TPP2 (tripeptidyl peptidase 2)

Gene

• Entrez ID: 7174
• Gene name: Tripeptidyl peptidase 2
• Gene symbol: TPP2
• Synonyms (NCBI Gene): IMD78, TPP-2, TPP-II, TPPII
• Chromosome: 13
• Chromosome location: 13q33.1
• 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 ma

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1566356753	G>C	Likely-pathogenic	Splice donor variant
rs1595184407	->A	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs1595188566	C>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT020939	hsa-miR-155-5p	Proteomics	18668040
MIRT032480	hsa-let-7b-5p	Proteomics	18668040
MIRT1450038	hsa-miR-1207-5p	CLIP-seq
MIRT1450039	hsa-miR-1299	CLIP-seq
MIRT1450040	hsa-miR-3646	CLIP-seq
MIRT1450041	hsa-miR-4514	CLIP-seq
MIRT1450042	hsa-miR-4652-3p	CLIP-seq
MIRT1450043	hsa-miR-4670-3p	CLIP-seq
MIRT1450044	hsa-miR-4692	CLIP-seq
MIRT1450045	hsa-miR-4736	CLIP-seq
MIRT1450046	hsa-miR-4763-3p	CLIP-seq
MIRT1450047	hsa-miR-4782-5p	CLIP-seq
MIRT1450048	hsa-miR-516b	CLIP-seq
MIRT1450049	hsa-miR-875-3p	CLIP-seq
MIRT1450050	hsa-miR-940	CLIP-seq
MIRT2134520	hsa-miR-1265	CLIP-seq
MIRT2134521	hsa-miR-1298	CLIP-seq
MIRT2134522	hsa-miR-3144-3p	CLIP-seq
MIRT2134523	hsa-miR-3163	CLIP-seq
MIRT2134524	hsa-miR-3194-3p	CLIP-seq
MIRT2134525	hsa-miR-335	CLIP-seq
MIRT2134526	hsa-miR-3605-5p	CLIP-seq
MIRT2134527	hsa-miR-376a	CLIP-seq
MIRT2134528	hsa-miR-376b	CLIP-seq
MIRT2134529	hsa-miR-3941	CLIP-seq
MIRT2134530	hsa-miR-4477a	CLIP-seq
MIRT2134531	hsa-miR-4502	CLIP-seq
MIRT2134532	hsa-miR-4539	CLIP-seq
MIRT2134533	hsa-miR-4643	CLIP-seq
MIRT2134534	hsa-miR-466	CLIP-seq
MIRT2134535	hsa-miR-4666-5p	CLIP-seq
MIRT2134536	hsa-miR-4672	CLIP-seq
MIRT2134537	hsa-miR-4762-3p	CLIP-seq
MIRT2134538	hsa-miR-4777-5p	CLIP-seq
MIRT2134539	hsa-miR-4789-3p	CLIP-seq
MIRT2134540	hsa-miR-630	CLIP-seq
MIRT2134541	hsa-miR-660	CLIP-seq
MIRT2134542	hsa-miR-664	CLIP-seq
MIRT2134521	hsa-miR-1298	CLIP-seq
MIRT2355830	hsa-miR-2681	CLIP-seq
MIRT2355831	hsa-miR-320e	CLIP-seq
MIRT2134527	hsa-miR-376a	CLIP-seq
MIRT2134528	hsa-miR-376b	CLIP-seq
MIRT2134529	hsa-miR-3941	CLIP-seq
MIRT2134531	hsa-miR-4502	CLIP-seq
MIRT2134533	hsa-miR-4643	CLIP-seq
MIRT2134534	hsa-miR-466	CLIP-seq
MIRT2134536	hsa-miR-4672	CLIP-seq
MIRT2355832	hsa-miR-4724-3p	CLIP-seq
MIRT2134537	hsa-miR-4762-3p	CLIP-seq
MIRT2134539	hsa-miR-4789-3p	CLIP-seq
MIRT2355833	hsa-miR-548n	CLIP-seq
MIRT2355834	hsa-miR-548t	CLIP-seq
MIRT2134540	hsa-miR-630	CLIP-seq
MIRT2134542	hsa-miR-664	CLIP-seq
MIRT2134520	hsa-miR-1265	CLIP-seq
MIRT2134521	hsa-miR-1298	CLIP-seq
MIRT2134524	hsa-miR-3194-3p	CLIP-seq
MIRT2134525	hsa-miR-335	CLIP-seq
MIRT2134526	hsa-miR-3605-5p	CLIP-seq
MIRT2396256	hsa-miR-3647-3p	CLIP-seq
MIRT2134527	hsa-miR-376a	CLIP-seq
MIRT2134528	hsa-miR-376b	CLIP-seq
MIRT2134531	hsa-miR-4502	CLIP-seq
MIRT2134532	hsa-miR-4539	CLIP-seq
MIRT2134537	hsa-miR-4762-3p	CLIP-seq
MIRT2396257	hsa-miR-4764-5p	CLIP-seq
MIRT2134540	hsa-miR-630	CLIP-seq
MIRT2134542	hsa-miR-664	CLIP-seq
MIRT2649356	hsa-miR-138	CLIP-seq
MIRT2649357	hsa-miR-2113	CLIP-seq
MIRT2649358	hsa-miR-218	CLIP-seq
MIRT2649359	hsa-miR-30a	CLIP-seq
MIRT2649360	hsa-miR-30b	CLIP-seq
MIRT2649361	hsa-miR-30c	CLIP-seq
MIRT2649362	hsa-miR-30d	CLIP-seq
MIRT2649363	hsa-miR-30e	CLIP-seq
MIRT2649364	hsa-miR-3127-3p	CLIP-seq
MIRT2649365	hsa-miR-3679-3p	CLIP-seq
MIRT2649366	hsa-miR-4252	CLIP-seq
MIRT2649367	hsa-miR-4446-5p	CLIP-seq
MIRT2649368	hsa-miR-4495	CLIP-seq
MIRT2649369	hsa-miR-4776-3p	CLIP-seq
MIRT2649370	hsa-miR-579	CLIP-seq
MIRT2134520	hsa-miR-1265	CLIP-seq
MIRT2134521	hsa-miR-1298	CLIP-seq
MIRT2649356	hsa-miR-138	CLIP-seq
MIRT2649357	hsa-miR-2113	CLIP-seq
MIRT2649358	hsa-miR-218	CLIP-seq
MIRT2649364	hsa-miR-3127-3p	CLIP-seq
MIRT2134524	hsa-miR-3194-3p	CLIP-seq
MIRT2134525	hsa-miR-335	CLIP-seq
MIRT2134526	hsa-miR-3605-5p	CLIP-seq
MIRT2396256	hsa-miR-3647-3p	CLIP-seq
MIRT2693982	hsa-miR-3662	CLIP-seq
MIRT2649365	hsa-miR-3679-3p	CLIP-seq
MIRT2134527	hsa-miR-376a	CLIP-seq
MIRT2134528	hsa-miR-376b	CLIP-seq
MIRT2134529	hsa-miR-3941	CLIP-seq
MIRT2649366	hsa-miR-4252	CLIP-seq
MIRT2649367	hsa-miR-4446-5p	CLIP-seq
MIRT2134531	hsa-miR-4502	CLIP-seq
MIRT2134532	hsa-miR-4539	CLIP-seq
MIRT2134533	hsa-miR-4643	CLIP-seq
MIRT2134534	hsa-miR-466	CLIP-seq
MIRT2134536	hsa-miR-4672	CLIP-seq
MIRT2134537	hsa-miR-4762-3p	CLIP-seq
MIRT2396257	hsa-miR-4764-5p	CLIP-seq
MIRT2134539	hsa-miR-4789-3p	CLIP-seq
MIRT2649370	hsa-miR-579	CLIP-seq
MIRT2134540	hsa-miR-630	CLIP-seq
MIRT2134542	hsa-miR-664	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000209	Process	Protein polyubiquitination	TAS
GO:0004175	Function	Endopeptidase activity	TAS	9974389
GO:0004177	Function	Aminopeptidase activity	EXP	9668046, 11062501
GO:0004177	Function	Aminopeptidase activity	IEA
GO:0004177	Function	Aminopeptidase activity	IMP	25525876, 30533531
GO:0004252	Function	Serine-type endopeptidase activity	IEA
GO:0005515	Function	Protein binding	IPI	25416956, 25910212, 31515488
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	9974389
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006508	Process	Proteolysis	IEA
GO:0006508	Process	Proteolysis	TAS	9974389
GO:0008233	Function	Peptidase activity	IEA
GO:0008236	Function	Serine-type peptidase activity	IEA
GO:0008238	Function	Exopeptidase activity	IEA
GO:0008240	Function	Tripeptidyl-peptidase activity	IBA
GO:0008240	Function	Tripeptidyl-peptidase activity	IEA
GO:0008240	Function	Tripeptidyl-peptidase activity	TAS	9974389
GO:0016604	Component	Nuclear body	IDA
GO:0016787	Function	Hydrolase activity	IEA
GO:0042802	Function	Identical protein binding	IPI	22483107
GO:0080144	Process	Intracellular amino acid homeostasis	IMP	25525876

Other IDs

• MIM: 190470
• HGNC: 12016
• e!Ensembl: ENSG00000134900

Protein

• UniProt ID: P29144
• Protein name: Tripeptidyl-peptidase 2 (TPP-2) (EC 3.4.14.10) (Tripeptidyl aminopeptidase) (Tripeptidyl-peptidase II) (TPP-II)
• Protein function: Cytosolic tripeptidyl-peptidase that releases N-terminal tripeptides from polypeptides and is a component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway (PubMed:25525876, PubMed:30533531).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00082	Peptidase_S8	35 → 500	Subtilase family	Domain
  PF12580	TPPII	777 → 964	Tripeptidyl peptidase II	Family

• Sequence:

  MATAATEEPFPFHGLLPKKETGAASFLCRYPEYDGRGVLIAVLDTGVDPGAPGMQVTTDG
  KPKIVDIIDTTGSGDVNTATEVEPKDGEIVGLSGRVLKIPASWTNPSGKYHIGIKNGYDF
  YPKALKERIQKERKEKIWDPVHRVALAEACRKQEEFDVANNGSSQANKLIKEELQSQVEL
  LNSFEKKYSDPGPVYDCLVWHDGEVWRACIDSNEDGDLSKSTVLRNYKEAQEYGSFGTAE
  MLNYSVNIYDDGNLLSIVTSGGAHGTHVASIAAGHFPEEPERNGVAPGAQILSIKIGDTR
  LSTMETGTGLIRAMIEVINHKCDLVNYSYGEATHWPNSGRICEVINEAVWKHNIIYVSSA
  GNNGPCLSTVGCPGGTTSSVIGVGAYVSPDMMVAEYSLREKLPANQYTWSSRGPSADGAL
  GVSISAPGGAIASVPNWTLRGTQLMNGTSMSSPNACGGIALILSGLKANNIDYTVHSVRR
  ALENTAVKADNIEVFAQGHGIIQVDKAYDYLVQNTSFANKLGFTVTVGNNRGIYLRDPVQ
  VAAPSDHGVGIEPVFPENTENSEKISLQLHLALTSNSSWVQCPSHLELMNQCRHINIRVD
  PRGLREGLHYTEVCGYDIASPNAGPLFRVPITAVIAAKVNESSHYDLAFTDVHFKPGQIR
  RHFIEVPEGATWAEVTVCSCSSEVSAKFVLHAVQLVKQRAYRSHEFYKFCSLPEKGTLTE
  AFPVLGGKAIEFCIARWWASLSDVNIDYTISFHGIVCTAPQLNIHASEGINRFDVQSSLK
  YEDLAPCITLKNWVQTLRPVSAKTKPLGSRDVLPNNRQLYEMVLTYNFHQPKSGEVTPSC
  PLLCELLYESEFDSQLWIIFDQNKRQMGSGDAYPHQYSLKLEKGDYTIRLQIRHEQISDL
  ERLKDLPFIVSHRLSNTLSLDIHENHSFALLGKKKSSNLTLPPKYNQPFFVTSLPDDKIP
  KGAGPGCYLAGSLTLSKTELGKKADVIPVHYYLIPPPTKTKNGSKDKEKDSEKEKDLKEE
  FTEALRDLKIQWMTKLDSSDIYNELKETYPNYLPLYVARLHQLDAEKERMKRLNEIVDAA
  NAVISHIDQTALAVYIAMKTDPRPDAATIKNDMDKQKSTLVDALCRKGCALADHLLHTQA
  QDGAISTDAEGKEEEGESPLDSLAETFWETTKWTDLFDNKVLTFAYKHALVNKMYGRGLK
  FATKLVEEKPTKENWKNCIQLMKLLGWTHCASFTENWLPIMYPPDYCVF

• Sequence length: 1249

Pathways

Reactome:

Antigen processing: Ubiquitination & Proteasome degradation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Pathogenic; Likely pathogenic	rs2139537621, rs2139547046, rs1397378666, rs2504031824, rs2503993076, rs1883911620, rs1882201496, rs772169780, rs1566356753, rs1595184407, rs1595188566	RCV001390879 RCV001998176 RCV003110361 RCV003014377 RCV003755478 RCV003755869 RCV003756070 RCV003756094 RCV000707230 RCV000806249 RCV000821135	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Immunodeficiency 78 with autoimmunity and developmental delay	Pathogenic	rs1039236504, rs1882325267, rs1880737834	RCV001327995 RCV001327996 RCV001327997	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOIMMUNE HEMOLYTIC ANEMIA, AUTOIMMUNE THROMBOCYTOPENIA, PRIMARY IMMUNODEFICIENCY SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOIMMUNE HEMOLYTIC ANEMIA-AUTOIMMUNE THROMBOCYTOPENIA-PRIMARY IMMUNODEFICIENCY SYNDROME	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOIMMUNE HEMOLYTIC ANEMIA-AUTOIMMUNE THROMBOCYTOPENIA-PRIMARY IMMUNODEFICIENCY SYNDROME DUE TO TPP2 DEFICIENCY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLOR VISION DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CUTIS MARMORATA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLOBAL DEVELOPMENTAL DELAY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THROMBOCYTOPENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TPP2-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Autoimmune Diseases	Autoimmune Diseases	BEFREE	25414442		★☆☆☆☆ Found in Text Mining only
Autoimmune hemolytic anemia	Autoimmune hemolytic anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome	Autoimmune Hemolytic Anemia-Autoimmune Thrombocytopenia-Primary Immunodeficiency Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Burkitt Lymphoma	Burkitt`s Lymphoma	BEFREE	15735022		★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic neoplasm	Pubtator	19000094	Stimulate	★☆☆☆☆ Found in Text Mining only
Congenital chromosomal disease	Congenital Chromosomal Disease	BEFREE	16762321		★☆☆☆☆ Found in Text Mining only
Encephalitis	Encephalitis	BEFREE	31108122		★☆☆☆☆ Found in Text Mining only
Evans syndrome	Evans Syndrome	BEFREE	25414442		★☆☆☆☆ Found in Text Mining only
Evans syndrome	Evans Syndrome	GENOMICS_ENGLAND_DG	25525876		★☆☆☆☆ Found in Text Mining only
Immune thrombocytopenic purpura	Immune Thrombocytopenic Purpura	HPO_DG			★☆☆☆☆ Found in Text Mining only
Late-Infantile Neuronal Ceroid Lipfuscinosis	Neuronal Ceroid Lipofuscinosis	BEFREE	20689811		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lymphopenia	Lymphopenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	31108122		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	17671184, 22986808		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	20689811		★☆☆☆☆ Found in Text Mining only
Primary immune deficiency disorder	immunodeficiency	BEFREE	25414442		★☆☆☆☆ Found in Text Mining only
Recurrent otitis media	Otitis media	HPO_DG			★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	16822484		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	22986808		★☆☆☆☆ Found in Text Mining only