TNFAIP8L2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTNFAIP8L2, TIPE2, TNF alpha induced protein 8 like 2
External IDsOMIM: 612112 MGI: 1917019 HomoloGene: 56998 GeneCards: TNFAIP8L2
Orthologs
SpeciesHumanMouse
Entrez

79626

69769

Ensembl

ENSG00000163154

ENSMUSG00000013707

UniProt

Q6P589

Q9D8Y7

RefSeq (mRNA)

NM_024575

NM_027206

RefSeq (protein)

NP_078851

NP_081482

Location (UCSC)Chr 1: 151.16 – 151.16 MbChr 3: 95.05 – 95.05 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

TNF alpha induced protein 8 like 2 (TNFAIP8L2), also known as TIPE2, is a protein that in humans is encoded by the TNFAIP8L2 gene. It is preferentially expressed in human myeloid cell types and serves as an immune checkpoint regulator of inflammation and metabolism.[5]

Function

TNFAIP8L2 is a member of the TNFAIP8 (tumor necrosis factor-α-induced protein 8, or TIPE) family that function as transfer proteins for the second messenger lipids PIP2 and PIP3. The other three family members are TNFAIP8, TNFAIP8L1 and TNFAIP8L3.[6]

Structure

The crystal structure of TIPE2 reveals that it contains a large, hydrophobic central cavity that is poised for cofactor binding.[7]

Clinical significance

TIPE2 acts as a negative regulator of the immune system.[5][8] It is down-regulated in patients with infectious and autoimmune diseases and also acts as a tumor suppressor in several types of cancer.[9] Its knockout leads to leukocytosis and systemic inflammatory disorders in mice.[6][10]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000163154 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000013707 - 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. 1 2 Li T, Wang W, et al. (May 2018). "Genome-wide analysis reveals TNFAIP8L2 as an immune checkpoint regulator of inflammation and metabolism". Molecular Immunology. 99: 154–162. doi:10.1016/j.molimm.2018.05.007. PMC 5995464. PMID 29787979.
  6. 1 2 Goldsmith JR, Chen YH (June 2017). "Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid transfer proteins". Cellular & Molecular Immunology. 14 (6): 482–487. doi:10.1038/cmi.2017.4. PMC 5719143. PMID 28287114.
  7. ↑ Zhang X, Wang J, Fan C, Li H, Sun H, Gong S, Chen YH, Shi Y (January 2009). "Crystal structure of TIPE2 provides insights into immune homeostasis". Nature Structural & Molecular Biology. 16 (1): 89–90. doi:10.1038/nsmb.1522. PMID 19079267. S2CID 11111978.
  8. ↑ Sun H, Gong S, et al. (2008). "TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis". Cell. 133 (3): 415–26. doi:10.1016/j.cell.2008.03.026. PMC 2398615. PMID 18455983.
  9. ↑ Li Z, Jia W, Niu J, Zhang L (February 2018). "Understanding the roles of negative immune regulator TIPE2 in different diseases and tumourigenesis". Histology and Histopathology. 33 (9): 919–928. doi:10.14670/HH-11-977. PMID 29480508.
  10. ↑ Lou Y, Liu S (October 2011). "The TIPE (TNFAIP8) family in inflammation, immunity, and cancer". Molecular Immunology. 49 (1–2): 4–7. doi:10.1016/j.molimm.2011.08.006. PMID 21924498.


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