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P29144

- TPP2_HUMAN

UniProt

P29144 - TPP2_HUMAN

Protein

Tripeptidyl-peptidase 2

Gene

TPP2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 132 (01 Oct 2014)
      Sequence version 4 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    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. Stimulates adipogenesis By similarity.By similarity

    Catalytic activityi

    Release of an N-terminal tripeptide from a polypeptide.PROSITE-ProRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei44 – 441Charge relay systemBy similarity
    Active sitei264 – 2641Charge relay systemBy similarity
    Active sitei449 – 4491Charge relay systemBy similarity

    GO - Molecular functioni

    1. aminopeptidase activity Source: UniProtKB-KW
    2. endopeptidase activity Source: ProtInc
    3. serine-type endopeptidase activity Source: RefGenome
    4. tripeptidyl-peptidase activity Source: ProtInc

    GO - Biological processi

    1. antigen processing and presentation of peptide antigen via MHC class I Source: Reactome
    2. protein polyubiquitination Source: Reactome
    3. proteolysis Source: RefGenome

    Keywords - Molecular functioni

    Aminopeptidase, Hydrolase, Protease, Serine protease

    Enzyme and pathway databases

    ReactomeiREACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
    SignaLinkiP29144.

    Protein family/group databases

    MEROPSiS08.090.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tripeptidyl-peptidase 2 (EC:3.4.14.10)
    Short name:
    TPP-2
    Alternative name(s):
    Tripeptidyl aminopeptidase
    Tripeptidyl-peptidase II
    Short name:
    TPP-II
    Gene namesi
    Name:TPP2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 13

    Organism-specific databases

    HGNCiHGNC:12016. TPP2.

    Subcellular locationi

    Cytoplasm 1 Publication. Nucleus 1 Publication
    Note: Translocates to the nucleus in responce to gamma-irradiation.

    GO - Cellular componenti

    1. cytoplasm Source: ProtInc
    2. cytosol Source: Reactome
    3. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA36695.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 12491248Tripeptidyl-peptidase 2PRO_0000076422Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine1 Publication
    Modified residuei401 – 4011N6-acetyllysineBy similarity
    Cross-linki1005 – 1005Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki1013 – 1013Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

    Keywords - PTMi

    Acetylation, Isopeptide bond, Ubl conjugation

    Proteomic databases

    MaxQBiP29144.
    PaxDbiP29144.
    PeptideAtlasiP29144.
    PRIDEiP29144.

    PTM databases

    PhosphoSiteiP29144.

    Expressioni

    Gene expression databases

    ArrayExpressiP29144.
    BgeeiP29144.
    CleanExiHS_TPP2.
    GenevestigatoriP29144.

    Organism-specific databases

    HPAiHPA021069.

    Interactioni

    Protein-protein interaction databases

    BioGridi113027. 7 interactions.
    DIPiDIP-50761N.
    IntActiP29144. 1 interaction.
    STRINGi9606.ENSP00000365233.

    Structurei

    3D structure databases

    ProteinModelPortaliP29144.
    SMRiP29144. Positions 20-55, 237-507.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini40 – 509470Peptidase S8Add
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase S8 family.Curated
    Contains 1 peptidase S8 domain.Curated

    Phylogenomic databases

    eggNOGiCOG1404.
    HOGENOMiHOG000008178.
    HOVERGENiHBG017992.
    KOiK01280.
    OrthoDBiEOG786H2B.
    PhylomeDBiP29144.
    TreeFamiTF105647.

    Family and domain databases

    Gene3Di3.40.50.200. 2 hits.
    InterProiIPR000209. 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]
    PANTHERiPTHR10795. PTHR10795. 1 hit.
    PfamiPF00082. Peptidase_S8. 1 hit.
    PF12580. TPPII. 1 hit.
    [Graphical view]
    PRINTSiPR00723. SUBTILISIN.
    SUPFAMiSSF52743. SSF52743. 2 hits.
    PROSITEiPS00137. SUBTILASE_HIS. 1 hit.
    PS00138. SUBTILASE_SER. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P29144-1 [UniParc]FASTAAdd to Basket

    « Hide

    MATAATEEPF PFHGLLPKKE TGAASFLCRY PEYDGRGVLI AVLDTGVDPG     50
    APGMQVTTDG KPKIVDIIDT TGSGDVNTAT EVEPKDGEIV GLSGRVLKIP 100
    ASWTNPSGKY HIGIKNGYDF YPKALKERIQ KERKEKIWDP VHRVALAEAC 150
    RKQEEFDVAN NGSSQANKLI KEELQSQVEL LNSFEKKYSD PGPVYDCLVW 200
    HDGEVWRACI DSNEDGDLSK STVLRNYKEA QEYGSFGTAE MLNYSVNIYD 250
    DGNLLSIVTS GGAHGTHVAS IAAGHFPEEP ERNGVAPGAQ ILSIKIGDTR 300
    LSTMETGTGL IRAMIEVINH KCDLVNYSYG EATHWPNSGR ICEVINEAVW 350
    KHNIIYVSSA GNNGPCLSTV GCPGGTTSSV IGVGAYVSPD MMVAEYSLRE 400
    KLPANQYTWS SRGPSADGAL GVSISAPGGA IASVPNWTLR GTQLMNGTSM 450
    SSPNACGGIA LILSGLKANN IDYTVHSVRR ALENTAVKAD NIEVFAQGHG 500
    IIQVDKAYDY LVQNTSFANK LGFTVTVGNN RGIYLRDPVQ VAAPSDHGVG 550
    IEPVFPENTE NSEKISLQLH LALTSNSSWV QCPSHLELMN QCRHINIRVD 600
    PRGLREGLHY TEVCGYDIAS PNAGPLFRVP ITAVIAAKVN ESSHYDLAFT 650
    DVHFKPGQIR RHFIEVPEGA TWAEVTVCSC SSEVSAKFVL HAVQLVKQRA 700
    YRSHEFYKFC SLPEKGTLTE AFPVLGGKAI EFCIARWWAS LSDVNIDYTI 750
    SFHGIVCTAP QLNIHASEGI NRFDVQSSLK YEDLAPCITL KNWVQTLRPV 800
    SAKTKPLGSR DVLPNNRQLY EMVLTYNFHQ PKSGEVTPSC PLLCELLYES 850
    EFDSQLWIIF DQNKRQMGSG DAYPHQYSLK LEKGDYTIRL QIRHEQISDL 900
    ERLKDLPFIV SHRLSNTLSL DIHENHSFAL LGKKKSSNLT LPPKYNQPFF 950
    VTSLPDDKIP KGAGPGCYLA GSLTLSKTEL GKKADVIPVH YYLIPPPTKT 1000
    KNGSKDKEKD SEKEKDLKEE FTEALRDLKI QWMTKLDSSD IYNELKETYP 1050
    NYLPLYVARL HQLDAEKERM KRLNEIVDAA NAVISHIDQT ALAVYIAMKT 1100
    DPRPDAATIK NDMDKQKSTL VDALCRKGCA LADHLLHTQA QDGAISTDAE 1150
    GKEEEGESPL DSLAETFWET TKWTDLFDNK VLTFAYKHAL VNKMYGRGLK 1200
    FATKLVEEKP TKENWKNCIQ LMKLLGWTHC ASFTENWLPI MYPPDYCVF 1249
    Length:1,249
    Mass (Da):138,350
    Last modified:January 23, 2007 - v4
    Checksum:iA26A6249DBF7F3DD
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti252 – 2521G → R in AAA36760. (PubMed:1670990)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS9502.1.
    PIRiS54376.
    RefSeqiNP_003282.2. NM_003291.2.
    UniGeneiHs.432424.

    Genome annotation databases

    EnsembliENST00000376065; ENSP00000365233; ENSG00000134900.
    GeneIDi7174.
    KEGGihsa:7174.
    UCSCiuc001vpi.4. human.

    Polymorphism databases

    DMDMi34223721.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS9502.1.
    PIRi S54376.
    RefSeqi NP_003282.2. NM_003291.2.
    UniGenei Hs.432424.

    3D structure databases

    ProteinModelPortali P29144.
    SMRi P29144. Positions 20-55, 237-507.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113027. 7 interactions.
    DIPi DIP-50761N.
    IntActi P29144. 1 interaction.
    STRINGi 9606.ENSP00000365233.

    Chemistry

    ChEMBLi CHEMBL6156.

    Protein family/group databases

    MEROPSi S08.090.

    PTM databases

    PhosphoSitei P29144.

    Polymorphism databases

    DMDMi 34223721.

    Proteomic databases

    MaxQBi P29144.
    PaxDbi P29144.
    PeptideAtlasi P29144.
    PRIDEi P29144.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000376065 ; ENSP00000365233 ; ENSG00000134900 .
    GeneIDi 7174.
    KEGGi hsa:7174.
    UCSCi uc001vpi.4. human.

    Organism-specific databases

    CTDi 7174.
    GeneCardsi GC13P103249.
    HGNCi HGNC:12016. TPP2.
    HPAi HPA021069.
    MIMi 190470. gene.
    neXtProti NX_P29144.
    PharmGKBi PA36695.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1404.
    HOGENOMi HOG000008178.
    HOVERGENi HBG017992.
    KOi K01280.
    OrthoDBi EOG786H2B.
    PhylomeDBi P29144.
    TreeFami TF105647.

    Enzyme and pathway databases

    Reactomei REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
    SignaLinki P29144.

    Miscellaneous databases

    GeneWikii Tripeptidyl_peptidase_II.
    GenomeRNAii 7174.
    NextBioi 28124.
    PROi P29144.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P29144.
    Bgeei P29144.
    CleanExi HS_TPP2.
    Genevestigatori P29144.

    Family and domain databases

    Gene3Di 3.40.50.200. 2 hits.
    InterProi IPR000209. 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 ]
    PANTHERi PTHR10795. PTHR10795. 1 hit.
    Pfami PF00082. Peptidase_S8. 1 hit.
    PF12580. TPPII. 1 hit.
    [Graphical view ]
    PRINTSi PR00723. SUBTILISIN.
    SUPFAMi SSF52743. SSF52743. 2 hits.
    PROSITEi PS00137. SUBTILASE_HIS. 1 hit.
    PS00138. SUBTILASE_SER. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiTPP2_HUMAN
    AccessioniPrimary (citable) accession number: P29144
    Secondary accession number(s): Q5VZU8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 1992
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 132 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    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.By similarity

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 13
      Human chromosome 13: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. Peptidase families
      Classification of peptidase families and list of entries
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3