TNFAIP8L2

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]

TNFAIP8L2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3F4M
Identifiers
Aliases	TNFAIP8L2, TIPE2, TNF alpha induced protein 8 like 2
External IDs	OMIM: 612112 MGI: 1917019 HomoloGene: 56998 GeneCards: TNFAIP8L2
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q21.3 Start 151,156,649 bp[1] End 151,159,749 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 F2.1 Start 95,139,521 bp[2] End 95,142,360 bp[2]
Gene ontology Molecular function • GO:0001948 protein binding Cellular component • cytoplasm Biological process • innate immune system • negative regulation of T cell activation • negative regulation of inflammatory response • immune system process • regulation of apoptotic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
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 Mb	Chr 3: 95.14 – 95.14 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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. GRCh38: Ensembl release 89: ENSG00000163154 - Ensembl, May 2017
2. 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. 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. 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.