S15A2_MOUSE
ID S15A2_MOUSE Reviewed; 729 AA.
AC Q9ES07;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Solute carrier family 15 member 2 {ECO:0000305};
DE AltName: Full=Kidney H(+)/peptide cotransporter {ECO:0000250|UniProtKB:P46029};
DE AltName: Full=Oligopeptide transporter, kidney isoform {ECO:0000250|UniProtKB:P46029};
DE AltName: Full=Peptide transporter 2 {ECO:0000303|PubMed:21183079};
GN Name=Slc15a2 {ECO:0000312|MGI:MGI:1890457};
GN Synonyms=Pept2 {ECO:0000303|PubMed:21183079};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=129/SvEvTacfBr;
RX PubMed=11027540; DOI=10.1006/bbrc.2000.3546;
RA Rubio-Aliaga I., Boll M., Daniel H.;
RT "Cloning and characterization of the gene encoding the mouse peptide
RT transporter PEPT2.";
RL Biochem. Biophys. Res. Commun. 276:734-741(2000).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9 AND THR-12, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [3]
RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE,
RP AND TISSUE SPECIFICITY.
RX PubMed=29784761; DOI=10.4049/jimmunol.1800210;
RA Hu Y., Song F., Jiang H., Nunez G., Smith D.E.;
RT "SLC15A2 and SLC15A4 mediate the transport of bacterially derived
RT di/tripeptides to enhance the nucleotide-binding oligomerization domain-
RT dependent immune response in mouse bone marrow-derived macrophages.";
RL J. Immunol. 201:652-662(2018).
CC -!- FUNCTION: Proton-coupled amino-acid transporter that transports
CC oligopeptides of 2 to 4 amino acids with a preference for dipeptides
CC (PubMed:11027540). Transports the dipeptide-like aminopeptidase
CC inhibitor bestatin (By similarity). Can also transport the
CC aminocephalosporin antibiotic cefadroxil (By similarity). Also able to
CC transport carnosine (By similarity). Involved in innate immunity by
CC promoting the detection of microbial pathogens by NOD-like receptors
CC (NLRs) (PubMed:29784761). Probably acts by mediating transport of
CC bacterial peptidoglycans across the plasma membrane: catalyzes the
CC transport of certain bacterial peptidoglycans, such as muramyl
CC dipeptide (MDP), the NOD2 ligand (PubMed:29784761).
CC {ECO:0000250|UniProtKB:P46029, ECO:0000250|UniProtKB:Q16348,
CC ECO:0000250|UniProtKB:Q63424, ECO:0000269|PubMed:11027540,
CC ECO:0000269|PubMed:29784761}.
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:11027540, ECO:0000269|PubMed:29784761};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64393;
CC Evidence={ECO:0000269|PubMed:11027540, ECO:0000269|PubMed:29784761};
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:29784761};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64409;
CC Evidence={ECO:0000269|PubMed:29784761};
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:Q16348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64405;
CC Evidence={ECO:0000250|UniProtKB:Q16348};
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:Q16348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64397;
CC Evidence={ECO:0000250|UniProtKB:Q16348};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=56.6 uM for D-Phe-Ala (at pH 6.0) {ECO:0000269|PubMed:11027540};
CC pH dependence:
CC Optimum pH is 6.0 or lower. {ECO:0000269|PubMed:11027540};
CC -!- SUBUNIT: Interacts (via extracellular domain region) with trypsin.
CC {ECO:0000250|UniProtKB:Q63424}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:29784761,
CC ECO:0000305|PubMed:11027540}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney brush border cells (at protein
CC level) (PubMed:11027540). Highly expressed in macrophages
CC (PubMed:29784761). {ECO:0000269|PubMed:11027540,
CC ECO:0000269|PubMed:29784761}.
CC -!- DOMAIN: The extracellular domain (ECD) region specifically binds
CC trypsin. {ECO:0000250|UniProtKB:Q63424}.
CC -!- DISRUPTION PHENOTYPE: Decreased dipeptide uptake in bone marrow
CC (PubMed:29784761). Decreased cytokine expression in response to LPS
CC stimulation (PubMed:29784761). {ECO:0000269|PubMed:29784761}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Proton-
CC dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.
CC {ECO:0000305}.
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DR EMBL; AF257711; AAG25926.1; -; Genomic_DNA.
DR PIR; JC7501; JC7501.
DR AlphaFoldDB; Q9ES07; -.
DR SMR; Q9ES07; -.
DR STRING; 10090.ENSMUSP00000023616; -.
DR ChEMBL; CHEMBL2073678; -.
DR TCDB; 2.A.17.4.4; the proton-dependent oligopeptide transporter (pot/ptr) family.
DR GlyGen; Q9ES07; 4 sites.
DR iPTMnet; Q9ES07; -.
DR PhosphoSitePlus; Q9ES07; -.
DR SwissPalm; Q9ES07; -.
DR jPOST; Q9ES07; -.
DR MaxQB; Q9ES07; -.
DR PaxDb; Q9ES07; -.
DR PRIDE; Q9ES07; -.
DR ProteomicsDB; 253352; -.
DR MGI; MGI:1890457; Slc15a2.
DR eggNOG; KOG1237; Eukaryota.
DR InParanoid; Q9ES07; -.
DR PhylomeDB; Q9ES07; -.
DR Reactome; R-MMU-427975; Proton/oligopeptide cotransporters.
DR ChiTaRS; Slc15a2; mouse.
DR PRO; PR:Q9ES07; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9ES07; protein.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0071916; F:dipeptide transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0015334; F:high-affinity oligopeptide transmembrane transporter activity; IDA:MGI.
DR GO; GO:0015333; F:peptide:proton symporter activity; ISO:MGI.
DR GO; GO:0140206; P:dipeptide import across plasma membrane; IMP:UniProtKB.
DR GO; GO:0042938; P:dipeptide transport; IMP:ARUK-UCL.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006857; P:oligopeptide transport; IDA:MGI.
DR GO; GO:0015835; P:peptidoglycan transport; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0070424; P:regulation of nucleotide-binding oligomerization domain containing signaling pathway; IMP:UniProtKB.
DR GO; GO:0070293; P:renal absorption; IMP:ARUK-UCL.
DR GO; GO:0042908; P:xenobiotic transport; IMP:ARUK-UCL.
DR Gene3D; 1.20.1250.20; -; 2.
DR InterPro; IPR029028; Alpha/beta_knot_MTases.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR004768; Oligopep_transport.
DR InterPro; IPR000109; POT_fam.
DR InterPro; IPR018456; PTR2_symporter_CS.
DR PANTHER; PTHR11654; PTHR11654; 1.
DR Pfam; PF00854; PTR2; 2.
DR SUPFAM; SSF103473; SSF103473; 1.
DR SUPFAM; SSF75217; SSF75217; 1.
DR TIGRFAMs; TIGR00926; 2A1704; 1.
DR PROSITE; PS01022; PTR2_1; 1.
DR PROSITE; PS01023; PTR2_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Immunity; Innate immunity; Membrane;
KW Peptide transport; Phosphoprotein; Protein transport; Reference proteome;
KW Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..729
FT /note="Solute carrier family 15 member 2"
FT /id="PRO_0000064309"
FT TOPO_DOM 1..57
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 58..78
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 79..87
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 109..113
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 135..139
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 140..160
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 161..183
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 184..204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 205..217
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 218..238
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 239..295
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 296..316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 317..343
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 344..364
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 365..380
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 381..401
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 402..611
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 612..632
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 633..643
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 644..664
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 665..674
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 675..695
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 696..729
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 402..611
FT /note="Extracellular domain (ECD)"
FT /evidence="ECO:0000250|UniProtKB:Q63424"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 12
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63424"
FT CARBOHYD 448
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 472
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 528
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 587
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 729 AA; 81632 MW; F3C9D3481B1F671C CRC64;
MNPFQKNESK ETLFSPVSTE EMLPGPPSPP KKSTPKLFGS SYPLSIAFIV VNEFCERFSY
YGMKAVLTLY FLYFLHWNED TSTSVYHAFS SLCYFTPILG AAIADSWLGK FKTIIYLSLV
YVLGHVFKSL GAIPILGGKM LHTILSLVGL SLIALGTGGI KPCVAAFGGD QFEEEHAEAR
TRYFSVFYLS INAGSLISTF ITPMLRGDVK CFGEDCYALA FGIPGLLMVL ALVVFAMGSK
MYRKPPPEGN IVAQVTKCIW FAICNRFRNR SEDIPKRQHW LDWAAEKYPK HLIMDVKALT
RILFLYIPLP MFWALLDQQG SRWTLQANKM DGDLGFFVLQ PDQMQVLNPF LVLVFIPLFD
LVIYRLISKC GVNFSSLRKM AVGMILACLA FAVAALVEIK INGMIHPQPA SQEIFLQVLN
LADGEIEVTV QGNRNNPLLV ESISSFQNTT HYSKLRLETK SQDLHFHLKY NNLSVHNEYS
VEEKNCYQLV VHENGESLSS MLVKDTGIKP ANGMTAIRFI NTLHKDMNIS LDANAPLSVG
KDYGVSEYRT VQRGKYPAVH CETEDNVFSL NLGQLDFGTT YLFVITNITN RGLQAWKAED
IPANKLSIAW QLPQYVLVTA AEVMFSVTGL EFSYSQAPSS MKSVLQAAWL LTVAVGNIIV
LIVAQFSGLV QWAEFVLFSC LLLVVCLIFS VMGYYYVPLK SEGIHEATEK QIPHIQGNMI
NLETKNTRL
