DPP8_MOUSE
ID DPP8_MOUSE Reviewed; 892 AA.
AC Q80YA7; Q9D4G6;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Dipeptidyl peptidase 8 {ECO:0000303|PubMed:27820798};
DE Short=DP8;
DE EC=3.4.14.5 {ECO:0000250|UniProtKB:Q6V1X1};
DE AltName: Full=Dipeptidyl peptidase VIII;
DE Short=DPP VIII;
GN Name=Dpp8 {ECO:0000303|PubMed:27820798, ECO:0000312|MGI:MGI:1921638};
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Lung, Spleen, and 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 [4]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=27820798; DOI=10.1038/nchembio.2229;
RA Okondo M.C., Johnson D.C., Sridharan R., Go E.B., Chui A.J., Wang M.S.,
RA Poplawski S.E., Wu W., Liu Y., Lai J.H., Sanford D.G., Arciprete M.O.,
RA Golub T.R., Bachovchin W.W., Bachovchin D.A.;
RT "DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and
RT macrophage pyroptosis.";
RL Nat. Chem. Biol. 13:46-53(2017).
RN [5]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=29396289; DOI=10.1016/j.chembiol.2017.12.013;
RA Okondo M.C., Rao S.D., Taabazuing C.Y., Chui A.J., Poplawski S.E.,
RA Johnson D.C., Bachovchin D.A.;
RT "Inhibition of Dpp8/9 activates the Nlrp1b inflammasome.";
RL Cell Chem. Biol. 25:262-267(2018).
CC -!- FUNCTION: Dipeptidyl peptidase that cleaves off N-terminal dipeptides
CC from proteins having a Pro or Ala residue at position 2 (By
CC similarity). Acts as a key inhibitor of caspase-1-dependent monocyte
CC and macrophage pyroptosis in resting cells by preventing activation of
CC NLRP1 and CARD8 (PubMed:27820798, PubMed:29396289). Sequesters the
CC cleaved C-terminal part of NLRP1 and CARD8, which respectively
CC constitute the active part of the NLRP1 and CARD8 inflammasomes, in a
CC ternary complex, thereby preventing their oligomerization and
CC activation (By similarity). The dipeptidyl peptidase activity is
CC required to suppress NLRP1 and CARD8; however, neither NLRP1 nor CARD8
CC are bona fide substrates of DPP8, suggesting the existence of
CC substrate(s) required for NLRP1 and CARD8 inhibition (By similarity).
CC {ECO:0000250|UniProtKB:Q6V1X1, ECO:0000250|UniProtKB:Q86TI2,
CC ECO:0000269|PubMed:27820798, ECO:0000269|PubMed:29396289}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, from a
CC polypeptide, preferentially when Yaa is Pro, provided Zaa is neither
CC Pro nor hydroxyproline.; EC=3.4.14.5;
CC Evidence={ECO:0000250|UniProtKB:Q6V1X1};
CC -!- ACTIVITY REGULATION: Inhibited by zinc (By similarity). Inhibited by
CC the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl
CC fluoride (AEBSF), and by di-isopropylfluorophosphate (By similarity).
CC Specifically inhibited by isoindoline derivatives (By similarity).
CC Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective
CC inhibitor, which triggers pyroptosis in monocytes and macrophages
CC (PubMed:27820798, PubMed:29396289). {ECO:0000250|UniProtKB:Q6V1X1,
CC ECO:0000269|PubMed:27820798, ECO:0000269|PubMed:29396289}.
CC -!- SUBUNIT: Homodimer (By similarity). Forms a ternary complex with NLRP1,
CC composed of a DPP8 homodimer, one full-length NLRP1 protein, and one
CC cleaved C-terminus of NLRP1 (NACHT, LRR and PYD domains-containing
CC protein 1, C-terminus) (By similarity). Forms a ternary complex with
CC CARD8, composed of a DPP8 homodimer, one full-length NLRP1 protein, and
CC one cleaved C-terminus of CARD8 (Caspase recruitment domain-containing
CC protein 8, C-terminus) (By similarity). In the ternary complex, only
CC one subunit of the DPP8 homodimer is bound to NLRP1 or CARD8 (By
CC similarity). {ECO:0000250|UniProtKB:Q6V1X1,
CC ECO:0000250|UniProtKB:Q86TI2}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6V1X1}.
CC -!- SIMILARITY: Belongs to the peptidase S9B family. DPPIV subfamily.
CC {ECO:0000305}.
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DR EMBL; AK016546; BAB30295.2; -; mRNA.
DR EMBL; BC043124; AAH43124.1; -; mRNA.
DR EMBL; BC059222; AAH59222.1; -; mRNA.
DR CCDS; CCDS23285.1; -.
DR RefSeq; NP_083182.2; NM_028906.2.
DR AlphaFoldDB; Q80YA7; -.
DR SMR; Q80YA7; -.
DR BioGRID; 216712; 7.
DR STRING; 10090.ENSMUSP00000034960; -.
DR ESTHER; mouse-dpp8; DPP4N_Peptidase_S9.
DR MEROPS; S09.018; -.
DR iPTMnet; Q80YA7; -.
DR PhosphoSitePlus; Q80YA7; -.
DR EPD; Q80YA7; -.
DR MaxQB; Q80YA7; -.
DR PaxDb; Q80YA7; -.
DR PeptideAtlas; Q80YA7; -.
DR PRIDE; Q80YA7; -.
DR ProteomicsDB; 277601; -.
DR Antibodypedia; 2238; 317 antibodies from 32 providers.
DR DNASU; 74388; -.
DR Ensembl; ENSMUST00000034960; ENSMUSP00000034960; ENSMUSG00000032393.
DR Ensembl; ENSMUST00000167773; ENSMUSP00000126065; ENSMUSG00000032393.
DR GeneID; 74388; -.
DR KEGG; mmu:74388; -.
DR UCSC; uc009qcq.1; mouse.
DR CTD; 54878; -.
DR MGI; MGI:1921638; Dpp8.
DR VEuPathDB; HostDB:ENSMUSG00000032393; -.
DR eggNOG; KOG2281; Eukaryota.
DR GeneTree; ENSGT00940000160717; -.
DR HOGENOM; CLU_006105_1_0_1; -.
DR InParanoid; Q80YA7; -.
DR OMA; ETETAHY; -.
DR OrthoDB; 137965at2759; -.
DR PhylomeDB; Q80YA7; -.
DR TreeFam; TF313309; -.
DR BioGRID-ORCS; 74388; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Dpp8; mouse.
DR PRO; PR:Q80YA7; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q80YA7; protein.
DR Bgee; ENSMUSG00000032393; Expressed in spermatocyte and 255 other tissues.
DR ExpressionAtlas; Q80YA7; baseline and differential.
DR Genevisible; Q80YA7; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0004177; F:aminopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0008239; F:dipeptidyl-peptidase activity; ISS:UniProtKB.
DR GO; GO:0008236; F:serine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR045785; Dpp_8/9_N.
DR InterPro; IPR001375; Peptidase_S9.
DR InterPro; IPR002469; Peptidase_S9B_N.
DR Pfam; PF19520; Dpp_8_9_N; 1.
DR Pfam; PF00930; DPPIV_N; 1.
DR Pfam; PF00326; Peptidase_S9; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Aminopeptidase; Cytoplasm; Hydrolase; Protease; Reference proteome;
KW Serine protease.
FT CHAIN 1..892
FT /note="Dipeptidyl peptidase 8"
FT /id="PRO_0000122414"
FT ACT_SITE 749
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q6V1X1"
FT ACT_SITE 827
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q6V1X1"
FT ACT_SITE 859
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q6V1X1"
FT CONFLICT 87
FT /note="G -> R (in Ref. 1; BAB30295)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 892 AA; 102186 MW; 59081CD9792E03ED CRC64;
MKIPSGRCNM AAAMETEQLG VEIFETAECE EGNGESQDRP KLEPFYVERY SWSQLKKLLA
DTRKYHGYMM AKAPHDFMFV KRTDPDGPHS DRVYYLAMSG ENRENTLFYS EIPKTINRAA
VLMLSWKPLL DLFQATLDYG MYSREEELLR ERKRIGTVGI AAYDYHPGSG TFLFQAGSGI
YHIKDGGPHG FTQQPLRPNL VETSCPNIRM DPKLCPADPD WIAFIHSNDI WISNLVTREE
RRITYVHNEL ANMEEDPRSA GVATFVLQEE FDRYSGYWWC PQAERTPSGG KILRILYEEN
DESEVEIIHV TSPMLETRRA DSFRYPKTGT ANPKVTFKMS EIVVDAAGGI IDVIDKELVQ
PFEILFEGVE YIARAGWTPE GKHAWSILLD RSQTHLQIVL ISPELFIPVE DDAMDRQRLI
ESVPDSVTPL IIYEETTDIW INIHDIFHVF PQTHEDEIEF IFASECKTGF RHLYKITSIL
KESKYKRSSG GLPAPSDFKC PIKEEITITS GEWEVLGRHG SNIWVDEARK LVYFEGTKDS
PLEHHLYVTS YANPGEVVRL TDRGYSHSCC LSRHCDFFIS KYSNQKNPHC VSLYKLSSPE
DDPVHKTKEF WATILDSAGP LPDYTPPEIF SFESTTGFTL YGMLYKPHDL QPGKKYPTVL
FIYGGPQVQL VNNRFKGVKY FRLNTLASLG YVVVVIDNRG SCHRGLKFEG AFKYKMGQIE
IDDQVEGLQY LASQYDFIDL DRVGIHGWSY GGYLSLMALM QRSDIFRVAI AGAPVTLWIF
YDTGYTERYM GHPDQNEQGY YLGSVAMQAE KFPSEPNRLL LLHGFLDENV HFAHTSILLS
FLVRAGKPYD LQIYPQERHS IRVPESGEHY ELHLLHYLQE NLGSRIAALK VI
