DPEP3_MOUSE
ID DPEP3_MOUSE Reviewed; 493 AA.
AC Q9DA79;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Dipeptidase 3;
DE AltName: Full=Membrane-bound dipeptidase 3 {ECO:0000303|PubMed:12738806};
DE Short=MBD-3 {ECO:0000303|PubMed:12738806};
DE AltName: Full=Protein expressed in male leptotene and zygotene spermatocytes 136;
DE Short=MLZ-136;
DE Flags: Precursor;
GN Name=Dpep3; Synonyms=Mbd3;
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], SUBCELLULAR LOCATION, PRELIMINARY FUNCTION, AND
RP CAUTION.
RC STRAIN=L129; TISSUE=Spleen, and Testis;
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].
RC STRAIN=C57BL/6J; TISSUE=Testis;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=20339383; DOI=10.1038/jhg.2010.26;
RA Kogo H., Kowa-Sugiyama H., Yamada K., Bolor H., Tsutsumi M., Ohye T.,
RA Inagaki H., Taniguchi M., Toda T., Kurahashi H.;
RT "Screening of genes involved in chromosome segregation during meiosis I:
RT toward the identification of genes responsible for infertility in humans.";
RL J. Hum. Genet. 55:293-299(2010).
RN [6]
RP INTERACTION WITH TEX101.
RX PubMed=21724266; DOI=10.1016/j.jri.2011.04.010;
RA Yoshitake H., Yanagida M., Maruyama M., Takamori K., Hasegawa A., Araki Y.;
RT "Molecular characterization and expression of dipeptidase 3, a testis-
RT specific membrane-bound dipeptidase: complex formation with TEX101, a germ-
RT cell-specific antigen in the mouse testis.";
RL J. Reprod. Immunol. 90:202-213(2011).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=31212048; DOI=10.1016/j.gene.2019.06.015;
RA Xie Y., Khan R., Wahab F., Hussain H.M.J., Ali A., Ma H., Jiang H., Xu J.,
RA Zaman Q., Khan M., Jiang X., Shi Q.;
RT "The testis-specifically expressed Dpep3 is not essential for male
RT fertility in mice.";
RL Gene 711:143925-143925(2019).
RN [8]
RP ABSENCE OF DIPEPTIDASE ACTIVITY, AND CAUTION.
RX PubMed=32325220; DOI=10.1016/j.jsb.2020.107512;
RA Hayashi K., Longenecker K.L., Koenig P., Prashar A., Hampl J., Stoll V.,
RA Vivona S.;
RT "Structure of human DPEP3 in complex with the SC-003 antibody Fab fragment
RT reveals basis for lack of dipeptidase activity.";
RL J. Struct. Biol. 211:107512-107512(2020).
CC -!- FUNCTION: Lacks dipeptidase activity and is unable to hydrolyze
CC cystinyl-bis-glycine (PubMed:32325220). The absence of activity may be
CC due to the inability of serine (instead of aspartate found in DPEP1/2)
CC at position 356 to function as the acid/base catalyst and activate the
CC nucleophilic water/hydroxide (PubMed:32325220). Does not hydrolyze
CC leukotriene D4 (LTD4) into leukotriene E4 (LTE4) (PubMed:12738806).
CC Does not hydrolyze the beta-lactam antibiotic imipenem (By similarity).
CC {ECO:0000250|UniProtKB:Q9H4B8, ECO:0000269|PubMed:12738806,
CC ECO:0000269|PubMed:32325220}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with
CC TEX101; co-localized on the cell surface of spermatocytes, spermatids,
CC and testicular spermatozoa, co-localized only in cytoplasmic droplets
CC of caput and corpus epididymal sperm (PubMed:21724266).
CC {ECO:0000255|PROSITE-ProRule:PRU10073, ECO:0000269|PubMed:21724266}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:12738806}; Lipid-
CC anchor, GPI-anchor {ECO:0000269|PubMed:12738806}.
CC -!- TISSUE SPECIFICITY: Expressed in testis but not ovary.
CC {ECO:0000269|PubMed:12738806, ECO:0000269|PubMed:20339383}.
CC -!- DEVELOPMENTAL STAGE: Expressed in ovary and testis at 15.5 dpc.
CC {ECO:0000269|PubMed:20339383}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are fertile despite a
CC significant reduction in sperm count. {ECO:0000269|PubMed:31212048}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Peptidase M19 family. {ECO:0000255|PROSITE-ProRule:PRU10073}.
CC -!- CAUTION: According to PubMed:12738806, exhibits dipeptidase activity
CC hydrolyzing cystinyl-bis-glycine but according to PubMed:32325220,
CC lacks this activity which may be due to the inability of serine
CC (instead of aspartate found in DPEP1/2) at position 356 to function as
CC the acid/base catalyst and activate the nucleophilic water/hydroxide.
CC {ECO:0000269|PubMed:12738806, ECO:0000269|PubMed:32325220}.
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DR EMBL; AF488553; AAP84987.1; -; mRNA.
DR EMBL; AK006085; BAB24402.1; -; mRNA.
DR EMBL; BC051148; AAH51148.1; -; mRNA.
DR CCDS; CCDS22624.1; -.
DR RefSeq; NP_082236.1; NM_027960.2.
DR AlphaFoldDB; Q9DA79; -.
DR SMR; Q9DA79; -.
DR BioGRID; 214981; 1.
DR IntAct; Q9DA79; 1.
DR MINT; Q9DA79; -.
DR STRING; 10090.ENSMUSP00000034371; -.
DR MEROPS; M19.011; -.
DR GlyGen; Q9DA79; 1 site.
DR iPTMnet; Q9DA79; -.
DR PhosphoSitePlus; Q9DA79; -.
DR PaxDb; Q9DA79; -.
DR PeptideAtlas; Q9DA79; -.
DR PRIDE; Q9DA79; -.
DR ProteomicsDB; 279802; -.
DR Antibodypedia; 54982; 101 antibodies from 17 providers.
DR DNASU; 71854; -.
DR Ensembl; ENSMUST00000034371; ENSMUSP00000034371; ENSMUSG00000031898.
DR GeneID; 71854; -.
DR KEGG; mmu:71854; -.
DR UCSC; uc009net.1; mouse.
DR CTD; 64180; -.
DR MGI; MGI:1919104; Dpep3.
DR VEuPathDB; HostDB:ENSMUSG00000031898; -.
DR eggNOG; KOG4127; Eukaryota.
DR GeneTree; ENSGT00940000162331; -.
DR HOGENOM; CLU_031404_4_1_1; -.
DR InParanoid; Q9DA79; -.
DR OMA; EEVQNSC; -.
DR OrthoDB; 1272387at2759; -.
DR PhylomeDB; Q9DA79; -.
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; 71854; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Dpep3; mouse.
DR PRO; PR:Q9DA79; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q9DA79; protein.
DR Bgee; ENSMUSG00000031898; Expressed in spermatocyte and 19 other tissues.
DR Genevisible; Q9DA79; MM.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:UniProtKB.
DR GO; GO:0031225; C:anchored component of membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0016805; F:dipeptidase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070573; F:metallodipeptidase activity; IEA:InterPro.
DR GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0006508; P:proteolysis; IDA:MGI.
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 Disulfide bond; Glycoprotein; GPI-anchor; Lipoprotein; Membrane;
KW Reference proteome; Signal.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..462
FT /note="Dipeptidase 3"
FT /id="PRO_0000231613"
FT PROPEP 463..493
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P16444"
FT /id="PRO_0000231614"
FT REGION 41..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 462
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 331
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 143..222
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT DISULFID 294..326
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT DISULFID 431
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
SQ SEQUENCE 493 AA; 54247 MW; B9A0D39BB7CEB619 CRC64;
MQPAGLEGPR ALGLRPLGHR LSLLGVLLLV PSLWVTCTLT TPSPSSAPTT PEASNATTAP
GIPNDTATSG VTSDPRLREQ ALALMRDFPL VDGHNDLPLL LRELFQNQLQ DVNLRNFTRG
QTNLDRLRDG LVGAQFWSAY IPCQTQDRDA VRLALEQIDL IRRMCSAYPE LELVTSADGL
NNTQKLACLI GVEGGHSLDT SLAVLRSFYE LGVRYLTLTF TCSTPWAESA TKFRHHFYTN
ISGLTSFGEK VVEEMNRLGM MIDLSHASDT LVKQTLEVSQ APVIFSHSAA RSVCDNLLNI
PDDILQLLKK NGGIVMVTLS MGVLQCSLFA NVSTVADHFD HIRTVIGSEF IGIGGSYDGS
GRFPQGLEDV STYPVLIEEL LSRGWDEREL QGVLRGNLLR VFRQVEQVRE KSLGQSPVEV
KFPERQQSNT CHSHLLPQPQ EDQHQDTHLK VTKLPNILQR ASKAPPHPLP GLMATLTSLA
LILWLCCSGH RAV
