DPEP3_HUMAN
ID DPEP3_HUMAN Reviewed; 488 AA.
AC Q9H4B8; B3KQ48; Q6PEZ5; Q6UXE4;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Dipeptidase 3;
DE Flags: Precursor;
GN Name=DPEP3; ORFNames=UNQ834/PRO1772;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RA Chen J.M., Fortunato M., Barrett A.J.;
RT "Cloning and sequencing of a second human homologue of renal membrane
RT dipeptidase.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
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 [7]
RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS), ABSENCE OF DIPEPTIDASE ACTIVITY,
RP SUBUNIT, AND MUTAGENESIS OF GLU-196.
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, leukotriene D4 and the beta-lactam antibiotic
CC imipenem (PubMed:32325220). The absence of activity may be due to the
CC inability of asparagine (instead of aspartate found in DPEP1/2) at
CC position 359 to function as the acid/base catalyst and activate the
CC nucleophilic water/hydroxide (PubMed:32325220). A tyrosine (instead of
CC histidine) at position 269 reduces affinity for the beta zinc and may
CC cause substrate steric hindrance (PubMed:32325220).
CC {ECO:0000269|PubMed:32325220}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:32325220). 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 (By similarity).
CC {ECO:0000250|UniProtKB:Q9DA79, ECO:0000255|PROSITE-ProRule:PRU10073,
CC ECO:0000269|PubMed:32325220}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q9DA79}; Lipid-
CC anchor, GPI-anchor {ECO:0000250|UniProtKB:Q9DA79}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Peptidase M19 family. {ECO:0000255|PROSITE-ProRule:PRU10073}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH57789.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG51910.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAC15385.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAW83198.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AJ291679; CAC15385.1; ALT_INIT; mRNA.
DR EMBL; AY358390; AAQ88756.1; -; mRNA.
DR EMBL; AK057401; BAG51910.1; ALT_INIT; mRNA.
DR EMBL; AC040162; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471092; EAW83198.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC057789; AAH57789.1; ALT_INIT; mRNA.
DR CCDS; CCDS10856.1; -.
DR RefSeq; NP_001123230.1; NM_001129758.1.
DR RefSeq; NP_071752.3; NM_022357.3.
DR PDB; 6VGO; X-ray; 1.82 A; A=1-488.
DR PDB; 6VGR; X-ray; 2.84 A; A/B=1-488.
DR PDBsum; 6VGO; -.
DR PDBsum; 6VGR; -.
DR AlphaFoldDB; Q9H4B8; -.
DR SMR; Q9H4B8; -.
DR BioGRID; 122099; 17.
DR IntAct; Q9H4B8; 5.
DR STRING; 9606.ENSP00000268793; -.
DR MEROPS; M19.004; -.
DR GlyGen; Q9H4B8; 1 site.
DR iPTMnet; Q9H4B8; -.
DR PhosphoSitePlus; Q9H4B8; -.
DR BioMuta; DPEP3; -.
DR DMDM; 91206587; -.
DR EPD; Q9H4B8; -.
DR jPOST; Q9H4B8; -.
DR MassIVE; Q9H4B8; -.
DR PaxDb; Q9H4B8; -.
DR PeptideAtlas; Q9H4B8; -.
DR PRIDE; Q9H4B8; -.
DR ProteomicsDB; 80820; -.
DR ABCD; Q9H4B8; 44 sequenced antibodies.
DR Antibodypedia; 54982; 101 antibodies from 17 providers.
DR DNASU; 64180; -.
DR Ensembl; ENST00000268793.6; ENSP00000268793.5; ENSG00000141096.6.
DR GeneID; 64180; -.
DR KEGG; hsa:64180; -.
DR MANE-Select; ENST00000268793.6; ENSP00000268793.5; NM_001370198.1; NP_001357127.1.
DR UCSC; uc002evc.5; human.
DR CTD; 64180; -.
DR DisGeNET; 64180; -.
DR GeneCards; DPEP3; -.
DR HGNC; HGNC:23029; DPEP3.
DR HPA; ENSG00000141096; Tissue enriched (testis).
DR MIM; 609926; gene.
DR neXtProt; NX_Q9H4B8; -.
DR OpenTargets; ENSG00000141096; -.
DR PharmGKB; PA134978786; -.
DR VEuPathDB; HostDB:ENSG00000141096; -.
DR eggNOG; KOG4127; Eukaryota.
DR GeneTree; ENSGT00940000162331; -.
DR HOGENOM; CLU_031404_4_1_1; -.
DR InParanoid; Q9H4B8; -.
DR OMA; EEVQNSC; -.
DR OrthoDB; 1272387at2759; -.
DR PhylomeDB; Q9H4B8; -.
DR TreeFam; TF324523; -.
DR PathwayCommons; Q9H4B8; -.
DR Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-HSA-5423646; Aflatoxin activation and detoxification.
DR Reactome; R-HSA-9664535; LTC4-CYSLTR mediated IL4 production.
DR SignaLink; Q9H4B8; -.
DR BioGRID-ORCS; 64180; 12 hits in 1069 CRISPR screens.
DR GeneWiki; DPEP3; -.
DR GenomeRNAi; 64180; -.
DR Pharos; Q9H4B8; Tbio.
DR PRO; PR:Q9H4B8; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9H4B8; protein.
DR Bgee; ENSG00000141096; Expressed in right testis and 88 other tissues.
DR ExpressionAtlas; Q9H4B8; baseline and differential.
DR Genevisible; Q9H4B8; HS.
DR GO; GO:0001669; C:acrosomal vesicle; ISS:UniProtKB.
DR GO; GO:0031225; C:anchored component of membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0016805; F:dipeptidase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070573; F:metallodipeptidase activity; IEA:InterPro.
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 3D-structure; Disulfide bond; Glycoprotein; GPI-anchor; Lipoprotein;
KW Membrane; Reference proteome; Signal.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..463
FT /note="Dipeptidase 3"
FT /id="PRO_0000231609"
FT PROPEP 464..488
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P16444"
FT /id="PRO_0000231610"
FT LIPID 463
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 146..225
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT DISULFID 297..329
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT DISULFID 434
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT MUTAGEN 196
FT /note="E->A: Loss of zinc binding."
FT /evidence="ECO:0000269|PubMed:32325220"
FT CONFLICT 48
FT /note="Missing (in Ref. 6; AAH57789)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="Missing (in Ref. 2; AAQ88756)"
FT /evidence="ECO:0000305"
FT HELIX 79..90
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 93..98
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 100..108
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 127..132
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 135..143
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:6VGO"
FT TURN 149..152
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 153..170
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 180..185
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 187..196
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 198..201
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 205..213
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 216..221
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 238..241
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 249..261
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 264..266
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 272..281
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 287..291
FT /evidence="ECO:0007829|PDB:6VGO"
FT TURN 294..296
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 305..314
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 317..320
FT /evidence="ECO:0007829|PDB:6VGO"
FT TURN 324..329
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 335..348
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 351..353
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:6VGO"
FT STRAND 362..364
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 373..375
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 376..385
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 390..397
FT /evidence="ECO:0007829|PDB:6VGO"
FT HELIX 399..414
FT /evidence="ECO:0007829|PDB:6VGO"
FT TURN 415..417
FT /evidence="ECO:0007829|PDB:6VGO"
SQ SEQUENCE 488 AA; 53687 MW; F14FEE5AFB3F4471 CRC64;
MQPTGREGSR ALSRRYLRRL LLLLLLLLLR QPVTRAETTP GAPRALSTLG SPSLFTTPGV
PSALTTPGLT TPGTPKTLDL RGRAQALMRS FPLVDGHNDL PQVLRQRYKN VLQDVNLRNF
SHGQTSLDRL RDGLVGAQFW SASVSCQSQD QTAVRLALEQ IDLIHRMCAS YSELELVTSA
EGLNSSQKLA CLIGVEGGHS LDSSLSVLRS FYVLGVRYLT LTFTCSTPWA ESSTKFRHHM
YTNVSGLTSF GEKVVEELNR LGMMIDLSYA SDTLIRRVLE VSQAPVIFSH SAARAVCDNL
LNVPDDILQL LKKNGGIVMV TLSMGVLQCN LLANVSTVAD HFDHIRAVIG SEFIGIGGNY
DGTGRFPQGL EDVSTYPVLI EELLSRSWSE EELQGVLRGN LLRVFRQVEK VREESRAQSP
VEAEFPYGQL STSCHSHLVP QNGHQATHLE VTKQPTNRVP WRSSNASPYL VPGLVAAATI
PTFTQWLC
