Q8N697 · S15A4_HUMAN
- ProteinSolute carrier family 15 member 4
- GeneSLC15A4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids577 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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.glycylglycylglycine (out)CHEBI:195214
+ n H+ (out)CHEBI:15378= glycylglycylglycine (in)CHEBI:195214+ n H+ (in)CHEBI:15378 - 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 μM | L-histidine | |||||
1690 μM | GlySar dipeptide |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
1317 pmol/min/mg | with L-histidine as substrate | ||||
100 pmol/min/mg | with GlySar dipeptide as substrate |
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
SLC15A4 interacts with CXorf21/TASL. SLC15A4 is required for the recruitment of CXorf21/TASL to endolysosomes.
Names & Taxonomy
Protein names
- Recommended nameSolute carrier family 15 member 4
- Alternative names
Gene names
- Community suggested namesSLC15A4
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ8N697
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 49-69 | Helical | ||||
Sequence: AAFYGITSNLVLFLNGAPFCW | ||||||
Transmembrane | 76-96 | Helical | ||||
Sequence: EALLLFMGLTYLGSPFGGWLA | ||||||
Transmembrane | 105-125 | Helical | ||||
Sequence: AILLSLALYLLGMLAFPLLAA | ||||||
Transmembrane | 158-178 | Helical | ||||
Sequence: FAGLVLVGLGVATVKANITPF | ||||||
Transmembrane | 194-214 | Helical | ||||
Sequence: FFNWFYWSINLGAILSLGGIA | ||||||
Transmembrane | 222-242 | Helical | ||||
Sequence: FVTGYAIPTVCVGLAFVVFLC | ||||||
Transmembrane | 318-338 | Helical | ||||
Sequence: LVKIVPVFLALIPYWTVYFQM | ||||||
Transmembrane | 363-383 | Helical | ||||
Sequence: TLPAAWLTMFDAVLILLLIPL | ||||||
Transmembrane | 405-425 | Helical | ||||
Sequence: IAVGMFFVMCSAFAAGILESK | ||||||
Transmembrane | 459-479 | Helical | ||||
Sequence: LLIGISEIFASIAGLEFAYSA | ||||||
Transmembrane | 490-510 | Helical | ||||
Sequence: GLFFFFSGVGSFVGSGLLALV | ||||||
Transmembrane | 535-555 | Helical | ||||
Sequence: YFFLLAAIQGATLLLFLIISV |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 14-15 | Abolished 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. | ||||
Sequence: LL → AA | ||||||
Mutagenesis | 44 | Does not affect interaction with TASL. | ||||
Sequence: E → A | ||||||
Mutagenesis | 47 | Does not affect interaction with TASL. | ||||
Sequence: E → A | ||||||
Natural variant | VAR_051611 | 239 | in dbSNP:rs33990080 | |||
Sequence: V → A | ||||||
Mutagenesis | 318-319 | Abolished localization to the lysosome membrane and promotes relocalization to the plasma membrane; when associated with 14-A-A-15. | ||||
Sequence: LV → AA | ||||||
Mutagenesis | 465 | Abolished transmembrane transporter activity. Abolished interaction with TASL. | ||||
Sequence: E → K |
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.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000338599 | 1-577 | UniProt | Solute carrier family 15 member 4 | |||
Sequence: MEGSGGGAGERAPLLGARRAAAAAAAAGAFAGRRAACGAVLLTELLERAAFYGITSNLVLFLNGAPFCWEGAQASEALLLFMGLTYLGSPFGGWLADARLGRARAILLSLALYLLGMLAFPLLAAPATRAALCGSARLLNCTAPGPDAAARCCSPATFAGLVLVGLGVATVKANITPFGADQVKDRGPEATRRFFNWFYWSINLGAILSLGGIAYIQQNVSFVTGYAIPTVCVGLAFVVFLCGQSVFITKPPDGSAFTDMFKILTYSCCSQKRSGERQSNGEGIGVFQQSSKQSLFDSCKMSHGGPFTEEKVEDVKALVKIVPVFLALIPYWTVYFQMQTTYVLQSLHLRIPEISNITTTPHTLPAAWLTMFDAVLILLLIPLKDKLVDPILRRHGLLPSSLKRIAVGMFFVMCSAFAAGILESKRLNLVKEKTINQTIGNVVYHAADLSLWWQVPQYLLIGISEIFASIAGLEFAYSAAPKSMQSAIMGLFFFFSGVGSFVGSGLLALVSIKAIGWMSSHTDFGNINGCYLNYYFFLLAAIQGATLLLFLIISVKYDHHRDHQRSRANGVPTSRRA | |||||||
Modified residue (large scale data) | 4 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 279 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 279 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 291 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 298 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 298 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8N697 | NOD2 Q9HC29 | 2 | EBI-4319594, EBI-7445625 | |
BINARY | Q8N697 | SLC15A3 Q8IY34 | 2 | EBI-4319594, EBI-12179023 | |
BINARY | Q8N697 | TASL Q9HAI6 | 15 | EBI-4319594, EBI-21895669 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
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.
- Name1
- Length577
- Mass (Da)62,034
- Last updated2002-10-01 v1
- Checksum701111038C752E70
Q8N697-2
- Name2
- Differences from canonical
- 1-337: Missing
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_034052 | 1-337 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 24 | in Ref. 6; AAI46804 | ||||
Sequence: A → T | ||||||
Sequence conflict | 34-35 | in Ref. 1; AAK95565 | ||||
Sequence: RA → LL | ||||||
Sequence conflict | 44 | in Ref. 6; AAI46804 | ||||
Sequence: E → G |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |