ID TPP2_MOUSE Reviewed; 1262 AA.
AC Q64514; Q5D072;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 179.
DE RecName: Full=Tripeptidyl-peptidase 2;
DE Short=TPP-2;
DE EC=3.4.14.10 {ECO:0000250|UniProtKB:P29144};
DE AltName: Full=Tripeptidyl aminopeptidase;
DE AltName: Full=Tripeptidyl-peptidase II;
DE Short=TPP-II;
GN Name=Tpp2;
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] (ISOFORMS LONG AND SHORT).
RC STRAIN=Leaden X A1;
RX PubMed=7998988; DOI=10.1042/bj3040517;
RA Tomkinson B.;
RT "Characterization of cDNA for murine tripeptidyl-peptidase II reveals
RT alternative splicing.";
RL Biochem. J. 304:517-523(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
RC TISSUE=Olfactory epithelium;
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 FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP ASP-44.
RX PubMed=17932511; DOI=10.1038/sj.embor.7401086;
RA McKay R.M., McKay J.P., Suh J.M., Avery L., Graff J.M.;
RT "Tripeptidyl peptidase II promotes fat formation in a conserved fashion.";
RL EMBO Rep. 8:1183-1189(2007).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=19747897; DOI=10.1016/j.bbrc.2009.09.021;
RA Preta G., de Klark R., Glas R.;
RT "A role for nuclear translocation of tripeptidyl-peptidase II in reactive
RT oxygen species-dependent DNA damage responses.";
RL Biochem. Biophys. Res. Commun. 389:575-579(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC 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 [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-401, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Cytosolic tripeptidyl-peptidase that releases N-terminal
CC tripeptides from polypeptides and is a component of the proteolytic
CC cascade acting downstream of the 26S proteasome in the ubiquitin-
CC proteasome pathway. It plays an important role in intracellular amino
CC acid homeostasis (By similarity). Stimulates adipogenesis
CC (PubMed:17932511). {ECO:0000250|UniProtKB:P29144,
CC ECO:0000269|PubMed:17932511}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal tripeptide from a polypeptide.;
CC EC=3.4.14.10; Evidence={ECO:0000250|UniProtKB:P29144};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19747897}. Nucleus
CC {ECO:0000269|PubMed:19747897}. Note=Translocates to the nucleus in
CC response to gamma-irradiation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=Q64514-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q64514-2; Sequence=VSP_005446;
CC -!- TISSUE SPECIFICITY: Expressed in the brain, skeletal muscle, gonadal
CC and mesenteric white adipose tissue and brown adipose tissues.
CC {ECO:0000269|PubMed:17932511}.
CC -!- DISRUPTION PHENOTYPE: Homozygous mutant mice die in utero before
CC embryonic day 9.0. Heterozygous mice display normal food intake but
CC appear lean with a significant reduction in body fat, smaller
CC adipocytes, decreased plasma insulin levels and less white adipose
CC tissue in the gonad, groin and mesenteric regions.
CC {ECO:0000269|PubMed:17932511}.
CC -!- MISCELLANEOUS: The limitation of proteolytic products to tripeptides is
CC achieved by tailoring the size of the substrate-binding cleft: the two
CC negatively charged residues Glu-305 and Glu-331 that are blocking
CC position P4 limit the number of residues that can be accommodated in
CC the binding cleft and thus create a molecular ruler. At the same time,
CC they orient substrates so that the tripeptides are removed exclusively
CC from the N-terminus (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000305}.
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DR EMBL; X81323; CAA57103.1; -; mRNA.
DR EMBL; BC058239; AAH58239.1; -; mRNA.
DR CCDS; CCDS14926.1; -. [Q64514-1]
DR CCDS; CCDS78577.1; -. [Q64514-2]
DR PIR; I48855; I48855.
DR RefSeq; NP_001297469.1; NM_001310540.1. [Q64514-2]
DR RefSeq; NP_033444.1; NM_009418.3. [Q64514-1]
DR AlphaFoldDB; Q64514; -.
DR SMR; Q64514; -.
DR BioGRID; 204295; 6.
DR CORUM; Q64514; -.
DR IntAct; Q64514; 1.
DR STRING; 10090.ENSMUSP00000085244; -.
DR ChEMBL; CHEMBL5512; -.
DR MEROPS; S08.A56; -.
DR GlyGen; Q64514; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q64514; -.
DR PhosphoSitePlus; Q64514; -.
DR SwissPalm; Q64514; -.
DR EPD; Q64514; -.
DR jPOST; Q64514; -.
DR MaxQB; Q64514; -.
DR PaxDb; 10090-ENSMUSP00000085244; -.
DR PeptideAtlas; Q64514; -.
DR ProteomicsDB; 258830; -. [Q64514-1]
DR ProteomicsDB; 258831; -. [Q64514-2]
DR Pumba; Q64514; -.
DR Antibodypedia; 11138; 174 antibodies from 26 providers.
DR DNASU; 22019; -.
DR Ensembl; ENSMUST00000087933.10; ENSMUSP00000085244.4; ENSMUSG00000041763.15. [Q64514-1]
DR Ensembl; ENSMUST00000188313.7; ENSMUSP00000139918.2; ENSMUSG00000041763.15. [Q64514-2]
DR GeneID; 22019; -.
DR KEGG; mmu:22019; -.
DR UCSC; uc007avs.1; mouse. [Q64514-1]
DR UCSC; uc007avt.1; mouse. [Q64514-2]
DR AGR; MGI:102724; -.
DR CTD; 7174; -.
DR MGI; MGI:102724; Tpp2.
DR VEuPathDB; HostDB:ENSMUSG00000041763; -.
DR eggNOG; KOG1114; Eukaryota.
DR GeneTree; ENSGT00390000014623; -.
DR InParanoid; Q64514; -.
DR OMA; SLRDFQC; -.
DR OrthoDB; 2441948at2759; -.
DR PhylomeDB; Q64514; -.
DR TreeFam; TF105647; -.
DR BRENDA; 3.4.14.10; 3474.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR BioGRID-ORCS; 22019; 1 hit in 61 CRISPR screens.
DR ChiTaRS; Tpp2; mouse.
DR PRO; PR:Q64514; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q64514; Protein.
DR Bgee; ENSMUSG00000041763; Expressed in spermatid and 248 other cell types or tissues.
DR ExpressionAtlas; Q64514; baseline and differential.
DR Genevisible; Q64514; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0004177; F:aminopeptidase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0042277; F:peptide binding; ISO:MGI.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0008240; F:tripeptidyl-peptidase activity; ISO:MGI.
DR GO; GO:0080144; P:intracellular amino acid homeostasis; ISO:MGI.
DR GO; GO:0030163; P:protein catabolic process; ISO:MGI.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd04857; Peptidases_S8_Tripeptidyl_Aminopeptidase_II; 1.
DR Gene3D; 1.25.40.710; -; 1.
DR Gene3D; 2.60.40.3170; -; 1.
DR Gene3D; 6.10.250.3080; -; 1.
DR Gene3D; 3.40.50.200; Peptidase S8/S53 domain; 2.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR022398; Peptidase_S8_His-AS.
DR InterPro; IPR023828; Peptidase_S8_Ser-AS.
DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR InterPro; IPR034051; TPP_II_domain.
DR InterPro; IPR022232; TPPII_C_art.
DR InterPro; IPR046939; TPPII_C_sf.
DR InterPro; IPR048384; TPPII_GBD.
DR InterPro; IPR048383; TPPII_Ig-like-1.
DR InterPro; IPR022229; TPPII_Ig-like-2.
DR InterPro; IPR046940; TPPII_Ig-like_sf.
DR PANTHER; PTHR43806; PEPTIDASE S8; 1.
DR PANTHER; PTHR43806:SF14; TRIPEPTIDYL-PEPTIDASE 2; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR Pfam; PF12580; TPPII; 1.
DR Pfam; PF12583; TPPII_C; 1.
DR Pfam; PF21316; TPPII_GBD; 1.
DR Pfam; PF21223; TPPII_Ig-like-1; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF52743; Subtilisin-like; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Aminopeptidase; Cytoplasm; Hydrolase;
KW Nucleus; Phosphoprotein; Protease; Reference proteome; Serine protease.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P29144"
FT CHAIN 2..1262
FT /note="Tripeptidyl-peptidase 2"
FT /id="PRO_0000076423"
FT DOMAIN 9..508
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT REGION 1010..1030
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1014..1030
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 44
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 264
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 449
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P29144"
FT MOD_RES 401
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 915
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29144"
FT VAR_SEQ 985..997
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7998988"
FT /id="VSP_005446"
FT MUTAGEN 44
FT /note="D->A: No effect on adipogenesis."
FT /evidence="ECO:0000269|PubMed:17932511"
SQ SEQUENCE 1262 AA; 139879 MW; D50D22C85544B034 CRC64;
MATAATEEPF PFHGLLPKKE TGASSFLCRY PEYDGRGVLI AVLDTGVDPG APGMQVTTDG
KPKIIDIIDT TGSGDVNTAT EVEPKDGEII GLSGRVLKIP ANWTNPLGKY HIGIKNGYDF
YPKALKERIQ KERKEKIWDP IHRVALAEAC RKQEEFDIAN NGSSQANKLI KEELQSQVEL
LNSFEKKYSD PGPVYDCLVW HDGETWRACV DSNENGDLSK CAVLRNYKEA QEYSSFGTAE
MLNYSVNIYD DGNLLSIVTS GGAHGTHVAS IAAGHFPEEP ERNGVAPGAQ ILSIKIGDTR
LSTMETGTGL IRAMIEVINH KCDLVNYSYG EATHWPNSGR ICEVINEAVW KHNTIYVSSA
GNNGPCLSTV GCPGGTTSSV IGVGAYVSPD MMVAEYSLRE KLPANQYTWS SRGPSADGAL
GVSISAPGGA IASVPNWTLR GTQLMNGTSM SSPNACGGIA LVLSGLKANN VDYTVHSVRR
ALENTAIKAD NIEVFAQGHG IIQVDKAYDY LIQNTSFANR LGFTVTVGNN RGIYLRDPVQ
VAAPSDHGVG IEPVFPENTE NSEKISFQLH LALTSNSSWV QCPSHLELMN QCRHINIRVD
PRGLREGLHY TEVCGYDIAS PNAGPLFRVP ITAVIAAKVN ESSHYDLAFT DVHFKPGQIR
RHFVEVPEGA TWAEVTVCSC SSEVSAKFVL HAVQLVKQRA YRSHEFYKFC SLPEKGTLIE
AFPVLGGKAI EFCIARWWAS LSDVNIDYTI SFHGIVCTAP QLNIHASEGI NRFDVQSSLK
YEDLAPCITL KSWVQTLRPV NAKTRPLGSR DVLPNNRQLY EMVLTYSFHQ PKSGEVTPSC
PLLCELLYES EFDSQLWIIF DQNKRQMGSG DAYPHQYSLK LEKGDYTIRL QIRHEQISDL
DRLKDLPFIV SHRLSNTLSL DIHENHSLAL LGKKKSSSLT LPPKYNQPFF VTSLPDDKIP
KGAGPGCYLA GSLTLSKTEL GKKAGQSAAK RQGKFKKDVI PVHYYLIPPP TKIKNGSKDK
EKDSEKEKDL KEEFTEALRD LKIQWMTKLD STDIYNELKE TYPAYLPLYV ARLHQLDAEK
ERMKRLNEIV DAANAVISHI DQTALAVYIA MKTDPRPDAA TIKNDMDKQK STLIDALCRK
GCALADHLLH TQPHDGAAAG DAEAKEEEGE STMESLSETY WETTKWTDLF DTKVLIFAYK
HALVNKMYGR GLKFATKLVE EKPTKENWKN CIQLMKLLGW THCASFTENW LPIMYPPDYC
VF
//
