DPP3_RAT
ID DPP3_RAT Reviewed; 738 AA.
AC O55096; Q32Q87;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Dipeptidyl peptidase 3;
DE EC=3.4.14.4;
DE AltName: Full=Dipeptidyl aminopeptidase III;
DE AltName: Full=Dipeptidyl arylamidase III;
DE AltName: Full=Dipeptidyl peptidase III;
DE Short=DPP III;
DE AltName: Full=Enkephalinase B;
GN Name=Dpp3;
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], AND CHARACTERIZATION.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=9425109; DOI=10.1042/bj3290275;
RA Fukasawa K., Fukusawa K.M., Kanai M., Fujii S., Hirose J., Harada M.;
RT "Dipeptidyl peptidase III is a zinc metallo-exopeptidase. Molecular cloning
RT and expression.";
RL Biochem. J. 329:275-282(1998).
RN [2]
RP SEQUENCE REVISION, MUTAGENESIS OF HIS-450; GLU-451 AND HIS-455, ACTIVE
RP SITE, AND COFACTOR.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=10387075; DOI=10.1021/bi9904959;
RA Fukasawa K., Fukasawa K.M., Iwamoto H., Hirose J., Harada M.;
RT "The HELLGH motif of rat liver dipeptidyl peptidase III is involved in zinc
RT coordination and the catalytic activity of the enzyme.";
RL Biochemistry 38:8299-8303(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [4]
RP MUTAGENESIS OF CYSTEINE RESIDUES.
RX PubMed=11027512; DOI=10.1006/bbrc.2000.3519;
RA Li Y.H., Maeda T., Yamane T., Ohkubo I.;
RT "Alteration of rat dipeptidyl peptidase III by site-directed mutagenesis:
RT cysteine(176) is a regulatory residue for the enzyme activity.";
RL Biochem. Biophys. Res. Commun. 276:553-558(2000).
RN [5]
RP CHARACTERIZATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Erythrocyte;
RX PubMed=11209758; DOI=10.1515/bc.2000.151;
RA Abramic M., Schleuder D., Dolovcak L., Schroeder W., Strupat K., Sagi D.,
RA Peter-Katalini J., Vitale L.;
RT "Human and rat dipeptidyl peptidase III: biochemical and mass spectrometric
RT arguments for similarities and differences.";
RL Biol. Chem. 381:1233-1243(2000).
CC -!- FUNCTION: Cleaves and degrades bioactive peptides, including
CC angiotensin, Leu-enkephalin and Met-enkephalin (By similarity). Also
CC cleaves Arg-Arg-beta-naphthylamide. {ECO:0000250|UniProtKB:Q9NY33}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal dipeptide from a peptide comprising
CC four or more residues, with broad specificity. Also acts on
CC dipeptidyl 2-naphthylamides.; EC=3.4.14.4;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:10387075};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:10387075};
CC -!- ACTIVITY REGULATION: Inhibited by spinorphin, an opioid peptide derived
CC from hemoglobin. {ECO:0000250}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 9.0.;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the peptidase M49 family. {ECO:0000305}.
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DR EMBL; D89340; BAA24608.2; -; mRNA.
DR EMBL; BC107673; AAI07674.1; -; mRNA.
DR RefSeq; NP_446200.1; NM_053748.1.
DR RefSeq; XP_006230695.1; XM_006230633.3.
DR AlphaFoldDB; O55096; -.
DR SMR; O55096; -.
DR STRING; 10116.ENSRNOP00000026968; -.
DR MEROPS; M49.001; -.
DR iPTMnet; O55096; -.
DR PhosphoSitePlus; O55096; -.
DR World-2DPAGE; 0004:O55096; -.
DR jPOST; O55096; -.
DR PaxDb; O55096; -.
DR PRIDE; O55096; -.
DR Ensembl; ENSRNOT00000026968; ENSRNOP00000026968; ENSRNOG00000031485.
DR GeneID; 114591; -.
DR KEGG; rno:114591; -.
DR UCSC; RGD:621127; rat.
DR CTD; 10072; -.
DR RGD; 621127; Dpp3.
DR eggNOG; KOG3675; Eukaryota.
DR GeneTree; ENSGT00390000007335; -.
DR HOGENOM; CLU_011977_0_0_1; -.
DR InParanoid; O55096; -.
DR OMA; HCQARFA; -.
DR OrthoDB; 1448344at2759; -.
DR PhylomeDB; O55096; -.
DR PRO; PR:O55096; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000031485; Expressed in stomach and 19 other tissues.
DR Genevisible; O55096; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0008239; F:dipeptidyl-peptidase activity; ISO:RGD.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IDA:RGD.
DR GO; GO:0030163; P:protein catabolic process; IDA:RGD.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
DR InterPro; IPR005317; Dipeptidyl-peptase3.
DR InterPro; IPR039461; Peptidase_M49.
DR PANTHER; PTHR23422; PTHR23422; 1.
DR Pfam; PF03571; Peptidase_M49; 1.
DR PIRSF; PIRSF007828; Dipeptidyl-peptidase_III; 1.
PE 1: Evidence at protein level;
KW Acetylation; Aminopeptidase; Cytoplasm; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9NY33"
FT CHAIN 2..738
FT /note="Dipeptidyl peptidase 3"
FT /id="PRO_0000078240"
FT ACT_SITE 451
FT /evidence="ECO:0000269|PubMed:10387075"
FT BINDING 450
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:10387075"
FT BINDING 455
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:10387075"
FT BINDING 508
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NY33"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9NY33"
FT MUTAGEN 176
FT /note="C->A: 25% to 35% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:11027512"
FT MUTAGEN 176
FT /note="C->E,G: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11027512"
FT MUTAGEN 450
FT /note="H->Y: Loss of activity and zinc binding."
FT /evidence="ECO:0000269|PubMed:10387075"
FT MUTAGEN 451
FT /note="E->A,D: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10387075"
FT MUTAGEN 455
FT /note="H->Y: Loss of activity and zinc binding."
FT /evidence="ECO:0000269|PubMed:10387075"
SQ SEQUENCE 738 AA; 83039 MW; 74BA736BA0806B78 CRC64;
MADTQYILPN DIGVSSLDCR EAFRLLSPTE RLYAHHLSRA AWYGGLAVLL QTSPEAPYIY
ALLSRLFRAQ DPDQLRQHAL AEGLTEEEYQ AFLVYAAGVY SNMGNYKSFG DTKFVPNLPK
EKLERVILGS KAAQQHPEEV RSLWQTCGEL MFSLEPRLRH LGLGKEGVTT YFSGDCAMED
AKLAQDFLDS QNLSAYNTRL FKVVGQEGKY HYEVRLASVL NTEPALDSEL TSKLKSYEFQ
GNHFQVTRGD YAPILQKVVE HLEKAKAYAA NSHQEQMLAQ YVESFTQGSI EAHKRGSRFW
IQDKGPIVES YIGFIESYRD PFGSRGEFEG FVAMVNKDMS AKFERLVASA EQLLKELPWP
PAFEKDKFLT PDFTSLDVLT FAGSGIPAGI NIPNYDDLRQ TEGFKNVSLG NVLAVAYATK
REKLTFMEEE DKDLYIRWKG PSFDVQVGLH ELLGHGSGKL FVQDEKGAFN FDQETVINPE
TGEQIQSWYR SGETWDSKFS TIASSYEECR AESVGLYLCL NPQVLQIFGF EGTDAEDVIY
VNWLNMVRAG LLALEFYTPE TANWRQAHMQ ARFVILRVLL EAGEGLVTVT PTTGSDGRPD
ARVHLDRSKI RSVGKPALER FLRRLQVLKS TGDVVAGRAL YEGYAAVTDA PPECFLTLRD
TVLLRKESRK LIVQPNTRLE GSEVQLVEYE ASAAGLIRSF CERFPEDGPE LEEVLTQLAT
ADAQFWRDQV QEAPSGQA
