Q8N697 · S15A4_HUMAN

  • Protein
    Solute carrier family 15 member 4
  • Gene
    SLC15A4
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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 (PubMed:16289537, PubMed:25238095, PubMed:29224352).
Able to transport a variety of di- and tripeptides, including carnosine and some peptidoglycans (PubMed:29224352, PubMed:31073693).
Transporter activity is pH-dependent and maximized in the acidic lysosomal environment (By similarity).
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 (PubMed:25238095, PubMed:29224352).
Required for TLR7, TLR8 and TLR9-mediated type I interferon (IFN-I) productions in plasmacytoid dendritic cells (pDCs) (PubMed:25238095).
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 (PubMed:32433612).
Required for isotype class switch recombination to IgG2c isotype in response to TLR9 stimulation (By similarity).
Required for mast cell secretory-granule homeostasis by limiting mast cell functions and inflammatory responses (By similarity).

Catalytic activity

  • glycylglycylglycine(out) + n H+(out) = glycylglycylglycine(in) + n H+(in)
    This reaction proceeds in the forward direction.
  • n H+(out) + N-acetyl-D-muramoyl-L-alanyl-D-isoglutamine(out) = n H+(in) + N-acetyl-D-muramoyl-L-alanyl-D-isoglutamine(in)
    This reaction proceeds in the forward direction.
  • n H+(out) + L-alanyl-gamma-D-glutamyl-meso-diaminoheptanedioate(out) = n H+(in) + L-alanyl-gamma-D-glutamyl-meso-diaminoheptanedioate(in)
    This reaction proceeds in the forward direction.
  • carnosine(out) + n H+(out) = carnosine(in) + n H+(in)
    This reaction proceeds in the forward direction.
  • n H+(out) + L-histidine(out) = n H+(in) + L-histidine(in)
    This reaction proceeds in the forward direction.

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
16.3 μML-histidine
1690 μMGlySar dipeptide
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
1317 pmol/min/mgwith L-histidine as substrate
100 pmol/min/mgwith GlySar dipeptide as substrate

GO annotations

AspectTerm
Cellular Componentearly endosome membrane
Cellular Componentendolysosome membrane
Cellular Componentlysosomal membrane
Cellular Componentmembrane
Cellular Componentplasma membrane
Cellular Componentspecific granule membrane
Molecular Functiondipeptide transmembrane transporter activity
Molecular FunctionL-histidine transmembrane transporter activity
Molecular Functionpeptide:proton symporter activity
Molecular Functionpeptidoglycan transmembrane transporter activity
Biological Processdipeptide import across plasma membrane
Biological Processhistidine transport
Biological Processinnate immune response
Biological ProcessL-histidine transmembrane export from vacuole
Biological Processmast cell homeostasis
Biological Processmonoatomic ion transport
Biological Processpeptide transport
Biological Processpeptidoglycan transport
Biological Processpositive regulation of innate immune response
Biological Processpositive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway
Biological Processpositive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
Biological Processpositive regulation of toll-like receptor 7 signaling pathway
Biological Processpositive regulation of toll-like receptor 8 signaling pathway
Biological Processpositive regulation of toll-like receptor 9 signaling pathway
Biological Processprotein transport
Biological Processregulation of isotype switching to IgG isotypes
Biological Processregulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Keywords

Enzyme and pathway databases

Protein family/group databases

    • 2.A.17.3.11the proton-dependent oligopeptide transporter (pot/ptr) family
Community curation (1)

SLC15A4 interacts with CXorf21/TASL. SLC15A4 is required for the recruitment of CXorf21/TASL to endolysosomes.

Names & Taxonomy

Protein names

  • Recommended name
    Solute carrier family 15 member 4
  • Alternative names
    • Peptide transporter 4
    • Peptide/histidine transporter 1
      (hPHT1
      )

Gene names

    • Name
      SLC15A4
    • Synonyms
      PHT1
      , PTR4
    • ORF names
      FP12591
Community curation (1)

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q8N697
  • Secondary accessions
    • A6H8Y9
    • B3KTK1
    • Q71M34
    • Q7Z5F8
    • Q8TAH0

Proteomes

Organism-specific databases

Subcellular Location

Lysosome membrane
; Multi-pass membrane protein
Endosome membrane
; Multi-pass membrane protein
Early endosome membrane
; Multi-pass membrane protein

Features

Showing features for transmembrane.

TypeIDPosition(s)Description
Transmembrane49-69Helical
Transmembrane76-96Helical
Transmembrane105-125Helical
Transmembrane158-178Helical
Transmembrane194-214Helical
Transmembrane222-242Helical
Transmembrane318-338Helical
Transmembrane363-383Helical
Transmembrane405-425Helical
Transmembrane459-479Helical
Transmembrane490-510Helical
Transmembrane535-555Helical

Keywords

Disease & Variants

Features

Showing features for mutagenesis, natural variant.

TypeIDPosition(s)Description
Mutagenesis14-15Abolished localization to the lysosome membrane and promotes relocalization to the plasma membrane; when associated with 318-A-A-319. Does not affect interaction with TASL.
Mutagenesis44Does not affect interaction with TASL.
Mutagenesis47Does not affect interaction with TASL.
Natural variantVAR_051611239in dbSNP:rs33990080
Mutagenesis318-319Abolished localization to the lysosome membrane and promotes relocalization to the plasma membrane; when associated with 14-A-A-15.
Mutagenesis465Abolished transmembrane transporter activity. Abolished interaction with TASL.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 707 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue (large scale data), modified residue.

TypeIDPosition(s)SourceDescription
ChainPRO_00003385991-577UniProtSolute carrier family 15 member 4
Modified residue (large scale data)4PRIDEPhosphoserine
Modified residue279UniProtPhosphoserine
Modified residue (large scale data)279PRIDEPhosphoserine
Modified residue (large scale data)291PRIDEPhosphoserine
Modified residue298UniProtPhosphoserine
Modified residue (large scale data)298PRIDEPhosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Highly expressed in skeletal muscle. Moderately expressed in kidney, liver, and heart. Weakly expressed in colon and brain. Expressed in low levels throughout the gastrointestinal tract and in Caco-2 cells. Expressed in retinal fragment epithelium (RPE) and neural retina. Expressed in small intestine, stomach, duodenum, jejunum, ileum and colon.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Interacts with TASL; leading to TASL recruitment to endolysosome.

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q8N697NOD2 Q9HC292EBI-4319594, EBI-7445625
BINARY Q8N697SLC15A3 Q8IY342EBI-4319594, EBI-12179023
BINARY Q8N697TASL Q9HAI615EBI-4319594, EBI-21895669

Protein-protein interaction databases

Miscellaneous

Family & Domains

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

Q8N697-1

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.

  • Length
    577
  • Mass (Da)
    62,034
  • Last updated
    2002-10-01 v1
  • Checksum
    701111038C752E70
MEGSGGGAGERAPLLGARRAAAAAAAAGAFAGRRAACGAVLLTELLERAAFYGITSNLVLFLNGAPFCWEGAQASEALLLFMGLTYLGSPFGGWLADARLGRARAILLSLALYLLGMLAFPLLAAPATRAALCGSARLLNCTAPGPDAAARCCSPATFAGLVLVGLGVATVKANITPFGADQVKDRGPEATRRFFNWFYWSINLGAILSLGGIAYIQQNVSFVTGYAIPTVCVGLAFVVFLCGQSVFITKPPDGSAFTDMFKILTYSCCSQKRSGERQSNGEGIGVFQQSSKQSLFDSCKMSHGGPFTEEKVEDVKALVKIVPVFLALIPYWTVYFQMQTTYVLQSLHLRIPEISNITTTPHTLPAAWLTMFDAVLILLLIPLKDKLVDPILRRHGLLPSSLKRIAVGMFFVMCSAFAAGILESKRLNLVKEKTINQTIGNVVYHAADLSLWWQVPQYLLIGISEIFASIAGLEFAYSAAPKSMQSAIMGLFFFFSGVGSFVGSGLLALVSIKAIGWMSSHTDFGNINGCYLNYYFFLLAAIQGATLLLFLIISVKYDHHRDHQRSRANGVPTSRRA

Q8N697-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
B6ZDF2B6ZDF2_HUMANSLC15A4155
H7BYB7H7BYB7_HUMANSLC15A4238

Sequence caution

The sequence AAI46804.1 differs from that shown. Reason: Frameshift
The sequence AAK95565.1 differs from that shown. Reason: Frameshift
The sequence AAQ04807.1 differs from that shown. Reason: Frameshift

Features

Showing features for alternative sequence, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0340521-337in isoform 2
Sequence conflict24in Ref. 6; AAI46804
Sequence conflict34-35in Ref. 1; AAK95565
Sequence conflict44in Ref. 6; AAI46804

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY050629
EMBL· GenBank· DDBJ
AAK95565.1
EMBL· GenBank· DDBJ
mRNA Frameshift
AY038999
EMBL· GenBank· DDBJ
AAK72099.1
EMBL· GenBank· DDBJ
mRNA
AF461893
EMBL· GenBank· DDBJ
AAQ04807.1
EMBL· GenBank· DDBJ
mRNA Frameshift
AK095717
EMBL· GenBank· DDBJ
BAG53113.1
EMBL· GenBank· DDBJ
mRNA
CH471054
EMBL· GenBank· DDBJ
EAW98494.1
EMBL· GenBank· DDBJ
Genomic DNA
BC028394
EMBL· GenBank· DDBJ
AAH28394.2
EMBL· GenBank· DDBJ
mRNA
BC146803
EMBL· GenBank· DDBJ
AAI46804.1
EMBL· GenBank· DDBJ
mRNA Frameshift

Genome annotation databases

Similar Proteins

Disclaimer

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