SLC7A5

SLC7A5
SLC7A5
Идентификаторы
Символы	SLC7A5, 4F2LC, CD98, D16S469E, E16, LAT1, MPE16, hLAT1, solute carrier family 7 member 5
Внешние IDs	OMIM: 600182 MGI: 1298205 HomoloGene: 55759 GeneCards: 8140
Генная онтология
Генная онтология
Функции	• peptide antigen binding; • L-amino acid transmembrane transporter activity; • amino acid transmembrane transporter activity; • neutral amino acid transmembrane transporter activity; • antiporter activity; • GO:0001948 связывание с белками плазмы; • GO:0022891 transmembrane transporter activity;
Компонент клетки	• часть мембраны; • мембрана; • intracellular membrane-bounded organelle; • клеточная мембрана; • apical plasma membrane; • Экзосомы; • часть клеточной мембраны; • цитоплазма; • цитозоль;
Биологический процесс	• amino acid transmembrane transport; • Дифференцировка клеток; • cellular amino acid metabolic process; • nervous system development; • multicellular organism development; • L-amino acid transport; • neutral amino acid transport; • leukocyte migration; • amino acid transport; • L-alpha-amino acid transmembrane transport; • перенос; • transmembrane transport;
	Источники:Amigo / QuickGO
Ортологи
	8140
	20539
	ENSG00000103257
	ENSMUSG00000040010
	Q01650
	Q9Z127
	NM_003486
	NM_011404
	NP_003477
	NP_035534
Править (человек)	Править (мышь)

SLC7A5 (solute carrier family 7 member 5), или лёгкая цепь 4F2 — мембранный белок семейства транспортёров растворённых веществ. Продукт гена человека SLC7A5[1].

Функции

Гетеродимер с лёгкой цепью SLC3A2 функционирует как натрий-независимый высокоаффинный транспортёр больших нейтральных аминокислот, таких как фенилаланин, тирозин, L-диоксифенилаланин (L-ДОФА), лейцин, гистидин, метионин и триптофан[2][3][4][5][6][7].

Играет роль антипорта аминокислот[4][8]. Может участвовать в транспорте L-ДОФА через гематоэнцефалический барьер и играть роль основного транспортёра тирозина в фибробластах. Может опосредовать транспорт тироидных гормонов трийодтиронина (T₃) и тироксина (T₄) через клеточную мембрану[9][10].

Белок также играет роль в поглощении метилртути (MeHg), назначенной в виде комплекса с L-цистеином или D,L-гомоцистеином[11]. Участвует в клеточной активности низкомолекулярных нитрозотиолов за счёт стереоселективного транспорта L-нитрозоцистеина через мембрану[12].

Примечания

Entrez Gene: solute carrier family 7 (cationic amino acid transporter (неопр.).
Mastroberardino L, Spindler B, Pfeiffer R, Skelly PJ, Loffing J, Shoemaker CB; et al. (1998). “Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family”. Nature. 395 (6699): 288—91. DOI:10.1038/26246. PMID 9751058.
Prasad PD, Wang H, Huang W, Kekuda R, Rajan DP, Leibach FH; et al. (1999). “Human LAT1, a subunit of system L amino acid transporter: molecular cloning and transport function”. Biochem Biophys Res Commun. 255 (2): 283—8. DOI:10.1006/bbrc.1999.0206. PMID 10049700.
Yanagida O, Kanai Y, Chairoungdua A, Kim DK, Segawa H, Nii T; et al. (2001). “Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines”. Biochim Biophys Acta. 1514 (2): 291—302. DOI:10.1016/s0005-2736(01)00384-4. PMID 11557028.
Pineda M, Fernández E, Torrents D, Estévez R, López C, Camps M; et al. (1999). “Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids”. J Biol Chem. 274 (28): 19738—44. DOI:10.1074/jbc.274.28.19738. PMID 10391915.
Rossier G, Meier C, Bauch C, Summa V, Sordat B, Verrey F; et al. (1999). “LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine”. J Biol Chem. 274 (49): 34948—54. DOI:10.1074/jbc.274.49.34948. PMID 10574970.
Bröer A, Friedrich B, Wagner CA, Fillon S, Ganapathy V, Lang F; et al. (2001). “Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires different domains”. Biochem J. 355 (Pt 3): 725—31. DOI:10.1042/bj3550725. PMC 1221788. PMID 11311135.
Yan R, Zhao X, Lei J, Zhou Q (2019). “Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex”. Nature. 568 (7750): 127—130. DOI:10.1038/s41586-019-1011-z. PMID 30867591.
Friesema EC, Docter R, Moerings EP, Verrey F, Krenning EP, Hennemann G; et al. (2001). “Thyroid hormone transport by the heterodimeric human system L amino acid transporter”. Endocrinology. 142 (10): 4339—48. DOI:10.1210/endo.142.10.8418. PMID 11564694.
Kim DK, Kanai Y, Choi HW, Tangtrongsup S, Chairoungdua A, Babu E; et al. (2002). “Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells”. Biochim Biophys Acta. 1565 (1): 112—21. DOI:10.1016/s0005-2736(02)00516-3. PMID 12225859.
Simmons-Willis TA, Koh AS, Clarkson TW, Ballatori N (2002). “Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2”. Biochem J. 367 (Pt 1): 239—46. DOI:10.1042/BJ20020841. PMC 1222880. PMID 12117417.
Li S, Whorton AR (2005). “Identification of stereoselective transporters for S-nitroso-L-cysteine: role of LAT1 and LAT2 in biological activity of S-nitrosothiols”. J Biol Chem. 280 (20): 20102—10. DOI:10.1074/jbc.M413164200. PMID 15769744.

Литература

Kaira K, Oriuchi N, Imai H, et al. (2009). “Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in stage I pulmonary adenocarcinoma”. Lung Cancer. 66 (1): 120—6. DOI:10.1016/j.lungcan.2008.12.015. PMID 19171406.
Verrey F, Jack DL, Paulsen IT, et al. (1999). “New glycoprotein-associated amino acid transporters”. J. Membr. Biol. 172 (3): 181—92. DOI:10.1007/s002329900595. PMID 10568788. Неизвестный параметр |s2cid= (справка)
Nawashiro H, Otani N, Shinomiya N, et al. (2006). “L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors”. Int. J. Cancer. 119 (3): 484—92. DOI:10.1002/ijc.21866. PMID 16496379. Неизвестный параметр |s2cid= (справка)
Nawashiro H, Otani N, Uozumi Y, et al. (2005). “High expression of L-type amino acid transporter 1 in infiltrating glioma cells”. Brain Tumor Pathol. 22 (2): 89—91. DOI:10.1007/s10014-005-0188-z. PMID 18095110. Неизвестный параметр |s2cid= (справка)
Ohno Y, Suda K, Masuko K, et al. (2008). “Production and characterization of highly tumor-specific rat monoclonal antibodies recognizing the extracellular domain of human L-type amino-acid transporter 1”. Cancer Sci. 99 (5): 1000—7. DOI:10.1111/j.1349-7006.2008.00770.x. PMID 18294274. Неизвестный параметр |s2cid= (справка)
Vumma R, Wiesel FA, Flyckt L, et al. (2008). “Functional characterization of tyrosine transport in fibroblast cells from healthy controls”. Neurosci. Lett. 434 (1): 56—60. DOI:10.1016/j.neulet.2008.01.028. PMID 18262359. Неизвестный параметр |s2cid= (справка)
Endou H, Kanai Y (1999). “[Amino acid transporter molecule as a drug target]”. Nippon Yakurigaku Zasshi. 114 Suppl 1: 11P—16P. DOI:10.1254/fpj.114.supplement_11. PMID 10629848.
Nakanishi K, Ogata S, Matsuo H, et al. (2007). “Expression of LAT1 predicts risk of progression of transitional cell carcinoma of the upper urinary tract”. Virchows Arch. 451 (3): 681—90. DOI:10.1007/s00428-007-0457-9. PMID 17622555. Неизвестный параметр |s2cid= (справка)
Kaira K, Oriuchi N, Imai H, et al. (2009). “L-type amino acid transporter 1 (LAT1) is frequently expressed in thymic carcinomas but is absent in thymomas”. J Surg Oncol. 99 (7): 433—8. DOI:10.1002/jso.21277. PMID 19347882. Неизвестный параметр |s2cid= (справка)
Anderson BM, Schnetz-Boutaud NC, Bartlett J, et al. (2009). “Examination of association of genes in the serotonin system to autism”. Neurogenetics. 10 (3): 209—16. DOI:10.1007/s10048-009-0171-7. PMC 2753863. PMID 19184136.
Ring BZ, Seitz RS, Beck RA, et al. (2009). “A novel five-antibody immunohistochemical test for subclassification of lung carcinoma”. Mod. Pathol. 22 (8): 1032—43. DOI:10.1038/modpathol.2009.60. PMID 19430419.
Kaira K, Oriuchi N, Imai H, et al. (2008). “Expression of L-type amino acid transporter 1 (LAT1) in neuroendocrine tumors of the lung”. Pathol. Res. Pract. 204 (8): 553—61. DOI:10.1016/j.prp.2008.02.003. PMID 18440724.
Kobayashi K, Ohnishi A, Promsuk J, et al. (2008). “Enhanced tumor growth elicited by L-type amino acid transporter 1 in human malignant glioma cells”. Neurosurgery. 62 (2): 493—503, discussion 503–4. DOI:10.1227/01.neu.0000316018.51292.19. PMID 18382329.
Kühne A, Kaiser R, Schirmer M, et al. (2007). “Genetic polymorphisms in the amino acid transporters LAT1 and LAT2 in relation to the pharmacokinetics and side effects of melphalan”. Pharmacogenet. Genomics. 17 (7): 505—17. DOI:10.1097/FPC.0b013e3280ea77cd. PMID 17558306. Неизвестный параметр |s2cid= (справка)
Kaira K, Oriuchi N, Imai H, et al. (2008). “Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I-III nonsmall cell lung cancer”. Br. J. Cancer. 98 (4): 742—8. DOI:10.1038/sj.bjc.6604235. PMC 2259171. PMID 18253116.
Bröer S (2008). “Amino acid transport across mammalian intestinal and renal epithelia”. Physiol. Rev. 88 (1): 249—86. DOI:10.1152/physrev.00018.2006. PMID 18195088.
Kaira K, Oriuchi N, Imai H, et al. (2008). “l-type amino acid transporter 1 and CD98 expression in primary and metastatic sites of human neoplasms”. Cancer Sci. 99 (12): 2380—6. DOI:10.1111/j.1349-7006.2008.00969.x. PMID 19018776. Неизвестный параметр |s2cid= (справка)
Imai H, Kaira K, Oriuchi N, et al. (2009). “L-type amino acid transporter 1 expression is a prognostic marker in patients with surgically resected stage I non-small cell lung cancer”. Histopathology. 54 (7): 804—13. DOI:10.1111/j.1365-2559.2009.03300.x. PMID 19635099. Неизвестный параметр |s2cid= (справка)
Shennan DB, Thomson J (2008). “Inhibition of system L (LAT1/CD98hc) reduces the growth of cultured human breast cancer cells”. Oncol. Rep. 20 (4): 885—9. DOI:10.3892/or_00000087. PMID 18813831.
Sakata T, Ferdous G, Tsuruta T, et al. (2009). “L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer”. Pathol. Int. 59 (1): 7—18. DOI:10.1111/j.1440-1827.2008.02319.x. PMID 19121087. Неизвестный параметр |s2cid= (справка)

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[entrez-1] Entrez Gene: solute carrier family 7 (cationic amino acid transporter (неопр.).

[pmid9751058-2] Mastroberardino L, Spindler B, Pfeiffer R, Skelly PJ, Loffing J, Shoemaker CB; et al. (1998). “Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family”. Nature. 395 (6699): 288—91. DOI:10.1038/26246. PMID 9751058.

[pmid10049700-3] Prasad PD, Wang H, Huang W, Kekuda R, Rajan DP, Leibach FH; et al. (1999). “Human LAT1, a subunit of system L amino acid transporter: molecular cloning and transport function”. Biochem Biophys Res Commun. 255 (2): 283—8. DOI:10.1006/bbrc.1999.0206. PMID 10049700.

[pmid11557028-4] Yanagida O, Kanai Y, Chairoungdua A, Kim DK, Segawa H, Nii T; et al. (2001). “Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines”. Biochim Biophys Acta. 1514 (2): 291—302. DOI:10.1016/s0005-2736(01)00384-4. PMID 11557028.

[pmid10391915-5] Pineda M, Fernández E, Torrents D, Estévez R, López C, Camps M; et al. (1999). “Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids”. J Biol Chem. 274 (28): 19738—44. DOI:10.1074/jbc.274.28.19738. PMID 10391915.

[pmid10574970-6] Rossier G, Meier C, Bauch C, Summa V, Sordat B, Verrey F; et al. (1999). “LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine”. J Biol Chem. 274 (49): 34948—54. DOI:10.1074/jbc.274.49.34948. PMID 10574970.

[pmid11311135-7] Bröer A, Friedrich B, Wagner CA, Fillon S, Ganapathy V, Lang F; et al. (2001). “Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires different domains”. Biochem J. 355 (Pt 3): 725—31. DOI:10.1042/bj3550725. PMC 1221788. PMID 11311135.

[pmid30867591-8] Yan R, Zhao X, Lei J, Zhou Q (2019). “Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex”. Nature. 568 (7750): 127—130. DOI:10.1038/s41586-019-1011-z. PMID 30867591.

[pmid11564694-9] Friesema EC, Docter R, Moerings EP, Verrey F, Krenning EP, Hennemann G; et al. (2001). “Thyroid hormone transport by the heterodimeric human system L amino acid transporter”. Endocrinology. 142 (10): 4339—48. DOI:10.1210/endo.142.10.8418. PMID 11564694.

[pmid12225859-10] Kim DK, Kanai Y, Choi HW, Tangtrongsup S, Chairoungdua A, Babu E; et al. (2002). “Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells”. Biochim Biophys Acta. 1565 (1): 112—21. DOI:10.1016/s0005-2736(02)00516-3. PMID 12225859.

[pmid12117417-11] Simmons-Willis TA, Koh AS, Clarkson TW, Ballatori N (2002). “Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2”. Biochem J. 367 (Pt 1): 239—46. DOI:10.1042/BJ20020841. PMC 1222880. PMID 12117417.

[pmid15769744-12] Li S, Whorton AR (2005). “Identification of stereoselective transporters for S-nitroso-L-cysteine: role of LAT1 and LAT2 in biological activity of S-nitrosothiols”. J Biol Chem. 280 (20): 20102—10. DOI:10.1074/jbc.M413164200. PMID 15769744.