S15A3_HUMAN
ID S15A3_HUMAN Reviewed; 581 AA.
AC Q8IY34; Q9P2X9;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Solute carrier family 15 member 3 {ECO:0000305};
DE AltName: Full=Osteoclast transporter {ECO:0000303|Ref.2};
DE AltName: Full=Peptide transporter 3 {ECO:0000303|Ref.1};
DE AltName: Full=Peptide/histidine transporter 2 {ECO:0000303|PubMed:31073693};
GN Name=SLC15A3 {ECO:0000312|HGNC:HGNC:18068};
GN Synonyms=OCTP {ECO:0000303|Ref.2}, PHT2 {ECO:0000303|PubMed:31073693},
GN PTR3 {ECO:0000303|Ref.1};
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].
RC TISSUE=Placenta;
RA Ishiabshi K., Imai M.;
RT "Molecular cloning of a new member of peptide transporter.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Synovial fluid;
RA Yamane S., Toyosaki-Maeda T., Tsuruta Y., Suzuki R., Ochi T.;
RT "Cloning of a novel gene of peptide transporter from human osteoclast.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PHE-349.
RC TISSUE=Blood, and Pancreas;
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 [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Placenta;
RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x;
RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H.,
RA Elsaesser H.-P., Mann M., Hasilik A.;
RT "Integral and associated lysosomal membrane proteins.";
RL Traffic 8:1676-1686(2007).
RN [6]
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).
CC -!- FUNCTION: Proton-coupled amino-acid transporter that transports free
CC histidine and certain di- and tripeptides, and is involved in innate
CC immune response (By similarity). Also able to transport carnosine
CC (PubMed:31073693). Involved in the detection of microbial pathogens by
CC toll-like receptors (TLRs) and NOD-like receptors (NLRs), probably by
CC 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 (By
CC similarity). {ECO:0000250|UniProtKB:Q8BPX9,
CC ECO:0000269|PubMed:31073693}.
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:Q924V4};
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:Q924V4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64393;
CC Evidence={ECO:0000250|UniProtKB:Q924V4};
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:Q8BPX9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64409;
CC Evidence={ECO:0000250|UniProtKB:Q8BPX9};
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 -!- INTERACTION:
CC Q8IY34; P49639: HOXA1; NbExp=3; IntAct=EBI-12179023, EBI-740785;
CC Q8IY34; P59991: KRTAP12-2; NbExp=4; IntAct=EBI-12179023, EBI-10176379;
CC Q8IY34; Q3LHN2: KRTAP19-2; NbExp=3; IntAct=EBI-12179023, EBI-12196745;
CC Q8IY34; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-12179023, EBI-3958099;
CC Q8IY34; Q9BYQ0: KRTAP9-8; NbExp=3; IntAct=EBI-12179023, EBI-11958364;
CC Q8IY34; Q99750: MDFI; NbExp=3; IntAct=EBI-12179023, EBI-724076;
CC Q8IY34; Q9HC29: NOD2; NbExp=2; IntAct=EBI-12179023, EBI-7445625;
CC Q8IY34; Q8N697: SLC15A4; NbExp=2; IntAct=EBI-12179023, EBI-4319594;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:17897319};
CC Multi-pass membrane protein {ECO:0000255}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q8BPX9}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Proton-
CC dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB020598; BAA93432.1; -; mRNA.
DR EMBL; AF135600; AAQ13565.1; -; mRNA.
DR EMBL; AP003721; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC037974; AAH37974.1; -; mRNA.
DR CCDS; CCDS7998.1; -.
DR RefSeq; NP_057666.1; NM_016582.2.
DR AlphaFoldDB; Q8IY34; -.
DR SMR; Q8IY34; -.
DR BioGRID; 119447; 232.
DR DIP; DIP-60838N; -.
DR IntAct; Q8IY34; 8.
DR STRING; 9606.ENSP00000227880; -.
DR TCDB; 2.A.17.3.9; the proton-dependent oligopeptide transporter (pot/ptr) family.
DR GlyGen; Q8IY34; 6 sites.
DR PhosphoSitePlus; Q8IY34; -.
DR BioMuta; SLC15A3; -.
DR DMDM; 296452890; -.
DR jPOST; Q8IY34; -.
DR MassIVE; Q8IY34; -.
DR MaxQB; Q8IY34; -.
DR PaxDb; Q8IY34; -.
DR PeptideAtlas; Q8IY34; -.
DR PRIDE; Q8IY34; -.
DR ProteomicsDB; 71102; -.
DR Antibodypedia; 50766; 103 antibodies from 16 providers.
DR DNASU; 51296; -.
DR Ensembl; ENST00000227880.8; ENSP00000227880.2; ENSG00000110446.12.
DR GeneID; 51296; -.
DR KEGG; hsa:51296; -.
DR MANE-Select; ENST00000227880.8; ENSP00000227880.2; NM_016582.3; NP_057666.1.
DR UCSC; uc001nqn.3; human.
DR CTD; 51296; -.
DR DisGeNET; 51296; -.
DR GeneCards; SLC15A3; -.
DR HGNC; HGNC:18068; SLC15A3.
DR HPA; ENSG00000110446; Low tissue specificity.
DR MIM; 610408; gene.
DR neXtProt; NX_Q8IY34; -.
DR OpenTargets; ENSG00000110446; -.
DR PharmGKB; PA134919658; -.
DR VEuPathDB; HostDB:ENSG00000110446; -.
DR eggNOG; KOG1237; Eukaryota.
DR GeneTree; ENSGT00940000161889; -.
DR HOGENOM; CLU_009313_6_1_1; -.
DR InParanoid; Q8IY34; -.
DR OMA; FPPINRI; -.
DR OrthoDB; 365203at2759; -.
DR PhylomeDB; Q8IY34; -.
DR TreeFam; TF330897; -.
DR PathwayCommons; Q8IY34; -.
DR Reactome; R-HSA-427975; Proton/oligopeptide cotransporters.
DR SignaLink; Q8IY34; -.
DR BioGRID-ORCS; 51296; 13 hits in 1072 CRISPR screens.
DR ChiTaRS; SLC15A3; human.
DR GenomeRNAi; 51296; -.
DR Pharos; Q8IY34; Tbio.
DR PRO; PR:Q8IY34; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8IY34; protein.
DR Bgee; ENSG00000110446; Expressed in granulocyte and 114 other tissues.
DR ExpressionAtlas; Q8IY34; baseline and differential.
DR Genevisible; Q8IY34; HS.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0071916; F:dipeptide transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015333; F:peptide:proton symporter activity; TAS:Reactome.
DR GO; GO:0015647; F:peptidoglycan transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0140206; P:dipeptide import across plasma membrane; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0015835; P:peptidoglycan transport; ISS:UniProtKB.
DR GO; GO:0070434; P:positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR000109; POT_fam.
DR PANTHER; PTHR11654; PTHR11654; 1.
DR Pfam; PF00854; PTR2; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
PE 1: Evidence at protein level;
KW Endosome; Glycoprotein; Immunity; Innate immunity; Lysosome; Membrane;
KW Peptide transport; Protein transport; Reference proteome; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..581
FT /note="Solute carrier family 15 member 3"
FT /id="PRO_0000295912"
FT TRANSMEM 38..58
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 76..96
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..175
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 200..220
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..252
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 310..330
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 369..389
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 411..431
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 458..478
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 497..517
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 540..560
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 61
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 223
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 356
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 439
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 349
FT /note="I -> F (in dbSNP:rs17855607)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_034592"
SQ SEQUENCE 581 AA; 63560 MW; 56768D2963DB13D4 CRC64;
MPAPRAREQP RVPGERQPLL PRGARGPRRW RRAAGAAVLL VEMLERAAFF GVTANLVLYL
NSTNFNWTGE QATRAALVFL GASYLLAPVG GWLADVYLGR YRAVALSLLL YLAASGLLPA
TAFPDGRSSF CGEMPASPLG PACPSAGCPR SSPSPYCAPV LYAGLLLLGL AASSVRSNLT
SFGADQVMDL GRDATRRFFN WFYWSINLGA VLSLLVVAFI QQNISFLLGY SIPVGCVGLA
FFIFLFATPV FITKPPMGSQ VSSMLKLALQ NCCPQLWQRH SARDRQCARV LADERSPQPG
ASPQEDIANF QVLVKILPVM VTLVPYWMVY FQMQSTYVLQ GLHLHIPNIF PANPANISVA
LRAQGSSYTI PEAWLLLANV VVVLILVPLK DRLIDPLLLR CKLLPSALQK MALGMFFGFT
SVIVAGVLEM ERLHYIHHNE TVSQQIGEVL YNAAPLSIWW QIPQYLLIGI SEIFASIPGL
EFAYSEAPRS MQGAIMGIFF CLSGVGSLLG SSLVALLSLP GGWLHCPKDF GNINNCRMDL
YFFLLAGIQA VTALLFVWIA GRYERASQGP ASHSRFSRDR G
