TPP2

Protein identityUniProt · HPA

UniProt accession

P29144

Gene

TPP2

Ensembl

ENSG00000134900

Chromosome

13

Canonical length

1249 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nuclear bodies,Cytosol

OverviewNCBI Gene

This gene encodes a mammalian peptidase that, at neutral pH, removes tripeptides from the N terminus of longer peptides. The protein has a specialized function that is essential for some MHC class I antigen presentation. The protein is a high molecular mass serine exopeptidase; the amino acid sequence surrounding the serine residue at the active site is similar to the peptidases of the subtilisin class rather than the trypsin class. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1249 residues, UniProt reviewed canonical sequence.

>P29144|TPP2
     1  MATAATEEPF PFHGLLPKKE TGAASFLCRY PEYDGRGVLI AVLDTGVDPG APGMQVTTDG
    61  KPKIVDIIDT TGSGDVNTAT EVEPKDGEIV GLSGRVLKIP ASWTNPSGKY HIGIKNGYDF
   121  YPKALKERIQ KERKEKIWDP VHRVALAEAC RKQEEFDVAN NGSSQANKLI KEELQSQVEL
   181  LNSFEKKYSD PGPVYDCLVW HDGEVWRACI DSNEDGDLSK STVLRNYKEA QEYGSFGTAE
   241  MLNYSVNIYD DGNLLSIVTS GGAHGTHVAS IAAGHFPEEP ERNGVAPGAQ ILSIKIGDTR
   301  LSTMETGTGL IRAMIEVINH KCDLVNYSYG EATHWPNSGR ICEVINEAVW KHNIIYVSSA
   361  GNNGPCLSTV GCPGGTTSSV IGVGAYVSPD MMVAEYSLRE KLPANQYTWS SRGPSADGAL
   421  GVSISAPGGA IASVPNWTLR GTQLMNGTSM SSPNACGGIA LILSGLKANN IDYTVHSVRR
   481  ALENTAVKAD NIEVFAQGHG IIQVDKAYDY LVQNTSFANK LGFTVTVGNN RGIYLRDPVQ
   541  VAAPSDHGVG IEPVFPENTE NSEKISLQLH LALTSNSSWV QCPSHLELMN QCRHINIRVD
   601  PRGLREGLHY TEVCGYDIAS PNAGPLFRVP ITAVIAAKVN ESSHYDLAFT DVHFKPGQIR
   661  RHFIEVPEGA TWAEVTVCSC SSEVSAKFVL HAVQLVKQRA YRSHEFYKFC SLPEKGTLTE
   721  AFPVLGGKAI EFCIARWWAS LSDVNIDYTI SFHGIVCTAP QLNIHASEGI NRFDVQSSLK
   781  YEDLAPCITL KNWVQTLRPV SAKTKPLGSR DVLPNNRQLY EMVLTYNFHQ PKSGEVTPSC
   841  PLLCELLYES EFDSQLWIIF DQNKRQMGSG DAYPHQYSLK LEKGDYTIRL QIRHEQISDL
   901  ERLKDLPFIV SHRLSNTLSL DIHENHSFAL LGKKKSSNLT LPPKYNQPFF VTSLPDDKIP
   961  KGAGPGCYLA GSLTLSKTEL GKKADVIPVH YYLIPPPTKT KNGSKDKEKD SEKEKDLKEE
  1021  FTEALRDLKI QWMTKLDSSD IYNELKETYP NYLPLYVARL HQLDAEKERM KRLNEIVDAA
  1081  NAVISHIDQT ALAVYIAMKT DPRPDAATIK NDMDKQKSTL VDALCRKGCA LADHLLHTQA
  1141  QDGAISTDAE GKEEEGESPL DSLAETFWET TKWTDLFDNK VLTFAYKHAL VNKMYGRGLK
  1201  FATKLVEEKP TKENWKNCIQ LMKLLGWTHC ASFTENWLPI MYPPDYCVF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TPP2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.23

Highest tissue expression

47 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TPP2.

Disease | AllUniProt

Conditions TPP2 is implicated in, by any mechanism.

• Immunodeficiency 78 with autoimmunity and developmental delay (IMD78) MIM:619220

Disease | GeneticClinVar

19 pathogenic / likely-pathogenic of 856 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency
• Immunodeficiency 78 with autoimmunity and developmental delay
• 7 conditions

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.26

gnomAD pLI

1

gnomAD missense Z

3.86

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• intracellular amino acid homeostasis
• protein polyubiquitination
• proteolysis

Molecular functions

• aminopeptidase activity
• endopeptidase activity
• identical protein binding
• serine-type endopeptidase activity
• tripeptidyl-peptidase activity

Cellular components

• cytoplasm
• cytosol
• nuclear body
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• Peptidase S8/S53 domain
• Peptidase S8, subtilisin-related
• Peptidase S8, subtilisin, His-active site
• Peptidase S8, subtilisin, Ser-active site
• Peptidase S8/S53 domain superfamily
• Subtilisin-like serine protease
• Subtilase family
• Tripeptidyl peptidase II, second Ig-like domain
• Tripeptidyl peptidase II, C-terminal domain, arthropoda
• Tripeptidyl-peptidase II domain
• Tripeptidyl-peptidase 2, C-terminal domain superfamily
• Tripeptidyl peptidase II, Ig-like domain superfamily
• Tripeptidyl-peptidase II, first Ig-like domain
• Tripeptidyl-peptidase II, galactose-binding domain-like
• Tripeptidyl peptidase II
• Tripeptidyl peptidase II, C-terminal
• Tripeptidyl-peptidase II, first Ig-like domain
• TPPII, galactose-binding domain-like

KeywordsUniProt

• Acetylation
• Aminopeptidase
• Cytoplasm
• Hydrolase
• Nucleus
• Phosphoprotein
• Protease
• Serine protease