SLC16A1

SLC16A1
Identifikatori
Aliasi	SLC16A1
Vanjski ID-jevi	OMIM: 600682 MGI: 106013 HomoloGene: 20662 GeneCards: SLC16A1
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	112,957,593 bp
Lokacija gena (miš)
Hrom.	Hromosom 3 (miš)
Kraj	104,565,778 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• protein homodimerization activity; • monocarboxylic acid transmembrane transporter activity; • mevalonate transmembrane transporter activity; • organic cyclic compound binding; • symporter activity; • lactate transmembrane transporter activity;
Ćelijska komponenta	• integral component of membrane; • centrosom; • membrana; • ćelijska membrana; • integral component of plasma membrane; • mitohondrija; • Egzosom; • međućelijske veze; • intracellular membrane-bounded organelle; • sinapsa;
Biološki proces	• monocarboxylic acid transport; • glucose homeostasis; • regulation of insulin secretion; • lipid metabolism; • behavioral response to nutrient; • GO:1904579 cellular response to organic cyclic compound; • lactate transmembrane transport; • pyruvate metabolic process; • response to food; • mevalonate transport; • leukocyte migration; • transmembrane transport; • plasma membrane lactate transport; • centrosome cycle; • GO:0015915 transport;
	Izvori:Amigo / QuickGO
Ortolozi
	6566
	20501
	ENSG00000155380; ENSG00000281917
	ENSMUSG00000032902
	P53985; Q5T8R3
	P53986
	NM_001166496; NM_003051
	NM_009196
	NP_001159968; NP_003042
	NP_033222
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Monokarboksilatni transporter 1, popznat i kao MCT1 jest sveprisutni protein koji je kod ljudi kodiran genom SLC16A1 sa hromosoma 1.^[5]^[6]^[7] To je protonski spregnuti monokarboksilatni transporter.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 500 aminokiselina, a molekulska težina 53.944 Da.^[8]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MPPAVGGPVG	YTPPDGGWGW	AVVIGAFISI	GFSYAFPKSI	TVFFKEIEGI
FHATTSEVSW	ISSIMLAVMY	GGGPISSILV	NKYGSRIVMI	VGGCLSGCGL
IAASFCNTVQ	QLYVCIGVIG	GLGLAFNLNP	ALTMIGKYFY	KRRPLANGLA
MAGSPVFLCT	LAPLNQVFFG	IFGWRGSFLI	LGGLLLNCCV	AGALMRPIGP
KPTKAGKDKS	KASLEKAGKS	GVKKDLHDAN	TDLIGRHPKQ	EKRSVFQTIN
QFLDLTLFTH	RGFLLYLSGN	VIMFFGLFAP	LVFLSSYGKS	QHYSSEKSAF
LLSILAFVDM	VARPSMGLVA	NTKPIRPRIQ	YFFAASVVAN	GVCHMLAPLS
TTYVGFCVYA	GFFGFAFGWL	SSVLFETLMD	LVGPQRFSSA	VGLVTIVECC
PVLLGPPLLG	RLNDMYGDYK	YTYWACGVVL	IISGIYLFIG	MGINYRLLAK
EQKANEQKKE	SKEEETSIDV	AGKPNEVTKA	AESPDQKDTD	GGPKEEESPV

Biohemija

Detaljna kinetička analiza transporta monokarboksilata u eritrocitima otkrila je da MCT1 djeluje preko uređenog mehanizma. MCT1 ima mjesto vezivanja supstrata otvoreno za vanćelijski matriks, koji prvo veže proton a zatim laktatni anion. Protein tada prolazi kroz konformacijsku promjenu u novu "zatvorenu" konformaciju koja izlaže i proton i laktat suprotnoj površini membrane, gdje se oslobađaju, prvo laktat, a zatim proton. Za neto transport mliječne kiseline, korak koji ograničava brzinu je povratak MCT1 bez vezanog supstrata u otvorenu konformaciju. Iz tog razloga, izmjena jednog monokarboksilata unutar ćelije s drugim izvan ćelije je znatno brža od neto transporta monokarboksilata kroz membranu.

Studije na životinjama

Pokazalo se da prekomjerna ekspresija MCT1 povećava efikasnost lijeka protiv raka koji se nalazi u kliničkim ispitivanjima pod nazivom 3-bromopiruvat u ćelijama raka dojke.^[9]

Klinički značaj

Većina slučajeva alveolskog mehkog sarkoma pokazuje PAS(+), rezistentne na dijastazu (PAS-D (+)) unutarcitoplazmatske kristale koji sadrže CD147 i monokarboksilatni transporter 1 (MCT1).^[10] Prekomjerna ekspresija MCT1 u pankreasnim beta ćelijama dovodi do hiperinsulinizma tokom vježbe.^[11]

Reference

^ ^a ^b ^c ENSG00000281917 GRCh38: Ensembl release 89: ENSG00000155380, ENSG00000281917 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000032902 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Garcia CK, Goldstein JL, Pathak RK, Anderson RG, Brown MS (Mar 1994). "Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle". Cell. 76 (5): 865–73. doi:10.1016/0092-8674(94)90361-1. PMID 8124722. S2CID 22137883.
^ Garcia CK, Li X, Luna J, Francke U (Sep 1994). "cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12". Genomics. 23 (2): 500–3. doi:10.1006/geno.1994.1532. PMID 7835905.
^ "Entrez Gene: SLC16A1 solute carrier family 16, member 1 (monocarboxylic acid transporter 1)".
^ "UniProt, P53985" (jezik: eng). Pristupljeno 5. 12. 2021.CS1 održavanje: nepoznati jezik (link)
^ Liu Z, Sun Y, Hong H, Zhao S, Zou X, Ma R, Jiang C, Wang Z, Li H, Liu H (15. 8. 2015). "3-bromopyruvate enhanced daunorubicin-induced cytotoxicity involved in monocarboxylate transporter 1 in breast cancer cells". American Journal of Cancer Research. 5 (9): 2673–85. PMC 4633897. PMID 26609475.
^ Ladanyi M, Antonescu CR, Drobnjak M, Baren A, Lui MY, Golde DW, Cordon-Cardo C (Apr 2002). "The precrystalline cytoplasmic granules of alveolar soft part sarcoma contain monocarboxylate transporter 1 and CD147". The American Journal of Pathology. 160 (4): 1215–21. doi:10.1016/S0002-9440(10)62548-5. PMC 1867200. PMID 11943706.
^ Pullen TJ, Sylow L, Sun G, Halestrap AP, Richter EA, Rutter GA (Jul 2012). "Overexpression of monocarboxylate transporter-1 (SLC16A1) in mouse pancreatic β-cells leads to relative hyperinsulinism during exercise". Diabetes. 61 (7): 1719–25. doi:10.2337/db11-1531. PMC 3379650. PMID 22522610.

Dopunska literatura

Bonen A (Nov 2001). "The expression of lactate transporters (MCT1 and MCT4) in heart and muscle". European Journal of Applied Physiology. 86 (1): 6–11. doi:10.1007/s004210100516. PMID 11820324. S2CID 12166288.
Halestrap AP, Meredith D (Feb 2004). "The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond". Pflügers Archiv: European Journal of Physiology. 447 (5): 619–28. doi:10.1007/s00424-003-1067-2. PMID 12739169. S2CID 15498611.
Kim CM, Goldstein JL, Brown MS (Nov 1992). "cDNA cloning of MEV, a mutant protein that facilitates cellular uptake of mevalonate, and identification of the point mutation responsible for its gain of function". The Journal of Biological Chemistry. 267 (32): 23113–21. doi:10.1016/S0021-9258(18)50064-8. PMID 1429658.
Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Ritzhaupt A, Wood IS, Ellis A, Hosie KB, Shirazi-Beechey SP (Dec 1998). "Identification and characterization of a monocarboxylate transporter (MCT1) in pig and human colon: its potential to transport L-lactate as well as butyrate". The Journal of Physiology. 513 (Pt 3): 719–32. doi:10.1111/j.1469-7793.1998.719ba.x. PMC 2231331. PMID 9824713.
Rahman B, Schneider HP, Bröer A, Deitmer JW, Bröer S (Aug 1999). "Helix 8 and helix 10 are involved in substrate recognition in the rat monocarboxylate transporter MCT1". Biochemistry. 38 (35): 11577–84. doi:10.1021/bi990973f. PMID 10471310.
Brooks GA, Brown MA, Butz CE, Sicurello JP, Dubouchaud H (Nov 1999). "Cardiac and skeletal muscle mitochondria have a monocarboxylate transporter MCT1". Journal of Applied Physiology. 87 (5): 1713–8. doi:10.1152/jappl.1999.87.5.1713. PMID 10562613.
Merezhinskaya N, Fishbein WN, Davis JI, Foellmer JW (Jan 2000). "Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport". Muscle & Nerve. 23 (1): 90–7. doi:10.1002/(SICI)1097-4598(200001)23:1<90::AID-MUS12>3.0.CO;2-M. PMID 10590411.
Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP (Aug 2000). "CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression". The EMBO Journal. 19 (15): 3896–904. doi:10.1093/emboj/19.15.3896. PMC 306613. PMID 10921872.
Cuff MA, Lambert DW, Shirazi-Beechey SP (Mar 2002). "Substrate-induced regulation of the human colonic monocarboxylate transporter, MCT1". The Journal of Physiology. 539 (Pt 2): 361–71. doi:10.1113/jphysiol.2001.014241. PMC 2290148. PMID 11882670.
Cuff MA, Shirazi-Beechey SP (Apr 2002). "The human monocarboxylate transporter, MCT1: genomic organization and promoter analysis". Biochemical and Biophysical Research Communications. 292 (4): 1048–56. doi:10.1006/bbrc.2002.6763. PMID 11944921.
Lambert DW, Wood IS, Ellis A, Shirazi-Beechey SP (Apr 2002). "Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy". British Journal of Cancer. 86 (8): 1262–9. doi:10.1038/sj.bjc.6600264. PMC 2375337. PMID 11953883.
Zhang GZ, Huang GJ, Li WL, Wu GM, Qian GS (Jul 2002). "[Effect of co-inhibition of MCT1 gene and NHE1 gene on proliferation and growth of human lung adenocarcinoma cells]". AI Zheng = Aizheng = Chinese Journal of Cancer. 21 (7): 719–23. PMID 12479094.
Philp NJ, Wang D, Yoon H, Hjelmeland LM (Apr 2003). "Polarized expression of monocarboxylate transporters in human retinal pigment epithelium and ARPE-19 cells". Investigative Ophthalmology & Visual Science. 44 (4): 1716–21. doi:10.1167/iovs.02-0287. PMID 12657613.
Asada K, Miyamoto K, Fukutomi T, Tsuda H, Yagi Y, Wakazono K, Oishi S, Fukui H, Sugimura T, Ushijima T (2003). "Reduced expression of GNA11 and silencing of MCT1 in human breast cancers". Oncology. 64 (4): 380–8. doi:10.1159/000070297. PMID 12759536. S2CID 9041712.

Vanjski linkovi

[refGRCh38Ensembl-1] ENSG00000281917 GRCh38: Ensembl release 89: ENSG00000155380, ENSG00000281917 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000032902 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8124722-5] Garcia CK, Goldstein JL, Pathak RK, Anderson RG, Brown MS (Mar 1994). "Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle". Cell. 76 (5): 865–73. doi:10.1016/0092-8674(94)90361-1. PMID 8124722. S2CID 22137883.

[pmid7835905-6] Garcia CK, Li X, Luna J, Francke U (Sep 1994). "cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12". Genomics. 23 (2): 500–3. doi:10.1006/geno.1994.1532. PMID 7835905.

[entrez-7] "Entrez Gene: SLC16A1 solute carrier family 16, member 1 (monocarboxylic acid transporter 1)".

[UniProt-8] "UniProt, P53985" (jezik: eng). Pristupljeno 5. 12. 2021.CS1 održavanje: nepoznati jezik (link)

[9] Liu Z, Sun Y, Hong H, Zhao S, Zou X, Ma R, Jiang C, Wang Z, Li H, Liu H (15. 8. 2015). "3-bromopyruvate enhanced daunorubicin-induced cytotoxicity involved in monocarboxylate transporter 1 in breast cancer cells". American Journal of Cancer Research. 5 (9): 2673–85. PMC 4633897. PMID 26609475.

[10] Ladanyi M, Antonescu CR, Drobnjak M, Baren A, Lui MY, Golde DW, Cordon-Cardo C (Apr 2002). "The precrystalline cytoplasmic granules of alveolar soft part sarcoma contain monocarboxylate transporter 1 and CD147". The American Journal of Pathology. 160 (4): 1215–21. doi:10.1016/S0002-9440(10)62548-5. PMC 1867200. PMID 11943706.

[11] Pullen TJ, Sylow L, Sun G, Halestrap AP, Richter EA, Rutter GA (Jul 2012). "Overexpression of monocarboxylate transporter-1 (SLC16A1) in mouse pancreatic β-cells leads to relative hyperinsulinism during exercise". Diabetes. 61 (7): 1719–25. doi:10.2337/db11-1531. PMC 3379650. PMID 22522610.

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