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Protein

Tripeptidyl-peptidase 2

Gene

TPP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

  • aminopeptidase activity Source: UniProtKB-KW
  • endopeptidase activity Source: ProtInc
  • peptide binding Source: Ensembl
  • serine-type endopeptidase activity Source: GO_Central
  • tripeptidyl-peptidase activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Aminopeptidase, Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BRENDAi3.4.14.10. 2681.
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 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:12016. TPP2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA36695.

Polymorphism and mutation databases

BioMutaiTPP2.
DMDMi34223721.

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
Modified residuei915 – 9151Phosphoserine1 Publication
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, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP29144.
PaxDbiP29144.
PeptideAtlasiP29144.
PRIDEiP29144.

PTM databases

PhosphoSiteiP29144.

Expressioni

Gene expression databases

BgeeiP29144.
CleanExiHS_TPP2.
ExpressionAtlasiP29144. baseline and differential.
GenevisibleiP29144. HS.

Organism-specific databases

HPAiHPA021069.
HPA049630.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
EHHADHQ084263EBI-1044672,EBI-2339219
POLBP067463EBI-1044672,EBI-713836
PPP1R16AQ96I343EBI-1044672,EBI-710402

Protein-protein interaction databases

BioGridi113027. 21 interactions.
DIPiDIP-50761N.
IntActiP29144. 4 interactions.
STRINGi9606.ENSP00000365233.

Structurei

3D structure databases

ProteinModelPortaliP29144.
SMRiP29144. Positions 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.
GeneTreeiENSGT00390000014623.
HOGENOMiHOG000008178.
HOVERGENiHBG017992.
InParanoidiP29144.
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

        10         20         30         40         50
MATAATEEPF PFHGLLPKKE TGAASFLCRY PEYDGRGVLI AVLDTGVDPG
60 70 80 90 100
APGMQVTTDG KPKIVDIIDT TGSGDVNTAT EVEPKDGEIV GLSGRVLKIP
110 120 130 140 150
ASWTNPSGKY HIGIKNGYDF YPKALKERIQ KERKEKIWDP VHRVALAEAC
160 170 180 190 200
RKQEEFDVAN NGSSQANKLI KEELQSQVEL LNSFEKKYSD PGPVYDCLVW
210 220 230 240 250
HDGEVWRACI DSNEDGDLSK STVLRNYKEA QEYGSFGTAE MLNYSVNIYD
260 270 280 290 300
DGNLLSIVTS GGAHGTHVAS IAAGHFPEEP ERNGVAPGAQ ILSIKIGDTR
310 320 330 340 350
LSTMETGTGL IRAMIEVINH KCDLVNYSYG EATHWPNSGR ICEVINEAVW
360 370 380 390 400
KHNIIYVSSA GNNGPCLSTV GCPGGTTSSV IGVGAYVSPD MMVAEYSLRE
410 420 430 440 450
KLPANQYTWS SRGPSADGAL GVSISAPGGA IASVPNWTLR GTQLMNGTSM
460 470 480 490 500
SSPNACGGIA LILSGLKANN IDYTVHSVRR ALENTAVKAD NIEVFAQGHG
510 520 530 540 550
IIQVDKAYDY LVQNTSFANK LGFTVTVGNN RGIYLRDPVQ VAAPSDHGVG
560 570 580 590 600
IEPVFPENTE NSEKISLQLH LALTSNSSWV QCPSHLELMN QCRHINIRVD
610 620 630 640 650
PRGLREGLHY TEVCGYDIAS PNAGPLFRVP ITAVIAAKVN ESSHYDLAFT
660 670 680 690 700
DVHFKPGQIR RHFIEVPEGA TWAEVTVCSC SSEVSAKFVL HAVQLVKQRA
710 720 730 740 750
YRSHEFYKFC SLPEKGTLTE AFPVLGGKAI EFCIARWWAS LSDVNIDYTI
760 770 780 790 800
SFHGIVCTAP QLNIHASEGI NRFDVQSSLK YEDLAPCITL KNWVQTLRPV
810 820 830 840 850
SAKTKPLGSR DVLPNNRQLY EMVLTYNFHQ PKSGEVTPSC PLLCELLYES
860 870 880 890 900
EFDSQLWIIF DQNKRQMGSG DAYPHQYSLK LEKGDYTIRL QIRHEQISDL
910 920 930 940 950
ERLKDLPFIV SHRLSNTLSL DIHENHSFAL LGKKKSSNLT LPPKYNQPFF
960 970 980 990 1000
VTSLPDDKIP KGAGPGCYLA GSLTLSKTEL GKKADVIPVH YYLIPPPTKT
1010 1020 1030 1040 1050
KNGSKDKEKD SEKEKDLKEE FTEALRDLKI QWMTKLDSSD IYNELKETYP
1060 1070 1080 1090 1100
NYLPLYVARL HQLDAEKERM KRLNEIVDAA NAVISHIDQT ALAVYIAMKT
1110 1120 1130 1140 1150
DPRPDAATIK NDMDKQKSTL VDALCRKGCA LADHLLHTQA QDGAISTDAE
1160 1170 1180 1190 1200
GKEEEGESPL DSLAETFWET TKWTDLFDNK VLTFAYKHAL VNKMYGRGLK
1210 1220 1230 1240
FATKLVEEKP TKENWKNCIQ LMKLLGWTHC ASFTENWLPI MYPPDYCVF
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:
EMBLi
GenBanki
DDBJi
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.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliP29144.
SMRiP29144. Positions 237-507.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113027. 21 interactions.
DIPiDIP-50761N.
IntActiP29144. 4 interactions.
STRINGi9606.ENSP00000365233.

Chemistry

BindingDBiP29144.
ChEMBLiCHEMBL6156.

Protein family/group databases

MEROPSiS08.090.

PTM databases

PhosphoSiteiP29144.

Polymorphism and mutation databases

BioMutaiTPP2.
DMDMi34223721.

Proteomic databases

MaxQBiP29144.
PaxDbiP29144.
PeptideAtlasiP29144.
PRIDEiP29144.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7174.
GeneCardsiGC13P103249.
HGNCiHGNC:12016. TPP2.
HPAiHPA021069.
HPA049630.
MIMi190470. gene.
neXtProtiNX_P29144.
PharmGKBiPA36695.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1404.
GeneTreeiENSGT00390000014623.
HOGENOMiHOG000008178.
HOVERGENiHBG017992.
InParanoidiP29144.
KOiK01280.
OrthoDBiEOG786H2B.
PhylomeDBiP29144.
TreeFamiTF105647.

Enzyme and pathway databases

BRENDAi3.4.14.10. 2681.
ReactomeiREACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiP29144.

Miscellaneous databases

ChiTaRSiTPP2. human.
GeneWikiiTripeptidyl_peptidase_II.
GenomeRNAii7174.
NextBioi28124.
PROiP29144.
SOURCEiSearch...

Gene expression databases

BgeeiP29144.
CleanExiHS_TPP2.
ExpressionAtlasiP29144. baseline and differential.
GenevisibleiP29144. HS.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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].
  13. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-915, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

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: June 24, 2015
This is version 141 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.