TPP2_RAT
ID TPP2_RAT Reviewed; 1249 AA.
AC Q64560;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 156.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=8602240; DOI=10.1038/380403a0;
RA Rose C., Vargas F., Facchinetti P., Bourgeat P., Bambal R.B., Bishop P.B.,
RA Chan S.M., Moore A.N., Ganellin C.R., Schwartz J.C.;
RT "Characterization and inhibition of a cholecystokinin-inactivating serine
RT peptidase.";
RL Nature 380:403-409(1996).
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 (By
CC similarity). {ECO:0000250|UniProtKB:P29144,
CC ECO:0000250|UniProtKB:Q64514}.
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. Nucleus. Note=Translocates to the
CC nucleus in response to gamma-irradiation. {ECO:0000250}.
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; U50194; AAA93458.1; -; mRNA.
DR PIR; S68431; S68431.
DR RefSeq; NP_112399.1; NM_031137.1.
DR AlphaFoldDB; Q64560; -.
DR SMR; Q64560; -.
DR BioGRID; 249673; 1.
DR IntAct; Q64560; 18.
DR STRING; 10116.ENSRNOP00000015393; -.
DR BindingDB; Q64560; -.
DR ChEMBL; CHEMBL4675; -.
DR MEROPS; S08.A56; -.
DR iPTMnet; Q64560; -.
DR PhosphoSitePlus; Q64560; -.
DR jPOST; Q64560; -.
DR PaxDb; Q64560; -.
DR PRIDE; Q64560; -.
DR GeneID; 81815; -.
DR KEGG; rno:81815; -.
DR UCSC; RGD:621584; rat.
DR CTD; 7174; -.
DR RGD; 621584; Tpp2.
DR VEuPathDB; HostDB:ENSRNOG00000011194; -.
DR eggNOG; KOG1114; Eukaryota.
DR InParanoid; Q64560; -.
DR OMA; SLRDFQC; -.
DR OrthoDB; 719835at2759; -.
DR BRENDA; 3.4.14.10; 5301.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR PRO; PR:Q64560; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000011194; Expressed in esophagus and 19 other tissues.
DR Genevisible; Q64560; RN.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004177; F:aminopeptidase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0042277; F:peptide binding; IDA:RGD.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0008240; F:tripeptidyl-peptidase activity; IDA:RGD.
DR GO; GO:0080144; P:amino acid homeostasis; ISO:RGD.
DR GO; GO:0030163; P:protein catabolic process; IDA:RGD.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd04857; Peptidases_S8_Tripeptidyl_Aminopeptidase_II; 1.
DR Gene3D; 3.40.50.200; -; 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; IPR022229; Peptidase_S8A_TPPII.
DR InterPro; IPR034051; TPP_II_domain.
DR Pfam; PF00082; Peptidase_S8; 1.
DR Pfam; PF12580; TPPII; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF52743; SSF52743; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Aminopeptidase; Cytoplasm; Hydrolase; Nucleus; Phosphoprotein;
KW Protease; Reference proteome; Serine protease.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P29144"
FT CHAIN 2..1249
FT /note="Tripeptidyl-peptidase 2"
FT /id="PRO_0000076424"
FT DOMAIN 9..508
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT REGION 998..1018
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1001..1018
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:0000250|UniProtKB:Q64514"
FT MOD_RES 915
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29144"
SQ SEQUENCE 1249 AA; 138293 MW; F4A41664028AAB2B CRC64;
MATAATEEPF PFHGLLPKKE TGASSFLCRY PEYDGRGVLI AVLDTGVDPG APGMQVTTDG
KPKIIDIIDT TGSGDVNTAT EVEPKDGEIT GLSGRVLKIP ANWTNPSGKY HIGIKNGYDF
YPKALKERIQ KERKEKIWDP IHRVALAEAC RKQEEFDIAN NGSSQANKLI KEELQSQVEL
LNSFEKKYSD PGPVYDCLVW HDGETWRACV DSNENGDLGK STVLRNYKEA QEYGSFGTAE
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 GKKADVIPVH YYLIPPPTKT KNGSKDKEKD SEKEKDLKEE
FTEALRDLKI QWMTKLDSTD IYNELKETYP AYLPLYVARL HQLDAEKERM KRLNEIVDAA
NAVISHIDQT ALAVYIAMKT DPRPDAATIK NDMDKQKSTL VDALCRKGCA LADHLLHAQP
HDGAAAGDAE AKEEEGESTL ESLSETYWET TKWTDLFDTK VLTFAYKHAL VNKMYGRGLK
FATKLVEEKP TKENWKNCIQ LMKLLGWTHC ASFTENWLPI MYPPDYCVF
