S15A4_HUMAN
ID S15A4_HUMAN Reviewed; 577 AA.
AC Q8N697; A6H8Y9; B3KTK1; Q71M34; Q7Z5F8; Q8TAH0;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Solute carrier family 15 member 4 {ECO:0000305};
DE AltName: Full=Peptide transporter 4 {ECO:0000303|Ref.2};
DE AltName: Full=Peptide/histidine transporter 1 {ECO:0000303|PubMed:16289537, ECO:0000303|PubMed:29224352};
DE Short=hPHT1 {ECO:0000303|PubMed:16289537, ECO:0000303|PubMed:29224352};
GN Name=SLC15A4 {ECO:0000312|HGNC:HGNC:23090};
GN Synonyms=PHT1 {ECO:0000303|PubMed:16289537, ECO:0000303|PubMed:29224352},
GN PTR4 {ECO:0000303|Ref.2}; ORFNames=FP12591;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Guo J.H., Yu L.;
RT "Cloning of a human novel gene with product of peptide/histidine.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Mondon P., Bouayadi K., Fournier J., Saubusse P., Lablie C.;
RT "Molecular cloning of a human brain peptide/histidine transporter, PTR4.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=11741232; DOI=10.1208/ps020216;
RA Botka C.W., Wittig T.W., Graul R.C., Nielsen C.U., Higaki K., Amidon G.L.,
RA Sadee W.;
RT "Human proton/oligopeptide transporter (POT) genes: identification of
RT putative human genes using bioinformatics.";
RL AAPS PharmSci 2:E16-E16(2000).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=11741260; DOI=10.1208/ps030109;
RA Herrera-Ruiz D., Wang Q., Gudmundsson O.S., Cook T.J., Smith R.L.,
RA Faria T.N., Knipp G.T.;
RT "Spatial expression patterns of peptide transporters in the human and rat
RT gastrointestinal tracts, Caco-2 in vitro cell culture model, and multiple
RT human tissues.";
RL AAPS PharmSci 3:E9-E9(2001).
RN [9]
RP FUNCTION, TRANSPORTER ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=16289537; DOI=10.1016/j.ejps.2005.09.014;
RA Bhardwaj R.K., Herrera-Ruiz D., Eltoukhy N., Saad M., Knipp G.T.;
RT "The functional evaluation of human peptide/histidine transporter 1 (hPHT1)
RT in transiently transfected COS-7 cells.";
RL Eur. J. Pharm. Sci. 27:533-542(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP GLU-465.
RX PubMed=25238095; DOI=10.1016/j.immuni.2014.08.011;
RA Kobayashi T., Shimabukuro-Demoto S., Yoshida-Sugitani R.,
RA Furuyama-Tanaka K., Karyu H., Sugiura Y., Shimizu Y., Hosaka T., Goto M.,
RA Kato N., Okamura T., Suematsu M., Yokoyama S., Toyama-Sorimachi N.;
RT "The histidine transporter SLC15A4 coordinates mTOR-dependent inflammatory
RT responses and pathogenic antibody production.";
RL Immunity 41:375-388(2014).
RN [12]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF 14-LEU-LEU-15 AND 318-LEU-VAL-319.
RX PubMed=29224352; DOI=10.1021/acs.molpharmaceut.7b00728;
RA Song F., Hu Y., Wang Y., Smith D.E., Jiang H.;
RT "Functional characterization of human peptide/histidine transporter 1 in
RT stably transfected MDCK Cells.";
RL Mol. Pharm. 15:385-393(2018).
RN [13]
RP FUNCTION, AND TRANSPORTER ACTIVITY.
RX PubMed=31073693; DOI=10.1007/s00726-019-02739-w;
RA Oppermann H., Heinrich M., Birkemeyer C., Meixensberger J., Gaunitz F.;
RT "The proton-coupled oligopeptide transporters PEPT2, PHT1 and PHT2 mediate
RT the uptake of carnosine in glioblastoma cells.";
RL Amino Acids 51:999-1008(2019).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TASL, AND MUTAGENESIS OF
RP 14-LEU-LEU-15; GLU-44; GLU-47 AND GLU-465.
RX PubMed=32433612; DOI=10.1038/s41586-020-2282-0;
RA Heinz L.X., Lee J., Kapoor U., Kartnig F., Sedlyarov V., Papakostas K.,
RA Cesar-Razquin A., Essletzbichler P., Goldmann U., Stefanovic A.,
RA Bigenzahn J.W., Scorzoni S., Pizzagalli M.D., Bensimon A., Mueller A.C.,
RA King F.J., Li J., Girardi E., Mbow M.L., Whitehurst C.E., Rebsamen M.,
RA Superti-Furga G.;
RT "TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9.";
RL Nature 581:316-322(2020).
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 (PubMed:16289537, PubMed:25238095, PubMed:29224352).
CC Able to transport a variety of di- and tripeptides, including carnosine
CC and some peptidoglycans (PubMed:29224352, PubMed:31073693). Transporter
CC activity is pH-dependent and maximized in the acidic lysosomal
CC environment (By similarity). Involved in the detection of microbial
CC pathogens by toll-like receptors (TLRs) and NOD-like receptors (NLRs),
CC probably by mediating transport of bacterial peptidoglycans across the
CC endolysosomal membrane: catalyzes the transport of certain bacterial
CC peptidoglycans, such as muramyl dipeptide (MDP), the NOD2 ligand, and
CC L-alanyl-gamma-D-glutamyl-meso-2,6-diaminoheptanedioate (tri-DAP), the
CC NOD1 ligand (PubMed:25238095, PubMed:29224352). Required for TLR7, TLR8
CC and TLR9-mediated type I interferon (IFN-I) productions in plasmacytoid
CC dendritic cells (pDCs) (PubMed:25238095). Independently of its
CC transporter activity, also promotes the recruitment of innate immune
CC adapter TASL to endolysosome downstream of TLR7, TLR8 and TLR9: TASL
CC recruitment leads to the specific recruitment and activation of IRF5
CC (PubMed:32433612). Required for isotype class switch recombination to
CC IgG2c isotype in response to TLR9 stimulation (By similarity). Required
CC for mast cell secretory-granule homeostasis by limiting mast cell
CC functions and inflammatory responses (By similarity).
CC {ECO:0000250|UniProtKB:O09014, ECO:0000250|UniProtKB:Q91W98,
CC ECO:0000269|PubMed:16289537, ECO:0000269|PubMed:25238095,
CC ECO:0000269|PubMed:29224352, ECO:0000269|PubMed:31073693,
CC ECO:0000269|PubMed:32433612}.
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:0000269|PubMed:16289537, ECO:0000269|PubMed:25238095};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37048;
CC Evidence={ECO:0000269|PubMed:16289537, ECO:0000269|PubMed:25238095};
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:0000269|PubMed:29224352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64393;
CC Evidence={ECO:0000269|PubMed:29224352};
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:0000269|PubMed:29224352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64401;
CC Evidence={ECO:0000269|PubMed:29224352};
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:0000269|PubMed:29224352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64409;
CC Evidence={ECO:0000269|PubMed:29224352};
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:0000269|PubMed:25238095, ECO:0000269|PubMed:29224352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64413;
CC Evidence={ECO:0000269|PubMed:25238095, ECO:0000269|PubMed:29224352};
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:0000269|PubMed:29224352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64397;
CC Evidence={ECO:0000269|PubMed:29224352};
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:0000269|PubMed:31073693};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64405;
CC Evidence={ECO:0000269|PubMed:31073693};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=16.3 uM for L-histidine {ECO:0000269|PubMed:29224352};
CC KM=1690 uM for GlySar dipeptide {ECO:0000269|PubMed:29224352};
CC Vmax=1317 pmol/min/mg enzyme with L-histidine as substrate
CC {ECO:0000269|PubMed:29224352};
CC Vmax=100 pmol/min/mg enzyme with GlySar dipeptide as substrate
CC {ECO:0000269|PubMed:29224352};
CC -!- SUBUNIT: Interacts with TASL; leading to TASL recruitment to
CC endolysosome. {ECO:0000269|PubMed:32433612}.
CC -!- INTERACTION:
CC Q8N697; Q9HC29: NOD2; NbExp=2; IntAct=EBI-4319594, EBI-7445625;
CC Q8N697; Q8IY34: SLC15A3; NbExp=2; IntAct=EBI-4319594, EBI-12179023;
CC Q8N697; Q9HAI6: TASL; NbExp=13; IntAct=EBI-4319594, EBI-21895669;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:25238095,
CC ECO:0000269|PubMed:29224352, ECO:0000269|PubMed:32433612}; Multi-pass
CC membrane protein {ECO:0000255}. Endosome membrane
CC {ECO:0000269|PubMed:32433612}; 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=Q8N697-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N697-2; Sequence=VSP_034052;
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle. Moderately
CC expressed in kidney, liver, and heart. Weakly expressed in colon and
CC brain. Expressed in low levels throughout the gastrointestinal tract
CC and in Caco-2 cells. Expressed in retinal fragment epithelium (RPE) and
CC neural retina. Expressed in small intestine, stomach, duodenum,
CC jejunum, ileum and colon. {ECO:0000269|PubMed:11741232,
CC ECO:0000269|PubMed:11741260, ECO:0000269|PubMed:16289537}.
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=AAI46804.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAK95565.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAQ04807.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY050629; AAK95565.1; ALT_FRAME; mRNA.
DR EMBL; AY038999; AAK72099.1; -; mRNA.
DR EMBL; AF461893; AAQ04807.1; ALT_FRAME; mRNA.
DR EMBL; AK095717; BAG53113.1; -; mRNA.
DR EMBL; CH471054; EAW98494.1; -; Genomic_DNA.
DR EMBL; BC028394; AAH28394.2; -; mRNA.
DR EMBL; BC146803; AAI46804.1; ALT_FRAME; mRNA.
DR CCDS; CCDS9264.1; -. [Q8N697-1]
DR RefSeq; NP_663623.1; NM_145648.3. [Q8N697-1]
DR AlphaFoldDB; Q8N697; -.
DR SMR; Q8N697; -.
DR BioGRID; 125714; 34.
DR DIP; DIP-60839N; -.
DR IntAct; Q8N697; 51.
DR MINT; Q8N697; -.
DR STRING; 9606.ENSP00000266771; -.
DR TCDB; 2.A.17.3.11; the proton-dependent oligopeptide transporter (pot/ptr) family.
DR GlyGen; Q8N697; 1 site.
DR iPTMnet; Q8N697; -.
DR PhosphoSitePlus; Q8N697; -.
DR SwissPalm; Q8N697; -.
DR BioMuta; SLC15A4; -.
DR DMDM; 74751048; -.
DR EPD; Q8N697; -.
DR jPOST; Q8N697; -.
DR MassIVE; Q8N697; -.
DR MaxQB; Q8N697; -.
DR PaxDb; Q8N697; -.
DR PeptideAtlas; Q8N697; -.
DR PRIDE; Q8N697; -.
DR ProteomicsDB; 72148; -. [Q8N697-1]
DR ProteomicsDB; 72149; -. [Q8N697-2]
DR Antibodypedia; 3084; 68 antibodies from 17 providers.
DR DNASU; 121260; -.
DR Ensembl; ENST00000266771.10; ENSP00000266771.5; ENSG00000139370.12. [Q8N697-1]
DR GeneID; 121260; -.
DR KEGG; hsa:121260; -.
DR MANE-Select; ENST00000266771.10; ENSP00000266771.5; NM_145648.4; NP_663623.1.
DR UCSC; uc001uhu.3; human. [Q8N697-1]
DR CTD; 121260; -.
DR DisGeNET; 121260; -.
DR GeneCards; SLC15A4; -.
DR HGNC; HGNC:23090; SLC15A4.
DR HPA; ENSG00000139370; Low tissue specificity.
DR MIM; 615806; gene.
DR neXtProt; NX_Q8N697; -.
DR OpenTargets; ENSG00000139370; -.
DR PharmGKB; PA134928948; -.
DR VEuPathDB; HostDB:ENSG00000139370; -.
DR eggNOG; KOG1237; Eukaryota.
DR GeneTree; ENSGT00940000159361; -.
DR HOGENOM; CLU_009313_6_1_1; -.
DR InParanoid; Q8N697; -.
DR OMA; QMMGVWF; -.
DR OrthoDB; 365203at2759; -.
DR PhylomeDB; Q8N697; -.
DR TreeFam; TF330897; -.
DR PathwayCommons; Q8N697; -.
DR Reactome; R-HSA-427975; Proton/oligopeptide cotransporters.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q8N697; -.
DR BioGRID-ORCS; 121260; 9 hits in 1081 CRISPR screens.
DR ChiTaRS; SLC15A4; human.
DR GenomeRNAi; 121260; -.
DR Pharos; Q8N697; Tbio.
DR PRO; PR:Q8N697; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8N697; protein.
DR Bgee; ENSG00000139370; Expressed in pancreatic ductal cell and 189 other tissues.
DR ExpressionAtlas; Q8N697; baseline and differential.
DR Genevisible; Q8N697; HS.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0036020; C:endolysosome membrane; IDA:UniProtKB.
DR GO; GO:0031303; C:integral component of endosome membrane; IEA:Ensembl.
DR GO; GO:1905103; C:integral component of lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0071916; F:dipeptide transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005290; F:L-histidine transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015333; F:peptide:proton symporter activity; IDA:UniProtKB.
DR GO; GO:0015647; F:peptidoglycan transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0140206; P:dipeptide import across plasma membrane; IDA: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:0006811; P:ion transport; TAS:Reactome.
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; IDA:UniProtKB.
DR GO; GO:0045089; P:positive regulation of innate immune response; IDA: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; IMP:UniProtKB.
DR GO; GO:0034161; P:positive regulation of toll-like receptor 8 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; IMP: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 1: Evidence at protein 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..577
FT /note="Solute carrier family 15 member 4"
FT /id="PRO_0000338599"
FT TRANSMEM 49..69
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 76..96
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 105..125
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 158..178
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 194..214
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..242
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 318..338
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 363..383
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 405..425
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 459..479
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 490..510
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 535..555
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 279
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91W98"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..337
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15498874"
FT /id="VSP_034052"
FT VARIANT 239
FT /note="V -> A (in dbSNP:rs33990080)"
FT /id="VAR_051611"
FT MUTAGEN 14..15
FT /note="LL->AA: Abolished localization to the lysosome
FT membrane and promotes relocalization to the plasma
FT membrane; when associated with 318-A-A-319. Does not affect
FT interaction with TASL."
FT /evidence="ECO:0000269|PubMed:29224352,
FT ECO:0000269|PubMed:32433612"
FT MUTAGEN 44
FT /note="E->A: Does not affect interaction with TASL."
FT /evidence="ECO:0000269|PubMed:32433612"
FT MUTAGEN 47
FT /note="E->A: Does not affect interaction with TASL."
FT /evidence="ECO:0000269|PubMed:32433612"
FT MUTAGEN 318..319
FT /note="LV->AA: Abolished localization to the lysosome
FT membrane and promotes relocalization to the plasma
FT membrane; when associated with 14-A-A-15."
FT /evidence="ECO:0000269|PubMed:29224352"
FT MUTAGEN 465
FT /note="E->K: Abolished transmembrane transporter activity.
FT Abolished interaction with TASL."
FT /evidence="ECO:0000269|PubMed:25238095,
FT ECO:0000269|PubMed:32433612"
FT CONFLICT 24
FT /note="A -> T (in Ref. 6; AAI46804)"
FT /evidence="ECO:0000305"
FT CONFLICT 34..35
FT /note="RA -> LL (in Ref. 1; AAK95565)"
FT /evidence="ECO:0000305"
FT CONFLICT 44
FT /note="E -> G (in Ref. 6; AAI46804)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 577 AA; 62034 MW; 701111038C752E70 CRC64;
MEGSGGGAGE RAPLLGARRA AAAAAAAGAF AGRRAACGAV LLTELLERAA FYGITSNLVL
FLNGAPFCWE GAQASEALLL FMGLTYLGSP FGGWLADARL GRARAILLSL ALYLLGMLAF
PLLAAPATRA ALCGSARLLN CTAPGPDAAA RCCSPATFAG LVLVGLGVAT VKANITPFGA
DQVKDRGPEA TRRFFNWFYW SINLGAILSL GGIAYIQQNV SFVTGYAIPT VCVGLAFVVF
LCGQSVFITK PPDGSAFTDM FKILTYSCCS QKRSGERQSN GEGIGVFQQS SKQSLFDSCK
MSHGGPFTEE KVEDVKALVK IVPVFLALIP YWTVYFQMQT TYVLQSLHLR IPEISNITTT
PHTLPAAWLT MFDAVLILLL IPLKDKLVDP ILRRHGLLPS SLKRIAVGMF FVMCSAFAAG
ILESKRLNLV KEKTINQTIG NVVYHAADLS LWWQVPQYLL IGISEIFASI AGLEFAYSAA
PKSMQSAIMG LFFFFSGVGS FVGSGLLALV SIKAIGWMSS HTDFGNINGC YLNYYFFLLA
AIQGATLLLF LIISVKYDHH RDHQRSRANG VPTSRRA
