Tripeptidyl peptidase II

Last updated
TPP2
Identifiers
Aliases TPP2 , TPP-2, TPPII, Tripeptidyl peptidase II, tripeptidyl peptidase 2, TPP-II, IMD78
External IDs OMIM: 190470 MGI: 102724 HomoloGene: 2471 GeneCards: TPP2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003291
NM_001330588
NM_001367947

NM_009418
NM_001310540

RefSeq (protein)

NP_001317517
NP_003282
NP_001354876

NP_001297469
NP_033444

Location (UCSC) Chr 13: 102.6 – 102.68 Mb Chr 1: 43.93 – 44 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Tripeptidyl-peptidase 2 is an enzyme that in humans is encoded by the TPP2 gene. [5] [6] Among other things it is heavily implicated in MHC (HLA) class-I processing, as it has both endopeptidase and exopeptidase activity. [7]

Contents

Clinical significance and genetic deficiency

Biallelic deleterious variants in the TPP2 gene may result in a recessive disorder with immune deficiency, autoimmune disease and intellectual disability. [8] [9] Some genetic variants may result in a milder disease with sterile brain inflammation mimicking multiple sclerosis. [10] These observations underline the fundamental role of TPP2 in cells of the immune system.

Related Research Articles

Cathepsin S

Cathepsin S is a protein that in humans is encoded by the CTSS gene. Transcript variants utilizing alternative polyadenylation signals exist for this gene.

HLA-DRA

HLA class II histocompatibility antigen, DR alpha chain is a protein that in humans is encoded by the HLA-DRA gene. HLA-DRA encodes the alpha subunit of HLA-DR. Unlike the alpha chains of other Human MHC class II molecules, the alpha subunit is practically invariable. However it can pair with, in any individual, the beta chain from 3 different DR beta loci, DRB1, and two of any DRB3, DRB4, or DRB5 alleles. Thus there is the potential that any given individual can form 4 different HLA-DR isoforms.

Complement factor B

Complement factor B is a protein that in humans is encoded by the CFB gene.

CD1D

CD1D is the human gene that encodes the protein CD1d, a member of the CD1 family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are non-classical MHC proteins, related to the class I MHC proteins, and are involved in the presentation of lipid antigens to T cells. CD1d is the only member of the group 2 CD1 molecules.

CD74

HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain or CD74, is a protein that in humans is encoded by the CD74 gene. The invariant chain is a polypeptide which plays a critical role in antigen presentation. It is involved in the formation and transport of MHC class II peptide complexes for the generation of CD4+ T cell responses. The cell surface form of the invariant chain is known as CD74. CD74 is a cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF).

HLA-DMB

HLA class II histocompatibility antigen, DM beta chain is a protein that in humans is encoded by the HLA-DMB gene.

Tripeptidyl peptidase I

Tripeptidyl-peptidase 1, also known as Lysosomal pepstatin-insensitive protease, is an enzyme that in humans is encoded by the TPP1 gene. TPP1 should not be confused with the TPP1 shelterin protein which protects telomeres and is encoded by the ACD gene. Mutations in the TPP1 gene leads to late infantile neuronal ceroid lipofuscinosis.

HLA-DMA

HLA class II histocompatibility antigen, DM alpha chain is a protein that in humans is encoded by the HLA-DMA gene.

SERPINB3

Serpin B3 is a protein that in humans is encoded by the SERPINB3 gene.

ERAP1

Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator, also known as endoplasmic reticulum aminopeptidase 1 (ARTS-1), is a protein which in humans is encoded by the ARTS-1 gene.

SERPINB4

Serpin B4 is a protein that in humans is encoded by the SERPINB4 gene.

LILRB2

Leukocyte immunoglobulin-like receptor subfamily B member 2 is a protein that in humans is encoded by the LILRB2 gene.

HLA-DOA

HLA class II histocompatibility antigen, DO alpha chain is a protein that in humans is encoded by the HLA-DOA gene.

HLA-DOB

HLA class II histocompatibility antigen, DO beta chain is a protein that in humans is encoded by the HLA-DOB gene.

SERPINB6

Serpin B6 is a protein that in humans is encoded by the SERPINB6 gene.

HM13

Minor histocompatibility antigen H13 is a protein that in humans is encoded by the HM13 gene.

HLA-DQA2

HLA class II histocompatibility antigen, DQ(6) alpha chain is a protein that in humans is encoded by the HLA-DQA2 gene. Also known as HLA-DXA or DAAP-381D23.2, it is part of the human leucocyte antigen system.

LAMP3

Lysosome-associated membrane glycoprotein 3 is a protein that in humans is encoded by the LAMP3 gene. It is one of the lysosome-associated membrane glycoproteins.

HLA-DQB2

HLA class II histocompatibility antigen, DX beta chain is a protein that in humans is encoded by the HLA-DQB2 gene.

LILRB5

Leukocyte immunoglobulin-like receptor subfamily B member 5 is a protein that in humans is encoded by the LILRB5 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000134900 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000041763 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Tomkinson B, Jonsson AK (January 1991). "Characterization of cDNA for human tripeptidyl peptidase II: the N-terminal part of the enzyme is similar to subtilisin". Biochemistry. 30 (1): 168–174. doi:10.1021/bi00215a025. PMID   1670990.
  6. "Entrez Gene: TPP2 tripeptidyl peptidase II".
  7. Reits E, Neijssen J, Herberts C, Benckhuijsen W, Janssen L, Drijfhout JW, Neefjes J (April 2004). "A major role for TPPII in trimming proteasomal degradation products for MHC class I antigen presentation". Immunity. 20 (4): 495–506. doi: 10.1016/S1074-7613(04)00074-3 . PMID   15084277.
  8. Lu W, Zhang Y, McDonald DO, Jing H, Carroll B, Robertson N, et al. (December 2014). "Dual proteolytic pathways govern glycolysis and immune competence". Cell. 159 (7): 1578–1590. doi:10.1016/j.cell.2014.12.001. PMID   25525876.
  9. Atallah I, Quinodoz M, Campos-Xavier B, Peter VG, Fouriki A, Bonvin C, et al. (June 2021). "Immune deficiency, autoimmune disease and intellectual disability: A pleiotropic disorder caused by biallelic variants in the TPP2 gene". Clinical Genetics. 99 (6): 780–788. doi:10.1111/cge.13942. PMID   33586135.
  10. Reinthaler EM, Graf E, Zrzavy T, Wieland T, Hotzy C, Kopecky C, et al. (December 2018). "TPP2 mutation associated with sterile brain inflammation mimicking MS". Neurology. Genetics. 4 (6): e285. doi:10.1212/NXG.0000000000000285. PMID   30533531.

Further reading