DPP8_HUMAN
ID DPP8_HUMAN Reviewed; 898 AA.
AC Q6V1X1; Q7Z4C8; Q7Z4D3; Q7Z4E1; Q8IWG7; Q8NEM5; Q96JX1; Q9HBM2; Q9HBM3;
AC Q9HBM4; Q9HBM5; Q9NXF4;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Dipeptidyl peptidase 8 {ECO:0000303|PubMed:11012666};
DE Short=DP8 {ECO:0000303|PubMed:12534281};
DE EC=3.4.14.5 {ECO:0000269|PubMed:11012666, ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077, ECO:0000269|PubMed:15664838, ECO:0000269|PubMed:29382749};
DE AltName: Full=Dipeptidyl peptidase IV-related protein 1;
DE Short=DPRP-1;
DE AltName: Full=Dipeptidyl peptidase VIII;
DE Short=DPP VIII;
DE AltName: Full=Prolyl dipeptidase DPP8;
GN Name=DPP8 {ECO:0000303|PubMed:11012666, ECO:0000312|HGNC:HGNC:16490};
GN Synonyms=DPRP1; ORFNames=MSTP097, MSTP135, MSTP141;
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] (ISOFORM 3), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 334-898 (ISOFORM 4), NUCLEOTIDE SEQUENCE [MRNA] OF 540-898 (ISOFORM 5),
RP NUCLEOTIDE SEQUENCE [MRNA] OF 260-792 (ISOFORM 6), FUNCTION, CATALYTIC
RP ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY, INDUCTION, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Placenta;
RX PubMed=11012666; DOI=10.1046/j.1432-1327.2000.01617.x;
RA Abbott C.A., Yu D.M.T., Woollatt E., Sutherland G.R., McCaughan G.W.,
RA Gorrell M.D.;
RT "Cloning, expression and chromosomal localization of a novel human
RT dipeptidyl peptidase (DPP) IV homolog, DPP8.";
RL Eur. J. Biochem. 267:6140-6150(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=12662155; DOI=10.1042/bj20021914;
RA Qi S.Y., Riviere P.J., Trojnar J., Junien J.-L., Akinsanya K.O.;
RT "Cloning and characterization of dipeptidyl peptidase 10, a new member of
RT an emerging subgroup of serine proteases.";
RL Biochem. J. 373:179-189(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RA Sha J.H., Zhou Z.M., Li J.M.;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 211-898 (ISOFORM 2).
RC TISSUE=Hepatoma, and Placenta;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 561-898.
RC TISSUE=Aorta;
RA Zhao B., Xu H.S., Tong Y.K., Sheng H., Qin B.M., Liu Y.Q., Liu B.,
RA Wang X.Y., Zhang Q., Song L., Gao Y., Zhang C.L., Ye J., Ji X.J., Liu B.H.,
RA Lu H., Chen J.Z., Cai M.Q., Zheng W.Y., Teng C.Y., Liu Q., Yu L.T., Lin J.,
RA Gong Q., Zhang A.M., Gao R.L., Hui R.T.;
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP FUNCTION, MUTAGENESIS OF GLU-275; SER-755; ASP-833 AND HIS-865, CATALYTIC
RP ACTIVITY, ACTIVE SITE, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12534281; DOI=10.1021/bi026846s;
RA Ajami K., Abbott C.A., Obradovic M., Gysbers V., Kaehne T., McCaughan G.W.,
RA Gorrell M.D.;
RT "Structural requirements for catalysis, expression, and dimerization in the
RT CD26/DPIV gene family.";
RL Biochemistry 42:694-701(2003).
RN [8]
RP BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15039077; DOI=10.1016/j.pep.2003.12.019;
RA Chen Y.-S., Chien C.-H., Goparaju C.M., Hsu J.T.-A., Liang P.-H., Chen X.;
RT "Purification and characterization of human prolyl dipeptidase DPP8 in Sf9
RT insect cells.";
RL Protein Expr. Purif. 35:142-146(2004).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=15664838; DOI=10.1016/j.bmcl.2004.11.023;
RA Jiaang W.-T., Chen Y.-S., Hsu T., Wu S.-H., Chien C.-H., Chang C.-N.,
RA Chang S.-P., Lee S.-J., Chen X.;
RT "Novel isoindoline compounds for potent and selective inhibition of prolyl
RT dipeptidase DPP8.";
RL Bioorg. Med. Chem. Lett. 15:687-691(2005).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF ASP-451 AND
RP ASP-788.
RX PubMed=20536396; DOI=10.1515/bc.2010.111;
RA Pitman M.R., Menz R.I., Abbott C.A.;
RT "Hydrophilic residues surrounding the S1 and S2 pockets contribute to
RT dimerisation and catalysis in human dipeptidyl peptidase 8 (DP8).";
RL Biol. Chem. 391:959-972(2010).
RN [11]
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 [12]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=29967349; DOI=10.1038/s41591-018-0082-y;
RA Johnson D.C., Taabazuing C.Y., Okondo M.C., Chui A.J., Rao S.D.,
RA Brown F.C., Reed C., Peguero E., de Stanchina E., Kentsis A.,
RA Bachovchin D.A.;
RT "DPP8/DPP9 inhibitor-induced pyroptosis for treatment of acute myeloid
RT leukemia.";
RL Nat. Med. 24:1151-1156(2018).
RN [13]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=32796818; DOI=10.1038/s41419-020-02865-4;
RA Johnson D.C., Okondo M.C., Orth E.L., Rao S.D., Huang H.C., Ball D.P.,
RA Bachovchin D.A.;
RT "DPP8/9 inhibitors activate the CARD8 inflammasome in resting
RT lymphocytes.";
RL Cell Death Dis. 11:628-628(2020).
RN [14]
RP FUNCTION.
RX PubMed=34019797; DOI=10.1016/j.immuni.2021.04.024;
RA Sharif H., Hollingsworth L.R., Griswold A.R., Hsiao J.C., Wang Q.,
RA Bachovchin D.A., Wu H.;
RT "Dipeptidyl peptidase 9 sets a threshold for CARD8 inflammasome formation
RT by sequestering its active C-terminal fragment.";
RL Immunity 54:1392-1404(2021).
RN [15]
RP FUNCTION.
RX PubMed=33731929; DOI=10.1038/s41586-021-03320-w;
RA Huang M., Zhang X., Toh G.A., Gong Q., Wang J., Han Z., Wu B., Zhong F.,
RA Chai J.;
RT "Structural and biochemical mechanisms of NLRP1 inhibition by DPP9.";
RL Nature 592:773-777(2021).
RN [16]
RP FUNCTION.
RX PubMed=33731932; DOI=10.1038/s41586-021-03350-4;
RA Hollingsworth L.R., Sharif H., Griswold A.R., Fontana P., Mintseris J.,
RA Dagbay K.B., Paulo J.A., Gygi S.P., Bachovchin D.A., Wu H.;
RT "DPP9 sequesters the C terminus of NLRP1 to repress inflammasome
RT activation.";
RL Nature 592:778-783(2021).
RN [17] {ECO:0007744|PDB:6EOO, ECO:0007744|PDB:6EOP, ECO:0007744|PDB:6EOS, ECO:0007744|PDB:6EOT}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEXES WITH SYNTHETIC
RP INHIBITORS, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND ACTIVE SITE.
RX PubMed=29382749; DOI=10.1073/pnas.1717565115;
RA Ross B., Krapp S., Augustin M., Kierfersauer R., Arciniega M.,
RA Geiss-Friedlander R., Huber R.;
RT "Structures and mechanism of dipeptidyl peptidases 8 and 9, important
RT players in cellular homeostasis and cancer.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E1437-E1445(2018).
CC -!- FUNCTION: Dipeptidyl peptidase that cleaves off N-terminal dipeptides
CC from proteins having a Pro or Ala residue at position 2
CC (PubMed:11012666, PubMed:12534281, PubMed:12662155, PubMed:15039077,
CC PubMed:15664838, PubMed:20536396, PubMed:29382749). Acts as a key
CC inhibitor of caspase-1-dependent monocyte and macrophage pyroptosis in
CC resting cells by preventing activation of NLRP1 and CARD8
CC (PubMed:27820798, PubMed:29967349, PubMed:32796818). 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 (PubMed:34019797, PubMed:33731929, PubMed:33731932). The
CC dipeptidyl peptidase activity is required to suppress NLRP1 and CARD8;
CC however, neither NLRP1 nor CARD8 are bona fide substrates of DPP8,
CC suggesting the existence of substrate(s) required for NLRP1 and CARD8
CC inhibition (By similarity). {ECO:0000250|UniProtKB:Q86TI2,
CC ECO:0000269|PubMed:11012666, ECO:0000269|PubMed:12534281,
CC ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077,
CC ECO:0000269|PubMed:15664838, ECO:0000269|PubMed:20536396,
CC ECO:0000269|PubMed:27820798, ECO:0000269|PubMed:29967349,
CC ECO:0000269|PubMed:32796818, ECO:0000269|PubMed:33731929,
CC ECO:0000269|PubMed:33731932, ECO:0000269|PubMed:34019797,
CC ECO:0000305|PubMed:29382749}.
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:0000269|PubMed:11012666, ECO:0000269|PubMed:12534281,
CC ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077,
CC ECO:0000269|PubMed:15664838, ECO:0000269|PubMed:20536396,
CC ECO:0000269|PubMed:29382749};
CC -!- ACTIVITY REGULATION: Inhibited by zinc. Inhibited by the serine
CC proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF),
CC and by di-isopropylfluorophosphate. Specifically inhibited by
CC isoindoline derivatives (PubMed:11012666, PubMed:12662155,
CC PubMed:15664838). Inhibited by Val-boroPro (Talabostat, PT-100), a non-
CC selective inhibitor, which triggers pyroptosis in monocytes and
CC macrophages (PubMed:27820798, PubMed:29967349, PubMed:32796818).
CC {ECO:0000250|UniProtKB:Q86TI2, ECO:0000269|PubMed:11012666,
CC ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15664838,
CC ECO:0000269|PubMed:27820798, ECO:0000269|PubMed:29967349,
CC ECO:0000269|PubMed:32796818}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=208 uM for Ala-Pro-AMC {ECO:0000269|PubMed:12534281,
CC ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077};
CC KM=130 uM for Ala-Pro-AFC {ECO:0000269|PubMed:12534281,
CC ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077};
CC KM=120 uM for H-Ala-Pro-pNa {ECO:0000269|PubMed:12534281,
CC ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077};
CC KM=1420 uM for H-Ala-Ala-pNa {ECO:0000269|PubMed:12534281,
CC ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077};
CC KM=310 uM for H-Arg-Pro-pNa {ECO:0000269|PubMed:12534281,
CC ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077};
CC KM=2050 uM for H-Asp-Pro-pNa {ECO:0000269|PubMed:12534281,
CC ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077};
CC KM=480 uM for H-Gly-Pro-pNa {ECO:0000269|PubMed:12534281,
CC ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077};
CC pH dependence:
CC Optimum pH is 7.4-8.5. Little activity below pH 6.5.
CC {ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155,
CC ECO:0000269|PubMed:15039077};
CC -!- SUBUNIT: Homodimer (PubMed:20536396, PubMed:29382749). Forms a ternary
CC complex with NLRP1, composed of a DPP8 homodimer, one full-length NLRP1
CC protein, and one cleaved C-terminus of NLRP1 (NACHT, LRR and PYD
CC domains-containing protein 1, C-terminus) (By similarity). Forms a
CC ternary complex with CARD8, composed of a DPP8 homodimer, one full-
CC length NLRP1 protein, and one cleaved C-terminus of CARD8 (Caspase
CC recruitment domain-containing protein 8, C-terminus) (By similarity).
CC In the ternary complex, only one subunit of the DPP8 homodimer is bound
CC to NLRP1 or CARD8 (By similarity). {ECO:0000250|UniProtKB:Q86TI2,
CC ECO:0000269|PubMed:20536396, ECO:0000305|PubMed:29382749}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11012666,
CC ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=Q6V1X1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6V1X1-2; Sequence=VSP_013864;
CC Name=3;
CC IsoId=Q6V1X1-3; Sequence=VSP_013860;
CC Name=4;
CC IsoId=Q6V1X1-4; Sequence=VSP_013860, VSP_013862;
CC Name=5;
CC IsoId=Q6V1X1-5; Sequence=VSP_013863;
CC Name=6;
CC IsoId=Q6V1X1-6; Sequence=VSP_013861;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in
CC testis, placenta, prostate, muscle and brain.
CC {ECO:0000269|PubMed:11012666, ECO:0000269|PubMed:12662155}.
CC -!- INDUCTION: In activated T-cells. {ECO:0000269|PubMed:11012666}.
CC -!- SIMILARITY: Belongs to the peptidase S9B family. DPPIV subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ13623.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAQ13650.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAQ13657.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA91059.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB55395.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF221634; AAG29766.1; -; mRNA.
DR EMBL; AF221635; AAG29767.1; -; mRNA.
DR EMBL; AF221636; AAG29768.1; -; mRNA.
DR EMBL; AF221637; AAG29769.1; -; mRNA.
DR EMBL; AY172659; AAO17261.1; -; mRNA.
DR EMBL; AY354202; AAQ63887.1; -; mRNA.
DR EMBL; AK000290; BAA91059.1; ALT_FRAME; mRNA.
DR EMBL; AK027826; BAB55395.1; ALT_INIT; mRNA.
DR EMBL; BC030688; AAH30688.3; -; mRNA.
DR EMBL; BC040203; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF176779; AAQ13657.1; ALT_INIT; mRNA.
DR EMBL; AF175225; AAQ13650.1; ALT_FRAME; mRNA.
DR EMBL; AF173382; AAQ13623.1; ALT_FRAME; mRNA.
DR CCDS; CCDS10207.1; -. [Q6V1X1-1]
DR CCDS; CCDS10208.1; -. [Q6V1X1-2]
DR CCDS; CCDS10209.1; -. [Q6V1X1-4]
DR CCDS; CCDS10210.1; -. [Q6V1X1-3]
DR RefSeq; NP_001307804.1; NM_001320875.1. [Q6V1X1-1]
DR RefSeq; NP_001307805.1; NM_001320876.1. [Q6V1X1-3]
DR RefSeq; NP_060213.2; NM_017743.5. [Q6V1X1-4]
DR RefSeq; NP_569118.1; NM_130434.4. [Q6V1X1-3]
DR RefSeq; NP_932064.1; NM_197960.3. [Q6V1X1-1]
DR RefSeq; NP_932065.1; NM_197961.3. [Q6V1X1-2]
DR RefSeq; XP_016877862.1; XM_017022373.1.
DR RefSeq; XP_016877863.1; XM_017022374.1. [Q6V1X1-2]
DR PDB; 6EOO; X-ray; 2.50 A; A/B/C=1-898.
DR PDB; 6EOP; X-ray; 2.40 A; A/B/C=1-898.
DR PDB; 6EOS; X-ray; 3.10 A; A/B/C/D/E/F=1-898.
DR PDB; 6EOT; X-ray; 3.50 A; A/B/D/G/I/K=1-898.
DR PDB; 6HP8; X-ray; 2.50 A; A/B/C=1-898.
DR PDB; 6QZW; X-ray; 3.20 A; A/B/C=1-898.
DR PDB; 6TRW; X-ray; 3.00 A; A/B/C=1-898.
DR PDB; 6TRX; X-ray; 3.20 A; A/B/C=1-898.
DR PDB; 7A3G; X-ray; 2.80 A; A/B=1-898.
DR PDB; 7A3I; X-ray; 2.80 A; A/B/C=1-898.
DR PDB; 7A3J; X-ray; 3.00 A; A/B/C=1-898.
DR PDB; 7A3K; X-ray; 2.65 A; A/B/C=1-898.
DR PDB; 7A3L; X-ray; 2.80 A; A/B/C=1-898.
DR PDB; 7AYQ; X-ray; 2.45 A; A/B=1-898.
DR PDB; 7AYR; X-ray; 2.69 A; A/B=1-898.
DR PDB; 7OR4; X-ray; 2.44 A; A/B=1-898.
DR PDB; 7OZ7; X-ray; 2.60 A; A/B=1-898.
DR PDBsum; 6EOO; -.
DR PDBsum; 6EOP; -.
DR PDBsum; 6EOS; -.
DR PDBsum; 6EOT; -.
DR PDBsum; 6HP8; -.
DR PDBsum; 6QZW; -.
DR PDBsum; 6TRW; -.
DR PDBsum; 6TRX; -.
DR PDBsum; 7A3G; -.
DR PDBsum; 7A3I; -.
DR PDBsum; 7A3J; -.
DR PDBsum; 7A3K; -.
DR PDBsum; 7A3L; -.
DR PDBsum; 7AYQ; -.
DR PDBsum; 7AYR; -.
DR PDBsum; 7OR4; -.
DR PDBsum; 7OZ7; -.
DR AlphaFoldDB; Q6V1X1; -.
DR SMR; Q6V1X1; -.
DR BioGRID; 120226; 44.
DR IntAct; Q6V1X1; 18.
DR MINT; Q6V1X1; -.
DR STRING; 9606.ENSP00000339208; -.
DR BindingDB; Q6V1X1; -.
DR ChEMBL; CHEMBL4657; -.
DR DrugCentral; Q6V1X1; -.
DR GuidetoPHARMACOLOGY; 2356; -.
DR ESTHER; human-DPP8; DPP4N_Peptidase_S9.
DR MEROPS; S09.018; -.
DR iPTMnet; Q6V1X1; -.
DR PhosphoSitePlus; Q6V1X1; -.
DR BioMuta; DPP8; -.
DR DMDM; 67460301; -.
DR EPD; Q6V1X1; -.
DR jPOST; Q6V1X1; -.
DR MassIVE; Q6V1X1; -.
DR MaxQB; Q6V1X1; -.
DR PaxDb; Q6V1X1; -.
DR PeptideAtlas; Q6V1X1; -.
DR PRIDE; Q6V1X1; -.
DR ProteomicsDB; 67709; -. [Q6V1X1-1]
DR ProteomicsDB; 67710; -. [Q6V1X1-2]
DR ProteomicsDB; 67711; -. [Q6V1X1-3]
DR ProteomicsDB; 67712; -. [Q6V1X1-4]
DR ProteomicsDB; 67713; -. [Q6V1X1-5]
DR ProteomicsDB; 67714; -. [Q6V1X1-6]
DR Antibodypedia; 2238; 317 antibodies from 32 providers.
DR DNASU; 54878; -.
DR Ensembl; ENST00000300141.11; ENSP00000300141.6; ENSG00000074603.19. [Q6V1X1-3]
DR Ensembl; ENST00000321147.10; ENSP00000318111.6; ENSG00000074603.19. [Q6V1X1-2]
DR Ensembl; ENST00000341861.9; ENSP00000339208.5; ENSG00000074603.19. [Q6V1X1-1]
DR Ensembl; ENST00000358939.8; ENSP00000351817.4; ENSG00000074603.19. [Q6V1X1-4]
DR Ensembl; ENST00000559233.5; ENSP00000453954.1; ENSG00000074603.19. [Q6V1X1-1]
DR GeneID; 54878; -.
DR KEGG; hsa:54878; -.
DR MANE-Select; ENST00000300141.11; ENSP00000300141.6; NM_130434.5; NP_569118.1. [Q6V1X1-3]
DR UCSC; uc002aov.4; human. [Q6V1X1-1]
DR CTD; 54878; -.
DR DisGeNET; 54878; -.
DR GeneCards; DPP8; -.
DR HGNC; HGNC:16490; DPP8.
DR HPA; ENSG00000074603; Low tissue specificity.
DR MIM; 606819; gene.
DR neXtProt; NX_Q6V1X1; -.
DR OpenTargets; ENSG00000074603; -.
DR PharmGKB; PA27470; -.
DR VEuPathDB; HostDB:ENSG00000074603; -.
DR eggNOG; KOG2281; Eukaryota.
DR GeneTree; ENSGT00940000160717; -.
DR HOGENOM; CLU_006105_1_0_1; -.
DR InParanoid; Q6V1X1; -.
DR OMA; ETETAHY; -.
DR PhylomeDB; Q6V1X1; -.
DR TreeFam; TF313309; -.
DR PathwayCommons; Q6V1X1; -.
DR SABIO-RK; Q6V1X1; -.
DR SignaLink; Q6V1X1; -.
DR BioGRID-ORCS; 54878; 9 hits in 1084 CRISPR screens.
DR ChiTaRS; DPP8; human.
DR GeneWiki; DPP8; -.
DR GenomeRNAi; 54878; -.
DR Pharos; Q6V1X1; Tchem.
DR PRO; PR:Q6V1X1; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q6V1X1; protein.
DR Bgee; ENSG00000074603; Expressed in buccal mucosa cell and 205 other tissues.
DR ExpressionAtlas; Q6V1X1; baseline and differential.
DR Genevisible; Q6V1X1; HS.
DR GO; GO:0005737; C:cytoplasm; NAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0004177; F:aminopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0008239; F:dipeptidyl-peptidase activity; IDA:UniProtKB.
DR GO; GO:0008236; F:serine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006955; P:immune response; TAS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; NAS:UniProtKB.
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 3D-structure; Alternative splicing; Aminopeptidase; Apoptosis; Cytoplasm;
KW Hydrolase; Protease; Reference proteome; Serine protease.
FT CHAIN 1..898
FT /note="Dipeptidyl peptidase 8"
FT /id="PRO_0000122413"
FT ACT_SITE 755
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:12534281,
FT ECO:0000305|PubMed:29382749"
FT ACT_SITE 833
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:12534281,
FT ECO:0000305|PubMed:29382749"
FT ACT_SITE 865
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:12534281,
FT ECO:0000305|PubMed:29382749"
FT VAR_SEQ 1..16
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:11012666,
FT ECO:0000303|PubMed:12662155, ECO:0000303|PubMed:14702039"
FT /id="VSP_013860"
FT VAR_SEQ 358..530
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:11012666"
FT /id="VSP_013861"
FT VAR_SEQ 674..773
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11012666,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_013862"
FT VAR_SEQ 674..722
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:11012666"
FT /id="VSP_013863"
FT VAR_SEQ 723..773
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_013864"
FT MUTAGEN 275
FT /note="E->K: 13-fold reduction in affinity for Ala-Pro-AFC;
FT no effect on subcellular location."
FT /evidence="ECO:0000269|PubMed:12534281"
FT MUTAGEN 451
FT /note="D->F: Reduced dimerization and reduced enzyme
FT activity."
FT /evidence="ECO:0000269|PubMed:20536396"
FT MUTAGEN 755
FT /note="S->A: Abolishes activity; no effect on subcellular
FT location."
FT /evidence="ECO:0000269|PubMed:12534281"
FT MUTAGEN 788
FT /note="D->A,S,V: Strongly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:20536396"
FT MUTAGEN 788
FT /note="D->E: Loss of enzyme activity. Loss of
FT dimerization."
FT /evidence="ECO:0000269|PubMed:20536396"
FT MUTAGEN 833
FT /note="D->A: Abolishes activity; no effect on subcellular
FT location."
FT /evidence="ECO:0000269|PubMed:12534281"
FT MUTAGEN 865
FT /note="H->A: Abolishes activity; no effect on subcellular
FT location."
FT /evidence="ECO:0000269|PubMed:12534281"
FT CONFLICT 233
FT /note="S -> G (in Ref. 5; BC040203)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="G -> S (in Ref. 4; BAB55395)"
FT /evidence="ECO:0000305"
FT CONFLICT 673
FT /note="Q -> K (in Ref. 6; AAQ13650)"
FT /evidence="ECO:0000305"
FT CONFLICT 686
FT /note="Y -> F (in Ref. 6; AAQ13650)"
FT /evidence="ECO:0000305"
FT CONFLICT 693..694
FT /note="AS -> PF (in Ref. 6; AAQ13650)"
FT /evidence="ECO:0000305"
FT CONFLICT 701
FT /note="V -> G (in Ref. 6; AAQ13650)"
FT /evidence="ECO:0000305"
FT CONFLICT 709
FT /note="H -> P (in Ref. 6; AAQ13650)"
FT /evidence="ECO:0000305"
FT CONFLICT 720
FT /note="Y -> F (in Ref. 6; AAQ13650)"
FT /evidence="ECO:0000305"
FT CONFLICT 799..803
FT /note="PDQNE -> LTRMN (in Ref. 6; AAQ13623)"
FT /evidence="ECO:0000305"
FT CONFLICT 820
FT /note="S -> F (in Ref. 6; AAQ13623)"
FT /evidence="ECO:0000305"
FT HELIX 58..69
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:6TRW"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 81..87
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 93..103
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:7AYQ"
FT STRAND 111..121
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 150..158
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 161..164
FT /evidence="ECO:0007829|PDB:7A3L"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:7OR4"
FT TURN 173..175
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 185..190
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 215..220
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 227..232
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 235..240
FT /evidence="ECO:0007829|PDB:6EOP"
FT TURN 241..243
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 255..257
FT /evidence="ECO:0007829|PDB:7AYQ"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 264..268
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 271..276
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 281..285
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:6EOT"
FT STRAND 297..307
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:7OZ7"
FT STRAND 313..317
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 321..323
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 326..330
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 340..350
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 356..366
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 368..371
FT /evidence="ECO:0007829|PDB:6EOP"
FT TURN 372..374
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 375..383
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 390..396
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 401..407
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 409..411
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 412..414
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 419..428
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 436..442
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 453..455
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 463..471
FT /evidence="ECO:0007829|PDB:6EOP"
FT TURN 472..474
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 478..485
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 493..495
FT /evidence="ECO:0007829|PDB:7OR4"
FT TURN 501..504
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 508..514
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 517..519
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 530..532
FT /evidence="ECO:0007829|PDB:6EOP"
FT TURN 533..536
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 537..542
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 551..559
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 569..577
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 581..589
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 591..593
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 596..603
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 609..611
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 613..621
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 634..639
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 643..651
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 660..667
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 678..680
FT /evidence="ECO:0007829|PDB:6EOP"
FT TURN 683..686
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 687..694
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 698..702
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 708..710
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 712..715
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 716..718
FT /evidence="ECO:0007829|PDB:6EOP"
FT TURN 722..724
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 726..740
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 744..754
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 756..767
FT /evidence="ECO:0007829|PDB:6EOP"
FT TURN 769..771
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 772..779
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 784..786
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 789..796
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 799..801
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 803..808
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 811..817
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 820..830
FT /evidence="ECO:0007829|PDB:6EOP"
FT TURN 834..838
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 839..850
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 856..860
FT /evidence="ECO:0007829|PDB:6EOP"
FT STRAND 864..866
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 870..887
FT /evidence="ECO:0007829|PDB:6EOP"
FT HELIX 891..895
FT /evidence="ECO:0007829|PDB:6EOP"
SQ SEQUENCE 898 AA; 103358 MW; 60B0D036F026DE2A CRC64;
MWKRSEQMKI KSGKCNMAAA METEQLGVEI FETADCEENI ESQDRPKLEP FYVERYSWSQ
LKKLLADTRK YHGYMMAKAP HDFMFVKRND PDGPHSDRIY YLAMSGENRE NTLFYSEIPK
TINRAAVLML SWKPLLDLFQ ATLDYGMYSR EEELLRERKR IGTVGIASYD YHQGSGTFLF
QAGSGIYHVK DGGPQGFTQQ PLRPNLVETS CPNIRMDPKL CPADPDWIAF IHSNDIWISN
IVTREERRLT YVHNELANME EDARSAGVAT FVLQEEFDRY SGYWWCPKAE TTPSGGKILR
ILYEENDESE VEIIHVTSPM LETRRADSFR YPKTGTANPK VTFKMSEIMI DAEGRIIDVI
DKELIQPFEI LFEGVEYIAR AGWTPEGKYA WSILLDRSQT RLQIVLISPE LFIPVEDDVM
ERQRLIESVP DSVTPLIIYE ETTDIWINIH DIFHVFPQSH EEEIEFIFAS ECKTGFRHLY
KITSILKESK YKRSSGGLPA PSDFKCPIKE EIAITSGEWE VLGRHGSNIQ VDEVRRLVYF
EGTKDSPLEH HLYVVSYVNP GEVTRLTDRG YSHSCCISQH CDFFISKYSN QKNPHCVSLY
KLSSPEDDPT CKTKEFWATI LDSAGPLPDY TPPEIFSFES TTGFTLYGML YKPHDLQPGK
KYPTVLFIYG GPQVQLVNNR FKGVKYFRLN TLASLGYVVV VIDNRGSCHR GLKFEGAFKY
KMGQIEIDDQ VEGLQYLASR YDFIDLDRVG IHGWSYGGYL SLMALMQRSD IFRVAIAGAP
VTLWIFYDTG YTERYMGHPD QNEQGYYLGS VAMQAEKFPS EPNRLLLLHG FLDENVHFAH
TSILLSFLVR AGKPYDLQIY PQERHSIRVP ESGEHYELHL LHYLQENLGS RIAALKVI
