DPEP2_MOUSE
ID DPEP2_MOUSE Reviewed; 478 AA.
AC Q8C255; Q3TAV9; Q3TBF7; Q3TBK3; Q3TBM9; Q7TQ53;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Dipeptidase 2;
DE EC=3.4.13.19 {ECO:0000269|PubMed:12738806};
DE AltName: Full=Membrane-bound dipeptidase 2 {ECO:0000303|PubMed:12738806};
DE Short=MBD-2 {ECO:0000303|PubMed:12738806};
DE Flags: Precursor;
GN Name=Dpep2; Synonyms=Mbd2;
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] (ISOFORM 2), TISSUE SPECIFICITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP CATALYTIC ACTIVITY, AND FUNCTION.
RC STRAIN=C57BL/6J; TISSUE=Heart, Lung, and Spleen;
RX PubMed=12738806; DOI=10.1096/fj.02-0899fje;
RA Habib G.M., Shi Z.-Z., Cuevas A.A., Lieberman M.W.;
RT "Identification of two additional members of the membrane-bound dipeptidase
RT family.";
RL FASEB J. 17:1313-1315(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Dendritic cell;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP INDUCTION, AND FUNCTION.
RX PubMed=30899700; DOI=10.3389/fcimb.2019.00057;
RA Yang X., Yue Y., Xiong S.;
RT "Dpep2 Emerging as a Modulator of Macrophage Inflammation Confers
RT Protection Against CVB3-Induced Viral Myocarditis.";
RL Front. Cell. Infect. Microbiol. 9:57-57(2019).
CC -!- FUNCTION: Dipeptidase that hydrolyzes leukotriene D4 (LTD4) into
CC leukotriene E4 (LTE4) (PubMed:12738806). Hydrolyzes cystinyl-bis-
CC glycine (By similarity). {ECO:0000250|UniProtKB:Q9H4A9,
CC ECO:0000269|PubMed:12738806}.
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:0000269|PubMed:30899700}.
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; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10073, ECO:0000269|PubMed:12738806};
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:0000269|PubMed:12738806};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48617;
CC Evidence={ECO:0000305|PubMed:12738806};
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:0000269|PubMed:12738806}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5 uM for LTD4 {ECO:0000269|PubMed:12738806};
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000255|PROSITE-
CC ProRule:PRU10073}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:12738806}; Lipid-
CC anchor, GPI-anchor {ECO:0000269|PubMed:12738806}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8C255-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C255-2; Sequence=VSP_017853, VSP_017854, VSP_017855;
CC Name=3;
CC IsoId=Q8C255-3; Sequence=VSP_017852;
CC -!- TISSUE SPECIFICITY: Expressed in heart, lung, testis, spleen and
CC skeletal muscle. Not detected in kidney and brain.
CC {ECO:0000269|PubMed:12738806}.
CC -!- INDUCTION: Up-regulated during CVB3-induced viral myocarditis in the
CC cardiac infiltrating macrophages. {ECO:0000269|PubMed:30899700}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Peptidase M19 family. {ECO:0000255|PROSITE-ProRule:PRU10073}.
CC -!- CAUTION: According to PubMed:12738806, does not hydrolyze cystinyl-bis-
CC glycine but data is not shown in paper. {ECO:0000269|PubMed:12738806}.
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DR EMBL; AF488552; AAP84986.1; -; mRNA.
DR EMBL; AK089244; BAC40810.1; -; mRNA.
DR EMBL; AK155417; BAE33255.1; -; mRNA.
DR EMBL; AK170094; BAE41559.1; -; mRNA.
DR EMBL; AK170970; BAE42149.1; -; mRNA.
DR EMBL; AK171044; BAE42209.1; -; mRNA.
DR EMBL; AK171122; BAE42264.1; -; mRNA.
DR EMBL; AK171155; BAE42280.1; -; mRNA.
DR EMBL; AK171196; BAE42306.1; -; mRNA.
DR EMBL; AK171268; BAE42354.1; -; mRNA.
DR EMBL; AK171503; BAE42494.1; -; mRNA.
DR EMBL; AK171606; BAE42559.1; -; mRNA.
DR CCDS; CCDS22625.1; -. [Q8C255-2]
DR CCDS; CCDS80925.1; -. [Q8C255-3]
DR CCDS; CCDS80926.1; -. [Q8C255-1]
DR RefSeq; NP_001288133.1; NM_001301204.1. [Q8C255-1]
DR RefSeq; NP_001288134.1; NM_001301205.1. [Q8C255-3]
DR RefSeq; NP_795887.2; NM_176913.4. [Q8C255-2]
DR AlphaFoldDB; Q8C255; -.
DR SMR; Q8C255; -.
DR STRING; 10090.ENSMUSP00000080659; -.
DR SwissLipids; SLP:000001462; -.
DR MEROPS; M19.002; -.
DR GlyGen; Q8C255; 2 sites.
DR PhosphoSitePlus; Q8C255; -.
DR CPTAC; non-CPTAC-3551; -.
DR MaxQB; Q8C255; -.
DR PaxDb; Q8C255; -.
DR PeptideAtlas; Q8C255; -.
DR PRIDE; Q8C255; -.
DR ProteomicsDB; 279473; -. [Q8C255-1]
DR ProteomicsDB; 279474; -. [Q8C255-2]
DR ProteomicsDB; 279475; -. [Q8C255-3]
DR DNASU; 319446; -.
DR Ensembl; ENSMUST00000034373; ENSMUSP00000034373; ENSMUSG00000053687. [Q8C255-1]
DR Ensembl; ENSMUST00000117555; ENSMUSP00000113877; ENSMUSG00000053687. [Q8C255-3]
DR Ensembl; ENSMUST00000227363; ENSMUSP00000154250; ENSMUSG00000115067. [Q8C255-2]
DR GeneID; 319446; -.
DR KEGG; mmu:319446; -.
DR UCSC; uc009nex.2; mouse. [Q8C255-3]
DR UCSC; uc009ney.2; mouse. [Q8C255-2]
DR UCSC; uc057amr.1; mouse. [Q8C255-1]
DR CTD; 64174; -.
DR MGI; MGI:2442042; Dpep2.
DR VEuPathDB; HostDB:ENSMUSG00000053687; -.
DR VEuPathDB; HostDB:ENSMUSG00000115067; -.
DR eggNOG; KOG4127; Eukaryota.
DR GeneTree; ENSGT00940000160211; -.
DR HOGENOM; CLU_031404_4_1_1; -.
DR InParanoid; Q8C255; -.
DR OMA; KHIFHIA; -.
DR OrthoDB; 1272387at2759; -.
DR PhylomeDB; Q8C255; -.
DR TreeFam; TF324523; -.
DR Reactome; R-MMU-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-MMU-5423646; Aflatoxin activation and detoxification.
DR BioGRID-ORCS; 319446; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Dpep2; mouse.
DR PRO; PR:Q8C255; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8C255; protein.
DR Bgee; ENSMUSG00000053687; Expressed in lung and 34 other tissues.
DR ExpressionAtlas; Q8C255; differential.
DR GO; GO:0031225; C:anchored component of membrane; IDA:UniProtKB.
DR GO; GO:0016805; F:dipeptidase activity; IDA:UniProtKB.
DR GO; GO:0008238; F:exopeptidase activity; IDA:MGI.
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; IDA: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 1: Evidence at protein level;
KW Alternative splicing; Dipeptidase; Disulfide bond; Glycoprotein;
KW GPI-anchor; Hydrolase; Lipid metabolism; Lipoprotein; Membrane;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Signal; Zinc.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..459
FT /note="Dipeptidase 2"
FT /id="PRO_0000231605"
FT PROPEP 460..478
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P16444"
FT /id="PRO_0000231606"
FT REGION 42..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 42..68
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 91
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 93
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 190
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 190
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 217
FT /ligand="substrate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 263
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 284
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 295
FT /ligand="substrate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 353
FT /ligand="substrate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT LIPID 459
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 140..219
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT DISULFID 291..323
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT DISULFID 428
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT VAR_SEQ 1..93
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_017852"
FT VAR_SEQ 1
FT /note="M -> MAWHGETYCLIGGYRVYGDAPLPTPAKAEQEEKPVPRRAPKRQRVQE
FT ESDQDLGCPGAKVPRLKLKHGGKGLSRPSSVPACSALSKM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12738806"
FT /id="VSP_017853"
FT VAR_SEQ 176..179
FT /note="ALNS -> VKWIYSG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12738806"
FT /id="VSP_017854"
FT VAR_SEQ 334..340
FT /note="DHFDHIR -> EKGQQKHQFTPPRDTHFV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12738806"
FT /id="VSP_017855"
FT CONFLICT 78
FT /note="A -> T (in Ref. 2; BAE42354)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="D -> G (in Ref. 2; BAE42559)"
FT /evidence="ECO:0000305"
FT CONFLICT 99
FT /note="R -> G (in Ref. 2; BAE42559)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 478 AA; 52664 MW; 0790B97009F5D41F CRC64;
MSLTGLKGHW VLGHGLSVFL LVLLLLGPSQ PLIWTQTKPG FSGASTTSSI PRALTKPDIS
SIPTTPGNPN FPDLRDRARA LMQEFPLIDG HNDMPLVLRQ FYQNGLQDAN LRNFTHGQTS
LDRLKDGLVG AQFWSAYVPC QTQDRDALRL TLEQIDLIRR ICASYSELEL VTSVKALNST
QKLACLIGVE GGHSLDNSLA VLRSFYLLGV RYLTLTHTCN TPWAETSSKG VHAFYSSVTG
LTSFGEKVVA EMNRLGMMVD LSHVSDAAAR RALEVSQAPV IFSHSAARAV CPNARNLPDD
LLQLLKKNGG IVMVTFSVGV LPCNPLANVS TVADHFDHIR SVIGSEFIGI GGDYDGTKQF
PQGLEDVSTY PVLIEELLRR GWNEQELQGI LRGNLLRVFR QVEQVRDKSK WQSPLEDMIP
EEQLDSACHS ALRPQKQHPE KNQPETPEYH ILKFSHSKSS PHIVPSLAIV ATLLGLIV
