Q969I6 (S38A4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium-coupled neutral amino acid transporter 4

Alternative name(s):
Amino acid transporter A3
Na(+)-coupled neutral amino acid transporter 4
Solute carrier family 38 member 4
System A amino acid transporter 3
System N amino acid transporter 3

Gene names

Name:	SLC38A4
Synonyms:	ATA3, NAT3, SNAT4

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	547 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Sodium-dependent amino acid transporter. Mediates electrogenic symport of neutral amino acids and sodium ions. Has a broad specificity, with a preference for Ala, followed by His, Cys, Asn, Ser, Gly, Val, Thr, Gln and Met. May mediate sodium-independent transport of cationic amino acids, such as Arg and Lys. Amino acid uptake is pH-dependent, with low transport activities at pH 6.5, intermediate at pH 7.0 and highest between pH 7.5 and 8.5. Ref.1 Ref.2
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.2 Ref.8.
Tissue specificity	Detected in embryonic and adult liver, and at lower levels in adult muscle, kidney and pancreas. Detected in placenta syncytiotrophoblasts throughout gestation. Detected in fetal blood vessels. Ref.1 Ref.2 Ref.8
Sequence similarities	Belongs to the amino acid/polyamine transporter 2 family.
Biophysicochemical properties	pH dependence: Optimum pH is 7.5-8.5. Ref.1

Ontologies

Keywords
Biological process	Amino-acid transport Ion transport Sodium transport Symport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	amino acid transport Traceable author statement. Source: Reactome sodium ion transport Inferred from electronic annotation. Source: UniProtKB-KW transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	amino acid transmembrane transporter activity Inferred from electronic annotation. Source: Compara symporter activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 547	547	Sodium-coupled neutral amino acid transporter 4		PRO_0000247860
Regions
	Topological domain	1 – 104	104	Extracellular Potential
	Transmembrane	105 – 125	21	Helical; Potential
	Topological domain	126 – 151	26	Cytoplasmic Potential
	Transmembrane	152 – 172	21	Helical; Potential
	Topological domain	173 – 195	23	Extracellular Potential
	Transmembrane	196 – 216	21	Helical; Potential
	Topological domain	217 – 220	4	Cytoplasmic Potential
	Transmembrane	221 – 241	21	Helical; Potential
	Topological domain	242 – 332	91	Extracellular Potential
	Transmembrane	333 – 353	21	Helical; Potential
	Topological domain	354 – 369	16	Cytoplasmic Potential
	Transmembrane	370 – 390	21	Helical; Potential
	Topological domain	391 – 411	21	Extracellular Potential
	Transmembrane	412 – 432	21	Helical; Potential
	Topological domain	433 – 453	21	Cytoplasmic Potential
	Transmembrane	454 – 474	21	Helical; Potential
	Topological domain	475 – 476	2	Extracellular Potential
	Transmembrane	477 – 497	21	Helical; Potential
	Topological domain	498 – 514	17	Cytoplasmic Potential
	Transmembrane	515 – 535	21	Helical; Potential
	Topological domain	536 – 547	12	Extracellular Potential
Amino acid modifications
	Modified residue	49	1	Phosphoserine By similarity
	Glycosylation	260	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	264	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	276	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	29	1	G → R. Corresponds to variant rs2429467 [ dbSNP | Ensembl ].		VAR_048123
	Natural variant	366	1	T → M. Corresponds to variant rs11183610 [ dbSNP | Ensembl ].		VAR_048124

Sequences

	Sequence		Length	Mass (Da)
	Q969I6 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: D47289AA386F3373	FASTA	547	60,764
	10 20 30 40 50 60 MDPMELRNVN IEPDDESSSG ESAPDSYIGI GNSEKAAMSS QFANEDTESQ KFLTNGFLGK 70 80 90 100 110 120 KKLADYADEH HPGTTSFGMS SFNLSNAIMG SGILGLSYAM ANTGIILFII MLLAVAILSL 130 140 150 160 170 180 YSVHLLLKTA KEGGSLIYEK LGEKAFGWPG KIGAFVSITM QNIGAMSSYL FIIKYELPEV 190 200 210 220 230 240 IRAFMGLEEN TGEWYLNGNY LIIFVSVGII LPLSLLKNLG YLGYTSGFSL TCMVFFVSVV 250 260 270 280 290 300 IYKKFQIPCP LPVLDHSVGN LSFNNTLPMH VVMLPNNSES SDVNFMMDYT HRNPAGLDEN 310 320 330 340 350 360 QAKGSLHDSG VEYEAHSDDK CEPKYFVFNS RTAYAIPILV FAFVCHPEVL PIYSELKDRS 370 380 390 400 410 420 RRKMQTVSNI SITGMLVMYL LAALFGYLTF YGEVEDELLH AYSKVYTLDI PLLMVRLAVL 430 440 450 460 470 480 VAVTLTVPIV LFPIRTSVIT LLFPKRPFSW IRHFLIAAVL IALNNVLVIL VPTIKYIFGF 490 500 510 520 530 540 IGASSATMLI FILPAVFYLK LVKKETFRSP QKVGALIFLV VGIFFMIGSM ALIIIDWIYD PPNSKHH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Evidence for the transport of neutral as well as cationic amino acids by ATA3, a novel and liver-specific subtype of amino acid transport system A." Hatanaka T., Huang W., Ling R., Prasad P.D., Sugawara M., Leibach F.H., Ganapathy V. Biochim. Biophys. Acta 1510:10-17(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY. Tissue: Hepatoma.
[2]	"A novel human amino acid transporter, hNAT3: cDNA cloning, chromosomal mapping, genomic structure, expression, and functional characterization." Gu S., Adan-Rice D., Leach R.J., Jiang J.X. Genomics 74:262-272(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]	"Molecular cloning and characterization of a novel system A amino acid transporter from human liver." Matsuo H., Kanai Y., Kim D.K., Cha S.H., Chairoungdua A., Fukuda J., Endou H. Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[4]	"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].
[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: Liver.
[7]	"Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family." Mackenzie B., Erickson J.D. Pflugers Arch. 447:784-795(2004) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW, GENE NOMENCLATURE.
[8]	"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, SUBCELLULAR LOCATION.
[9]	"Membrane topological structure of neutral system N/A amino acid transporter 4 (SNAT4) protein." Shi Q., Padmanabhan R., Villegas C.J., Gu S., Jiang J.X. J. Biol. Chem. 286:38086-38094(2011) [PubMed] [Europe PMC] [Abstract] Cited for: TOPOLOGY, GLYCOSYLATION AT ASN-260 AND ASN-264.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF305814 mRNA. Translation: AAK43528.1. AF193836 mRNA. Translation: AAK71508.1. AB055003 mRNA. Translation: BAB84090.1. AK291168 mRNA. Translation: BAF83857.1. CH471111 Genomic DNA. Translation: EAW57919.1. BC069819 mRNA. Translation: AAH69819.1. BC101827 mRNA. Translation: AAI01828.1. BC104913 mRNA. Translation: AAI04914.1.
IPI	IPI00100002.
RefSeq	NP_001137296.1. NM_001143824.1. NP_060488.2. NM_018018.4.
UniGene	Hs.446077.
3D structure databases
ProteinModelPortal	Q969I6.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000266579.
PTM databases
PhosphoSite	Q969I6.
Polymorphism databases
DMDM	74731046.
Proteomic databases
PaxDb	Q969I6.
PRIDE	Q969I6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000266579; ENSP00000266579; ENSG00000139209. ENST00000447411; ENSP00000389843; ENSG00000139209.
GeneID	55089.
KEGG	hsa:55089.
UCSC	uc001rpi.2. human.
Organism-specific databases
CTD	55089.
GeneCards	GC12M047138.
HGNC	HGNC:14679. SLC38A4.
HPA	HPA038910.
MIM	608065. gene.
neXtProt	NX_Q969I6.
PharmGKB	PA37908.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0814.
HOGENOM	HOG000013088.
HOVERGEN	HBG059571.
InParanoid	Q969I6.
KO	K14991.
OMA	DDKCQPK.
OrthoDB	EOG46HG9S.
PhylomeDB	Q969I6.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules. REACT_19419. Amino acid and oligopeptide SLC transporters.
Gene expression databases
ArrayExpress	Q969I6.
Bgee	Q969I6.
CleanEx	HS_SLC38A4.
Genevestigator	Q969I6.
GermOnline	ENSG00000139209. Homo sapiens.
Family and domain databases
InterPro	IPR013057. AA_transpt_TM. [Graphical view]
Pfam	PF01490. Aa_trans. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	55089.
NextBio	58661.
SOURCE	Search...

Entry information

Entry name

S38A4_HUMAN

Accession

Primary (citable) accession number: Q969I6
Secondary accession number(s): A8K553

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 25, 2006
Last sequence update:	December 1, 2001
Last modified:	April 3, 2013
This is version 94 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.