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TPP2 tripeptidyl peptidase 2 [ Homo sapiens (human) ]

Gene ID: 7174, updated on 3-Apr-2024

Summary

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Official Symbol
TPP2provided by HGNC
Official Full Name
tripeptidyl peptidase 2provided by HGNC
Primary source
HGNC:HGNC:12016
See related
Ensembl:ENSG00000134900 MIM:190470; AllianceGenome:HGNC:12016
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IMD78; TPP-2; TPPII; TPP-II
Summary
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]
Expression
Ubiquitous expression in testis (RPKM 27.4), thyroid (RPKM 15.8) and 25 other tissues See more
Orthologs
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Genomic context

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See TPP2 in Genome Data Viewer
Location:
13q33.1
Exon count:
31
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (102596986..102679958)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (101812992..101895917)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (103249336..103332308)

Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene fibroblast growth factor 14 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7964 Neighboring gene FGF14 antisense RNA 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7965 Neighboring gene H3K27ac-H3K4me1 hESC enhancers GRCh37_chr13:103244249-103244798 and GRCh37_chr13:103244799-103245346 Neighboring gene uncharacterized LOC107984588 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7968 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7969 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5481 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5482 Neighboring gene ReSE screen-validated silencer GRCh37_chr13:103368105-103368334 Neighboring gene small nucleolar RNA U13 Neighboring gene methyltransferase 21C, AARS1 lysine

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Immune deficiency, autoimmune disease and intellectual disability: A pleiotropic disorder caused by biallelic variants in the TPP2 gene. Atallah I, et al. Clin Genet, 2021 Jun. PMID 33586135
  2. TPP2 mutation associated with sterile brain inflammation mimicking MS. Reinthaler EM, et al. Neurol Genet, 2018 Dec. PMID 30533531, Free PMC Article
  3. Dual proteolytic pathways govern glycolysis and immune competence. Lu W, et al. Cell, 2014 Dec 18. PMID 25525876, Free PMC Article
  4. Tripeptidyl peptidase II in human oral squamous cell carcinoma. Usukura K, et al. J Cancer Res Clin Oncol, 2013 Jan. PMID 22986808
  5. Structure and function of tripeptidyl peptidase II, a giant cytosolic protease. Rockel B, et al. Biochim Biophys Acta, 2012 Jan. PMID 21771670

See all (86) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Unveiling a novel serpinB2-tripeptidyl peptidase II signaling axis during senescence.
    Title: Unveiling a novel serpinB2-tripeptidyl peptidase II signaling axis during senescence.
  2. Immune deficiency, autoimmune disease and intellectual disability: A pleiotropic disorder caused by biallelic variants in the TPP2 gene.
    Title: Immune deficiency, autoimmune disease and intellectual disability: A pleiotropic disorder caused by biallelic variants in the TPP2 gene.
  3. Novel interactions of TPPII, p53, and SIRT7 presented in this study might contribute to the knowledge of the regulatory effects of these proteins on apoptotic pathways and to the understanding mechanisms of aging and lifespan regulation.
    Title: Novel protein-protein interactions of TPPII, p53, and SIRT7.
  4. TPP2 mediates many important cellular functions by controlling ERK1 and ERK2 phosphorylation.
    Title: Tripeptidyl Peptidase II Mediates Levels of Nuclear Phosphorylated ERK1 and ERK2.
  5. Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with TPP2 deficiency have been described in two consanguineous siblings.
    Title: Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency.
  6. Study found that autosomal recessive TPP2 mutations cause recurrent infections, autoimmunity, and neurodevelopmental delay in humans.
    Title: Dual proteolytic pathways govern glycolysis and immune competence.
  7. TPPII, MYBBP1A and CDK2 form a protein-protein interaction network.
    Title: TPPII, MYBBP1A and CDK2 form a protein-protein interaction network.
  8. Previously unknown differences between TPP II orthologues and subtilisin as well as features that might be conserved within the entire family of subtilisin-like serine peptidases.
    Title: Exploring the active site of tripeptidyl-peptidase II through studies of pH dependence of reaction kinetics.
  9. Study showed that overexpression of Tripeptidyl peptidase II (TPP2) occurs frequently during oral carcinogenesis and might be associated with the progression of Oral Squamous Cell Carcinoma (OSCC) via Spindle Assembly Checkpoint(SAC) activation.
    Title: Tripeptidyl peptidase II in human oral squamous cell carcinoma.
  10. obtained a 3D structure of the human TPPII
    Title: The structure of human tripeptidyl peptidase II as determined by a hybrid approach.
Submit: New GeneRIF Correction See all GeneRIFs (21)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Immunodeficiency 78 with autoimmunity and developmental delay
MedGen: C5543159 OMIM: 619220 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ40359

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables aminopeptidase activity EXP
Inferred from Experiment
more info
 PubMed 
enables aminopeptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables endopeptidase activity TAS
Traceable Author Statement
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables serine-type endopeptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables tripeptidyl-peptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in intracellular amino acid homeostasis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein polyubiquitination TAS
Traceable Author Statement
more info
  
involved_in proteolysis IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytoplasm TAS
Traceable Author Statement
more info
 PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in nuclear body IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
tripeptidyl-peptidase 2
Names
tripeptidyl aminopeptidase
tripeptidyl-peptidase II
NP_001317517.1
NP_001354876.1
NP_003282.2
XP_005254127.1
XP_047286534.1
XP_047286535.1
XP_047286536.1
XP_054230883.1
XP_054230884.1
XP_054230885.1
XP_054230886.1
XP_054230887.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_063544.1 RefSeqGene

    Range
    5001..87973
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1341

mRNA and Protein(s)

  1. NM_001330588.2 → NP_001317517.1  tripeptidyl-peptidase 2 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains an alternate in-frame exon in the 3' coding region, compared to variant 1. The encoded isoform (2) has the same N- and C-termini, but is longer than isoform 1.
    Source sequence(s)
    AU132468, BC039905, BF514671, BM684792, BX370108, DB303355, M73047, N27441
    Consensus CDS
    CCDS81777.1
    UniProtKB/TrEMBL
    A0A494C0U1, Q5VZU9
    Related
    ENSP00000365220.3, ENST00000376052.5
    Conserved Domains (2) summary
    cd04857
    Location:14 → 489
    Peptidases_S8_Tripeptidyl_Aminopeptidase_II; Peptidase S8 family domain in Tripeptidyl aminopeptidases_II
    pfam12580
    Location:777 → 960
    TPPII; Tripeptidyl peptidase II

  2. NM_001367947.1 → NP_001354876.1  tripeptidyl-peptidase 2 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate in-frame exon in the 3' coding region, compared to variant 1. The encoded isoform (3) has the same N- and C-termini, but is longer than isoform 1.
    Source sequence(s)
    AL158063
    UniProtKB/TrEMBL
    A0A494C0U1
    Conserved Domains (2) summary
    cd04857
    Location:14 → 489
    Peptidases_S8_Tripeptidyl_Aminopeptidase_II; Peptidase S8 family domain in Tripeptidyl aminopeptidases_II
    pfam12580
    Location:777 → 960
    TPPII; Tripeptidyl peptidase II

  3. NM_003291.4 → NP_003282.2  tripeptidyl-peptidase 2 isoform 1

    See identical proteins and their annotated locations for NP_003282.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the shortest transcript and encodes the shortest, but most predominant, isoform (1).
    Source sequence(s)
    AU132468, BC039905, BF514671, BM684792, DB303355, M73047, N27441
    Consensus CDS
    CCDS9502.1
    UniProtKB/Swiss-Prot
    P29144, Q5VZU8
    UniProtKB/TrEMBL
    A0A494C0U1
    Related
    ENSP00000365233.4, ENST00000376065.8
    Conserved Domains (2) summary
    cd04857
    Location:14 → 489
    Peptidases_S8_Tripeptidyl_Aminopeptidase_II; Peptidase S8 family domain in Tripeptidyl aminopeptidases_II
    pfam12580
    Location:777 → 960
    TPPII; Tripeptidyl peptidase II

RNA

  1. NR_160411.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate splice site in the 3' region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AL158063

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

    Range
    102596986..102679958
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005254070.3 → XP_005254127.1  tripeptidyl-peptidase 2 isoform X1

    See identical proteins and their annotated locations for XP_005254127.1

    UniProtKB/TrEMBL
    A0A494C0U1
    Conserved Domains (2) summary
    cd04857
    Location:14 → 489
    Peptidases_S8_Tripeptidyl_Aminopeptidase_II; Peptidase S8 family domain in Tripeptidyl aminopeptidases_II
    pfam12580
    Location:777 → 960
    TPPII; Tripeptidyl peptidase II

  2. XM_047430580.1 → XP_047286536.1  tripeptidyl-peptidase 2 isoform X4

  3. XM_047430579.1 → XP_047286535.1  tripeptidyl-peptidase 2 isoform X3

  4. XM_047430578.1 → XP_047286534.1  tripeptidyl-peptidase 2 isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060937.1 Alternate T2T-CHM13v2.0

    Range
    101812992..101895917
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054374908.1 → XP_054230883.1  tripeptidyl-peptidase 2 isoform X1

  2. XM_054374911.1 → XP_054230886.1  tripeptidyl-peptidase 2 isoform X4

  3. XM_054374910.1 → XP_054230885.1  tripeptidyl-peptidase 2 isoform X3

  4. XM_054374909.1 → XP_054230884.1  tripeptidyl-peptidase 2 isoform X2

  5. XM_054374912.1 → XP_054230887.1  tripeptidyl-peptidase 2 isoform X5

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P29144.4 GenPept UniProtKB/Swiss-Prot:P29144

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