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    TPP2 tripeptidyl peptidase 2 [ Homo sapiens (human) ]

    Gene ID: 7174, updated on 2-Nov-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (102596986..102679958)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (101812992..101895917)
    RS_2024_09 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 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. Active site of tripeptidyl peptidase II from human erythrocytes is of the subtilisin type. Tomkinson B, et al. Proc Natl Acad Sci U S A, 1987 Nov. PMID 3313395, Free PMC Article
    2. Characterization of the promoter of the gene encoding human tripeptidyl-peptidase II and identification of upstream silencer elements. Lindås AC, et al. Gene, 2007 May 15. PMID 17343995
    3. Tripeptidyl peptidase II is dispensable for the generation of both proteasome-dependent and proteasome-independent ligands of HLA-B27 and other class I molecules. Marcilla M, et al. Eur J Immunol, 2008 Mar. PMID 18286573
    4. 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
    5. Tripeptidyl peptidase II serves as an alternative to impaired proteasome to maintain viral growth in the host cells. Zhang J, et al. FEBS Lett, 2011 Jan 3. PMID 21134372, Free PMC Article

    See all (94) 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
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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_2024_08

    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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