650.
PIR	A55568.
RefSeq	NP_001159968.1. NM_001166496.1. NP_003042.3. NM_003051.3.
UniGene	Hs.75231.
3D structure databases
ProteinModelPortal	P53985.
ModBase	Search...
Protein-protein interaction databases
IntAct	P53985. 3 interactions.
STRING	P53985.
Protein family/group databases
TCDB	2.A.1.13.1. major facilitator superfamily (MFS).
PTM databases
PhosphoSite	P53985.
Polymorphism databases
DMDM	13432183.
Proteomic databases
PRIDE	P53985.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000369626; ENSP00000358640; ENSG00000155380.
GeneID	6566.
KEGG	hsa:6566.
Organism-specific databases
CTD	6566.
GeneCards	GC01M113454.
H-InvDB	HIX0000897.
HGNC	HGNC:10922. SLC16A1.
HPA	CAB017489. HPA003324.
MIM	245340. phenotype. 600682. gene. 610021. phenotype.
neXtProt	NX_P53985.
Orphanet	165991. Exercise-induced hyperinsulinism. 171690. Metabolic myopathy due to lactate transporter defect.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG08079.
HOGENOM	HBG444740.
HOVERGEN	HBG006384.
InParanoid	P53985.
OMA	EKQSFFQ.
OrthoDB	EOG41G341.
PhylomeDB	P53985.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000155380-MONOMER.
Reactome	REACT_111217. Metabolism. REACT_15518. Transmembrane transport of small molecules. REACT_20633. Bile salt and organic anion SLC transporters. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P53985.
Bgee	P53985.
CleanEx	HS_SLC16A1.
Genevestigator	P53985.
GermOnline	ENSG00000155380. Homo sapiens.
Family and domain databases
InterPro	IPR011701. MFS. IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. IPR004743. Monocarb_transpt. [Graphical view]
KO	K08179.
Pfam	PF07690. MFS_1. 1 hit. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
TIGRFAMs	TIGR00892. 2A0113. 1 hit.
PROSITE	PS50850. MFS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00119. Pyruvic acid.
NextBio	25547.
PMAP-CutDB	P53985.
SOURCE	Search...

Entry information

Entry name

MOT1_HUMAN

Accession

Primary (citable) accession number: P53985
Secondary accession number(s): Q5T8R6, Q9NSJ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 30, 2010
Last modified:	January 25, 2012
This is version 116 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.