Protein-coding gene in humans
TNFAIP8L2 |
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Available structures |
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PDB | Ortholog search: PDBe RCSB |
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Identifiers |
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Aliases | TNFAIP8L2, TIPE2, TNF alpha induced protein 8 like 2 |
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External IDs | OMIM: 612112; MGI: 1917019; HomoloGene: 56998; GeneCards: TNFAIP8L2; OMA:TNFAIP8L2 - orthologs |
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Gene location (Human) |
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| Chr. | Chromosome 1 (human)[1] |
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| Band | 1q21.3 | Start | 151,156,649 bp[1] |
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End | 151,159,749 bp[1] |
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Gene location (Mouse) |
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| Chr. | Chromosome 3 (mouse)[2] |
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| Band | 3|3 F2.1 | Start | 95,046,832 bp[2] |
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End | 95,049,671 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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Top expressed in | - granulocyte
- monocyte
- blood
- mucosa of ileum
- spleen
- appendix
- lymph node
- gonad
- testicle
- trabecular bone
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| Top expressed in | - granulocyte
- mesenteric lymph nodes
- blood
- stroma of bone marrow
- blastocyst
- spleen
- subcutaneous adipose tissue
- thymus
- jejunum
- morula
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| More reference expression data |
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BioGPS | |
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Gene ontology |
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Molecular function | | Cellular component | | Biological process | - innate immune response
- negative regulation of T cell activation
- negative regulation of inflammatory response
- immune system process
- regulation of apoptotic process
| Sources:Amigo / QuickGO |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | | |
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RefSeq (protein) | | |
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Location (UCSC) | Chr 1: 151.16 – 151.16 Mb | Chr 3: 95.05 – 95.05 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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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
- ^ a b c GRCh38: Ensembl release 89: ENSG00000163154 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000013707 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b 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.
- ^ a b 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.