Full text data of TPP2
TPP2
[Confidence: high (present in two of the MS resources)]
Tripeptidyl-peptidase 2; TPP-2; 3.4.14.10 (Tripeptidyl aminopeptidase; Tripeptidyl-peptidase II; TPP-II)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Tripeptidyl-peptidase 2; TPP-2; 3.4.14.10 (Tripeptidyl aminopeptidase; Tripeptidyl-peptidase II; TPP-II)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00020416
IPI00020416 Tripeptidyl peptidase II Release of an N-terminal tripeptide from a polypeptide, lymphocytes soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00020416 Tripeptidyl peptidase II Release of an N-terminal tripeptide from a polypeptide, lymphocytes soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P29144
ID TPP2_HUMAN Reviewed; 1249 AA.
AC P29144; Q5VZU8;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 124.
DE RecName: Full=Tripeptidyl-peptidase 2;
DE Short=TPP-2;
DE EC=3.4.14.10;
DE AltName: Full=Tripeptidyl aminopeptidase;
DE AltName: Full=Tripeptidyl-peptidase II;
DE Short=TPP-II;
GN Name=TPP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E.,
RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
RA Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M.,
RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
RA Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-55, AND PROTEIN SEQUENCE OF 6-26.
RX PubMed=1840501;
RA Tomkinson B.;
RT "Nucleotide sequence of cDNA covering the N-terminus of human
RT tripeptidyl peptidase II.";
RL Biomed. Biochim. Acta 50:727-729(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 56-1249.
RC TISSUE=Lymphocyte;
RX PubMed=1670990; DOI=10.1021/bi00215a025;
RA Tomkinson B., Jonsson A.-K.;
RT "Characterization of cDNA for human tripeptidyl peptidase II: the N-
RT terminal part of the enzyme is similar to subtilisin.";
RL Biochemistry 30:168-174(1991).
RN [6]
RP PROTEIN SEQUENCE OF 2-18 AND 1036-1046, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V., Quadroni M.;
RL Submitted (JUL-2005) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 13-26; 1099-1118 AND 440-450.
RX PubMed=1691635;
RA Tomkinson B., Zetterqvist O.;
RT "Immunological cross-reactivity between human tripeptidyl peptidase II
RT and fibronectin.";
RL Biochem. J. 267:149-154(1990).
RN [8]
RP PROTEIN SEQUENCE OF 441-450.
RX PubMed=3313395; DOI=10.1073/pnas.84.21.7508;
RA Tomkinson B., Wernstedt C., Hellman U., Zetterqvist O.;
RT "Active site of tripeptidyl peptidase II from human erythrocytes is of
RT the subtilisin type.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:7508-7512(1987).
RN [9]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-1005 AND LYS-1013, AND
RP MASS SPECTROMETRY.
RC TISSUE=Mammary cancer;
RX PubMed=17370265; DOI=10.1002/pmic.200600410;
RA Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.;
RT "Tryptic digestion of ubiquitin standards reveals an improved strategy
RT for identifying ubiquitinated proteins by mass spectrometry.";
RL Proteomics 7:868-874(2007).
RN [10]
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
RT reactive oxygen species-dependent DNA damage responses.";
RL Biochem. Biophys. Res. Commun. 389:575-579(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Component of the proteolytic cascade acting downstream
CC of the 26S proteasome in the ubiquitin-proteasome pathway. May be
CC able to complement the 26S proteasome function to some extent
CC under conditions in which the latter is inhibited (By similarity).
CC -!- CATALYTIC ACTIVITY: Release of an N-terminal tripeptide from a
CC polypeptide.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocates to the
CC nucleus in responce to gamma-irradiation.
CC -!- MISCELLANEOUS: The limitation of proteolytic products to
CC tripeptides is achieved by tailoring the size of the substrate-
CC binding cleft: the two negatively charged residues Glu-305 and
CC Glu-331 that are blocking position P4 limit the number of residues
CC that can be accommodated in the binding cleft and thus create a
CC molecular ruler. At the same time, they orient substrates so that
CC the tripeptides are removed exclusively from the N-terminus (By
CC similarity).
CC -!- SIMILARITY: Belongs to the peptidase S8 family.
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DR EMBL; AL158063; CAH72179.1; -; Genomic_DNA.
DR EMBL; CH471085; EAX09059.1; -; Genomic_DNA.
DR EMBL; BC039905; AAH39905.1; -; mRNA.
DR EMBL; M73047; AAA36760.1; -; mRNA.
DR EMBL; M55169; AAA63263.1; -; mRNA.
DR PIR; S54376; S54376.
DR RefSeq; NP_003282.2; NM_003291.2.
DR UniGene; Hs.432424; -.
DR ProteinModelPortal; P29144; -.
DR SMR; P29144; 20-55, 237-507.
DR DIP; DIP-50761N; -.
DR STRING; 9606.ENSP00000365233; -.
DR ChEMBL; CHEMBL6156; -.
DR MEROPS; S08.090; -.
DR PhosphoSite; P29144; -.
DR DMDM; 34223721; -.
DR PaxDb; P29144; -.
DR PeptideAtlas; P29144; -.
DR PRIDE; P29144; -.
DR Ensembl; ENST00000376065; ENSP00000365233; ENSG00000134900.
DR GeneID; 7174; -.
DR KEGG; hsa:7174; -.
DR UCSC; uc001vpi.4; human.
DR CTD; 7174; -.
DR GeneCards; GC13P103249; -.
DR HGNC; HGNC:12016; TPP2.
DR HPA; HPA021069; -.
DR MIM; 190470; gene.
DR neXtProt; NX_P29144; -.
DR PharmGKB; PA36695; -.
DR eggNOG; COG1404; -.
DR HOGENOM; HOG000008178; -.
DR HOVERGEN; HBG017992; -.
DR KO; K01280; -.
DR OrthoDB; EOG786H2B; -.
DR PhylomeDB; P29144; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P29144; -.
DR GeneWiki; Tripeptidyl_peptidase_II; -.
DR GenomeRNAi; 7174; -.
DR NextBio; 28124; -.
DR PRO; PR:P29144; -.
DR ArrayExpress; P29144; -.
DR Bgee; P29144; -.
DR CleanEx; HS_TPP2; -.
DR Genevestigator; P29144; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004177; F:aminopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:RefGenome.
DR GO; GO:0008240; F:tripeptidyl-peptidase activity; TAS:ProtInc.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:Reactome.
DR GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; IBA:RefGenome.
DR Gene3D; 3.40.50.200; -; 2.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
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 PANTHER; PTHR10795; PTHR10795; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR Pfam; PF12580; TPPII; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF52743; SSF52743; 2.
DR PROSITE; PS00136; SUBTILASE_ASP; FALSE_NEG.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 1: Evidence at protein level;
KW Acetylation; Aminopeptidase; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Isopeptide bond; Nucleus;
KW Protease; Reference proteome; Serine protease; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1249 Tripeptidyl-peptidase 2.
FT /FTId=PRO_0000076422.
FT ACT_SITE 44 44 Charge relay system (By similarity).
FT ACT_SITE 264 264 Charge relay system (By similarity).
FT ACT_SITE 449 449 Charge relay system (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT CROSSLNK 1005 1005 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT CROSSLNK 1013 1013 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT CONFLICT 252 252 G -> R (in Ref. 5; AAA36760).
SQ SEQUENCE 1249 AA; 138350 MW; A26A6249DBF7F3DD CRC64;
MATAATEEPF PFHGLLPKKE TGAASFLCRY PEYDGRGVLI AVLDTGVDPG APGMQVTTDG
KPKIVDIIDT TGSGDVNTAT EVEPKDGEIV GLSGRVLKIP ASWTNPSGKY HIGIKNGYDF
YPKALKERIQ KERKEKIWDP VHRVALAEAC RKQEEFDVAN NGSSQANKLI KEELQSQVEL
LNSFEKKYSD PGPVYDCLVW HDGEVWRACI DSNEDGDLSK STVLRNYKEA QEYGSFGTAE
MLNYSVNIYD DGNLLSIVTS GGAHGTHVAS IAAGHFPEEP ERNGVAPGAQ ILSIKIGDTR
LSTMETGTGL IRAMIEVINH KCDLVNYSYG EATHWPNSGR ICEVINEAVW KHNIIYVSSA
GNNGPCLSTV GCPGGTTSSV IGVGAYVSPD MMVAEYSLRE KLPANQYTWS SRGPSADGAL
GVSISAPGGA IASVPNWTLR GTQLMNGTSM SSPNACGGIA LILSGLKANN IDYTVHSVRR
ALENTAVKAD NIEVFAQGHG IIQVDKAYDY LVQNTSFANK LGFTVTVGNN RGIYLRDPVQ
VAAPSDHGVG IEPVFPENTE NSEKISLQLH LALTSNSSWV QCPSHLELMN QCRHINIRVD
PRGLREGLHY TEVCGYDIAS PNAGPLFRVP ITAVIAAKVN ESSHYDLAFT DVHFKPGQIR
RHFIEVPEGA TWAEVTVCSC SSEVSAKFVL HAVQLVKQRA YRSHEFYKFC SLPEKGTLTE
AFPVLGGKAI EFCIARWWAS LSDVNIDYTI SFHGIVCTAP QLNIHASEGI NRFDVQSSLK
YEDLAPCITL KNWVQTLRPV SAKTKPLGSR DVLPNNRQLY EMVLTYNFHQ PKSGEVTPSC
PLLCELLYES EFDSQLWIIF DQNKRQMGSG DAYPHQYSLK LEKGDYTIRL QIRHEQISDL
ERLKDLPFIV SHRLSNTLSL DIHENHSFAL LGKKKSSNLT LPPKYNQPFF VTSLPDDKIP
KGAGPGCYLA GSLTLSKTEL GKKADVIPVH YYLIPPPTKT KNGSKDKEKD SEKEKDLKEE
FTEALRDLKI QWMTKLDSSD IYNELKETYP NYLPLYVARL HQLDAEKERM KRLNEIVDAA
NAVISHIDQT ALAVYIAMKT DPRPDAATIK NDMDKQKSTL VDALCRKGCA LADHLLHTQA
QDGAISTDAE GKEEEGESPL DSLAETFWET TKWTDLFDNK VLTFAYKHAL VNKMYGRGLK
FATKLVEEKP TKENWKNCIQ LMKLLGWTHC ASFTENWLPI MYPPDYCVF
//
ID TPP2_HUMAN Reviewed; 1249 AA.
AC P29144; Q5VZU8;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 124.
DE RecName: Full=Tripeptidyl-peptidase 2;
DE Short=TPP-2;
DE EC=3.4.14.10;
DE AltName: Full=Tripeptidyl aminopeptidase;
DE AltName: Full=Tripeptidyl-peptidase II;
DE Short=TPP-II;
GN Name=TPP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E.,
RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
RA Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M.,
RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
RA Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-55, AND PROTEIN SEQUENCE OF 6-26.
RX PubMed=1840501;
RA Tomkinson B.;
RT "Nucleotide sequence of cDNA covering the N-terminus of human
RT tripeptidyl peptidase II.";
RL Biomed. Biochim. Acta 50:727-729(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 56-1249.
RC TISSUE=Lymphocyte;
RX PubMed=1670990; DOI=10.1021/bi00215a025;
RA Tomkinson B., Jonsson A.-K.;
RT "Characterization of cDNA for human tripeptidyl peptidase II: the N-
RT terminal part of the enzyme is similar to subtilisin.";
RL Biochemistry 30:168-174(1991).
RN [6]
RP PROTEIN SEQUENCE OF 2-18 AND 1036-1046, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V., Quadroni M.;
RL Submitted (JUL-2005) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 13-26; 1099-1118 AND 440-450.
RX PubMed=1691635;
RA Tomkinson B., Zetterqvist O.;
RT "Immunological cross-reactivity between human tripeptidyl peptidase II
RT and fibronectin.";
RL Biochem. J. 267:149-154(1990).
RN [8]
RP PROTEIN SEQUENCE OF 441-450.
RX PubMed=3313395; DOI=10.1073/pnas.84.21.7508;
RA Tomkinson B., Wernstedt C., Hellman U., Zetterqvist O.;
RT "Active site of tripeptidyl peptidase II from human erythrocytes is of
RT the subtilisin type.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:7508-7512(1987).
RN [9]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-1005 AND LYS-1013, AND
RP MASS SPECTROMETRY.
RC TISSUE=Mammary cancer;
RX PubMed=17370265; DOI=10.1002/pmic.200600410;
RA Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.;
RT "Tryptic digestion of ubiquitin standards reveals an improved strategy
RT for identifying ubiquitinated proteins by mass spectrometry.";
RL Proteomics 7:868-874(2007).
RN [10]
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
RT reactive oxygen species-dependent DNA damage responses.";
RL Biochem. Biophys. Res. Commun. 389:575-579(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Component of the proteolytic cascade acting downstream
CC of the 26S proteasome in the ubiquitin-proteasome pathway. May be
CC able to complement the 26S proteasome function to some extent
CC under conditions in which the latter is inhibited (By similarity).
CC -!- CATALYTIC ACTIVITY: Release of an N-terminal tripeptide from a
CC polypeptide.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocates to the
CC nucleus in responce to gamma-irradiation.
CC -!- MISCELLANEOUS: The limitation of proteolytic products to
CC tripeptides is achieved by tailoring the size of the substrate-
CC binding cleft: the two negatively charged residues Glu-305 and
CC Glu-331 that are blocking position P4 limit the number of residues
CC that can be accommodated in the binding cleft and thus create a
CC molecular ruler. At the same time, they orient substrates so that
CC the tripeptides are removed exclusively from the N-terminus (By
CC similarity).
CC -!- SIMILARITY: Belongs to the peptidase S8 family.
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DR EMBL; AL158063; CAH72179.1; -; Genomic_DNA.
DR EMBL; CH471085; EAX09059.1; -; Genomic_DNA.
DR EMBL; BC039905; AAH39905.1; -; mRNA.
DR EMBL; M73047; AAA36760.1; -; mRNA.
DR EMBL; M55169; AAA63263.1; -; mRNA.
DR PIR; S54376; S54376.
DR RefSeq; NP_003282.2; NM_003291.2.
DR UniGene; Hs.432424; -.
DR ProteinModelPortal; P29144; -.
DR SMR; P29144; 20-55, 237-507.
DR DIP; DIP-50761N; -.
DR STRING; 9606.ENSP00000365233; -.
DR ChEMBL; CHEMBL6156; -.
DR MEROPS; S08.090; -.
DR PhosphoSite; P29144; -.
DR DMDM; 34223721; -.
DR PaxDb; P29144; -.
DR PeptideAtlas; P29144; -.
DR PRIDE; P29144; -.
DR Ensembl; ENST00000376065; ENSP00000365233; ENSG00000134900.
DR GeneID; 7174; -.
DR KEGG; hsa:7174; -.
DR UCSC; uc001vpi.4; human.
DR CTD; 7174; -.
DR GeneCards; GC13P103249; -.
DR HGNC; HGNC:12016; TPP2.
DR HPA; HPA021069; -.
DR MIM; 190470; gene.
DR neXtProt; NX_P29144; -.
DR PharmGKB; PA36695; -.
DR eggNOG; COG1404; -.
DR HOGENOM; HOG000008178; -.
DR HOVERGEN; HBG017992; -.
DR KO; K01280; -.
DR OrthoDB; EOG786H2B; -.
DR PhylomeDB; P29144; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P29144; -.
DR GeneWiki; Tripeptidyl_peptidase_II; -.
DR GenomeRNAi; 7174; -.
DR NextBio; 28124; -.
DR PRO; PR:P29144; -.
DR ArrayExpress; P29144; -.
DR Bgee; P29144; -.
DR CleanEx; HS_TPP2; -.
DR Genevestigator; P29144; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004177; F:aminopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:RefGenome.
DR GO; GO:0008240; F:tripeptidyl-peptidase activity; TAS:ProtInc.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:Reactome.
DR GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; IBA:RefGenome.
DR Gene3D; 3.40.50.200; -; 2.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
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 PANTHER; PTHR10795; PTHR10795; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR Pfam; PF12580; TPPII; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF52743; SSF52743; 2.
DR PROSITE; PS00136; SUBTILASE_ASP; FALSE_NEG.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 1: Evidence at protein level;
KW Acetylation; Aminopeptidase; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Isopeptide bond; Nucleus;
KW Protease; Reference proteome; Serine protease; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1249 Tripeptidyl-peptidase 2.
FT /FTId=PRO_0000076422.
FT ACT_SITE 44 44 Charge relay system (By similarity).
FT ACT_SITE 264 264 Charge relay system (By similarity).
FT ACT_SITE 449 449 Charge relay system (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT CROSSLNK 1005 1005 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT CROSSLNK 1013 1013 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT CONFLICT 252 252 G -> R (in Ref. 5; AAA36760).
SQ SEQUENCE 1249 AA; 138350 MW; A26A6249DBF7F3DD CRC64;
MATAATEEPF PFHGLLPKKE TGAASFLCRY PEYDGRGVLI AVLDTGVDPG APGMQVTTDG
KPKIVDIIDT TGSGDVNTAT EVEPKDGEIV GLSGRVLKIP ASWTNPSGKY HIGIKNGYDF
YPKALKERIQ KERKEKIWDP VHRVALAEAC RKQEEFDVAN NGSSQANKLI KEELQSQVEL
LNSFEKKYSD PGPVYDCLVW HDGEVWRACI DSNEDGDLSK STVLRNYKEA QEYGSFGTAE
MLNYSVNIYD DGNLLSIVTS GGAHGTHVAS IAAGHFPEEP ERNGVAPGAQ ILSIKIGDTR
LSTMETGTGL IRAMIEVINH KCDLVNYSYG EATHWPNSGR ICEVINEAVW KHNIIYVSSA
GNNGPCLSTV GCPGGTTSSV IGVGAYVSPD MMVAEYSLRE KLPANQYTWS SRGPSADGAL
GVSISAPGGA IASVPNWTLR GTQLMNGTSM SSPNACGGIA LILSGLKANN IDYTVHSVRR
ALENTAVKAD NIEVFAQGHG IIQVDKAYDY LVQNTSFANK LGFTVTVGNN RGIYLRDPVQ
VAAPSDHGVG IEPVFPENTE NSEKISLQLH LALTSNSSWV QCPSHLELMN QCRHINIRVD
PRGLREGLHY TEVCGYDIAS PNAGPLFRVP ITAVIAAKVN ESSHYDLAFT DVHFKPGQIR
RHFIEVPEGA TWAEVTVCSC SSEVSAKFVL HAVQLVKQRA YRSHEFYKFC SLPEKGTLTE
AFPVLGGKAI EFCIARWWAS LSDVNIDYTI SFHGIVCTAP QLNIHASEGI NRFDVQSSLK
YEDLAPCITL KNWVQTLRPV SAKTKPLGSR DVLPNNRQLY EMVLTYNFHQ PKSGEVTPSC
PLLCELLYES EFDSQLWIIF DQNKRQMGSG DAYPHQYSLK LEKGDYTIRL QIRHEQISDL
ERLKDLPFIV SHRLSNTLSL DIHENHSFAL LGKKKSSNLT LPPKYNQPFF VTSLPDDKIP
KGAGPGCYLA GSLTLSKTEL GKKADVIPVH YYLIPPPTKT KNGSKDKEKD SEKEKDLKEE
FTEALRDLKI QWMTKLDSSD IYNELKETYP NYLPLYVARL HQLDAEKERM KRLNEIVDAA
NAVISHIDQT ALAVYIAMKT DPRPDAATIK NDMDKQKSTL VDALCRKGCA LADHLLHTQA
QDGAISTDAE GKEEEGESPL DSLAETFWET TKWTDLFDNK VLTFAYKHAL VNKMYGRGLK
FATKLVEEKP TKENWKNCIQ LMKLLGWTHC ASFTENWLPI MYPPDYCVF
//
MIM
190470
*RECORD*
*FIELD* NO
190470
*FIELD* TI
*190470 TRIPEPTIDYL PEPTIDASE II; TPP2
*FIELD* TX
CLONING
Balow et al. (1983) discovered a mammalian peptidase that, at neutral
read morepH, removes tripeptides from the N terminus of longer peptides. Later
designated tripeptidyl peptidase II, it is a high molecular mass serine
exopeptidase, consisting of subunits with molecular mass 135,000. The
amino acid sequence surrounding the serine residue at the active site is
similar to the peptidases of the subtilisin class, whereas other
mammalian serine peptidases are of the trypsin class. The enzyme has
been purified from human erythrocytes. Tomkinson and Jonsson (1991) and
Tomkinson (1991) isolated cDNA clones for the enzyme. The deduced amino
acid sequence, 1,196 residues, shows 56% similarity between its
N-terminal part and the bacterial enzyme subtilisin.
GENE FUNCTION
Geier et al. (1999) reported that mouse TppII copurified with 26S
proteasomes (see 603146) as a large particle. Electron microscopy
displayed a rod-shaped, dynamic supramolecular structure. TppII
exhibited enhanced activity in proteasome inhibitor-adapted cells and
degraded polypeptides by exo- as well as predominantly trypsin-like
endoproteolytic cleavage. The authors suggested that TppII may
participate in extralysosomal polypeptide degradation and may in part
account for nonproteasomal epitope generation as postulated for certain
major histocompatibility complex class I alleles. In addition, TppII may
be able to substitute for some metabolic functions of the proteasome.
Seifert et al. (2003) determined that TPP2 was essential for the
generation of a human immunodeficiency virus-1 (HIV-1)-Nef protein
epitope in dendritic cells and did not require 20S or 26S proteasomes,
which were incapable of generating the epitope in vitro. In vivo,
TPP2-specific small interfering (si)RNA abrogated epitope presentation.
The authors concluded that TPP2 can work in combination with or
independently of the proteasome.
Huai et al. (2008) generated mice lacking Tpp2, which were viable and
appeared normal, but after 1 year had an aged appearance and elevated
mortality. Likewise, thymic involution and thymocyte subpopulations were
slightly altered in the older mutant mice. Splenic and peripheral CD8+ T
cells were decreased in younger and older mice, respectively. The older
mice had pronounced lymphopenia due to apoptosis of stimulated T cells.
Premature cellular senescence also occurred in fibroblasts coinciding
with upregulation of p53 (191170) and dysregulation of Nfkb1 (164011).
Huai et al. (2008) concluded that TPP2 is important for maintaining
normal cellular and systemic physiology.
MAPPING
Martinsson et al. (1993) assigned the TPP2 gene to 13q32-q33 using 2
different methods: first, a full-length TTP2 cDNA was used as a probe on
Southern blots of DNA from a panel of human/rodent somatic cell hybrids;
and second, fluorescence in situ hybridization with the same probe
defined the localization to the region stated. Bermingham et al. (1996)
mapped Tpp2 to mouse chromosome 1, approximately 7 cM distal to Col3a1
(120180).
*FIELD* RF
1. Balow, R.-M.; Ragnarsson, U.; Zetterqvist, O.: Tripeptidyl aminopeptidase
in the extralysosomal fraction of rat liver. J. Biol. Chem. 258:
11622-11628, 1983.
2. Bermingham, N. A.; McKay, T.; Hoyle, J.; Hernandez, D.; Martin,
J. E.; Fisher, E. M. C.: The gene encoding tripeptidyl peptidase
II maps to chromosome 1 in the mouse. Mammalian Genome 7: 390 only,
1996.
3. Geier, E.; Pfeifer, G.; Wilm, M.; Lucchiari-Hartz, M.; Baumeister,
W.; Eichmann, K.; Niedermann, G.: A giant protease with potential
to substitute for some functions of the proteasome. Science 283:
978-981, 1999.
4. Huai, J.; Firat, E.; Nil, A.; Million, D.; Gaedicke, S.; Kanzler,
B.; Freudenberg, M.; van Endert, P.; Kohler, G.; Pahl, H. L.; Aichele,
P.; Eichmann, K.; Niedermann, G.: Activation of cellular death programs
associated with immunosenescence-like phenotype in TPPII knockout
mice. Proc. Nat. Acad. Sci. 105: 5177-5182, 2008.
5. Martinsson, T.; Vujic, M.; Tomkinson, B.: Localization of the
human tripeptidyl peptidase II gene (TPP2) to 13q32-q33 by nonradioactive
in situ hybridization and somatic cell hybrids. Genomics 17: 493-495,
1993.
6. Seifert, U.; Maranon, C.; Shmueli, A.; Desoutter, J.-F.; Wesoloski,
L.; Janek, K.; Henklein, P.; Diescher, S.; Andrieu, M.; de la Salle,
H.; Weinschenk, T.; Schild, H.; Laderach, D.; Galy, A.; Haas, G.;
Kloetzel, P.-M.; Reiss, Y.; Hosmalin, A.: An essential role for tripeptidyl
peptidase in the generation of an MHC class I epitope. Nature Immun. 4:
375-379, 2003.
7. Tomkinson, B.: Nucleotide sequence of cDNA covering the N-terminus
of human tripeptidyl peptidase II. Biomed. Biochim. Acta 50: 727-729,
1991.
8. Tomkinson, B.; Jonsson, A.-K.: Characterization of cDNA for human
tripeptidyl peptidase II: the N-terminal part of the enzyme is similar
to subtilisin. Biochemistry 30: 168-174, 1991.
*FIELD* CN
Paul J. Converse - updated: 6/24/2008
Paul J. Converse - updated: 3/5/2003
Rebekah S. Rasooly - updated: 2/11/1999
*FIELD* CD
Victor A. McKusick: 7/1/1993
*FIELD* ED
alopez: 06/26/2008
terry: 6/24/2008
alopez: 4/2/2003
mgross: 3/5/2003
kayiaros: 7/13/1999
alopez: 2/11/1999
terry: 6/11/1996
carol: 11/10/1993
carol: 10/28/1993
carol: 8/23/1993
carol: 7/1/1993
*RECORD*
*FIELD* NO
190470
*FIELD* TI
*190470 TRIPEPTIDYL PEPTIDASE II; TPP2
*FIELD* TX
CLONING
Balow et al. (1983) discovered a mammalian peptidase that, at neutral
read morepH, removes tripeptides from the N terminus of longer peptides. Later
designated tripeptidyl peptidase II, it is a high molecular mass serine
exopeptidase, consisting of subunits with molecular mass 135,000. The
amino acid sequence surrounding the serine residue at the active site is
similar to the peptidases of the subtilisin class, whereas other
mammalian serine peptidases are of the trypsin class. The enzyme has
been purified from human erythrocytes. Tomkinson and Jonsson (1991) and
Tomkinson (1991) isolated cDNA clones for the enzyme. The deduced amino
acid sequence, 1,196 residues, shows 56% similarity between its
N-terminal part and the bacterial enzyme subtilisin.
GENE FUNCTION
Geier et al. (1999) reported that mouse TppII copurified with 26S
proteasomes (see 603146) as a large particle. Electron microscopy
displayed a rod-shaped, dynamic supramolecular structure. TppII
exhibited enhanced activity in proteasome inhibitor-adapted cells and
degraded polypeptides by exo- as well as predominantly trypsin-like
endoproteolytic cleavage. The authors suggested that TppII may
participate in extralysosomal polypeptide degradation and may in part
account for nonproteasomal epitope generation as postulated for certain
major histocompatibility complex class I alleles. In addition, TppII may
be able to substitute for some metabolic functions of the proteasome.
Seifert et al. (2003) determined that TPP2 was essential for the
generation of a human immunodeficiency virus-1 (HIV-1)-Nef protein
epitope in dendritic cells and did not require 20S or 26S proteasomes,
which were incapable of generating the epitope in vitro. In vivo,
TPP2-specific small interfering (si)RNA abrogated epitope presentation.
The authors concluded that TPP2 can work in combination with or
independently of the proteasome.
Huai et al. (2008) generated mice lacking Tpp2, which were viable and
appeared normal, but after 1 year had an aged appearance and elevated
mortality. Likewise, thymic involution and thymocyte subpopulations were
slightly altered in the older mutant mice. Splenic and peripheral CD8+ T
cells were decreased in younger and older mice, respectively. The older
mice had pronounced lymphopenia due to apoptosis of stimulated T cells.
Premature cellular senescence also occurred in fibroblasts coinciding
with upregulation of p53 (191170) and dysregulation of Nfkb1 (164011).
Huai et al. (2008) concluded that TPP2 is important for maintaining
normal cellular and systemic physiology.
MAPPING
Martinsson et al. (1993) assigned the TPP2 gene to 13q32-q33 using 2
different methods: first, a full-length TTP2 cDNA was used as a probe on
Southern blots of DNA from a panel of human/rodent somatic cell hybrids;
and second, fluorescence in situ hybridization with the same probe
defined the localization to the region stated. Bermingham et al. (1996)
mapped Tpp2 to mouse chromosome 1, approximately 7 cM distal to Col3a1
(120180).
*FIELD* RF
1. Balow, R.-M.; Ragnarsson, U.; Zetterqvist, O.: Tripeptidyl aminopeptidase
in the extralysosomal fraction of rat liver. J. Biol. Chem. 258:
11622-11628, 1983.
2. Bermingham, N. A.; McKay, T.; Hoyle, J.; Hernandez, D.; Martin,
J. E.; Fisher, E. M. C.: The gene encoding tripeptidyl peptidase
II maps to chromosome 1 in the mouse. Mammalian Genome 7: 390 only,
1996.
3. Geier, E.; Pfeifer, G.; Wilm, M.; Lucchiari-Hartz, M.; Baumeister,
W.; Eichmann, K.; Niedermann, G.: A giant protease with potential
to substitute for some functions of the proteasome. Science 283:
978-981, 1999.
4. Huai, J.; Firat, E.; Nil, A.; Million, D.; Gaedicke, S.; Kanzler,
B.; Freudenberg, M.; van Endert, P.; Kohler, G.; Pahl, H. L.; Aichele,
P.; Eichmann, K.; Niedermann, G.: Activation of cellular death programs
associated with immunosenescence-like phenotype in TPPII knockout
mice. Proc. Nat. Acad. Sci. 105: 5177-5182, 2008.
5. Martinsson, T.; Vujic, M.; Tomkinson, B.: Localization of the
human tripeptidyl peptidase II gene (TPP2) to 13q32-q33 by nonradioactive
in situ hybridization and somatic cell hybrids. Genomics 17: 493-495,
1993.
6. Seifert, U.; Maranon, C.; Shmueli, A.; Desoutter, J.-F.; Wesoloski,
L.; Janek, K.; Henklein, P.; Diescher, S.; Andrieu, M.; de la Salle,
H.; Weinschenk, T.; Schild, H.; Laderach, D.; Galy, A.; Haas, G.;
Kloetzel, P.-M.; Reiss, Y.; Hosmalin, A.: An essential role for tripeptidyl
peptidase in the generation of an MHC class I epitope. Nature Immun. 4:
375-379, 2003.
7. Tomkinson, B.: Nucleotide sequence of cDNA covering the N-terminus
of human tripeptidyl peptidase II. Biomed. Biochim. Acta 50: 727-729,
1991.
8. Tomkinson, B.; Jonsson, A.-K.: Characterization of cDNA for human
tripeptidyl peptidase II: the N-terminal part of the enzyme is similar
to subtilisin. Biochemistry 30: 168-174, 1991.
*FIELD* CN
Paul J. Converse - updated: 6/24/2008
Paul J. Converse - updated: 3/5/2003
Rebekah S. Rasooly - updated: 2/11/1999
*FIELD* CD
Victor A. McKusick: 7/1/1993
*FIELD* ED
alopez: 06/26/2008
terry: 6/24/2008
alopez: 4/2/2003
mgross: 3/5/2003
kayiaros: 7/13/1999
alopez: 2/11/1999
terry: 6/11/1996
carol: 11/10/1993
carol: 10/28/1993
carol: 8/23/1993
carol: 7/1/1993