S15A4_BOVIN
ID S15A4_BOVIN Reviewed; 566 AA.
AC A6QQL0;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 2.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Solute carrier family 15 member 4 {ECO:0000305};
DE AltName: Full=Peptide/histidine transporter 1 {ECO:0000303|PubMed:14567629};
GN Name=SLC15A4 {ECO:0000250|UniProtKB:Q8N697};
GN Synonyms=PHT1 {ECO:0000303|PubMed:14567629};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=Hereford; TISSUE=Basal ganglia;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=14567629; DOI=10.1023/a:1025741723724;
RA Ocheltree S.M., Keep R.F., Shen H., Yang D., Hughes B.A., Smith D.E.;
RT "Preliminary investigation into the expression of proton-coupled
RT oligopeptide transporters in neural retina and retinal pigment epithelium
RT (RPE): lack of functional activity in RPE plasma membranes.";
RL Pharm. Res. 20:1364-1372(2003).
CC -!- FUNCTION: Proton-coupled amino-acid transporter that mediates the
CC transmembrane transport of L-histidine and some di- and tripeptides
CC from inside the lysosome to the cytosol, and plays a key role in innate
CC immune response. Able to transport a variety of di- and tripeptides,
CC including carnosine and some peptidoglycans (By similarity).
CC Transporter activity is pH-dependent and maximized in the acidic
CC lysosomal environment (By similarity). Involved in the detection of
CC microbial pathogens by toll-like receptors (TLRs) and NOD-like
CC receptors (NLRs), probably by mediating transport of bacterial
CC peptidoglycans across the endolysosomal membrane: catalyzes the
CC transport of certain bacterial peptidoglycans, such as muramyl
CC dipeptide (MDP), the NOD2 ligand, and L-alanyl-gamma-D-glutamyl-meso-
CC 2,6-diaminoheptanedioate (tri-DAP), the NOD1 ligand. Required for TLR7,
CC TLR8 and TLR9-mediated type I interferon (IFN-I) productions in
CC plasmacytoid dendritic cells (pDCs). Independently of its transporter
CC activity, also promotes the recruitment of innate immune adapter TASL
CC to endolysosome downstream of TLR7, TLR8 and TLR9: TASL recruitment
CC leads to the specific recruitment and activation of IRF5 (By
CC similarity). Required for isotype class switch recombination to IgG2c
CC isotype in response to TLR9 stimulation. Required for mast cell
CC secretory-granule homeostasis by limiting mast cell functions and
CC inflammatory responses (By similarity). {ECO:0000250|UniProtKB:O09014,
CC ECO:0000250|UniProtKB:Q8N697, ECO:0000250|UniProtKB:Q91W98}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(out) + L-histidine(out) = H(+)(in) + L-histidine(in);
CC Xref=Rhea:RHEA:37047, ChEBI:CHEBI:15378, ChEBI:CHEBI:57595;
CC Evidence={ECO:0000250|UniProtKB:Q8N697};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37048;
CC Evidence={ECO:0000250|UniProtKB:Q8N697};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a dipeptide(out) + H(+)(out) = a dipeptide(in) + H(+)(in);
CC Xref=Rhea:RHEA:64392, ChEBI:CHEBI:15378, ChEBI:CHEBI:90799;
CC Evidence={ECO:0000250|UniProtKB:Q8N697};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64393;
CC Evidence={ECO:0000250|UniProtKB:Q8N697};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an L-amino acid tripeptide(out) + H(+)(out) = an L-amino acid
CC tripeptide(in) + H(+)(in); Xref=Rhea:RHEA:64400, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:155837; Evidence={ECO:0000250|UniProtKB:Q8N697};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64401;
CC Evidence={ECO:0000250|UniProtKB:Q8N697};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(out) + N-acetylmuramyl-L-alanyl-D-isoglutamine(out) =
CC H(+)(in) + N-acetylmuramyl-L-alanyl-D-isoglutamine(in);
CC Xref=Rhea:RHEA:64408, ChEBI:CHEBI:15378, ChEBI:CHEBI:155830;
CC Evidence={ECO:0000250|UniProtKB:Q8N697};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64409;
CC Evidence={ECO:0000250|UniProtKB:Q8N697};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(out) + L-alanyl-gamma-D-glutamyl-meso-
CC diaminoheptanedioate(out) = H(+)(in) + L-alanyl-gamma-D-glutamyl-
CC meso-diaminoheptanedioate(in); Xref=Rhea:RHEA:64412,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:61401;
CC Evidence={ECO:0000250|UniProtKB:Q8N697};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64413;
CC Evidence={ECO:0000250|UniProtKB:Q8N697};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycyl-sarcosine(out) + H(+)(out) = glycyl-sarcosine(in) +
CC H(+)(in); Xref=Rhea:RHEA:64396, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:155838; Evidence={ECO:0000250|UniProtKB:Q8N697};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64397;
CC Evidence={ECO:0000250|UniProtKB:Q8N697};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=carnosine(out) + H(+)(out) = carnosine(in) + H(+)(in);
CC Xref=Rhea:RHEA:64404, ChEBI:CHEBI:15378, ChEBI:CHEBI:57485;
CC Evidence={ECO:0000250|UniProtKB:Q8N697};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64405;
CC Evidence={ECO:0000250|UniProtKB:Q8N697};
CC -!- SUBUNIT: Interacts with TASL; leading to TASL recruitment to
CC endolysosome. {ECO:0000250|UniProtKB:Q8N697}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q8N697};
CC Multi-pass membrane protein {ECO:0000255}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q8N697}; Multi-pass membrane protein
CC {ECO:0000255}. Early endosome membrane {ECO:0000250|UniProtKB:Q91W98};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A6QQL0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A6QQL0-2; Sequence=VSP_034050, VSP_034051;
CC -!- TISSUE SPECIFICITY: Expressed in retinal fragment epithelium (RPE) and
CC neural retina. {ECO:0000269|PubMed:14567629}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Proton-
CC dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BC149430; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; BC149430; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC149880; AAI49881.1; -; mRNA.
DR RefSeq; NP_001095397.2; NM_001101927.2. [A6QQL0-1]
DR AlphaFoldDB; A6QQL0; -.
DR SMR; A6QQL0; -.
DR STRING; 9913.ENSBTAP00000012083; -.
DR PaxDb; A6QQL0; -.
DR PRIDE; A6QQL0; -.
DR Ensembl; ENSBTAT00000053948; ENSBTAP00000050067; ENSBTAG00000009167. [A6QQL0-2]
DR Ensembl; ENSBTAT00000086426; ENSBTAP00000065627; ENSBTAG00000009167. [A6QQL0-1]
DR GeneID; 510499; -.
DR KEGG; bta:510499; -.
DR CTD; 121260; -.
DR VEuPathDB; HostDB:ENSBTAG00000009167; -.
DR eggNOG; KOG1237; Eukaryota.
DR GeneTree; ENSGT00940000159361; -.
DR InParanoid; A6QQL0; -.
DR OMA; QMMGVWF; -.
DR OrthoDB; 365203at2759; -.
DR Proteomes; UP000009136; Chromosome 17.
DR Bgee; ENSBTAG00000009167; Expressed in pons and 104 other tissues.
DR ExpressionAtlas; A6QQL0; baseline and differential.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0036020; C:endolysosome membrane; ISS:UniProtKB.
DR GO; GO:0031303; C:integral component of endosome membrane; IEA:Ensembl.
DR GO; GO:1905103; C:integral component of lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0071916; F:dipeptide transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005290; F:L-histidine transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015333; F:peptide:proton symporter activity; ISS:UniProtKB.
DR GO; GO:0015647; F:peptidoglycan transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0140206; P:dipeptide import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0015817; P:histidine transport; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0089708; P:L-histidine transmembrane export from vacuole; IEA:Ensembl.
DR GO; GO:0033023; P:mast cell homeostasis; ISS:UniProtKB.
DR GO; GO:0015835; P:peptidoglycan transport; ISS:UniProtKB.
DR GO; GO:0045089; P:positive regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:0070430; P:positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway; ISS:UniProtKB.
DR GO; GO:0070434; P:positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway; ISS:UniProtKB.
DR GO; GO:0034157; P:positive regulation of toll-like receptor 7 signaling pathway; ISS:UniProtKB.
DR GO; GO:0034161; P:positive regulation of toll-like receptor 8 signaling pathway; ISS:UniProtKB.
DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0048302; P:regulation of isotype switching to IgG isotypes; ISS:UniProtKB.
DR GO; GO:0070424; P:regulation of nucleotide-binding oligomerization domain containing signaling pathway; ISS:UniProtKB.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR000109; POT_fam.
DR InterPro; IPR018456; PTR2_symporter_CS.
DR PANTHER; PTHR11654; PTHR11654; 1.
DR Pfam; PF00854; PTR2; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS01023; PTR2_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Endosome; Immunity; Innate immunity; Lysosome;
KW Membrane; Peptide transport; Phosphoprotein; Protein transport;
KW Reference proteome; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..566
FT /note="Solute carrier family 15 member 4"
FT /id="PRO_0000338598"
FT TRANSMEM 38..58
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 65..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 94..114
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 146..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 187..207
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 215..235
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 311..331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 356..376
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 398..418
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 452..472
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 483..503
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 528..548
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 291
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N697"
FT VAR_SEQ 275..318
FT /note="EGIGVFQQSSKHSLFDSCKMSRGGPFPEDKVEDVKALVKIVPVF -> DFGK
FT QEAGPREGEDHQPDHRKRRVLRRGLAHLVAGPAVRADRCQ (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_034050"
FT VAR_SEQ 319..566
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_034051"
SQ SEQUENCE 566 AA; 61380 MW; 437361975646548E CRC64;
MEGAGDERAP LLGARRTAFA GRRAACAAVL LTELLERAAF YGVTANLVLF LNGTAFGWEG
AEASQALLLF MGLTYLVSPF GGWLADARLG RARAILLSLA LYLLGMLAFP LLAAPATRSA
LCGAPGPTNV RNCSAPPCTD TPTRYCAPAV LSALALVGLG VGAVKANITP FGADQVKDRG
PEATRRFFNW FYWSINLGAI VSLGGIAYIQ QNVSFVTGYA IPAVCIGVAF VVFLCGQTFF
ITKPPDGSAF TDMFRILVYS CRPQKRIREH SPSGEGIGVF QQSSKHSLFD SCKMSRGGPF
PEDKVEDVKA LVKIVPVFLA LIPYWTVYFQ MQTTYVLQSL HLKIPEISSI TTNPHTFPAA
WLTMFDAVLI LLLIPLKDKL VDPILKRNGL LPSSLKRIAV GMFFVMCSAF AAGILESKRL
DLVKEKTINQ TIGNVVYYAA DLPIWWQVPQ YVLIGVSEIF ASIAGLEFAY SAAPKSMQSA
IMGLFFFFSG VGSFVGSGLL ALVSLKAIGW MSSHTDFGNI NGCYLNYYFF LLAAIQGATL
LLFLIVSVKY DRQRSRANGT PASRRT
