ID SATT_HUMAN Reviewed; 532 AA. AC P43007; B7Z3C0; D6W5F0; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 02-SEP-2026, entry version 208. DE RecName: Full=Neutral amino acid transporter A {ECO:0000303|PubMed:8101838}; DE AltName: Full=Alanine/serine/cysteine/threonine transporter 1 {ECO:0000303|PubMed:7896285}; DE Short=ASCT-1 {ECO:0000303|PubMed:7896285}; DE AltName: Full=Solute carrier family 1 member 4; GN Name=SLC1A4 {ECO:0000303|PubMed:7896285, ECO:0000312|HGNC:HGNC:10942}; GN Synonyms=ASCT1 {ECO:0000303|PubMed:7896285}, SATT GN {ECO:0000303|PubMed:8340364}; 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), AND FUNCTION. RC TISSUE=Brain cortex; RX PubMed=8101838; DOI=10.1016/s0021-9258(18)82257-8; RA Arriza J.L., Kavanaugh M.P., Fairman W.A., Wu Y.-N., Murdoch G.H., RA North R.A., Amara S.G.; RT "Cloning and expression of a human neutral amino acid transporter with RT structural similarity to the glutamate transporter gene family."; RL J. Biol. Chem. 268:15329-15332(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION. RC TISSUE=Hippocampus; RX PubMed=8340364; DOI=10.1016/s0021-9258(18)82263-3; RA Shafqat S., Tamarappoo B.K., Kilberg M.S., Puranam R.S., McNamara J.O., RA Guadano-Ferraz A., Fremeau R.T. Jr.; RT "Cloning and expression of a novel Na(+)-dependent neutral amino acid RT transporter structurally related to mammalian Na+/glutamate RT cotransporters."; RL J. Biol. Chem. 268:15351-15355(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Placenta; RX PubMed=7896285; DOI=10.1006/geno.1994.1577; RA Hofmann K., Dueker M., Fink T., Lichter P., Stoffel W.; RT "Human neutral amino acid transporter ASCT1: structure of the gene (SLC1A4) RT and localization to chromosome 2p13-p15."; RL Genomics 24:20-26(1994). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Hippocampus; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph, and PNS; 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 [8] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=8910405; DOI=10.1074/jbc.271.45.27991; RA Zerangue N., Kavanaugh M.P.; RT "ASCT-1 is a neutral amino acid exchanger with chloride channel activity."; RL J. Biol. Chem. 271:27991-27994(1996). RN [9] RP FUNCTION. RX PubMed=14502423; DOI=10.1007/s00232-003-2041-9; RA Pinilla-Tenas J., Barber A., Lostao M.P.; RT "Transport of proline and hydroxyproline by the neutral amino-acid RT exchanger ASCT1."; RL J. Membr. Biol. 195:27-32(2003). RN [10] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=17081065; DOI=10.1021/pr060363j; RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.; RT "Proteomic and bioinformatic characterization of the biogenesis and RT function of melanosomes."; RL J. Proteome Res. 5:3135-3144(2006). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-507, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [12] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-201 AND ASN-206. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N-linked RT cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [18] RP FUNCTION, AND MUTAGENESIS OF THR-124; THR-125; ASP-380; GLY-422; GLU-465 RP AND ASP-467. RX PubMed=24808181; DOI=10.1074/jbc.m114.565242; RA Scopelliti A.J., Heinzelmann G., Kuyucak S., Ryan R.M., Vandenberg R.J.; RT "Na+ interactions with the neutral amino acid transporter ASCT1."; RL J. Biol. Chem. 289:17468-17479(2014). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [20] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=27272177; DOI=10.1371/journal.pone.0156551; RA Foster A.C., Farnsworth J., Lind G.E., Li Y.X., Yang J.Y., Dang V., RA Penjwini M., Viswanath V., Staubli U., Kavanaugh M.P.; RT "D-Serine Is a Substrate for Neutral Amino Acid Transporters ASCT1/SLC1A4 RT and ASCT2/SLC1A5, and Is Transported by Both Subtypes in Rat Hippocampal RT Astrocyte Cultures."; RL PLoS ONE 11:e0156551-e0156551(2016). RN [21] RP INDUCTION. RX PubMed=35195906; DOI=10.1002/glia.24161; RA Tapanes S.A., Arizanovska D., Diaz M.M., Folorunso O.O., Harvey T., RA Brown S.E., Radzishevsky I., Close L.N., Jagid J.R., Graciolli Cordeiro J., RA Wolosker H., Balu D.T., Liebl D.J.; RT "Inhibition of glial D-serine release rescues synaptic damage after brain RT injury."; RL Glia 70:1133-1152(2022). RN [22] RP INVOLVEMENT IN SPATCCM, AND VARIANT SPATCCM LYS-256. RX PubMed=25930971; DOI=10.1111/cge.12605; RA Srour M., Hamdan F.F., Gan-Or Z., Labuda D., Nassif C., Oskoui M., RA Gana-Weisz M., Orr-Urtreger A., Rouleau G.A., Michaud J.L.; RT "A homozygous mutation in SLC1A4 in siblings with severe intellectual RT disability and microcephaly."; RL Clin. Genet. 88:E1-E4(2015). RN [23] RP INVOLVEMENT IN SPATCCM, AND VARIANT SPATCCM LYS-256. RX PubMed=26138499; DOI=10.1111/cge.12637; RA Heimer G., Marek-Yagel D., Eyal E., Barel O., Oz Levi D., Hoffmann C., RA Ruzzo E.K., Ganelin-Cohen E., Lancet D., Pras E., Rechavi G., RA Nissenkorn A., Anikster Y., Goldstein D.B., Ben Zeev B.; RT "SLC1A4 mutations cause a novel disorder of intellectual disability, RT progressive microcephaly, spasticity and thin corpus callosum."; RL Clin. Genet. 88:327-335(2015). RN [24] RP INVOLVEMENT IN SPATCCM, VARIANTS SPATCCM LYS-256 AND TRP-457, RP CHARACTERIZATION OF VARIANTS SPATCCM LYS-256 AND TRP-457, FUNCTION, AND RP SUBCELLULAR LOCATION. RX PubMed=26041762; DOI=10.1136/jmedgenet-2015-103104; RA Damseh N., Simonin A., Jalas C., Picoraro J.A., Shaag A., Cho M.T., RA Yaacov B., Neidich J., Al-Ashhab M., Juusola J., Bale S., Telegrafi A., RA Retterer K., Pappas J.G., Moran E., Cappell J., Anyane Yeboa K., RA Abu-Libdeh B., Hediger M.A., Chung W.K., Elpeleg O., Edvardson S.; RT "Mutations in SLC1A4, encoding the brain serine transporter, are associated RT with developmental delay, microcephaly and hypomyelination."; RL J. Med. Genet. 52:541-547(2015). RN [25] RP STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS), FUNCTION, TRANSPORTER RP ACTIVITY, SUBUNIT, TOPOLOGY, VARIANTS SPATCCM LYS-256 AND TRP-457, AND RP CHARACTERIZATION OF VARIANTS SPATCCM LYS-256 AND TRP-457. RX PubMed=34630942; DOI=10.1016/j.csbj.2021.09.015; RA Stehantsev P., Stetsenko A., Nemchinova M., Aduri N.G., Marrink S.J., RA Gati C., Guskov A.; RT "A structural view onto disease-linked mutations in the human neutral amino RT acid exchanger ASCT1."; RL Comput. Struct. Biotechnol. J. 19:5246-5254(2021). CC -!- FUNCTION: Sodium-coupled antiporter of neutral amino acids. In a tri- CC substrate transport cycle, exchanges neutral amino acids between the CC extracellular and intracellular compartments, coupled to the inward CC cotransport of at least one sodium ion (PubMed:24808181, CC PubMed:27272177, PubMed:34630942, PubMed:8910405). Exchanges neutral CC amino acids such as L- and D-serine, L-threonine, L-asparagine and L- CC alanine in a bidirectional way (PubMed:14502423, PubMed:26041762, CC PubMed:27272177, PubMed:34630942, PubMed:8101838, PubMed:8340364, CC PubMed:8910405). Involved in homeostasis of D-serine, a coagonist of CC synaptic NMDA receptors. In astrocytes at excitatory synapses, mediates CC electrogenic D-serine influx coupled to L-serine efflux and L-serine CC shuttling to neurons for de novo D-serine synthesis (By similarity). CC Displays sodium- and amino acid-dependent but uncoupled channel-like CC anion conductance with a preference SCN(-) > NO3(-) > I(-) > Cl(-) CC (PubMed:8910405). {ECO:0000250|UniProtKB:O35874, CC ECO:0000269|PubMed:14502423, ECO:0000269|PubMed:24808181, CC ECO:0000269|PubMed:26041762, ECO:0000269|PubMed:27272177, CC ECO:0000269|PubMed:34630942, ECO:0000269|PubMed:8101838, CC ECO:0000269|PubMed:8340364, ECO:0000269|PubMed:8910405}. CC -!- CATALYTIC ACTIVITY: CC Reaction=D-serine(out) + L-serine(in) + Na(+)(out) = D-serine(in) + L- CC serine(out) + Na(+)(in); Xref=Rhea:RHEA:84319, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:33384, ChEBI:CHEBI:35247; CC Evidence={ECO:0000269|PubMed:27272177}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-serine(in) + L-serine(out) + Na(+)(out) = D-serine(out) + L- CC serine(in) + Na(+)(in); Xref=Rhea:RHEA:84363, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:33384, ChEBI:CHEBI:35247; CC Evidence={ECO:0000269|PubMed:34630942}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-serine(out) + L-alanine(in) + Na(+)(out) = D-serine(in) + L- CC alanine(out) + Na(+)(in); Xref=Rhea:RHEA:84323, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:35247, ChEBI:CHEBI:57972; CC Evidence={ECO:0000269|PubMed:27272177}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-serine(in) + L-alanine(out) + Na(+)(out) = D-serine(out) + CC L-alanine(in) + Na(+)(in); Xref=Rhea:RHEA:75311, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:35247, ChEBI:CHEBI:57972; CC Evidence={ECO:0000269|PubMed:27272177}; CC -!- CATALYTIC ACTIVITY: CC Reaction=trans-4-hydroxy-L-proline(out) + L-serine(in) + Na(+)(out) = CC trans-4-hydroxy-L-proline(in) + L-serine(out) + Na(+)(in); CC Xref=Rhea:RHEA:84331, ChEBI:CHEBI:29101, ChEBI:CHEBI:33384, CC ChEBI:CHEBI:58375; Evidence={ECO:0000250|UniProtKB:O35874}; CC -!- CATALYTIC ACTIVITY: CC Reaction=trans-4-hydroxy-L-proline(out) + L-alanine(in) + Na(+)(out) = CC trans-4-hydroxy-L-proline(in) + L-alanine(out) + Na(+)(in); CC Xref=Rhea:RHEA:84335, ChEBI:CHEBI:29101, ChEBI:CHEBI:57972, CC ChEBI:CHEBI:58375; Evidence={ECO:0000250|UniProtKB:O35874}; CC -!- CATALYTIC ACTIVITY: CC Reaction=trans-4-hydroxy-L-proline(out) + L-threonine(in) + Na(+)(out) CC = trans-4-hydroxy-L-proline(in) + L-threonine(out) + Na(+)(in); CC Xref=Rhea:RHEA:84339, ChEBI:CHEBI:29101, ChEBI:CHEBI:57926, CC ChEBI:CHEBI:58375; Evidence={ECO:0000250|UniProtKB:O35874}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-asparagine(in) + L-serine(out) + Na(+)(out) = L- CC asparagine(out) + L-serine(in) + Na(+)(in); Xref=Rhea:RHEA:84367, CC ChEBI:CHEBI:29101, ChEBI:CHEBI:33384, ChEBI:CHEBI:58048; CC Evidence={ECO:0000269|PubMed:34630942}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-proline(in) + L-serine(out) + Na(+)(out) = L-proline(out) + CC L-serine(in) + Na(+)(in); Xref=Rhea:RHEA:84371, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:33384, ChEBI:CHEBI:60039; CC Evidence={ECO:0000269|PubMed:34630942}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-serine(out) + L-alanine(in) + Na(+)(out) = L-serine(in) + L- CC alanine(out) + Na(+)(in); Xref=Rhea:RHEA:84359, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:33384, ChEBI:CHEBI:57972; CC Evidence={ECO:0000269|PubMed:8910405}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-asparagine(out) + L-alanine(in) + Na(+)(out) = L- CC asparagine(in) + L-alanine(out) + Na(+)(in); Xref=Rhea:RHEA:84355, CC ChEBI:CHEBI:29101, ChEBI:CHEBI:57972, ChEBI:CHEBI:58048; CC Evidence={ECO:0000269|PubMed:8910405}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-proline(out) + L-alanine(in) + Na(+)(out) = L-proline(in) + CC L-alanine(out) + Na(+)(in); Xref=Rhea:RHEA:84351, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:57972, ChEBI:CHEBI:60039; CC Evidence={ECO:0000269|PubMed:8910405}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-cysteine(out) + L-alanine(in) + Na(+)(out) = L-cysteine(in) CC + L-alanine(out) + Na(+)(in); Xref=Rhea:RHEA:84347, CC ChEBI:CHEBI:29101, ChEBI:CHEBI:35235, ChEBI:CHEBI:57972; CC Evidence={ECO:0000269|PubMed:8910405}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonine(out) + L-alanine(in) + Na(+)(out) = L- CC threonine(in) + L-alanine(out) + Na(+)(in); Xref=Rhea:RHEA:84343, CC ChEBI:CHEBI:29101, ChEBI:CHEBI:57926, ChEBI:CHEBI:57972; CC Evidence={ECO:0000269|PubMed:8910405}; CC -!- CATALYTIC ACTIVITY: CC Reaction=thiocyanate(in) = thiocyanate(out); Xref=Rhea:RHEA:75347, CC ChEBI:CHEBI:18022; Evidence={ECO:0000269|PubMed:8910405}; CC -!- CATALYTIC ACTIVITY: CC Reaction=nitrate(in) = nitrate(out); Xref=Rhea:RHEA:34923, CC ChEBI:CHEBI:17632; Evidence={ECO:0000269|PubMed:8910405}; CC -!- CATALYTIC ACTIVITY: CC Reaction=iodide(out) = iodide(in); Xref=Rhea:RHEA:66324, CC ChEBI:CHEBI:16382; Evidence={ECO:0000269|PubMed:8910405}; CC -!- CATALYTIC ACTIVITY: CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823, CC ChEBI:CHEBI:17996; Evidence={ECO:0000269|PubMed:8910405}; CC -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:34630942}. CC -!- INTERACTION: CC P43007; Q02410: APBA1; NbExp=2; IntAct=EBI-11343290, EBI-368690; CC P43007; Q99767: APBA2; NbExp=2; IntAct=EBI-11343290, EBI-81711; CC P43007; Q12959: DLG1; NbExp=2; IntAct=EBI-11343290, EBI-357481; CC P43007; Q92796: DLG3; NbExp=2; IntAct=EBI-11343290, EBI-80440; CC P43007; P78352: DLG4; NbExp=2; IntAct=EBI-11343290, EBI-80389; CC P43007; Q68DX3: FRMPD2; NbExp=3; IntAct=EBI-11343290, EBI-53993476; CC P43007; A4D2P6: GRID2IP; NbExp=2; IntAct=EBI-11343290, EBI-15893226; CC P43007; Q9Y3R0: GRIP1; NbExp=5; IntAct=EBI-11343290, EBI-5349621; CC P43007; Q9C0E4: GRIP2; NbExp=5; IntAct=EBI-11343290, EBI-949557; CC P43007; Q14005: IL16; NbExp=2; IntAct=EBI-11343290, EBI-2831580; CC P43007; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-11343290, EBI-739832; CC P43007; Q8N448: LNX2; NbExp=2; IntAct=EBI-11343290, EBI-2340947; CC P43007; Q96QZ7: MAGI1; NbExp=2; IntAct=EBI-11343290, EBI-924464; CC P43007; Q86UL8: MAGI2; NbExp=5; IntAct=EBI-11343290, EBI-311035; CC P43007; O75970: MPDZ; NbExp=3; IntAct=EBI-11343290, EBI-821405; CC P43007; Q86UT5: NHERF4; NbExp=2; IntAct=EBI-11343290, EBI-8744528; CC P43007; Q8NI35: PATJ; NbExp=8; IntAct=EBI-11343290, EBI-724390; CC P43007; Q5T2W1: PDZK1; NbExp=3; IntAct=EBI-11343290, EBI-349819; CC P43007; Q14160: SCRIB; NbExp=3; IntAct=EBI-11343290, EBI-357345; CC P43007; Q07157: TJP1; NbExp=2; IntAct=EBI-11343290, EBI-79553; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26041762}; CC Multi-pass membrane protein {ECO:0000255}. Melanosome membrane CC {ECO:0000269|PubMed:17081065}; Multi-pass membrane protein CC {ECO:0000255}. Note=Identified by mass spectrometry in melanosome CC fractions from stage I to stage IV. {ECO:0000269|PubMed:17081065}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P43007-1; Sequence=Displayed; CC Name=2; CC IsoId=P43007-2; Sequence=VSP_042880, VSP_042881; CC -!- TISSUE SPECIFICITY: Expressed mostly in brain, muscle, and pancreas but CC detected in all tissues examined. {ECO:0000269|PubMed:8340364}. CC -!- INDUCTION: Up-regulated in the brain cortex upon traumatic brain CC injury. {ECO:0000269|PubMed:35195906}. CC -!- DOMAIN: The transport domain consists of four transmembrane regions 3, CC 6, 7 and 8 and two helical hairpins HP1 and HP2. According to the one- CC gate elevator transport model, substrate binding and release is CC controlled by the helical hairpin 2 (HP2) which acts as a gate for the CC transport domain. HP2 gate opening enables substrate binding or CC release. The gate closes once one amino acid and up to three sodium CC ions bind to the transport domain, which subsequently triggers CC transmembrane elevator-like motion of the transporter across the plasma CC membrane. {ECO:0000250|UniProtKB:Q15758, ECO:0000305|PubMed:34630942}. CC -!- DOMAIN: The beta-hairpin (aa 191-216) located between the helical CC segments of TM4 protrudes in the extracellular space and forms a CC docking platform for proteins of retroviral origin. CC {ECO:0000250|UniProtKB:Q15758, ECO:0000305|PubMed:34630942}. CC -!- DISEASE: Spastic tetraplegia, thin corpus callosum, and progressive CC microcephaly (SPATCCM) [MIM:616657]: A neurodevelopmental disorder CC characterized by thin corpus callosum, severe progressive microcephaly, CC severe intellectual disability, seizures, spasticity, and global CC developmental delay. Most patients are unable to achieve independent CC walking or speech. {ECO:0000269|PubMed:25930971, CC ECO:0000269|PubMed:26041762, ECO:0000269|PubMed:26138499, CC ECO:0000269|PubMed:34630942}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the dicarboxylate/amino acid:cation symporter CC (DAACS) (TC 2.A.23) family. SLC1A4 subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L14595; AAA02761.1; -; mRNA. DR EMBL; L19444; AAA19438.1; -; mRNA. DR EMBL; U05235; AAC51349.1; -; Genomic_DNA. DR EMBL; U05229; AAC51349.1; JOINED; Genomic_DNA. DR EMBL; U05230; AAC51349.1; JOINED; Genomic_DNA. DR EMBL; U05231; AAC51349.1; JOINED; Genomic_DNA. DR EMBL; U05232; AAC51349.1; JOINED; Genomic_DNA. DR EMBL; U05233; AAC51349.1; JOINED; Genomic_DNA. DR EMBL; U05234; AAC51349.1; JOINED; Genomic_DNA. DR EMBL; AK295687; BAH12156.1; -; mRNA. DR EMBL; AC007386; AAF03519.1; -; Genomic_DNA. DR EMBL; CH471053; EAW99932.1; -; Genomic_DNA. DR EMBL; CH471053; EAW99933.1; -; Genomic_DNA. DR EMBL; BC026216; AAH26216.1; -; mRNA. DR EMBL; BC072423; AAH72423.1; -; mRNA. DR CCDS; CCDS1879.1; -. [P43007-1] DR CCDS; CCDS54362.1; -. [P43007-2] DR PIR; I37188; I37188. DR PIR; I55389; I55389. DR RefSeq; NP_001180422.1; NM_001193493.2. [P43007-2] DR RefSeq; NP_003029.2; NM_003038.5. [P43007-1] DR PDB; 7P4I; EM; 4.20 A; A/B/C=1-532. DR AlphaFoldDB; P43007; -. DR EMDB; EMD-13193; -. DR SMR; P43007; -. DR BioGRID; 112400; 51. DR FunCoup; P43007; 85. DR IntAct; P43007; 109. DR MINT; P43007; -. DR NDEx; IQUERY-CP-SLC1A4; 4 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000234256; -. DR ChEMBL; CHEMBL2315; -. DR DrugBank; DB00160; Alanine. DR TCDB; 2.A.23.3.1; the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family. DR GlyCosmos; P43007; 2 sites, No reported glycans. DR GlyGen; P43007; 3 sites, 2 N-linked glycans (2 sites), 1 O-linked glycan (1 site). DR iPTMnet; P43007; -. DR PhosphoSitePlus; P43007; -. DR SwissPalm; P43007; -. DR BioMuta; SLC1A4; -. DR DMDM; 1173365; -. DR jPOST; P43007; -. DR MassIVE; P43007; -. DR PaxDb; 9606-ENSP00000234256; -. DR PeptideAtlas; P43007; -. DR ProteomicsDB; 55572; -. [P43007-1] DR ProteomicsDB; 55573; -. [P43007-2] DR Pumba; P43007; -. DR Antibodypedia; 30840; 253 antibodies from 34 providers. DR DNASU; 6509; -. DR Ensembl; ENST00000234256.4; ENSP00000234256.3; ENSG00000115902.12. [P43007-1] DR Ensembl; ENST00000531327.5; ENSP00000431942.1; ENSG00000115902.12. [P43007-2] DR Ensembl; ENST00000906286.1; ENSP00000576345.1; ENSG00000115902.12. [P43007-1] DR GeneID; 6509; -. DR KEGG; hsa:6509; -. DR MANE-Select; ENST00000234256.4; ENSP00000234256.3; NM_003038.5; NP_003029.2. DR UCSC; uc010ypz.3; human. [P43007-1] DR AGR; HGNC:10942; -. DR ClinPGx; PA35829; -. DR CTD; 6509; -. DR DisGeNET; 6509; -. DR GeneCards; SLC1A4; -. DR HGNC; HGNC:10942; SLC1A4. DR HPA; ENSG00000115902; Tissue enhanced (brain). DR MalaCards; SLC1A4; -. DR MIM; 600229; gene. DR MIM; 616657; phenotype. DR OpenTargets; ENSG00000115902; -. DR Orphanet; 447997; Spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome. DR VEuPathDB; HostDB:ENSG00000115902; -. DR eggNOG; KOG3787; Eukaryota. DR GeneTree; ENSGT00940000157081; -. DR HOGENOM; CLU_019375_6_2_1; -. DR InParanoid; P43007; -. DR OMA; GIMFVVH; -. DR OrthoDB; 5877963at2759; -. DR PAN-GO; P43007; 7 GO annotations based on evolutionary models. DR PhylomeDB; P43007; -. DR PathwayCommons; P43007; -. DR Reactome; R-HSA-352230; Amino acid transport across the plasma membrane. DR SignaLink; P43007; -. DR Agora; ENSG00000115902; -. DR BioGRID-ORCS; 6509; 10 hits in 1161 CRISPR screens. DR ChiTaRS; SLC1A4; human. DR GeneWiki; SLC1A4; -. DR GenomeRNAi; 6509; -. DR Pharos; P43007; Tbio. DR PRO; PR:P43007; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P43007; protein. DR Bgee; ENSG00000115902; Expressed in buccal mucosa cell and 206 other cell types or tissues. DR GO; GO:0009986; C:cell surface; HDA:UniProtKB. DR GO; GO:0005813; C:centrosome; IDA:HPA. DR GO; GO:0030425; C:dendrite; IEA:Ensembl. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005882; C:intermediate filament; ISS:UniProtKB. DR GO; GO:0033162; C:melanosome membrane; EXP:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:ARUK-UCL. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IMP:ARUK-UCL. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0015171; F:amino acid transmembrane transporter activity; TAS:Reactome. DR GO; GO:0005254; F:chloride channel activity; IDA:UniProtKB. DR GO; GO:0015180; F:L-alanine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015183; F:L-aspartate transmembrane transporter activity; ISS:ARUK-UCL. DR GO; GO:0015184; F:L-cystine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0005313; F:L-glutamate transmembrane transporter activity; TAS:BHF-UCL. DR GO; GO:0015186; F:L-glutamine transmembrane transporter activity; IEA:UniProtKB-ARBA. DR GO; GO:0034590; F:L-hydroxyproline transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015193; F:L-proline transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015194; F:L-serine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015195; F:L-threonine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015293; F:symporter activity; IEA:InterPro. DR GO; GO:0006865; P:amino acid transport; TAS:Reactome. DR GO; GO:0050890; P:cognition; IMP:UniProtKB. DR GO; GO:0034589; P:hydroxyproline transport; IDA:UniProtKB. DR GO; GO:0090461; P:intracellular glutamate homeostasis; TAS:BHF-UCL. DR GO; GO:1904273; P:L-alanine import across plasma membrane; IMP:ARUK-UCL. DR GO; GO:0015808; P:L-alanine transport; IDA:UniProtKB. DR GO; GO:0140009; P:L-aspartate import across plasma membrane; ISS:ARUK-UCL. DR GO; GO:0015811; P:L-cystine transport; IDA:UniProtKB. DR GO; GO:0098712; P:L-glutamate import across plasma membrane; TAS:BHF-UCL. DR GO; GO:0015813; P:L-glutamate transmembrane transport; IBA:GO_Central. DR GO; GO:1903812; P:L-serine import across plasma membrane; IMP:ARUK-UCL. DR GO; GO:0015825; P:L-serine transport; IDA:UniProtKB. DR GO; GO:0015824; P:proline transport; IDA:UniProtKB. DR GO; GO:0035249; P:synaptic transmission, glutamatergic; NAS:UniProtKB. DR GO; GO:0015826; P:threonine transport; IDA:UniProtKB. DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL. DR FunFam; 1.10.3860.10:FF:000005; Amino acid transporter; 1. DR Gene3D; 1.10.3860.10; Sodium:dicarboxylate symporter; 1. DR InterPro; IPR050746; DAACS. DR InterPro; IPR001991; Na-dicarboxylate_symporter. DR InterPro; IPR018107; Na-dicarboxylate_symporter_CS. DR InterPro; IPR036458; Na:dicarbo_symporter_sf. DR PANTHER; PTHR11958:SF20; NEUTRAL AMINO ACID TRANSPORTER A; 1. DR PANTHER; PTHR11958; SODIUM/DICARBOXYLATE SYMPORTER-RELATED; 1. DR Pfam; PF00375; SDF; 1. DR PRINTS; PR00173; EDTRNSPORT. DR SUPFAM; SSF118215; Proton glutamate symport protein; 1. DR PROSITE; PS00713; NA_DICARBOXYL_SYMP_1; 1. DR PROSITE; PS00714; NA_DICARBOXYL_SYMP_2; 1. DR PDBsum; 7P4I; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Amino-acid transport; KW Antiport; Cell membrane; Disease variant; Epilepsy; Glycoprotein; KW Intellectual disability; Membrane; Metal-binding; Phosphoprotein; KW Proteomics identification; Reference proteome; Sodium; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..532 FT /note="Neutral amino acid transporter A" FT /id="PRO_0000202079" FT TOPO_DOM 1..41 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 42..67 FT /note="Helical; Name=1" FT /evidence="ECO:0000250|UniProtKB:Q15758, FT ECO:0000305|PubMed:34630942" FT TOPO_DOM 68..80 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 81..102 FT /note="Helical; Name=2" FT /evidence="ECO:0000250|UniProtKB:Q15758, FT ECO:0000305|PubMed:34630942" FT TOPO_DOM 103..116 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 117..139 FT /note="Helical; Name=3" FT /evidence="ECO:0000250|UniProtKB:Q15758, FT ECO:0000305|PubMed:34630942" FT TOPO_DOM 140..216 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 217..240 FT /note="Helical; Name=4" FT /evidence="ECO:0000250|UniProtKB:Q15758, FT ECO:0000305|PubMed:34630942" FT TOPO_DOM 241..249 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 250..277 FT /note="Helical; Name=5" FT /evidence="ECO:0000250|UniProtKB:Q15758, FT ECO:0000305|PubMed:34630942" FT TOPO_DOM 278..298 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 299..320 FT /note="Helical; Name=6" FT /evidence="ECO:0000250|UniProtKB:Q15758, FT ECO:0000305|PubMed:34630942" FT TOPO_DOM 321..325 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT INTRAMEM 326..356 FT /note="Discontinuously helical; Name=HP1" FT /evidence="ECO:0000250|UniProtKB:Q15758, FT ECO:0000305|PubMed:34630942" FT TOPO_DOM 357..365 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 366..392 FT /note="Helical; Name=7" FT /evidence="ECO:0000250|UniProtKB:Q15758, FT ECO:0000305|PubMed:34630942" FT TOPO_DOM 393..405 FT /note="Extracellular" FT /evidence="ECO:0000305" FT INTRAMEM 406..439 FT /note="Discontinuously helical; Name=HP2" FT /evidence="ECO:0000250|UniProtKB:Q15758, FT ECO:0000305|PubMed:34630942" FT TOPO_DOM 440..452 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 453..474 FT /note="Helical; Name=8" FT /evidence="ECO:0000250|UniProtKB:Q15758, FT ECO:0000305|PubMed:34630942" FT TOPO_DOM 475..532 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 1..25 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 191..216 FT /note="Beta-hairpin" FT /evidence="ECO:0000303|PubMed:34630942" FT REGION 500..532 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..10 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 14..25 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 121 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 124 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 125 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 345 FT /ligand="L-alanine" FT /ligand_id="ChEBI:CHEBI:57972" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 374 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 376 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 378 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 378 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 380 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 417 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 418 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 420 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 423 FT /ligand="L-alanine" FT /ligand_id="ChEBI:CHEBI:57972" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 456 FT /ligand="L-alanine" FT /ligand_id="ChEBI:CHEBI:57972" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 460 FT /ligand="L-alanine" FT /ligand_id="ChEBI:CHEBI:57972" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 463 FT /ligand="L-alanine" FT /ligand_id="ChEBI:CHEBI:57972" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 463 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT BINDING 467 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q15758" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 507 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 527 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O35874" FT MOD_RES 530 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O35874" FT CARBOHYD 201 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973" FT CARBOHYD 206 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973" FT VAR_SEQ 1..220 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042880" FT VAR_SEQ 267..345 FT /note="WYVPVGIMFLVGSKIVEMKDIIVLVTSLGKYIFASILGHVIHGGIVLPLIYF FT VFTRKNPFRFLLGLLAPFATAFATCSS -> C (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042881" FT VARIANT 37 FT /note="G -> R (in dbSNP:rs1064512)" FT /id="VAR_011878" FT VARIANT 256 FT /note="E -> K (in SPATCCM; does not affect localization at FT the cell surface; decreased uptake of L-serine and FT L-alanine; Vmax is decreased by at least 50% for both FT substrates; 3-fold increase of affinity for L-serine; FT 2-fold increase of affinity for L-alanine; FT dbSNP:rs201278558)" FT /evidence="ECO:0000269|PubMed:25930971, FT ECO:0000269|PubMed:26041762, ECO:0000269|PubMed:26138499, FT ECO:0000269|PubMed:34630942" FT /id="VAR_075085" FT VARIANT 399 FT /note="V -> I (in dbSNP:rs759458)" FT /id="VAR_011879" FT VARIANT 457 FT /note="R -> W (in SPATCCM; does not affect localization at FT the cell surface; loss of uptake of L-serine and L-alanine; FT dbSNP:rs761533681)" FT /evidence="ECO:0000269|PubMed:26041762, FT ECO:0000269|PubMed:34630942" FT /id="VAR_075086" FT MUTAGEN 124 FT /note="T->A: Impairs Na(+) binding. 3-fold reduction of FT L-serine transport rate." FT /evidence="ECO:0000269|PubMed:24808181" FT MUTAGEN 125 FT /note="T->A: No effect on affinity for Na(+) ions. No FT effect on L-serine transport rate. Causes a shift of FT Na(+):L-serine transport stoichiometry from 1.2 to 2." FT /evidence="ECO:0000269|PubMed:24808181" FT MUTAGEN 380 FT /note="D->A: Decreases the affinity for Na(+) ions and FT L-serine. Impairs L-serine transport." FT /evidence="ECO:0000269|PubMed:24808181" FT MUTAGEN 380 FT /note="D->N: Decreases the affinity for Na(+) ions and FT L-serine. No effect on L-serine transport rate. Decreases FT the affinity for Na(+) ions by 2-fold, increases FT L-serine-induced anion conductance by 3.8 fold and impairs FT L-serine transport; when associated with Ser-467. 2-fold FT reduction of L-serine transport rate; when associated with FT Leu-465." FT /evidence="ECO:0000269|PubMed:24808181" FT MUTAGEN 380 FT /note="D->S: No significant effect on affinity for Na(+) FT ions. 3.5-fold reduction of L-serine transport rate." FT /evidence="ECO:0000269|PubMed:24808181" FT MUTAGEN 422 FT /note="G->S: Impairs Na(+) binding. No effect on L-serine FT transport rate." FT /evidence="ECO:0000269|PubMed:24808181" FT MUTAGEN 465 FT /note="E->L: No effect on affinity for Na(+) ions. 2-fold FT reduction of L-serine transport rate; when associated with FT Asn-380." FT /evidence="ECO:0000269|PubMed:24808181" FT MUTAGEN 467 FT /note="D->A: Decreases the affinity for Na(+) ions. Impairs FT L-serine transport." FT /evidence="ECO:0000269|PubMed:24808181" FT MUTAGEN 467 FT /note="D->N: No effect on affinity for Na(+) ions. No FT effect on Na(+):L-serine transport stoichiometry. 3-fold FT decreased L-serine transport rate." FT /evidence="ECO:0000269|PubMed:24808181" FT MUTAGEN 467 FT /note="D->S: No effect on affinity for Na(+) ions. No FT effect on L-serine transport rate and Na(+):L-serine FT transport stoichiometry. Decreases the affinity for Na(+) FT ions by 2-fold, increases L-serine-induced anion FT conductance by 3.8 fold and impairs L-serine transport; FT when associated with Asn-380." FT /evidence="ECO:0000269|PubMed:24808181" FT MUTAGEN 467 FT /note="D->T: Decreases the affinity for Na(+) ions. Impairs FT L-serine transport." FT /evidence="ECO:0000269|PubMed:24808181" FT CONFLICT 117 FT /note="A -> R (in Ref. 1; AAA02761)" FT /evidence="ECO:0000305" FT CONFLICT 127 FT /note="S -> T (in Ref. 2; AAA19438)" FT /evidence="ECO:0000305" SQ SEQUENCE 532 AA; 55723 MW; 57925860042FCEB6 CRC64; MEKSNETNGY LDSAQAGPAA GPGAPGTAAG RARRCAGFLR RQALVLLTVS GVLAGAGLGA ALRGLSLSRT QVTYLAFPGE MLLRMLRMII LPLVVCSLVS GAASLDASCL GRLGGIAVAY FGLTTLSASA LAVALAFIIK PGSGAQTLQS SDLGLEDSGP PPVPKETVDS FLDLARNLFP SNLVVAAFRT YATDYKVVTQ NSSSGNVTHE KIPIGTEIEG MNILGLVLFA LVLGVALKKL GSEGEDLIRF FNSLNEATMV LVSWIMWYVP VGIMFLVGSK IVEMKDIIVL VTSLGKYIFA SILGHVIHGG IVLPLIYFVF TRKNPFRFLL GLLAPFATAF ATCSSSATLP SMMKCIEENN GVDKRISRFI LPIGATVNMD GAAIFQCVAA VFIAQLNNVE LNAGQIFTIL VTATASSVGA AGVPAGGVLT IAIILEAIGL PTHDLPLILA VDWIVDRTTT VVNVEGDALG AGILHHLNQK ATKKGEQELA EVKVEAIPNC KSEEETSPLV THQNPAGPVA SAPELESKES VL //