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Q96QD8 (S38A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium-coupled neutral amino acid transporter 2
Alternative name(s):
Amino acid transporter A2
Protein 40-9-1
Solute carrier family 38 member 2
System A amino acid transporter 2
System A transporter 1
System N amino acid transporter 2
Gene names
Name:SLC38A2
Synonyms:ATA2, KIAA1382, SAT2, SNAT2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length506 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Functions as a sodium-dependent amino acid transporter. Mediates the saturable, pH-sensitive and electrogenic cotransport of neutral amino acids and sodium ions with a stoichiometry of 1:1. May function in the transport of amino acids at the blood-brain barrier and in the supply of maternal nutrients to the fetus through the placenta. Ref.1 Ref.11

Enzyme regulation

Inhibited by N-methyl-D-glucamine and probably choline. Ref.1

Subcellular location

Cell membrane; Multi-pass membrane protein. Note: Insulin promotes recruitment to the plasma membrane from a pool localized in the trans-Golgi network or endosomes By similarity. Enriched in the somatodendritic compartment of neurons, it is also detected at the axonal shaft but excluded from the nerve terminal. Ref.12 Ref.14

Tissue specificity

Ubiquitously expressed. Widely expressed in the central nervous system with higher concentrations in caudal regions. Expressed by glutamatergic and GABAergic neurons together with astrocytes and other non-neuronal cells in the cerebral cortex (at protein level). Ref.1 Ref.12 Ref.14

Induction

Up-regulated upon hypertonic conditions and amino acid deprivation. Ref.1 Ref.10 Ref.11 Ref.13

Post-translational modification

Polyubiquitination by NEDD4L regulates the degradation and the activity of SLC38A2 By similarity.

Miscellaneous

Depletion of SCL38A2 by siRNA prevents the recovery of cells from hypertonic stress.

Sequence similarities

Belongs to the amino acid/polyamine transporter 2 family.

Biophysicochemical properties

Kinetic parameters:

KM=0.39 mM for 2-methylamino-isobutyric acid (MeAIB) (at pH 8.0)

Sequence caution

The sequence BAD18765.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96QD8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q96QD8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-100: Missing.
     101-105: IALFI → MKQNL

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 506506Sodium-coupled neutral amino acid transporter 2
PRO_0000311369

Regions

Topological domain1 – 7676Cytoplasmic Potential
Transmembrane77 – 9721Helical; Potential
Topological domain98 – 1025Extracellular Potential
Transmembrane103 – 12321Helical; Potential
Topological domain124 – 15835Cytoplasmic Potential
Transmembrane159 – 17921Helical; Potential
Topological domain180 – 1889Extracellular Potential
Transmembrane189 – 20921Helical; Potential
Topological domain210 – 2178Cytoplasmic Potential
Transmembrane218 – 23821Helical; Potential
Topological domain239 – 29254Extracellular Potential
Transmembrane293 – 31321Helical; Potential
Topological domain314 – 32916Cytoplasmic Potential
Transmembrane330 – 35021Helical; Potential
Topological domain351 – 37121Extracellular Potential
Transmembrane372 – 39221Helical; Potential
Topological domain393 – 41321Cytoplasmic Potential
Transmembrane414 – 43421Helical; Potential
Topological domain435 – 4362Extracellular Potential
Transmembrane437 – 45721Helical; Potential
Topological domain458 – 47417Cytoplasmic Potential
Transmembrane475 – 49521Helical; Potential
Topological domain496 – 50611Extracellular Potential
Region1 – 9696Regulates protein turnover upon amino acid deprivation By similarity

Amino acid modifications

Modified residue101Phosphoserine Ref.15
Modified residue121Phosphoserine Ref.15
Modified residue221Phosphoserine Ref.16
Modified residue551Phosphoserine By similarity
Glycosylation2581N-linked (GlcNAc...) Potential
Glycosylation2741N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 100100Missing in isoform 2.
VSP_029553
Alternative sequence101 – 1055IALFI → MKQNL in isoform 2.
VSP_029554
Natural variant481N → K.
Corresponds to variant rs11183450 [ dbSNP | Ensembl ].
VAR_037235

Experimental info

Sequence conflict1561M → V in CAC51434. Ref.3
Sequence conflict2731H → R in BAA91846. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 4, 2007. Version 2.
Checksum: 125C70875793D031

FASTA50656,026
        10         20         30         40         50         60 
MKKAEMGRFS ISPDEDSSSY SSNSDFNYSY PTKQAALKSH YADVDPENQN FLLESNLGKK 

        70         80         90        100        110        120 
KYETEFHPGT TSFGMSVFNL SNAIVGSGIL GLSYAMANTG IALFIILLTF VSIFSLYSVH 

       130        140        150        160        170        180 
LLLKTANEGG SLLYEQLGYK AFGLVGKLAA SGSITMQNIG AMSSYLFIVK YELPLVIQAL 

       190        200        210        220        230        240 
TNIEDKTGLW YLNGNYLVLL VSLVVILPLS LFRNLGYLGY TSGLSLLCMV FFLIVVICKK 

       250        260        270        280        290        300 
FQVPCPVEAA LIINETINTT LTQPTALVPA LSHNVTENDS CRPHYFIFNS QTVYAVPILI 

       310        320        330        340        350        360 
FSFVCHPAVL PIYEELKDRS RRRMMNVSKI SFFAMFLMYL LAALFGYLTF YEHVESELLH 

       370        380        390        400        410        420 
TYSSILGTDI LLLIVRLAVL MAVTLTVPVV IFPIRSSVTH LLCASKDFSW WRHSLITVSI 

       430        440        450        460        470        480 
LAFTNLLVIF VPTIRDIFGF IGASAASMLI FILPSAFYIK LVKKEPMKSV QKIGALFFLL 

       490        500 
SGVLVMTGSM ALIVLDWVHN APGGGH 

« Hide

Isoform 2 [UniParc].

Checksum: C72772C3238776CE
Show »

FASTA40645,179

References

« Hide 'large scale' references
[1]"Primary structure, functional characteristics and tissue expression pattern of human ATA2, a subtype of amino acid transport system A."
Hatanaka T., Huang W., Wang H., Sugawara M., Prasad P.D., Leibach F.H., Ganapathy V.
Biochim. Biophys. Acta 1467:1-6(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY.
Tissue: Hepatoma.
[2]"Expression studies of the human amino acid transporter, hATA2."
Powell J., Brock A.P., Hart I.R.
Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]Schmidt T.
Thesis (2001), University of Goettingen, Germany
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[5]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Hepatoma and Teratocarcinoma.
[7]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Eye.
[10]"Transcriptional control of the human sodium-coupled neutral amino acid transporter system A gene by amino acid availability is mediated by an intronic element."
Palii S.S., Chen H., Kilberg M.S.
J. Biol. Chem. 279:3463-3471(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[11]"SNAT2 silencing prevents the osmotic induction of transport system A and hinders cell recovery from hypertonic stress."
Bevilacqua E., Bussolati O., Dall'Asta V., Gaccioli F., Sala R., Gazzola G.C., Franchi-Gazzola R.
FEBS Lett. 579:3376-3380(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[12]"Immunohistochemical localization of the amino acid transporter SNAT2 in the rat brain."
Gonzalez-Gonzalez I.M., Cubelos B., Gimenez C., Zafra F.
Neuroscience 130:61-73(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[13]"Amino acid starvation induces the SNAT2 neutral amino acid transporter by a mechanism that involves eukaryotic initiation factor 2alpha phosphorylation and cap-independent translation."
Gaccioli F., Huang C.C., Wang C., Bevilacqua E., Franchi-Gazzola R., Gazzola G.C., Bussolati O., Snider M.D., Hatzoglou M.
J. Biol. Chem. 281:17929-17940(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[14]"Localization of the Na(+)-coupled neutral amino acid transporter 2 in the cerebral cortex."
Melone M., Varoqui H., Erickson J.D., Conti F.
Neuroscience 140:281-292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[15]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10 AND SER-12, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[17]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[18]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF259799 mRNA. Translation: AAK38510.1.
AF298897 mRNA. Translation: AAG24618.1.
AJ344099 mRNA. Translation: CAC51434.1.
AB037803 mRNA. Translation: BAA92620.2.
AK001700 mRNA. Translation: BAA91846.1.
AK172784 mRNA. Translation: BAD18765.1. Different initiation.
CR457267 mRNA. Translation: CAG33548.1.
CH471111 Genomic DNA. Translation: EAW57900.1.
CH471111 Genomic DNA. Translation: EAW57901.1.
BC040342 mRNA. Translation: AAH40342.1.
CCDSCCDS8749.1. [Q96QD8-1]
RefSeqNP_061849.2. NM_018976.4. [Q96QD8-1]
XP_005269040.1. XM_005268983.1. [Q96QD8-2]
UniGeneHs.221847.

3D structure databases

ProteinModelPortalQ96QD8.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119943. 7 interactions.
IntActQ96QD8. 1 interaction.
MINTMINT-1398587.
STRING9606.ENSP00000256689.

Chemistry

GuidetoPHARMACOLOGY1170.

Protein family/group databases

TCDB2.A.18.6.5. the amino acid/auxin permease (aaap) family.

Polymorphism databases

DMDM162416227.

Proteomic databases

MaxQBQ96QD8.
PaxDbQ96QD8.
PeptideAtlasQ96QD8.
PRIDEQ96QD8.

Protocols and materials databases

DNASU54407.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256689; ENSP00000256689; ENSG00000134294. [Q96QD8-1]
GeneID54407.
KEGGhsa:54407.
UCSCuc001rpg.3. human. [Q96QD8-1]
uc001rph.3. human. [Q96QD8-2]

Organism-specific databases

CTD54407.
GeneCardsGC12M046751.
HGNCHGNC:13448. SLC38A2.
HPAHPA035180.
MIM605180. gene.
neXtProtNX_Q96QD8.
PharmGKBPA37773.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG236441.
HOGENOMHOG000013088.
HOVERGENHBG059571.
InParanoidQ96QD8.
KOK14207.
OMAYEHVESE.
PhylomeDBQ96QD8.
TreeFamTF328787.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
REACT_15518. Transmembrane transport of small molecules.
REACT_19419. Amino acid and oligopeptide SLC transporters.

Gene expression databases

ArrayExpressQ96QD8.
BgeeQ96QD8.
CleanExHS_SAT2.
HS_SLC38A2.
GenevestigatorQ96QD8.

Family and domain databases

InterProIPR013057. AA_transpt_TM.
[Graphical view]
PfamPF01490. Aa_trans. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSLC38A2. human.
GeneWikiSLC38A2.
GenomeRNAi54407.
NextBio56613.
PROQ96QD8.
SOURCESearch...

Entry information

Entry nameS38A2_HUMAN
AccessionPrimary (citable) accession number: Q96QD8
Secondary accession number(s): Q6IA88 expand/collapse secondary AC list , Q6ZMG2, Q9HAV3, Q9NVA8, Q9P2G5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: December 4, 2007
Last modified: July 9, 2014
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM