UniProtKB - Q91W98 (S15A4_MOUSE)
Protein
Solute carrier family 15 member 4
Gene
Slc15a4
Organism
Mus musculus (Mouse)
Status
Functioni
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:19570976, PubMed:21277849, PubMed:25238095, PubMed:27845049, PubMed:29305823). Able to transport a variety of di- and tripeptides, including carnosine and some peptidoglycans (PubMed:29784761). 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:19570976, PubMed:23028315, PubMed:25238095, PubMed:24695226, PubMed:29784761). Required for TLR7, TLR8 and TLR9-mediated type I interferon (IFN-I) productions in plasmacytoid dendritic cells (pDCs) (PubMed:21045126, PubMed:23382217, PubMed:25238095, PubMed:30262916). 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 (By similarity). Required for isotype class switch recombination to IgG2c isotype in response to TLR9 stimulation (PubMed:25310967). Required for mast cell secretory-granule homeostasis by limiting mast cell functions and inflammatory responses (PubMed:29155995).By similarity13 Publications
Catalytic activityi
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- H+(out) + N-acetylmuramyl-L-alanyl-D-isoglutamine(out) = H+(in) + N-acetylmuramyl-L-alanyl-D-isoglutamine(in)1 PublicationThis reaction proceeds in the forwardBy similarity direction.
- H+(out) + L-alanyl-γ-D-glutamyl-meso-diaminoheptanedioate(out) = H+(in) + L-alanyl-γ-D-glutamyl-meso-diaminoheptanedioate(in)By similarityThis reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
GO - Molecular functioni
- dipeptide transmembrane transporter activity Source: UniProtKB
- L-histidine transmembrane transporter activity Source: UniProtKB
- peptide:proton symporter activity Source: UniProtKB
- peptidoglycan transmembrane transporter activity Source: UniProtKB
GO - Biological processi
- dipeptide import across plasma membrane Source: UniProtKB
- histidine transport Source: MGI
- innate immune response Source: UniProtKB-KW
- L-histidine transmembrane export from vacuole Source: UniProtKB
- mast cell homeostasis Source: UniProtKB
- peptidoglycan transport Source: UniProtKB
- positive regulation of innate immune response Source: UniProtKB
- positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway Source: UniProtKB
- positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKB
- positive regulation of toll-like receptor 7 signaling pathway Source: UniProtKB
- positive regulation of toll-like receptor 8 signaling pathway Source: Ensembl
- positive regulation of toll-like receptor 9 signaling pathway Source: UniProtKB
- protein transport Source: UniProtKB-KW
- regulation of isotype switching to IgG isotypes Source: UniProtKB
- regulation of nucleotide-binding oligomerization domain containing signaling pathway Source: UniProtKB
Keywordsi
Biological process | Immunity, Innate immunity, Peptide transport, Protein transport, Symport, Transport |
Enzyme and pathway databases
Reactomei | R-MMU-427975, Proton/oligopeptide cotransporters R-MMU-6798695, Neutrophil degranulation |
Names & Taxonomyi
Protein namesi | Recommended name: Solute carrier family 15 member 4CuratedAlternative name(s): Peptide/histidine transporter 11 Publication |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2140796, Slc15a4 |
Subcellular locationi
Endosome
- Endosome membrane 2 Publications; Multi-pass membrane protein Sequence analysis
- Early endosome membrane 1 Publication; Multi-pass membrane protein Sequence analysis
Lysosome
- Lysosome membrane 3 Publications; Multi-pass membrane protein Sequence analysis
Endosome
- early endosome membrane Source: UniProtKB
- endolysosome membrane Source: UniProtKB
- endosome membrane Source: UniProtKB
- integral component of endosome membrane Source: UniProtKB
Lysosome
- endolysosome membrane Source: UniProtKB
- integral component of lysosomal membrane Source: UniProtKB
- lysosomal membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 42 – 62 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 69 – 89 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 98 – 118 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 161 – 181 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 197 – 217 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 225 – 245 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 319 – 339 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 364 – 384 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 406 – 426 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 460 – 480 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 491 – 511 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 536 – 556 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Endosome, Lysosome, MembranePathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000338600 | 1 – 574 | Solute carrier family 15 member 4Add BLAST | 574 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 281 | PhosphoserineCombined sources | 1 | |
Modified residuei | 299 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q91W98 |
jPOSTi | Q91W98 |
MaxQBi | Q91W98 |
PaxDbi | Q91W98 |
PeptideAtlasi | Q91W98 |
PRIDEi | Q91W98 |
PTM databases
iPTMneti | Q91W98 |
PhosphoSitePlusi | Q91W98 |
SwissPalmi | Q91W98 |
Expressioni
Tissue specificityi
Preferentially expressed in immune tissues, including B-cells and dendritic cells (PubMed:21277849). Highly expressed in macrophages (PubMed:29784761).2 Publications
Gene expression databases
Bgeei | ENSMUSG00000029416, Expressed in bone marrow macrophage and 285 other tissues |
Genevisiblei | Q91W98, MM |
Interactioni
Subunit structurei
Interacts with TASL; leading to TASL recruitment to endolysosome.
By similarityProtein-protein interaction databases
STRINGi | 10090.ENSMUSP00000031367 |
Miscellaneous databases
RNActi | Q91W98, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the major facilitator superfamily. Proton-dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family. [View classification]Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1237, Eukaryota |
GeneTreei | ENSGT00940000159361 |
HOGENOMi | CLU_009313_6_1_1 |
InParanoidi | Q91W98 |
OMAi | QMMGVWF |
OrthoDBi | 365203at2759 |
PhylomeDBi | Q91W98 |
TreeFami | TF330897 |
Family and domain databases
InterProi | View protein in InterPro IPR036259, MFS_trans_sf IPR000109, POT_fam IPR018456, PTR2_symporter_CS |
PANTHERi | PTHR11654, PTHR11654, 1 hit |
Pfami | View protein in Pfam PF00854, PTR2, 1 hit |
SUPFAMi | SSF103473, SSF103473, 1 hit |
PROSITEi | View protein in PROSITE PS01023, PTR2_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 6 potential isoforms that are computationally mapped.Show allAlign All
Q91W98-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MEGERAPLLG SRRPAVSAAS AVFAGRRAAC GAVLLAELLE RAAFYGVTAN
60 70 80 90 100
LVLFLNGAPF DWEGAQASQA LLLFMGLTYL GSPFGGWLAD ARLGRARAIL
110 120 130 140 150
LSLALYLLGL LAFPLLAAPR SRSFLCGDPR PELVRNCSAP FPNGSASCPE
160 170 180 190 200
NAARRCAPAT FAGLVLVGLG VATVKANITP FGADQVKDRG PEATRRFFNW
210 220 230 240 250
FYWSINLGAI LSLGGIAYIQ QNVSFFTGYL IPTVCVAIAF LVFLCGQSVF
260 270 280 290 300
ITKPPDGSAF TDMFRILTYS CCSQRGGQRR SGEGLGVFQQ SSKHSLFDSC
310 320 330 340 350
KMSRGGPFTE DKVEDVKALV KIVPVFLALI PYWTVYFQMQ TTYALQSLHL
360 370 380 390 400
KIPEISSITT THHTLPAAWL TMFDAVLILL LIPLKDKLVD PVLRRHGLLP
410 420 430 440 450
SSLKRIAVGM FFVMCSAFAA GILESKRLDL VKEKTINQTI GGVVYHAADL
460 470 480 490 500
PIWWQIPQYV LIGISEIFAS IAGLEFAYSA APKSMQSAIM GLFFFFSGIG
510 520 530 540 550
SFVGSGLLAL VSLKAIGWMS SHTDFGNINS CHLHYYFFLL AAIQGATLLL
560 570
FLIVSVKYDR QRARTDGGPA STRT
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD3Z5E9 | D3Z5E9_MOUSE | Solute carrier family 15 member 4 | Slc15a4 | 105 | Annotation score: | ||
D6RDC2 | D6RDC2_MOUSE | Solute carrier family 15 member 4 | Slc15a4 | 296 | Annotation score: | ||
F6QFB4 | F6QFB4_MOUSE | Solute carrier family 15 member 4 | Slc15a4 | 246 | Annotation score: | ||
F7AZ26 | F7AZ26_MOUSE | Solute carrier family 15 member 4 | Slc15a4 | 127 | Annotation score: | ||
D3Z4X0 | D3Z4X0_MOUSE | Solute carrier family 15 member 4 | Slc15a4 | 81 | Annotation score: | ||
A0A0G2JDS1 | A0A0G2JDS1_MOUSE | Solute carrier family 15 member 4 | Slc15a4 | 169 | Annotation score: |
Sequence cautioni
The sequence AAK95566 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 218 | Y → I in AAK95566 (Ref. 1) Curated | 1 | |
Sequence conflicti | 254 | P → L in AAK95566 (Ref. 1) Curated | 1 | |
Sequence conflicti | 258 | S → G in AAK95566 (Ref. 1) Curated | 1 | |
Sequence conflicti | 347 | S → N in AAK95566 (Ref. 1) Curated | 1 | |
Sequence conflicti | 427 | R → K in AAK95566 (Ref. 1) Curated | 1 | |
Sequence conflicti | 445 | Y → F in AAK95566 (Ref. 1) Curated | 1 | |
Sequence conflicti | 457 | P → L in AAK95566 (Ref. 1) Curated | 1 | |
Sequence conflicti | 473 – 474 | GL → RQ in AAK95566 (Ref. 1) Curated | 2 | |
Sequence conflicti | 498 | G → C in AAK95566 (Ref. 1) Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY050630 mRNA Translation: AAK95566.1 Frameshift. BC016233 mRNA Translation: AAH16233.1 |
CCDSi | CCDS19688.1 |
RefSeqi | NP_598656.1, NM_133895.1 |
Genome annotation databases
Ensembli | ENSMUST00000031367; ENSMUSP00000031367; ENSMUSG00000029416 |
GeneIDi | 100561 |
KEGGi | mmu:100561 |
UCSCi | uc008zsb.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY050630 mRNA Translation: AAK95566.1 Frameshift. BC016233 mRNA Translation: AAH16233.1 |
CCDSi | CCDS19688.1 |
RefSeqi | NP_598656.1, NM_133895.1 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000031367 |
PTM databases
iPTMneti | Q91W98 |
PhosphoSitePlusi | Q91W98 |
SwissPalmi | Q91W98 |
Proteomic databases
EPDi | Q91W98 |
jPOSTi | Q91W98 |
MaxQBi | Q91W98 |
PaxDbi | Q91W98 |
PeptideAtlasi | Q91W98 |
PRIDEi | Q91W98 |
Protocols and materials databases
Antibodypediai | 3084, 64 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000031367; ENSMUSP00000031367; ENSMUSG00000029416 |
GeneIDi | 100561 |
KEGGi | mmu:100561 |
UCSCi | uc008zsb.1, mouse |
Organism-specific databases
CTDi | 121260 |
MGIi | MGI:2140796, Slc15a4 |
Phylogenomic databases
eggNOGi | KOG1237, Eukaryota |
GeneTreei | ENSGT00940000159361 |
HOGENOMi | CLU_009313_6_1_1 |
InParanoidi | Q91W98 |
OMAi | QMMGVWF |
OrthoDBi | 365203at2759 |
PhylomeDBi | Q91W98 |
TreeFami | TF330897 |
Enzyme and pathway databases
Reactomei | R-MMU-427975, Proton/oligopeptide cotransporters R-MMU-6798695, Neutrophil degranulation |
Miscellaneous databases
BioGRID-ORCSi | 100561, 1 hit in 17 CRISPR screens |
ChiTaRSi | Slc15a4, mouse |
PROi | PR:Q91W98 |
RNActi | Q91W98, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000029416, Expressed in bone marrow macrophage and 285 other tissues |
Genevisiblei | Q91W98, MM |
Family and domain databases
InterProi | View protein in InterPro IPR036259, MFS_trans_sf IPR000109, POT_fam IPR018456, PTR2_symporter_CS |
PANTHERi | PTHR11654, PTHR11654, 1 hit |
Pfami | View protein in Pfam PF00854, PTR2, 1 hit |
SUPFAMi | SSF103473, SSF103473, 1 hit |
PROSITEi | View protein in PROSITE PS01023, PTR2_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | S15A4_MOUSE | |
Accessioni | Q91W98Primary (citable) accession number: Q91W98 Secondary accession number(s): Q7TPL5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 10, 2008 |
Last sequence update: | December 1, 2001 | |
Last modified: | December 2, 2020 | |
This is version 122 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families