Details of Protein

General Information of Protein (ID: PRT01124)
Name Solute carrier family 15 member 4 (SLC15A4)
Synonyms   Click to Show/Hide Synonyms of This Protein
Peptide transporter 4; Peptide/histidine transporter 1; hPHT1; FP12591; SLC15A4; PHT1; PTR4
Gene Name SLC15A4 Gene ID
121260
UniProt ID
Q8N697
Family Proton-dependent oligopeptide transporter (POT/PTR)
TC Number   TC: 2.A.17.3.11  (Click to Show/Hide the Complete TC Tree)
The Proton-dependent Oligopeptide Transporter (POT/PTR) Family
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TC: 2.A.17.3.11
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MEGSGGGAGERAPLLGARRAAAAAAAAGAFAGRRAACGAVLLTELLERAAFYGITSNLVL
FLNGAPFCWEGAQASEALLLFMGLTYLGSPFGGWLADARLGRARAILLSLALYLLGMLAF
PLLAAPATRAALCGSARLLNCTAPGPDAAARCCSPATFAGLVLVGLGVATVKANITPFGA
DQVKDRGPEATRRFFNWFYWSINLGAILSLGGIAYIQQNVSFVTGYAIPTVCVGLAFVVF
LCGQSVFITKPPDGSAFTDMFKILTYSCCSQKRSGERQSNGEGIGVFQQSSKQSLFDSCK
MSHGGPFTEEKVEDVKALVKIVPVFLALIPYWTVYFQMQTTYVLQSLHLRIPEISNITTT
PHTLPAAWLTMFDAVLILLLIPLKDKLVDPILRRHGLLPSSLKRIAVGMFFVMCSAFAAG
ILESKRLNLVKEKTINQTIGNVVYHAADLSLWWQVPQYLLIGISEIFASIAGLEFAYSAA
PKSMQSAIMGLFFFFSGVGSFVGSGLLALVSIKAIGWMSSHTDFGNINGCYLNYYFFLLA
AIQGATLLLFLIISVKYDHHRDHQRSRANGVPTSRRA
Function Proton-coupled amino-acid transporter that mediates the transmembrane transport of L-histidine and some di- and tripeptides from inside the lysosome to the cytosol, and plays a key role in innate immune response. Able to transport a variety of di- and tripeptides, including carnosine and some peptidoglycans. Transporter activity is pH-dependent and maximized in the acidic lysosomal environment. Involved in the detection of microbial pathogens by toll-like receptors (TLRs) and NOD-like receptors (NLRs), probably by mediating transport of bacterial peptidoglycans across the endolysosomal membrane: catalyzes the transport of certain bacterial peptidoglycans, such as muramyl dipeptide (MDP), the NOD2 ligand, and L-alanyl-gamma-D-glutamyl-meso-2,6-diaminoheptanedioate (tri-DAP), the NOD1 ligand. Required for TLR7, TLR8 and TLR9-mediated type I interferon (IFN-I) productions in plasmacytoid dendritic cells (pDCs). Independently of its transporter activity, also promotes the recruitment of innate immune adapter TASL to endolysosome downstream of TLR7, TLR8 and TLR9: TASL recruitment leads to the specific recruitment and activation of IRF5. Required for isotype class switch recombination to IgG2c isotype in response to TLR9 stimulation. Required for mast cell secretory-granule homeostasis by limiting mast cell functions and inflammatory responses.
Regulatory Network
Full List of Metabolite(s) Regulated by This Protein
      Organic acids and derivatives
            Carnosine Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Overexpression of SLC15A4
                      Induced Change Carnosine concentration: increase (FC = 10)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC15A4 leads to the increase of carnosine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Mutation (L14A, L15A, L318A, V319A) of SLC15A4
                      Induced Change Carnosine concentration: increase (FC = 2 - 4)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (L14A and L15A or L318A and V319A) of SLC15A4 leads to the increase of carnosine levels compared with control group.
            Glycylglycylglycine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Mutation (L14A, L15A, L318A, V319A) of SLC15A4
                      Induced Change Glycylglycylglycine concentration: increase (FC = 2 - 4)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (L14A and L15A or L318A and V319A) of SLC15A4 leads to the increase of glycylglycylglycine levels compared with control group.
            Glycylsarcosine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Mutation (L14A, L15A, L318A, V319A) of SLC15A4
                      Induced Change Glycylsarcosine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (L14A and L15A or L318A and V319A) of SLC15A4 leads to the increase of glycylsarcosine levels compared with control group.
            Histidine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Mutation (L14A, L15A, L318A, V319A) of SLC15A4
                      Induced Change Histidine concentration: increase (FC = 2)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (L14A and L15A or L318A and V319A) of SLC15A4 leads to the increase of histidine levels compared with control group.
            Muramyl Dipeptide Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Mutation (L14A, L15A, L318A, V319A) of SLC15A4
                      Induced Change Muramyl Dipeptide concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (L14A and L15A or L318A and V319A) of SLC15A4 leads to the increase of muramyl dipeptide levels compared with control group.
            Tripeptide l-Ala-gamma-d-Glu-meso-DAP Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Mutation (L14A, L15A, L318A, V319A) of SLC15A4
                      Induced Change Tripeptide l-Ala-gamma-d-Glu-meso-DAP concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (L14A and L15A or L318A and V319A) of SLC15A4 leads to the increase of tripeptide l-Ala-gamma-d-Glu-meso-DAP levels compared with control group.
References
1 Cloning and functional expression of a brain peptide/histidine transporter. J Biol Chem. 1997 Apr 11;272(15):10205-11.
2 Functional Characterization of Human Peptide/Histidine Transporter 1 in Stably Transfected MDCK Cells. Mol Pharm. 2018 Feb 5;15(2):385-393.

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