S15A2_RABIT
ID S15A2_RABIT Reviewed; 729 AA.
AC P46029;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Solute carrier family 15 member 2 {ECO:0000305};
DE AltName: Full=Kidney H(+)/peptide cotransporter {ECO:0000303|PubMed:8552623};
DE AltName: Full=Oligopeptide transporter, kidney isoform {ECO:0000303|PubMed:8552623};
DE AltName: Full=Peptide transporter 2 {ECO:0000303|PubMed:8552623};
GN Name=SLC15A2 {ECO:0000250|UniProtKB:Q16348};
GN Synonyms=PEPT2 {ECO:0000303|PubMed:8552623};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=8552623; DOI=10.1073/pnas.93.1.284;
RA Boll M., Herget M., Wagener M., Weber W., Markovich D., Biber J.,
RA Clauss W., Murer H., Daniel H.;
RT "Expression cloning and functional characterization of the kidney cortex
RT high-affinity proton-coupled peptide transporter.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:284-289(1996).
CC -!- FUNCTION: Proton-coupled amino-acid transporter that transports
CC oligopeptides of 2 to 4 amino acids with a preference for dipeptides
CC (PubMed:8552623). Transports the dipeptide-like aminopeptidase
CC inhibitor bestatin (By similarity). Can also transport the
CC aminocephalosporin antibiotic cefadroxil (PubMed:8552623). 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). Probably acts by mediating transport of bacterial
CC peptidoglycans across the plasma membrane: catalyzes the transport of
CC certain bacterial peptidoglycans, such as muramyl dipeptide (MDP), the
CC NOD2 ligand (By similarity). {ECO:0000250|UniProtKB:Q16348,
CC ECO:0000250|UniProtKB:Q63424, ECO:0000250|UniProtKB:Q9ES07,
CC ECO:0000269|PubMed:8552623}.
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:8552623};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64393;
CC Evidence={ECO:0000269|PubMed:8552623};
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:Q9ES07};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64409;
CC Evidence={ECO:0000250|UniProtKB:Q9ES07};
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=25.8 uM for cefadroxil (at pH 6.0) {ECO:0000269|PubMed:8552623};
CC KM=23.8 uM for cefadroxil (at pH 6.5) {ECO:0000269|PubMed:8552623};
CC KM=32.5 uM for cefadroxil (at pH 7.4) {ECO:0000269|PubMed:8552623};
CC KM=40.9 uM for cefadroxil (at pH 8.0) {ECO:0000269|PubMed:8552623};
CC pH dependence:
CC Optimum pH is 6.0 or lower. {ECO:0000269|PubMed:8552623};
CC -!- SUBUNIT: Interacts (via extracellular domain region) with trypsin.
CC {ECO:0000250|UniProtKB:Q63424}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:8552623};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in kidney. Also detected in
CC brain, lung, liver and heart. {ECO:0000269|PubMed:8552623}.
CC -!- DOMAIN: The extracellular domain (ECD) region specifically binds
CC trypsin. {ECO:0000250|UniProtKB:Q63424}.
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; U32507; AAC48495.1; -; mRNA.
DR RefSeq; NP_001076169.1; NM_001082700.1.
DR AlphaFoldDB; P46029; -.
DR SMR; P46029; -.
DR STRING; 9986.ENSOCUP00000001594; -.
DR GeneID; 100009433; -.
DR KEGG; ocu:100009433; -.
DR CTD; 6565; -.
DR eggNOG; KOG1237; Eukaryota.
DR InParanoid; P46029; -.
DR OrthoDB; 365203at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0071916; F:dipeptide transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0140206; P:dipeptide import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0015835; P:peptidoglycan transport; ISS: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; ISS:UniProtKB.
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_0000064310"
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..26
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ES07"
FT MOD_RES 12
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9ES07"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63424"
FT CARBOHYD 435
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 508
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; 81664 MW; 0D22A35D7E024312 CRC64;
MNPFQQNESK ETLFSPVSTE ETPPRLSSPA KKTPPKICGS NYPLSIAFIV VNEFCERFSY
YGMKAVLTLY FLYFLHWNED TSTSVYHAFS SLCYFTPILG AAIADSWLGK FKTIIYLSLV
NVLGHVIKSL SAFPILGGKV VHTVLSLVGL CLIALGTGGI KPCVAAFGGD QFEEKHAEER
TRYFSGFYLA INAGSLISTF ITPMLRGDVQ CFGEDCYALA FGVPGLLMVI ALVVFAMGSK
MYKKPPPEGN IVAQVVKCIW FAISNRFKNR SEDIPKRQHW LDWAAEKYPK QLIMDVKTLT
RVLFLYIPLP MFWALLDQQG SRWTLQATKM NGNLGFFVLQ PDQMQVLNPL LVLIFIPLFD
LVIYRLISKC GINFTSLRKM AVGMVLACLA FAAAATVEIK INEMAPPQPG SQEILLQVLN
LADDEVKLTV LGNNNNSLLA DSIKSFQKTP HYSKIHLNTK SQDFYFHLKY HNLSIYTEHS
VEERNWYSLI IREDGKSISS IMVKDMENET TYGMTAIRFI NTLQENVNIS LGTDISLNVG
ENYGVSAYRT VQRGEYPAVH CKTEDKDFSL NLGLLDFGAS YLFVITNSTK QGLQAWKMED
IPANKVSIAW QLPQYALVTA GEVMFSVTGL EFSYSQAPSS MKSVLQAAWL LTVAIGNIIV
LVVAQFSGLV QWAEFVLFSC LLLVVCLIFS IMGYYYIPIK SEDIQGPEDK QIPHMQGNMI
NLETKKTKL
