Q9H2H9 (S38A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium-coupled neutral amino acid transporter 1

Alternative name(s):
Amino acid transporter A1
N-system amino acid transporter 2
Solute carrier family 38 member 1
System A amino acid transporter 1
System N amino acid transporter 1

Gene names

Name:	SLC38A1
Synonyms:	ATA1, NAT2, SAT1, SNAT1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	487 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions as a sodium-dependent amino acid transporter. Mediates the saturable, pH-sensitive and electrogenic cotransport of glutamine and sodium ions with a stoichiometry of 1:1. May also transport small zwitterionic and aliphatic amino acids with a lower affinity. May supply glutamatergic and GABAergic neurons with glutamine which is required for the synthesis of the neurotransmitters glutamate and GABA. Ref.1
Enzyme regulation	Inhibited by potassium, choline ions and 2-methylamino-isobutyric acid (MeAIB) By similarity. Inhibited by lithium and N-methyl-D-glucamine. Ref.1
Subcellular location	Cell membrane; Multi-pass membrane protein. Note: Restricted to the somatodendritic compartment of neurons. Found in the cellular processes of neurons in the developing brain By similarity. Ref.8
Tissue specificity	Expressed in the cerebral cortex by pyramidal and GABAergic neurons, astrocytes and other non-neuronal cells (at protein level). Expressed in placenta, heart, lung, skeletal muscle, spleen, stomach and testis. Ref.1 Ref.7 Ref.8 Ref.9
Induction	Down-regulated by bacterial lipopolysaccharides (LPS) in glial cells. Down-regulated upon hypoxia. Ref.1 Ref.7 Ref.11
Sequence similarities	Belongs to the amino acid/polyamine transporter 2 family.
Biophysicochemical properties	Kinetic parameters: KM=890 µM for 2-methylamino-isobutyric acid (MeAIB) (at pH 8.5) Ref.1
Sequence caution	The sequence AAG44546.1 differs from that shown. Reason: Frameshift at position 443. The sequence BAC11186.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Amino-acid transport Ion transport Sodium transport Symport Transport
Cellular component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	neurotransmitter uptake Traceable author statement. Source: Reactome
Cellular_component	axon Inferred from electronic annotation. Source: Compara integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Molecular_function	L-glutamine transmembrane transporter activity Inferred from electronic annotation. Source: Compara neutral amino acid transmembrane transporter activity Non-traceable author statement Ref.1. Source: UniProtKB sodium:amino acid symporter activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 487	487	Sodium-coupled neutral amino acid transporter 1		PRO_0000310475
Regions
	Topological domain	1 – 74	74	Cytoplasmic Potential
	Transmembrane	75 – 97	23	Helical; Potential
	Topological domain	98 – 112	15	Extracellular Potential
	Transmembrane	113 – 133	21	Helical; Potential
	Topological domain	134 – 147	14	Cytoplasmic Potential
	Transmembrane	148 – 168	21	Helical; Potential
	Topological domain	169 – 188	20	Extracellular Potential
	Transmembrane	189 – 211	23	Helical; Potential
	Topological domain	212 – 216	5	Cytoplasmic Potential
	Transmembrane	217 – 237	21	Helical; Potential
	Topological domain	238 – 275	38	Extracellular Potential
	Transmembrane	276 – 296	21	Helical; Potential
	Topological domain	297 – 312	16	Cytoplasmic Potential
	Transmembrane	313 – 333	21	Helical; Potential
	Topological domain	334 – 350	17	Extracellular Potential
	Transmembrane	351 – 371	21	Helical; Potential
	Topological domain	372 – 393	22	Cytoplasmic Potential
	Transmembrane	394 – 414	21	Helical; Potential
	Topological domain	415 – 416	2	Extracellular Potential
	Transmembrane	417 – 437	21	Helical; Potential
	Topological domain	438 – 452	15	Cytoplasmic Potential
	Transmembrane	453 – 473	21	Helical; Potential
	Topological domain	474 – 487	14	Extracellular Potential
Amino acid modifications
	Modified residue	25	1	Phosphoserine Ref.13
	Modified residue	28	1	Phosphoserine Ref.13
	Modified residue	52	1	Phosphoserine Ref.13 Ref.14 Ref.15
	Modified residue	54	1	Phosphothreonine Ref.13 Ref.14 Ref.15
	Modified residue	56	1	Phosphoserine Ref.13 Ref.14
	Glycosylation	251	1	N-linked (GlcNAc...) Potential
	Glycosylation	257	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	107	1	L → P in BAB55394. Ref.3
	Sequence conflict	203	1	F → V in BAC11310. Ref.4
	Sequence conflict	375	1	V → D in AAG44546. Ref.2
	Sequence conflict	483 – 484	2	SD → NG in AAG44546. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9H2H9 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 5CBC96880D7BDE03	FASTA	487	54,048
	10 20 30 40 50 60 MMHFKSGLEL TELQNMTVPE DDNISNDSND FTEVENGQIN SKFISDRESR RSLTNSHLEK 70 80 90 100 110 120 KKCDEYIPGT TSLGMSVFNL SNAIMGSGIL GLAFALANTG ILLFLVLLTS VTLLSIYSIN 130 140 150 160 170 180 LLLICSKETG CMVYEKLGEQ VFGTTGKFVI FGATSLQNTG AMLSYLFIVK NELPSAIKFL 190 200 210 220 230 240 MGKEETFSAW YVDGRVLVVI VTFGIILPLC LLKNLGYLGY TSGFSLSCMV FFLIVVIYKK 250 260 270 280 290 300 FQIPCIVPEL NSTISANSTN ADTCTPKYVT FNSKTVYALP TIAFAFVCHP SVLPIYSELK 310 320 330 340 350 360 DRSQKKMQMV SNISFFAMFV MYFLTAIFGY LTFYDNVQSD LLHKYQSKDD ILILTVRLAV 370 380 390 400 410 420 IVAVILTVPV LFFTVRSSLF ELAKKTKFNL CRHTVVTCIL LVVINLLVIF IPSMKDIFGV 430 440 450 460 470 480 VGVTSANMLI FILPSSLYLK ITDQDGDKGT QRIWAALFLG LGVLFSLVSI PLVIYDWACS SSSDEGH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and functional expression of ATA1, a subtype of amino acid transporter A, from human placenta." Wang H., Huang W., Sugawara M., Devoe L.D., Leibach F.H., Prasad P.D., Ganapathy V. Biochem. Biophys. Res. Commun. 273:1175-1179(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY. Tissue: Placenta.
[2]	Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hypothalamus.
[3]	"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. , 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]. Tissue: Placenta and Teratocarcinoma.
[4]	"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries." Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T. DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Teratocarcinoma.
[5]	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. , 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].
[6]	"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]. Tissue: Eye.
[7]	"Hypoxia reduces expression and function of system A amino acid transporters in cultured term human trophoblasts." Nelson D.M., Smith S.D., Furesz T.C., Sadovsky Y., Ganapathy V., Parvin C.A., Smith C.H. Am. J. Physiol. 284:C310-C315(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION.
[8]	"Localization of the glutamine transporter SNAT1 in rat cerebral cortex and neighboring structures, with a note on its localization in human cortex." Melone M., Quagliano F., Barbaresi P., Varoqui H., Erickson J.D., Conti F. Cereb. Cortex 14:562-574(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]	"SNAT4 isoform of system A amino acid transporter is expressed in human placenta." Desforges M., Lacey H.A., Glazier J.D., Greenwood S.L., Mynett K.J., Speake P.F., Sibley C.P. Am. J. Physiol. 290:C305-C312(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[11]	"Functional expression of a glutamine transporter responsive to down-regulation by lipopolysaccharide through reduced promoter activity in cultured rat neocortical astrocytes." Ogura M., Nakamichi N., Takano K., Oikawa H., Kambe Y., Ohno Y., Taniura H., Yoneda Y. J. Neurosci. Res. 83:1447-1460(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY LPS.
[12]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[13]	"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-25; SER-28; SER-52; THR-54 AND SER-56, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52; THR-54 AND SER-56, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52 AND THR-54, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF271070 mRNA. Translation: AAG39354.1. AF247166 mRNA. Translation: AAG44546.1. Frameshift. AK027825 mRNA. Translation: BAB55394.1. AK074758 mRNA. Translation: BAC11186.1. Different initiation. AK074949 mRNA. Translation: BAC11310.1. CH471111 Genomic DNA. Translation: EAW57895.1. BC010620 mRNA. Translation: AAH10620.1.
IPI	IPI00023030.
PIR	JC7328.
RefSeq	NP_001070952.1. NM_001077484.1. NP_109599.3. NM_030674.3.
UniGene	Hs.533770.
3D structure databases
ProteinModelPortal	Q9H2H9.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000381634.
PTM databases
PhosphoSite	Q9H2H9.
Polymorphism databases
DMDM	74733561.
Proteomic databases
PaxDb	Q9H2H9.
PRIDE	Q9H2H9.
Protocols and materials databases
DNASU	81539.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000398637; ENSP00000381634; ENSG00000111371. ENST00000439706; ENSP00000398142; ENSG00000111371. ENST00000546893; ENSP00000447853; ENSG00000111371. ENST00000549049; ENSP00000449607; ENSG00000111371.
GeneID	81539.
KEGG	hsa:81539.
UCSC	uc001rpa.3. human.
Organism-specific databases
CTD	81539.
GeneCards	GC12M046576.
HGNC	HGNC:13447. SLC38A1.
HPA	HPA052272.
MIM	608490. gene.
neXtProt	NX_Q9H2H9.
PharmGKB	PA37772.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0814.
HOGENOM	HOG000013088.
HOVERGEN	HBG059571.
KO	K14990.
OrthoDB	EOG4CJVH4.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System. REACT_15518. Transmembrane transport of small molecules. REACT_19419. Amino acid and oligopeptide SLC transporters.
Gene expression databases
ArrayExpress	Q9H2H9.
Bgee	Q9H2H9.
CleanEx	HS_NAT2. HS_SAT1. HS_SLC38A1.
Genevestigator	Q9H2H9.
Family and domain databases
InterPro	IPR013057. AA_transpt_TM. [Graphical view]
Pfam	PF01490. Aa_trans. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SLC38A1. human.
GenomeRNAi	81539.
NextBio	71767.
SOURCE	Search...

Entry information

Entry name

S38A1_HUMAN

Accession

Primary (citable) accession number: Q9H2H9
Secondary accession number(s): Q8NC61 , Q8NCF8, Q96JX2, Q9H2Q2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 13, 2007
Last sequence update:	March 1, 2001
Last modified:	April 3, 2013
This is version 86 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.