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Protein

Sodium-coupled neutral amino acid transporter 9

Gene

SLC38A9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Lysosomal amino acid transporter involved in the activation of mTORC1 in response to amino acids. Probably acts as an amino acid sensor of the Rag GTPases and Ragulator complexes, 2 complexes involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (PubMed:25561175, PubMed:25567906). Following activation by amino acids, the Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. SLC38A9 mediates transport of amino acids with low capacity and specificity with a slight preference for polar amino acids, suggesting that it acts as an amino acid sensor instead (PubMed:25561175, PubMed:25567906). The high concentration of arginine in lysosomes suggests that it acts as an arginine sensor (PubMed:25567906).2 Publications

GO - Molecular functioni

  • amino acid transmembrane transporter activity Source: UniProtKB

GO - Biological processi

  • amino acid transmembrane transport Source: UniProtKB
  • cellular response to amino acid stimulus Source: UniProtKB
  • positive regulation of TOR signaling Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Amino-acid transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000177058-MONOMER.

Protein family/group databases

TCDBi2.A.18.9.1. the amino acid/auxin permease (aaap) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium-coupled neutral amino acid transporter 9Curated
Alternative name(s):
Solute carrier family 38 member 9Imported
Up-regulated in lung cancer 111 Publication
Gene namesi
Name:SLC38A9Imported
Synonyms:URLC111 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:26907. SLC38A9.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 119Cytoplasmic1 PublicationAdd BLAST119
Transmembranei120 – 140Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini141 – 144LumenalCurated4
Transmembranei145 – 165Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini166 – 198CytoplasmicCuratedAdd BLAST33
Transmembranei199 – 219Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini220 – 290LumenalCuratedAdd BLAST71
Transmembranei291 – 311Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini312 – 313CytoplasmicCurated2
Transmembranei314 – 334Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini335 – 358LumenalCuratedAdd BLAST24
Transmembranei359 – 379Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini380 – 392CytoplasmicCuratedAdd BLAST13
Transmembranei393 – 413Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini414 – 440LumenalCuratedAdd BLAST27
Transmembranei441 – 461Helical; Name=8Sequence analysisAdd BLAST21
Topological domaini462 – 477CytoplasmicCuratedAdd BLAST16
Transmembranei478 – 498Helical; Name=9Sequence analysisAdd BLAST21
Topological domaini499 – 509LumenalCuratedAdd BLAST11
Transmembranei510 – 530Helical; Name=10Sequence analysisAdd BLAST21
Topological domaini531 – 540CytoplasmicCurated10
Transmembranei541 – 561Helical; Name=11Sequence analysisAdd BLAST21

GO - Cellular componenti

  • endoplasmic reticulum Source: GO_Central
  • integral component of membrane Source: UniProtKB-KW
  • late endosome Source: UniProtKB
  • late endosome membrane Source: UniProtKB-SubCell
  • lysosomal membrane Source: UniProtKB-SubCell
  • lysosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi38 – 40RPF → AAA: Abolishes interaction with the Ragulator and Rag GTPases complexes. 1 Publication3
Mutagenesisi60H → A: Does not affect association with the Ragulator complex. 1 Publication1
Mutagenesisi68I → A: Abolishes association with the Ragulator complex. 1 Publication1
Mutagenesisi70 – 73YYSR → AAAA: Abolishes interaction with the Ragulator and Rag GTPases complexes. 1 Publication4
Mutagenesisi71Y → A: Abolishes association with the Ragulator complex. 1 Publication1
Mutagenesisi74L → A: Abolishes association with the Ragulator complex. 1 Publication1
Mutagenesisi85 – 87PDH → AAA: Abolishes interaction with the Ragulator and Rag GTPases complexes. 1 Publication3
Mutagenesisi85P → A: Abolishes association with the Ragulator complex. 1 Publication1
Mutagenesisi90P → A: Abolishes association with the Ragulator complex. 1 Publication1
Mutagenesisi98 – 101YSPL → AAAA: Does not affect interaction with the Ragulator and Rag GTPases complexes. 1 Publication4
Mutagenesisi128N → A: Moderately affects amino acid transport. 1 Publication1

Organism-specific databases

DisGeNETi153129.
OpenTargetsiENSG00000177058.
PharmGKBiPA162403774.

Polymorphism and mutation databases

BioMutaiSLC38A9.
DMDMi296452888.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003288401 – 561Sodium-coupled neutral amino acid transporter 9Add BLAST561

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi239N-linked (GlcNAc...)PROSITE-ProRule annotation1
Glycosylationi248N-linked (GlcNAc...)PROSITE-ProRule annotation1
Glycosylationi266N-linked (GlcNAc...)PROSITE-ProRule annotation1
Glycosylationi274N-linked (GlcNAc...)PROSITE-ProRule annotation1

Post-translational modificationi

Glycosylated.2 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ8NBW4.
PaxDbiQ8NBW4.
PeptideAtlasiQ8NBW4.
PRIDEiQ8NBW4.

PTM databases

iPTMnetiQ8NBW4.
PhosphoSitePlusiQ8NBW4.

Expressioni

Gene expression databases

BgeeiENSG00000177058.
CleanExiHS_SLC38A9.
ExpressionAtlasiQ8NBW4. baseline and differential.
GenevisibleiQ8NBW4. HS.

Organism-specific databases

HPAiHPA043785.

Interactioni

Subunit structurei

Associated component of the Ragulator complex (composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5). Associated component of the Rag GTPases heterodimers (composed of RRAGA, RRAGB, RRAGC and RRAGD).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LAMTOR1Q6IAA89EBI-9978316,EBI-715385
LAMTOR3Q9UHA45EBI-9978316,EBI-1038192
LAMTOR4Q0VGL13EBI-9978316,EBI-5658976
LAMTOR5O435043EBI-9978316,EBI-713382
RRAGAQ7L52311EBI-9978316,EBI-752376
RRAGCQ9HB909EBI-9978316,EBI-752390

Protein-protein interaction databases

BioGridi127480. 11 interactors.
DIPiDIP-61480N.
IntActiQ8NBW4. 15 interactors.
STRINGi9606.ENSP00000316596.

Structurei

3D structure databases

ProteinModelPortaliQ8NBW4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The cytosolic N-terminus part of the protein mediates interaction with the Ragulator complex and the Rag GTPases heterodimers.2 Publications

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1305. Eukaryota.
COG0814. LUCA.
GeneTreeiENSGT00390000005646.
HOGENOMiHOG000294102.
HOVERGENiHBG106242.
InParanoidiQ8NBW4.
KOiK14995.
OMAiDCIEQNF.
OrthoDBiEOG091G04X6.
PhylomeDBiQ8NBW4.
TreeFamiTF312989.

Family and domain databases

InterProiIPR013057. AA_transpt_TM.
[Graphical view]
PfamiPF01490. Aa_trans. 2 hits.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8NBW4-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MANMNSDSRH LGTSEVDHER DPGPMNIQFE PSDLRSKRPF CIEPTNIVNV
60 70 80 90 100
NHVIQRVSDH ASAMNKRIHY YSRLTTPADK ALIAPDHVVP APEECYVYSP
110 120 130 140 150
LGSAYKLQSY TEGYGKNTSL VTIFMIWNTM MGTSILSIPW GIKQAGFTTG
160 170 180 190 200
MCVIILMGLL TLYCCYRVVK SRTMMFSLDT TSWEYPDVCR HYFGSFGQWS
210 220 230 240 250
SLLFSLVSLI GAMIVYWVLM SNFLFNTGKF IFNFIHHIND TDTILSTNNS
260 270 280 290 300
NPVICPSAGS GGHPDNSSMI FYANDTGAQQ FEKWWDKSRT VPFYLVGLLL
310 320 330 340 350
PLLNFKSPSF FSKFNILGTV SVLYLIFLVT FKAVRLGFHL EFHWFIPTEF
360 370 380 390 400
FVPEIRFQFP QLTGVLTLAF FIHNCIITLL KNNKKQENNV RDLCIAYMLV
410 420 430 440 450
TLTYLYIGVL VFASFPSPPL SKDCIEQNFL DNFPSSDTLS FIARIFLLFQ
460 470 480 490 500
MMTVYPLLGY LARVQLLGHI FGDIYPSIFH VLILNLIIVG AGVIMACFYP
510 520 530 540 550
NIGGIIRYSG AACGLAFVFI YPSLIYIISL HQEERLTWPK LIFHVFIIIL
560
GVANLIVQFF M
Length:561
Mass (Da):63,776
Last modified:May 18, 2010 - v2
Checksum:i0C1A3A136158168A
GO
Isoform 2 (identifier: Q8NBW4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     428-561: NFLDNFPSSD...VANLIVQFFM → VRHRVPSLCDCVHFHVFIVGRVIQWQDITSDRPGF

Note: No experimental confirmation available.
Show »
Length:462
Mass (Da):52,717
Checksum:iFB8344A9CFD7392F
GO
Isoform 3 (identifier: Q8NBW4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-37: MANMNSDSRHLGTSEVDHERDPGPMNIQFEPSDLRSK → MAICILTWRI
     318-353: Missing.

Show »
Length:498
Mass (Da):56,542
Checksum:iA54A4DA31CC0B696
GO
Isoform 4 (identifier: Q8NBW4-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-63: Missing.

Show »
Length:498
Mass (Da):56,695
Checksum:iD213355DA1CD5C13
GO

Sequence cautioni

The sequence BAQ19756 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti84A → P in AAH66891 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042546182S → T.3 PublicationsCorresponds to variant rs4865615dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0451101 – 63Missing in isoform 4. 1 PublicationAdd BLAST63
Alternative sequenceiVSP_0451111 – 37MANMN…DLRSK → MAICILTWRI in isoform 3. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_045112318 – 353Missing in isoform 3. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_032815428 – 561NFLDN…VQFFM → VRHRVPSLCDCVHFHVFIVG RVIQWQDITSDRPGF in isoform 2. 1 PublicationAdd BLAST134

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK075190 mRNA. Translation: BAC11460.1.
AK127988 mRNA. Translation: BAG54613.1.
AK301850 mRNA. Translation: BAH13566.1.
AB105188 mRNA. Translation: BAQ19756.1. Different initiation.
AC008784 Genomic DNA. No translation available.
AC016632 Genomic DNA. No translation available.
CH471123 Genomic DNA. Translation: EAW54926.1.
BC066891 mRNA. Translation: AAH66891.1.
BC101362 mRNA. Translation: AAI01363.1.
BX641065 mRNA. Translation: CAE46032.1.
CCDSiCCDS3968.1. [Q8NBW4-1]
CCDS58947.1. [Q8NBW4-4]
CCDS58948.1. [Q8NBW4-3]
RefSeqiNP_001245215.1. NM_001258286.1. [Q8NBW4-4]
NP_001245216.1. NM_001258287.1. [Q8NBW4-3]
NP_775785.2. NM_173514.3. [Q8NBW4-1]
XP_006714600.1. XM_006714537.2. [Q8NBW4-1]
XP_006714601.1. XM_006714538.3. [Q8NBW4-1]
XP_006714602.1. XM_006714539.3. [Q8NBW4-1]
XP_011541475.1. XM_011543173.1. [Q8NBW4-1]
XP_011541476.1. XM_011543174.1. [Q8NBW4-1]
UniGeneiHs.742101.
Hs.745105.

Genome annotation databases

EnsembliENST00000318672; ENSP00000316596; ENSG00000177058. [Q8NBW4-1]
ENST00000396865; ENSP00000380074; ENSG00000177058. [Q8NBW4-1]
ENST00000512595; ENSP00000427335; ENSG00000177058. [Q8NBW4-3]
ENST00000515629; ENSP00000420934; ENSG00000177058. [Q8NBW4-4]
GeneIDi153129.
KEGGihsa:153129.
UCSCiuc003jqd.4. human. [Q8NBW4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK075190 mRNA. Translation: BAC11460.1.
AK127988 mRNA. Translation: BAG54613.1.
AK301850 mRNA. Translation: BAH13566.1.
AB105188 mRNA. Translation: BAQ19756.1. Different initiation.
AC008784 Genomic DNA. No translation available.
AC016632 Genomic DNA. No translation available.
CH471123 Genomic DNA. Translation: EAW54926.1.
BC066891 mRNA. Translation: AAH66891.1.
BC101362 mRNA. Translation: AAI01363.1.
BX641065 mRNA. Translation: CAE46032.1.
CCDSiCCDS3968.1. [Q8NBW4-1]
CCDS58947.1. [Q8NBW4-4]
CCDS58948.1. [Q8NBW4-3]
RefSeqiNP_001245215.1. NM_001258286.1. [Q8NBW4-4]
NP_001245216.1. NM_001258287.1. [Q8NBW4-3]
NP_775785.2. NM_173514.3. [Q8NBW4-1]
XP_006714600.1. XM_006714537.2. [Q8NBW4-1]
XP_006714601.1. XM_006714538.3. [Q8NBW4-1]
XP_006714602.1. XM_006714539.3. [Q8NBW4-1]
XP_011541475.1. XM_011543173.1. [Q8NBW4-1]
XP_011541476.1. XM_011543174.1. [Q8NBW4-1]
UniGeneiHs.742101.
Hs.745105.

3D structure databases

ProteinModelPortaliQ8NBW4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127480. 11 interactors.
DIPiDIP-61480N.
IntActiQ8NBW4. 15 interactors.
STRINGi9606.ENSP00000316596.

Protein family/group databases

TCDBi2.A.18.9.1. the amino acid/auxin permease (aaap) family.

PTM databases

iPTMnetiQ8NBW4.
PhosphoSitePlusiQ8NBW4.

Polymorphism and mutation databases

BioMutaiSLC38A9.
DMDMi296452888.

Proteomic databases

MaxQBiQ8NBW4.
PaxDbiQ8NBW4.
PeptideAtlasiQ8NBW4.
PRIDEiQ8NBW4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000318672; ENSP00000316596; ENSG00000177058. [Q8NBW4-1]
ENST00000396865; ENSP00000380074; ENSG00000177058. [Q8NBW4-1]
ENST00000512595; ENSP00000427335; ENSG00000177058. [Q8NBW4-3]
ENST00000515629; ENSP00000420934; ENSG00000177058. [Q8NBW4-4]
GeneIDi153129.
KEGGihsa:153129.
UCSCiuc003jqd.4. human. [Q8NBW4-1]

Organism-specific databases

CTDi153129.
DisGeNETi153129.
GeneCardsiSLC38A9.
HGNCiHGNC:26907. SLC38A9.
HPAiHPA043785.
MIMi616203. gene.
neXtProtiNX_Q8NBW4.
OpenTargetsiENSG00000177058.
PharmGKBiPA162403774.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1305. Eukaryota.
COG0814. LUCA.
GeneTreeiENSGT00390000005646.
HOGENOMiHOG000294102.
HOVERGENiHBG106242.
InParanoidiQ8NBW4.
KOiK14995.
OMAiDCIEQNF.
OrthoDBiEOG091G04X6.
PhylomeDBiQ8NBW4.
TreeFamiTF312989.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000177058-MONOMER.

Miscellaneous databases

GenomeRNAii153129.
PROiQ8NBW4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000177058.
CleanExiHS_SLC38A9.
ExpressionAtlasiQ8NBW4. baseline and differential.
GenevisibleiQ8NBW4. HS.

Family and domain databases

InterProiIPR013057. AA_transpt_TM.
[Graphical view]
PfamiPF01490. Aa_trans. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiS38A9_HUMAN
AccessioniPrimary (citable) accession number: Q8NBW4
Secondary accession number(s): A0A0A8K8P2
, B3KXV1, B7Z7D0, Q0P5S0, Q6MZJ8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: May 18, 2010
Last modified: November 2, 2016
This is version 112 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.