S15A2_RAT
ID S15A2_RAT Reviewed; 729 AA.
AC Q63424;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 140.
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:8639691};
GN Name=Slc15a2 {ECO:0000312|RGD:61972};
GN Synonyms=Pept2 {ECO:0000303|PubMed:8639691};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=8639691; DOI=10.1016/0005-2736(96)00024-7;
RA Saito H., Terada T., Okuda M., Sasaki S., Inui K.;
RT "Molecular cloning and tissue distribution of rat peptide transporter
RT PEPT2.";
RL Biochim. Biophys. Acta 1280:173-177(1996).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [3] {ECO:0007744|PDB:5A9H, ECO:0007744|PDB:5A9I}
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 410-601, FUNCTION, TRANSPORTER
RP ACTIVITY, DOMAIN, AND INTERACTION WITH TRYPSIN.
RX PubMed=26320580; DOI=10.1016/j.str.2015.07.016;
RA Beale J.H., Parker J.L., Samsudin F., Barrett A.L., Senan A., Bird L.E.,
RA Scott D., Owens R.J., Sansom M.S.P., Tucker S.J., Meredith D., Fowler P.W.,
RA Newstead S.;
RT "Crystal structures of the extracellular domain from PepT1 and PepT2
RT provide novel insights into mammalian peptide transport.";
RL Structure 23:1889-1899(2015).
CC -!- FUNCTION: Proton-coupled amino-acid transporter that transports
CC oligopeptides of 2 to 4 amino acids with a preference for dipeptides
CC (PubMed:8639691, PubMed:26320580). Transports the dipeptide-like
CC aminopeptidase inhibitor bestatin (PubMed:8639691). Can also transport
CC the aminocephalosporin antibiotic cefadroxil (By similarity). Also able
CC to 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:P46029,
CC ECO:0000250|UniProtKB:Q16348, ECO:0000250|UniProtKB:Q9ES07,
CC ECO:0000269|PubMed:26320580, ECO:0000269|PubMed:8639691}.
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:26320580, ECO:0000269|PubMed:8639691};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64393;
CC Evidence={ECO:0000269|PubMed:26320580, ECO:0000269|PubMed:8639691};
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 -!- SUBUNIT: Interacts (via extracellular domain region) with trypsin.
CC {ECO:0000269|PubMed:26320580}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:8639691};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in kidney cortex and medulla.
CC Also detected in brain, lung and spleen. {ECO:0000269|PubMed:8639691}.
CC -!- DOMAIN: The extracellular domain (ECD) region specifically binds
CC trypsin. {ECO:0000269|PubMed:26320580}.
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; D63149; BAA09631.1; -; mRNA.
DR PDB; 5A9H; X-ray; 2.06 A; A=410-601.
DR PDB; 5A9I; X-ray; 2.84 A; A/B/C=410-601.
DR PDB; 7NQK; EM; 3.50 A; A=1-729.
DR PDBsum; 5A9H; -.
DR PDBsum; 5A9I; -.
DR PDBsum; 7NQK; -.
DR AlphaFoldDB; Q63424; -.
DR SMR; Q63424; -.
DR STRING; 10116.ENSRNOP00000003189; -.
DR BindingDB; Q63424; -.
DR ChEMBL; CHEMBL3325; -.
DR GlyGen; Q63424; 4 sites.
DR iPTMnet; Q63424; -.
DR PhosphoSitePlus; Q63424; -.
DR PaxDb; Q63424; -.
DR UCSC; RGD:61972; rat.
DR RGD; 61972; Slc15a2.
DR eggNOG; KOG1237; Eukaryota.
DR HOGENOM; CLU_004790_3_0_1; -.
DR InParanoid; Q63424; -.
DR PhylomeDB; Q63424; -.
DR BRENDA; 7.4.2.5; 5301.
DR Reactome; R-RNO-427975; Proton/oligopeptide cotransporters.
DR PRO; PR:Q63424; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; Q63424; RN.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0071916; F:dipeptide transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015334; F:high-affinity oligopeptide transmembrane transporter activity; ISO:RGD.
DR GO; GO:0015333; F:peptide:proton symporter activity; IDA:UniProtKB.
DR GO; GO:0140206; P:dipeptide import across plasma membrane; IDA:UniProtKB.
DR GO; GO:0042938; P:dipeptide transport; IDA:RGD.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006857; P:oligopeptide transport; ISO:RGD.
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 GO; GO:0070293; P:renal absorption; ISO:RGD.
DR GO; GO:0042908; P:xenobiotic transport; ISO:RGD.
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 3D-structure; Cell membrane; Glycoprotein; Immunity; Innate immunity;
KW Membrane; Peptide transport; Phosphoprotein; Protein transport;
KW Reference proteome; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..729
FT /note="Solute carrier family 15 member 2"
FT /id="PRO_0000064311"
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..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 402..611
FT /note="Extracellular domain (ECD)"
FT /evidence="ECO:0000303|PubMed:26320580"
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: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:0007744|PubMed:22673903"
FT CARBOHYD 435
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 448
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, ECO:0000255|PROSITE-
FT ProRule:PRU00498"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 47..73
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 79..95
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 97..105
FT /evidence="ECO:0007829|PDB:7NQK"
FT STRAND 110..112
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 113..129
FT /evidence="ECO:0007829|PDB:7NQK"
FT TURN 130..132
FT /evidence="ECO:0007829|PDB:7NQK"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 141..170
FT /evidence="ECO:0007829|PDB:7NQK"
FT TURN 175..178
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 179..201
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:7NQK"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:7NQK"
FT TURN 211..213
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 218..236
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 237..240
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 251..262
FT /evidence="ECO:0007829|PDB:7NQK"
FT STRAND 278..281
FT /evidence="ECO:0007829|PDB:7NQK"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 290..305
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 309..317
FT /evidence="ECO:0007829|PDB:7NQK"
FT TURN 318..321
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 322..327
FT /evidence="ECO:0007829|PDB:7NQK"
FT STRAND 335..337
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 341..346
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 347..361
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 363..367
FT /evidence="ECO:0007829|PDB:7NQK"
FT TURN 368..371
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 378..401
FT /evidence="ECO:0007829|PDB:7NQK"
FT STRAND 413..420
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 422..424
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 426..431
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 437..443
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 453..456
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 458..470
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 473..484
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 486..494
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 497..504
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 514..521
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 523..525
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 527..532
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 537..539
FT /evidence="ECO:0007829|PDB:5A9H"
FT TURN 541..543
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 549..555
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 557..565
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 567..570
FT /evidence="ECO:0007829|PDB:5A9H"
FT STRAND 573..575
FT /evidence="ECO:0007829|PDB:5A9I"
FT STRAND 580..585
FT /evidence="ECO:0007829|PDB:5A9H"
FT TURN 589..591
FT /evidence="ECO:0007829|PDB:7NQK"
FT STRAND 595..599
FT /evidence="ECO:0007829|PDB:5A9H"
FT HELIX 612..635
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 639..641
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 644..664
FT /evidence="ECO:0007829|PDB:7NQK"
FT HELIX 671..694
FT /evidence="ECO:0007829|PDB:7NQK"
SQ SEQUENCE 729 AA; 81320 MW; 66F5E88B9DF83DAD CRC64;
MNPFQKNESK ETLFSPVSTE EMLPRPPSPP KKSPPKIFGS SYPVSIAFIV VNEFCERFSY
YGMKAVLTLY FLYFLHWNED TSTSVYHAFS SLCYFTPILG AAIADSWLGK FKTIIYLSLV
YVLGHVFKSL GAIPILGGKM LHTILSLVGL SLIALGTGGI KPCVAAFGGD QFEEEHAEAR
TRYFSVFYLA INAGSLISTF ITPMLRGDVK CFGQDCYALA FGVPGLLMVL ALVVFAMGSK
MYRKPPPEGN IVAQVIKCIW FALCNRFRNR SGDLPKRQHW LDWAAEKYPK HLIADVKALT
RVLFLYIPLP MFWALLDQQG SRWTLQANKM NGDLGFFVLQ PDQMQVLNPF LVLIFIPLFD
LVIYRLISKC RINFSSLRKM AVGMILACLA FAVAALVETK INGMIHPQPA SQEIFLQVLN
LADGDVKVTV LGSRNNSLLV ESVSSFQNTT HYSKLHLEAK SQDLHFHLKY NSLSVHNDHS
VEEKNCYQLL IHQDGESISS MLVKDTGIKP ANGMAAIRFI NTLHKDLNIS LDTDAPLSVG
KDYGVSAYRT VLRGKYPAVH CETEDKVFSL DLGQLDFGTT YLFVITNITS QGLQAWKAED
IPVNKLSIAW QLPQYVLVTA AEVMFSVTGL EFSYSQAPSS MKSVLQAAWL LTVAVGNIIV
LVVAQFSGLA QWAEFVLFSC LLLVVCLIFS VMAYYYVPLK SEDTREATDK QIPAVQGNMI
NLETKNTRL
