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P29144 (TPP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tripeptidyl-peptidase 2

Short name=TPP-2
EC=3.4.14.10
Alternative name(s):
Tripeptidyl aminopeptidase
Tripeptidyl-peptidase II
Short name=TPP-II
Gene names
Name:TPP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1249 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway. May be able to complement the 26S proteasome function to some extent under conditions in which the latter is inhibited By similarity.

Catalytic activity

Release of an N-terminal tripeptide from a polypeptide.

Subcellular location

Cytoplasm. Nucleus. Note: Translocates to the nucleus in responce to gamma-irradiation. Ref.10

Miscellaneous

The limitation of proteolytic products to tripeptides is achieved by tailoring the size of the substrate-binding cleft: the two negatively charged residues Glu-305 and Glu-331 that are blocking position P4 limit the number of residues that can be accommodated in the binding cleft and thus create a molecular ruler. At the same time, they orient substrates so that the tripeptides are removed exclusively from the N-terminus By similarity.

Sequence similarities

Belongs to the peptidase S8 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.6
Chain2 – 12491248Tripeptidyl-peptidase 2
PRO_0000076422

Sites

Active site441Charge relay system By similarity
Active site2641Charge relay system By similarity
Active site4491Charge relay system By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.6
Modified residue4011N6-acetyllysine By similarity
Cross-link1005Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
Cross-link1013Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9

Experimental info

Sequence conflict2521G → R in AAA36760. Ref.5

Sequences

Sequence LengthMass (Da)Tools
P29144 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: A26A6249DBF7F3DD

FASTA1,249138,350
        10         20         30         40         50         60 
MATAATEEPF PFHGLLPKKE TGAASFLCRY PEYDGRGVLI AVLDTGVDPG APGMQVTTDG 

        70         80         90        100        110        120 
KPKIVDIIDT TGSGDVNTAT EVEPKDGEIV GLSGRVLKIP ASWTNPSGKY HIGIKNGYDF 

       130        140        150        160        170        180 
YPKALKERIQ KERKEKIWDP VHRVALAEAC RKQEEFDVAN NGSSQANKLI KEELQSQVEL 

       190        200        210        220        230        240 
LNSFEKKYSD PGPVYDCLVW HDGEVWRACI DSNEDGDLSK STVLRNYKEA QEYGSFGTAE 

       250        260        270        280        290        300 
MLNYSVNIYD DGNLLSIVTS GGAHGTHVAS IAAGHFPEEP ERNGVAPGAQ ILSIKIGDTR 

       310        320        330        340        350        360 
LSTMETGTGL IRAMIEVINH KCDLVNYSYG EATHWPNSGR ICEVINEAVW KHNIIYVSSA 

       370        380        390        400        410        420 
GNNGPCLSTV GCPGGTTSSV IGVGAYVSPD MMVAEYSLRE KLPANQYTWS SRGPSADGAL 

       430        440        450        460        470        480 
GVSISAPGGA IASVPNWTLR GTQLMNGTSM SSPNACGGIA LILSGLKANN IDYTVHSVRR 

       490        500        510        520        530        540 
ALENTAVKAD NIEVFAQGHG IIQVDKAYDY LVQNTSFANK LGFTVTVGNN RGIYLRDPVQ 

       550        560        570        580        590        600 
VAAPSDHGVG IEPVFPENTE NSEKISLQLH LALTSNSSWV QCPSHLELMN QCRHINIRVD 

       610        620        630        640        650        660 
PRGLREGLHY TEVCGYDIAS PNAGPLFRVP ITAVIAAKVN ESSHYDLAFT DVHFKPGQIR 

       670        680        690        700        710        720 
RHFIEVPEGA TWAEVTVCSC SSEVSAKFVL HAVQLVKQRA YRSHEFYKFC SLPEKGTLTE 

       730        740        750        760        770        780 
AFPVLGGKAI EFCIARWWAS LSDVNIDYTI SFHGIVCTAP QLNIHASEGI NRFDVQSSLK 

       790        800        810        820        830        840 
YEDLAPCITL KNWVQTLRPV SAKTKPLGSR DVLPNNRQLY EMVLTYNFHQ PKSGEVTPSC 

       850        860        870        880        890        900 
PLLCELLYES EFDSQLWIIF DQNKRQMGSG DAYPHQYSLK LEKGDYTIRL QIRHEQISDL 

       910        920        930        940        950        960 
ERLKDLPFIV SHRLSNTLSL DIHENHSFAL LGKKKSSNLT LPPKYNQPFF VTSLPDDKIP 

       970        980        990       1000       1010       1020 
KGAGPGCYLA GSLTLSKTEL GKKADVIPVH YYLIPPPTKT KNGSKDKEKD SEKEKDLKEE 

      1030       1040       1050       1060       1070       1080 
FTEALRDLKI QWMTKLDSSD IYNELKETYP NYLPLYVARL HQLDAEKERM KRLNEIVDAA 

      1090       1100       1110       1120       1130       1140 
NAVISHIDQT ALAVYIAMKT DPRPDAATIK NDMDKQKSTL VDALCRKGCA LADHLLHTQA 

      1150       1160       1170       1180       1190       1200 
QDGAISTDAE GKEEEGESPL DSLAETFWET TKWTDLFDNK VLTFAYKHAL VNKMYGRGLK 

      1210       1220       1230       1240 
FATKLVEEKP TKENWKNCIQ LMKLLGWTHC ASFTENWLPI MYPPDYCVF 

« Hide

References

« Hide 'large scale' references
[1]"The DNA sequence and analysis of human chromosome 13."
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[4]"Nucleotide sequence of cDNA covering the N-terminus of human tripeptidyl peptidase II."
Tomkinson B.
Biomed. Biochim. Acta 50:727-729(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-55, PROTEIN SEQUENCE OF 6-26.
[5]"Characterization of cDNA for human tripeptidyl peptidase II: the N-terminal part of the enzyme is similar to subtilisin."
Tomkinson B., Jonsson A.-K.
Biochemistry 30:168-174(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 56-1249.
Tissue: Lymphocyte.
[6]Bienvenut W.V., Quadroni M.
Submitted (JUL-2005) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-18 AND 1036-1046, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: B-cell lymphoma.
[7]"Immunological cross-reactivity between human tripeptidyl peptidase II and fibronectin."
Tomkinson B., Zetterqvist O.
Biochem. J. 267:149-154(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 13-26; 1099-1118 AND 440-450.
[8]"Active site of tripeptidyl peptidase II from human erythrocytes is of the subtilisin type."
Tomkinson B., Wernstedt C., Hellman U., Zetterqvist O.
Proc. Natl. Acad. Sci. U.S.A. 84:7508-7512(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 441-450.
[9]"Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry."
Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.
Proteomics 7:868-874(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-1005 AND LYS-1013.
Tissue: Mammary cancer.
[10]"A role for nuclear translocation of tripeptidyl-peptidase II in reactive oxygen species-dependent DNA damage responses."
Preta G., de Klark R., Glas R.
Biochem. Biophys. Res. Commun. 389:575-579(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[11]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AL158063 Genomic DNA. Translation: CAH72179.1.
CH471085 Genomic DNA. Translation: EAX09059.1.
BC039905 mRNA. Translation: AAH39905.1.
M73047 mRNA. Translation: AAA36760.1.
M55169 mRNA. Translation: AAA63263.1.
CCDSCCDS9502.1.
PIRS54376.
RefSeqNP_003282.2. NM_003291.2.
UniGeneHs.432424.

3D structure databases

ProteinModelPortalP29144.
SMRP29144. Positions 20-55, 237-507.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113027. 7 interactions.
DIPDIP-50761N.
STRING9606.ENSP00000365233.

Chemistry

ChEMBLCHEMBL6156.

Protein family/group databases

MEROPSS08.090.

PTM databases

PhosphoSiteP29144.

Polymorphism databases

DMDM34223721.

Proteomic databases

MaxQBP29144.
PaxDbP29144.
PeptideAtlasP29144.
PRIDEP29144.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000376065; ENSP00000365233; ENSG00000134900.
GeneID7174.
KEGGhsa:7174.
UCSCuc001vpi.4. human.

Organism-specific databases

CTD7174.
GeneCardsGC13P103249.
HGNCHGNC:12016. TPP2.
HPAHPA021069.
MIM190470. gene.
neXtProtNX_P29144.
PharmGKBPA36695.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1404.
HOGENOMHOG000008178.
HOVERGENHBG017992.
KOK01280.
OrthoDBEOG786H2B.
PhylomeDBP29144.
TreeFamTF105647.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkP29144.

Gene expression databases

ArrayExpressP29144.
BgeeP29144.
CleanExHS_TPP2.
GenevestigatorP29144.

Family and domain databases

Gene3D3.40.50.200. 2 hits.
InterProIPR000209. Peptidase_S8/S53_dom.
IPR022398. Peptidase_S8_His-AS.
IPR023828. Peptidase_S8_Ser-AS.
IPR015500. Peptidase_S8_subtilisin-rel.
IPR022229. Peptidase_S8A_TPPII.
[Graphical view]
PANTHERPTHR10795. PTHR10795. 1 hit.
PfamPF00082. Peptidase_S8. 1 hit.
PF12580. TPPII. 1 hit.
[Graphical view]
PRINTSPR00723. SUBTILISIN.
SUPFAMSSF52743. SSF52743. 2 hits.
PROSITEPS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTripeptidyl_peptidase_II.
GenomeRNAi7174.
NextBio28124.
PROP29144.
SOURCESearch...

Entry information

Entry nameTPP2_HUMAN
AccessionPrimary (citable) accession number: P29144
Secondary accession number(s): Q5VZU8
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 130 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM