ID S38A2_HUMAN Reviewed; 506 AA. AC Q96QD8; Q6IA88; Q6ZMG2; Q9HAV3; Q9NVA8; Q9P2G5; DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot. DT 04-DEC-2007, sequence version 2. DT 27-MAR-2024, entry version 170. DE RecName: Full=Sodium-coupled neutral amino acid symporter 2 {ECO:0000305}; DE AltName: Full=Amino acid transporter A2; DE AltName: Full=Protein 40-9-1; DE AltName: Full=Solute carrier family 38 member 2; DE AltName: Full=System A amino acid transporter 2; DE AltName: Full=System A transporter 1; DE AltName: Full=System N amino acid transporter 2; GN Name=SLC38A2 {ECO:0000312|HGNC:HGNC:13448}; GN Synonyms=ATA2 {ECO:0000303|PubMed:10930503}, KIAA1382, SAT2, SNAT2; 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), FUNCTION, ACTIVITY REGULATION, AND RP TISSUE SPECIFICITY. RC TISSUE=Hepatoma; RX PubMed=10930503; DOI=10.1016/s0005-2736(00)00252-2; RA Hatanaka T., Huang W., Wang H., Sugawara M., Prasad P.D., Leibach F.H., RA Ganapathy V.; RT "Primary structure, functional characteristics and tissue expression RT pattern of human ATA2, a subtype of amino acid transport system A."; RL Biochim. Biophys. Acta 1467:1-6(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Powell J., Brock A.P., Hart I.R.; RT "Expression studies of the human amino acid transporter, hATA2."; RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Schmidt T.; RL Thesis (2001), University of Goettingen, Germany. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10718198; DOI=10.1093/dnares/7.1.65; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVI. The RT complete sequences of 150 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:65-73(2000). RN [5] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Hepatoma, and Teratocarcinoma; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [8] 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Eye; 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 [10] RP INDUCTION. RX PubMed=14623874; DOI=10.1074/jbc.m310483200; RA Palii S.S., Chen H., Kilberg M.S.; RT "Transcriptional control of the human sodium-coupled neutral amino acid RT transporter system A gene by amino acid availability is mediated by an RT intronic element."; RL J. Biol. Chem. 279:3463-3471(2004). RN [11] RP FUNCTION, AND INDUCTION. RX PubMed=15922329; DOI=10.1016/j.febslet.2005.05.002; RA Bevilacqua E., Bussolati O., Dall'Asta V., Gaccioli F., Sala R., RA Gazzola G.C., Franchi-Gazzola R.; RT "SNAT2 silencing prevents the osmotic induction of transport system A and RT hinders cell recovery from hypertonic stress."; RL FEBS Lett. 579:3376-3380(2005). RN [12] RP INDUCTION, FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=15774260; DOI=10.1016/j.neulet.2004.12.030; RA Tanaka K., Yamamoto A., Fujita T.; RT "Functional expression and adaptive regulation of Na+ -dependent neutral RT amino acid transporter SNAT2/ATA2 in normal human astrocytes under amino RT acid starved condition."; RL Neurosci. Lett. 378:70-75(2005). RN [13] RP FUNCTION, AND INDUCTION. RX PubMed=16621798; DOI=10.1074/jbc.m600341200; RA Gaccioli F., Huang C.C., Wang C., Bevilacqua E., Franchi-Gazzola R., RA Gazzola G.C., Bussolati O., Snider M.D., Hatzoglou M.; RT "Amino acid starvation induces the SNAT2 neutral amino acid transporter by RT a mechanism that involves eukaryotic initiation factor 2alpha RT phosphorylation and cap-independent translation."; RL J. Biol. Chem. 281:17929-17940(2006). RN [14] RP TISSUE SPECIFICITY. RX PubMed=16616430; DOI=10.1016/j.neuroscience.2006.02.042; RA Melone M., Varoqui H., Erickson J.D., Conti F.; RT "Localization of the Na(+)-coupled neutral amino acid transporter 2 in the RT cerebral cortex."; RL Neuroscience 140:281-292(2006). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10 AND SER-12, AND RP IDENTIFICATION BY 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, AND IDENTIFICATION BY RP 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 [17] 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 [18] 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 [19] RP IDENTIFICATION BY MASS 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 [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55, AND IDENTIFICATION BY RP 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 [21] RP UBIQUITINATION BY NEDD4L. RX PubMed=26374858; DOI=10.1042/cs20150511; RA Chen Y.Y., Rosario F.J., Shehab M.A., Powell T.L., Gupta M.B., Jansson T.; RT "Increased ubiquitination and reduced plasma membrane trafficking of RT placental amino acid transporter SNAT-2 in human IUGR."; RL Clin. Sci. 129:1131-1141(2015). CC -!- FUNCTION: Symporter that cotransports neutral amino acids and sodium CC ions from the extraccellular to the intracellular side of the cell CC membrane (PubMed:10930503, PubMed:15922329, PubMed:16621798, CC PubMed:15774260). The trasnport is pH-sensitive, Li(+)-intolerant, CC electrogenic, driven by the Na(+) electrochemical gradient and CC cotransports of neutral amino acids and sodium ions with a CC stoichiometry of 1:1. May function in the transport of amino acids at CC the blood-brain barrier (PubMed:10930503, PubMed:15774260). May CC function in the transport of amino acids in the supply of maternal CC nutrients to the fetus through the placenta (By similarity). Maintains CC a key metabolic glutamine/glutamate balance underpinning retrograde CC signaling by dendritic release of the neurotransmitter glutamate (By CC similarity). Transports L-proline in differentiating osteoblasts for CC the efficient synthesis of proline-enriched proteins and provides CC proline essential for osteoblast differentiation and bone formation CC during bone development (By similarity). {ECO:0000250|UniProtKB:Q8CFE6, CC ECO:0000250|UniProtKB:Q9JHE5, ECO:0000269|PubMed:10930503, CC ECO:0000269|PubMed:15774260, ECO:0000269|PubMed:15922329, CC ECO:0000269|PubMed:16621798}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-alanine(in) + Na(+)(in) = L-alanine(out) + Na(+)(out); CC Xref=Rhea:RHEA:29283, ChEBI:CHEBI:29101, ChEBI:CHEBI:57972; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29285; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=glycine(in) + Na(+)(in) = glycine(out) + Na(+)(out); CC Xref=Rhea:RHEA:68228, ChEBI:CHEBI:29101, ChEBI:CHEBI:57305; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68230; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-serine(in) + Na(+)(in) = L-serine(out) + Na(+)(out); CC Xref=Rhea:RHEA:29575, ChEBI:CHEBI:29101, ChEBI:CHEBI:33384; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29577; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-proline(in) + Na(+)(in) = L-proline(out) + Na(+)(out); CC Xref=Rhea:RHEA:28967, ChEBI:CHEBI:29101, ChEBI:CHEBI:60039; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:28969; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-methionine(in) + Na(+)(in) = L-methionine(out) + Na(+)(out); CC Xref=Rhea:RHEA:68240, ChEBI:CHEBI:29101, ChEBI:CHEBI:57844; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68242; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-histidine(in) + Na(+)(in) = L-histidine(out) + Na(+)(out); CC Xref=Rhea:RHEA:71583, ChEBI:CHEBI:29101, ChEBI:CHEBI:57595; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71585; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-asparagine(in) + Na(+)(in) = L-asparagine(out) + Na(+)(out); CC Xref=Rhea:RHEA:71383, ChEBI:CHEBI:29101, ChEBI:CHEBI:58048; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71385; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-glutamine(in) + Na(+)(in) = L-glutamine(out) + Na(+)(out); CC Xref=Rhea:RHEA:68236, ChEBI:CHEBI:29101, ChEBI:CHEBI:58359; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68238; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonine(in) + Na(+)(in) = L-threonine(out) + Na(+)(out); CC Xref=Rhea:RHEA:69999, ChEBI:CHEBI:29101, ChEBI:CHEBI:57926; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70001; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-leucine(in) + Na(+)(in) = L-leucine(out) + Na(+)(out); CC Xref=Rhea:RHEA:29263, ChEBI:CHEBI:29101, ChEBI:CHEBI:57427; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29265; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-phenylalanine(in) + Na(+)(in) = L-phenylalanine(out) + CC Na(+)(out); Xref=Rhea:RHEA:68244, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:58095; Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68246; CC Evidence={ECO:0000250|UniProtKB:Q9JHE5}; CC -!- ACTIVITY REGULATION: Inhibited by N-methyl-D-glucamine CC (PubMed:10930503). Inhibited by choline. Allosteric regulation of CC sodium ions binding by pH (By similarity). CC {ECO:0000250|UniProtKB:Q9JHE5, ECO:0000269|PubMed:10930503}. CC -!- INTERACTION: CC Q96QD8; Q9UHG0: DCDC2; NbExp=3; IntAct=EBI-723083, EBI-10303987; CC Q96QD8; Q99942: RNF5; NbExp=3; IntAct=EBI-723083, EBI-348482; CC Q96QD8; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-723083, EBI-10982110; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9JHE5}; CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9JHE5}. CC Note=Insulin promotes recruitment to the plasma membrane from a pool CC localized in the trans-Golgi network or endosomes. Enriched in the CC somatodendritic compartment of neurons, it is also detected at the CC axonal shaft but excluded from the nerve terminal. CC {ECO:0000250|UniProtKB:Q9JHE5}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96QD8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96QD8-2; Sequence=VSP_029553, VSP_029554; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed (PubMed:10930503). Expressed CC in neocortex (PubMed:16616430). Widely expressed in the central nervous CC system with higher concentrations in caudal regions. Expressed by CC glutamatergic and GABAergic neurons together with astrocytes and other CC non-neuronal cells in the cerebral cortex (at protein level) CC (PubMed:15774260). {ECO:0000269|PubMed:10930503, CC ECO:0000269|PubMed:15774260, ECO:0000269|PubMed:16616430}. CC -!- INDUCTION: Up-regulated upon amino acid deprivation (PubMed:14623874, CC PubMed:16621798, PubMed:15774260). Up-regulated upon hypertonic CC conditions (PubMed:15922329, PubMed:16621798). CC {ECO:0000269|PubMed:14623874, ECO:0000269|PubMed:15774260, CC ECO:0000269|PubMed:15922329, ECO:0000269|PubMed:16621798}. CC -!- DOMAIN: The extracellular C-terminal domain controls the voltage CC dependence for amino acid transports activity. CC {ECO:0000250|UniProtKB:Q9JHE5}. CC -!- PTM: Polyubiquitination by NEDD4L regulates the degradation and the CC activity of SLC38A2. {ECO:0000269|PubMed:26374858}. CC -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD18765.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; AF259799; AAK38510.1; -; mRNA. DR EMBL; AF298897; AAG24618.1; -; mRNA. DR EMBL; AJ344099; CAC51434.1; -; mRNA. DR EMBL; AB037803; BAA92620.2; -; mRNA. DR EMBL; AK001700; BAA91846.1; -; mRNA. DR EMBL; AK172784; BAD18765.1; ALT_INIT; mRNA. DR EMBL; CR457267; CAG33548.1; -; mRNA. DR EMBL; CH471111; EAW57900.1; -; Genomic_DNA. DR EMBL; CH471111; EAW57901.1; -; Genomic_DNA. DR EMBL; BC040342; AAH40342.1; -; mRNA. DR CCDS; CCDS76551.1; -. [Q96QD8-2] DR CCDS; CCDS8749.1; -. [Q96QD8-1] DR RefSeq; NP_001294865.1; NM_001307936.1. [Q96QD8-2] DR RefSeq; NP_061849.2; NM_018976.4. [Q96QD8-1] DR AlphaFoldDB; Q96QD8; -. DR SMR; Q96QD8; -. DR BioGRID; 119943; 144. DR IntAct; Q96QD8; 47. DR MINT; Q96QD8; -. DR STRING; 9606.ENSP00000256689; -. DR DrugBank; DB00174; Asparagine. DR DrugBank; DB00130; L-Glutamine. DR TCDB; 2.A.18.6.5; the amino acid/auxin permease (aaap) family. DR GlyCosmos; Q96QD8; 2 sites, No reported glycans. DR GlyGen; Q96QD8; 3 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q96QD8; -. DR MetOSite; Q96QD8; -. DR PhosphoSitePlus; Q96QD8; -. DR SwissPalm; Q96QD8; -. DR BioMuta; SLC38A2; -. DR DMDM; 162416227; -. DR EPD; Q96QD8; -. DR jPOST; Q96QD8; -. DR MassIVE; Q96QD8; -. DR MaxQB; Q96QD8; -. DR PaxDb; 9606-ENSP00000256689; -. DR PeptideAtlas; Q96QD8; -. DR ProteomicsDB; 77855; -. [Q96QD8-1] DR ProteomicsDB; 77856; -. [Q96QD8-2] DR Pumba; Q96QD8; -. DR Antibodypedia; 13370; 152 antibodies from 23 providers. DR DNASU; 54407; -. DR Ensembl; ENST00000256689.10; ENSP00000256689.5; ENSG00000134294.14. [Q96QD8-1] DR Ensembl; ENST00000612232.1; ENSP00000482873.1; ENSG00000134294.14. [Q96QD8-2] DR GeneID; 54407; -. DR KEGG; hsa:54407; -. DR MANE-Select; ENST00000256689.10; ENSP00000256689.5; NM_018976.5; NP_061849.2. DR UCSC; uc001rpg.4; human. [Q96QD8-1] DR AGR; HGNC:13448; -. DR CTD; 54407; -. DR DisGeNET; 54407; -. DR GeneCards; SLC38A2; -. DR HGNC; HGNC:13448; SLC38A2. DR HPA; ENSG00000134294; Low tissue specificity. DR MIM; 605180; gene. DR neXtProt; NX_Q96QD8; -. DR OpenTargets; ENSG00000134294; -. DR PharmGKB; PA37773; -. DR VEuPathDB; HostDB:ENSG00000134294; -. DR eggNOG; KOG1305; Eukaryota. DR GeneTree; ENSGT00940000155486; -. DR HOGENOM; CLU_009020_0_1_1; -. DR InParanoid; Q96QD8; -. DR OMA; SHYADMD; -. DR OrthoDB; 935269at2759; -. DR PhylomeDB; Q96QD8; -. DR TreeFam; TF328787; -. DR PathwayCommons; Q96QD8; -. DR Reactome; R-HSA-210500; Glutamate Neurotransmitter Release Cycle. DR Reactome; R-HSA-352230; Amino acid transport across the plasma membrane. DR SignaLink; Q96QD8; -. DR SIGNOR; Q96QD8; -. DR BioGRID-ORCS; 54407; 121 hits in 1165 CRISPR screens. DR ChiTaRS; SLC38A2; human. DR GeneWiki; SLC38A2; -. DR GenomeRNAi; 54407; -. DR Pharos; Q96QD8; Tbio. DR PRO; PR:Q96QD8; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q96QD8; Protein. DR Bgee; ENSG00000134294; Expressed in tibia and 217 other cell types or tissues. DR ExpressionAtlas; Q96QD8; baseline and differential. DR GO; GO:0030424; C:axon; IEA:Ensembl. DR GO; GO:0005903; C:brush border; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:ARUK-UCL. DR GO; GO:0030425; C:dendrite; IEA:Ensembl. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL. DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl. DR GO; GO:0015172; F:acidic amino acid transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0015655; F:alanine:sodium symporter activity; ISS:UniProtKB. DR GO; GO:0015171; F:amino acid transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0005283; F:amino acid:sodium symporter activity; IDA:UniProtKB. DR GO; GO:0015186; F:L-glutamine transmembrane transporter activity; ISS:ARUK-UCL. DR GO; GO:0015194; F:L-serine transmembrane transporter activity; ISS:ARUK-UCL. DR GO; GO:0005295; F:neutral L-amino acid:sodium symporter activity; IDA:ARUK-UCL. DR GO; GO:0005298; F:proline:sodium symporter activity; ISS:UniProtKB. DR GO; GO:0032328; P:alanine transport; ISS:UniProtKB. DR GO; GO:0043090; P:amino acid import; ISS:UniProtKB. DR GO; GO:0003333; P:amino acid transmembrane transport; IMP:ARUK-UCL. DR GO; GO:0006865; P:amino acid transport; IDA:UniProtKB. DR GO; GO:0034198; P:cellular response to amino acid starvation; IEA:Ensembl. DR GO; GO:1903841; P:cellular response to arsenite(3-); IMP:ARUK-UCL. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl. DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl. DR GO; GO:0006868; P:glutamine transport; ISS:ARUK-UCL. DR GO; GO:0031460; P:glycine betaine transport; IEA:Ensembl. DR GO; GO:1903803; P:L-glutamine import across plasma membrane; ISS:UniProtKB. DR GO; GO:1904271; P:L-proline import across plasma membrane; ISS:UniProtKB. DR GO; GO:1903812; P:L-serine import across plasma membrane; ISS:UniProtKB. DR GO; GO:0015825; P:L-serine transport; ISS:ARUK-UCL. DR GO; GO:0006836; P:neurotransmitter transport; TAS:Reactome. DR GO; GO:0015804; P:neutral amino acid transport; IDA:ARUK-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IPI:ARUK-UCL. DR GO; GO:0033120; P:positive regulation of RNA splicing; IPI:ARUK-UCL. DR GO; GO:0015824; P:proline transport; ISS:UniProtKB. DR GO; GO:0080135; P:regulation of cellular response to stress; IMP:ARUK-UCL. DR GO; GO:1903294; P:regulation of glutamate secretion, neurotransmission; ISS:UniProtKB. DR GO; GO:0014850; P:response to muscle activity; IEA:Ensembl. DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL. DR InterPro; IPR013057; AA_transpt_TM. DR PANTHER; PTHR22950; AMINO ACID TRANSPORTER; 1. DR PANTHER; PTHR22950:SF207; SODIUM-COUPLED NEUTRAL AMINO ACID TRANSPORTER 2; 1. DR Pfam; PF01490; Aa_trans; 1. DR Genevisible; Q96QD8; HS. PE 1: Evidence at protein level; KW Alternative splicing; Amino-acid transport; Cell membrane; Disulfide bond; KW Glycoprotein; Ion transport; Membrane; Phosphoprotein; Reference proteome; KW Sodium; Sodium transport; Symport; Transmembrane; Transmembrane helix; KW Transport; Ubl conjugation. FT CHAIN 1..506 FT /note="Sodium-coupled neutral amino acid symporter 2" FT /id="PRO_0000311369" FT TOPO_DOM 1..76 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TRANSMEM 77..96 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 97..102 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TRANSMEM 103..123 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TOPO_DOM 124..158 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TRANSMEM 159..177 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TOPO_DOM 178..188 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 189..209 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TOPO_DOM 210..217 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TRANSMEM 218..238 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TOPO_DOM 239..292 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TRANSMEM 293..313 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TOPO_DOM 314..329 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TRANSMEM 330..350 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 351..371 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TRANSMEM 372..392 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 393..413 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TRANSMEM 414..434 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 435..436 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TRANSMEM 437..457 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TOPO_DOM 458..472 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 473..495 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT TOPO_DOM 496..506 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255" FT REGION 1..96 FT /note="Regulates protein turnover upon amino acid FT deprivation" FT /evidence="ECO:0000250" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 82 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5" FT BINDING 386 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /evidence="ECO:0000250|UniProtKB:Q9JHE5" FT MOD_RES 10 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 12 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 21 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8CFE6" FT MOD_RES 22 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 55 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CARBOHYD 258 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 274 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 245..281 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT VAR_SEQ 1..100 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.7" FT /id="VSP_029553" FT VAR_SEQ 101..105 FT /note="IALFI -> MKQNL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.7" FT /id="VSP_029554" FT VARIANT 48 FT /note="N -> K (in dbSNP:rs11183450)" FT /id="VAR_037235" FT CONFLICT 156 FT /note="M -> V (in Ref. 3; CAC51434)" FT /evidence="ECO:0000305" FT CONFLICT 273 FT /note="H -> R (in Ref. 6; BAA91846)" FT /evidence="ECO:0000305" SQ SEQUENCE 506 AA; 56026 MW; 125C70875793D031 CRC64; MKKAEMGRFS ISPDEDSSSY SSNSDFNYSY PTKQAALKSH YADVDPENQN FLLESNLGKK KYETEFHPGT TSFGMSVFNL SNAIVGSGIL GLSYAMANTG IALFIILLTF VSIFSLYSVH LLLKTANEGG SLLYEQLGYK AFGLVGKLAA SGSITMQNIG AMSSYLFIVK YELPLVIQAL TNIEDKTGLW YLNGNYLVLL VSLVVILPLS LFRNLGYLGY TSGLSLLCMV FFLIVVICKK FQVPCPVEAA LIINETINTT LTQPTALVPA LSHNVTENDS CRPHYFIFNS QTVYAVPILI FSFVCHPAVL PIYEELKDRS RRRMMNVSKI SFFAMFLMYL LAALFGYLTF YEHVESELLH TYSSILGTDI LLLIVRLAVL MAVTLTVPVV IFPIRSSVTH LLCASKDFSW WRHSLITVSI LAFTNLLVIF VPTIRDIFGF IGASAASMLI FILPSAFYIK LVKKEPMKSV QKIGALFFLL SGVLVMTGSM ALIVLDWVHN APGGGH //