DPEP2_RAT
ID DPEP2_RAT Reviewed; 481 AA.
AC Q5M872;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Dipeptidase 2;
DE EC=3.4.13.19 {ECO:0000250|UniProtKB:Q8C255};
DE Flags: Precursor;
GN Name=Dpep2;
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 [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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).
CC -!- FUNCTION: Dipeptidase that hydrolyzes leukotriene D4 (LTD4) into
CC leukotriene E4 (LTE4) and cystinyl-bis-glycine.
CC {ECO:0000250|UniProtKB:Q9H4A9}.
CC -!- FUNCTION: Independently of its dipeptidase activity can also modulate
CC macrophage inflammatory response by acting as a regulator of NF-kappa-B
CC inflammatory signaling pathway. {ECO:0000250|UniProtKB:Q8C255}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an L-aminoacyl-L-amino acid + H2O = 2 an L-alpha-amino acid;
CC Xref=Rhea:RHEA:48940, ChEBI:CHEBI:15377, ChEBI:CHEBI:59869,
CC ChEBI:CHEBI:77460; EC=3.4.13.19;
CC Evidence={ECO:0000250|UniProtKB:Q8C255, ECO:0000255|PROSITE-
CC ProRule:PRU10073};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + leukotriene D4 = glycine + leukotriene E4;
CC Xref=Rhea:RHEA:48616, ChEBI:CHEBI:15377, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:57462, ChEBI:CHEBI:63166;
CC Evidence={ECO:0000250|UniProtKB:Q8C255};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48617;
CC Evidence={ECO:0000250|UniProtKB:Q8C255};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H2O + L-cystine-bis-glycine = 2 glycine + L-cystine;
CC Xref=Rhea:RHEA:60520, ChEBI:CHEBI:15377, ChEBI:CHEBI:35491,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:143812;
CC Evidence={ECO:0000250|UniProtKB:Q9H4A9};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P16444,
CC ECO:0000255|PROSITE-ProRule:PRU10073};
CC -!- ACTIVITY REGULATION: Inhibited by L-penicillamine.
CC {ECO:0000250|UniProtKB:Q8C255}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000255|PROSITE-
CC ProRule:PRU10073}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q8C255}; Lipid-
CC anchor, GPI-anchor {ECO:0000250|UniProtKB:Q8C255}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Peptidase M19 family. {ECO:0000255|PROSITE-ProRule:PRU10073}.
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DR EMBL; BC088195; AAH88195.1; -; mRNA.
DR RefSeq; NP_001011928.1; NM_001011928.1.
DR AlphaFoldDB; Q5M872; -.
DR SMR; Q5M872; -.
DR STRING; 10116.ENSRNOP00000031955; -.
DR MEROPS; M19.002; -.
DR GlyGen; Q5M872; 2 sites.
DR PaxDb; Q5M872; -.
DR GeneID; 291984; -.
DR KEGG; rno:291984; -.
DR UCSC; RGD:1305746; rat.
DR CTD; 64174; -.
DR RGD; 1305746; Dpep2.
DR VEuPathDB; HostDB:ENSRNOG00000023303; -.
DR eggNOG; KOG4127; Eukaryota.
DR HOGENOM; CLU_031404_4_1_1; -.
DR InParanoid; Q5M872; -.
DR OMA; KHIFHIA; -.
DR OrthoDB; 1272387at2759; -.
DR PhylomeDB; Q5M872; -.
DR TreeFam; TF324523; -.
DR Reactome; R-RNO-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-RNO-5423646; Aflatoxin activation and detoxification.
DR PRO; PR:Q5M872; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000023303; Expressed in spleen and 16 other tissues.
DR Genevisible; Q5M872; RN.
DR GO; GO:0031225; C:anchored component of membrane; ISS:UniProtKB.
DR GO; GO:0016805; F:dipeptidase activity; ISS:UniProtKB.
DR GO; GO:0008238; F:exopeptidase activity; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070573; F:metallodipeptidase activity; IEA:InterPro.
DR GO; GO:1901749; P:leukotriene D4 catabolic process; ISS:UniProtKB.
DR GO; GO:0006691; P:leukotriene metabolic process; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd01301; rDP_like; 1.
DR InterPro; IPR000180; Dipep_AS.
DR InterPro; IPR028531; Dpep2/3.
DR InterPro; IPR032466; Metal_Hydrolase.
DR InterPro; IPR008257; Pept_M19.
DR PANTHER; PTHR10443; PTHR10443; 1.
DR PANTHER; PTHR10443:SF14; PTHR10443:SF14; 1.
DR Pfam; PF01244; Peptidase_M19; 1.
DR SUPFAM; SSF51556; SSF51556; 1.
DR PROSITE; PS00869; RENAL_DIPEPTIDASE_1; 1.
DR PROSITE; PS51365; RENAL_DIPEPTIDASE_2; 1.
PE 2: Evidence at transcript level;
KW Dipeptidase; Disulfide bond; Glycoprotein; GPI-anchor; Hydrolase;
KW Lipid metabolism; Lipoprotein; Membrane; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Signal; Zinc.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..462
FT /note="Dipeptidase 2"
FT /id="PRO_0000231607"
FT PROPEP 463..481
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P16444"
FT /id="PRO_0000231608"
FT REGION 434..464
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 434..451
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 90
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 92
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 189
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 189
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 216
FT /ligand="substrate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 262
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 283
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 294
FT /ligand="substrate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 352
FT /ligand="substrate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT LIPID 462
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 139..218
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT DISULFID 290..322
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT DISULFID 427
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
SQ SEQUENCE 481 AA; 53285 MW; DC39B50C10A96AC1 CRC64;
MSLKGLEGHW VLSQVFLLVV VLLLLGPSEP LIRAQTKPGI ADASTAPSPL RTLTKPAIFS
IPTTPGNPNF PDLRDRTRAL MQDFPLIDGH NDLPLVLRQF YQNGLQDTNL RNFTHGQTSL
NRLKDGFVGA QFWSAYVPCQ TQDRDALRLT LEQIDLIRRM CASYSELELV TSVQALNSTQ
KLACLIGVEG GHSLDNSLAV LRSFYLLGVR YLTLTHTCNT PWAESSSKDV HSFYSSVKGL
TSFGEKVVAE MNRLGMMIDL SHVSDATARQ ALEVSQAPVI FSHSAARAVC PNARNLPDDI
LQLLKKNGGI VMVTFAVGVL PCNPLANVST VADHFDHIRT VIGSEFIGVG GDYDGTKQFP
QGLEDVSTYP VLIEELLRRG WGEQELQGVL RGNLLRVFRQ VEQVREKNKW QSPLEDMIPE
EQLDSACHSV LPHRRQYPEK DPPETPDSHT HKLSPKMPYS KSSPLRASSL TIMATFLGLL
I
