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2.A.18.9.1
Na+-coupled high affinity, lysosomal arginine transporter vand sensor, SLC38A9 (561aas; 11 TMSs) (Gu et al. 2017).  The rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that responds to multiple environmental cues. Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar ATPase-dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb. Wang et al. 2015 showed that lysosomal SLC38A9 interacts with Rag GTPases and Ragulator in an amino acid-sensitive fashion. SLC38A9 transports arginine, and loss of SLC38A9 represses mTORC1 activation by amino acids, particularly arginine. Overexpression of SLC38A9 or just its Ragulator-binding domain makes mTORC1 signaling insensitive to amino acid starvation but not to Rag activity. Thus, SLC38A9 functions upstream of the Rag GTPases and is probably the arginine sensor for the mTORC1 pathway.  Jung et al. 2015 confirmed SLC38A9 to be a Rag-Ragulator complex member, transducing amino acid availability to mTORC1. Lysosomal cholesterol activates TORC1 via an SLC38A9-Niemann-Pick C1 signaling complex (Castellano et al. 2017). The Niemann-Pick C1 (NPC1) protein, which regulates cholesterol export from the lysosome, binds to SLC38A9 and inhibits mTORC1 signaling through its sterol transport function (Castellano et al. 2017).

Accession Number:Q8NBW4
Protein Name:Putative sodium-coupled neutral amino acid transporter 9
Length:561
Molecular Weight:63776.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Arginine, Na+

Cross database links:

Genevestigator: Q8NBW4 Q8NBW4
eggNOG: prNOG07268 NOG294315
HEGENOM: HBG717223 HOG000294102
Entrez Gene ID: 153129   
Pfam: PF01490   
KEGG: hsa:153129    hsa:153129   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0006865 P:amino acid transport
GO:0006814 P:sodium ion transport

References (10)

[1] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[2] “The DNA sequence and comparative analysis of human chromosome 5.”  Schmutz J.et.al.   15372022
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “The full-ORF clone resource of the German cDNA consortium.”  Bechtel S.et.al.   17974005
[5] “Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling.”  Wang Y.et.al.   17053785
[6] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[7] “The DNA sequence and comparative analysis of human chromosome 5.”  Schmutz J.et.al.   15372022
[8] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[9] “The full-ORF clone resource of the German cDNA consortium.”  Bechtel S.et.al.   17974005
[10] “Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling.”  Wang Y.et.al.   17053785

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MANMNSDSRH LGTSEVDHER DPGPMNIQFE PSDLRSKRPF CIEPTNIVNV NHVIQRVSDH 
61:	ASAMNKRIHY YSRLTTPADK ALIAPDHVVP APEECYVYSP LGSAYKLQSY TEGYGKNTSL 
121:	VTIFMIWNTM MGTSILSIPW GIKQAGFTTG MCVIILMGLL TLYCCYRVVK SRTMMFSLDT 
181:	TSWEYPDVCR HYFGSFGQWS SLLFSLVSLI GAMIVYWVLM SNFLFNTGKF IFNFIHHIND 
241:	TDTILSTNNS NPVICPSAGS GGHPDNSSMI FYANDTGAQQ FEKWWDKSRT VPFYLVGLLL 
301:	PLLNFKSPSF FSKFNILGTV SVLYLIFLVT FKAVRLGFHL EFHWFIPTEF FVPEIRFQFP 
361:	QLTGVLTLAF FIHNCIITLL KNNKKQENNV RDLCIAYMLV TLTYLYIGVL VFASFPSPPL 
421:	SKDCIEQNFL DNFPSSDTLS FIARIFLLFQ MMTVYPLLGY LARVQLLGHI FGDIYPSIFH 
481:	VLILNLIIVG AGVIMACFYP NIGGIIRYSG AACGLAFVFI YPSLIYIISL HQEERLTWPK 
541:	LIFHVFIIIL GVANLIVQFF M