The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TNFAIP1  -  tumor necrosis factor, alpha-induced...

Homo sapiens

Synonyms: B12, B61, BACURD2, BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 2, BTB/POZ domain-containing protein TNFAIP1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TNFAIP1

  • Dietary cobalamin (Cbl; vitamin B12) deficiency resulted in severe growth retardation in rats, and body weight in the Cbl-deficient rats at 20 wk of age was significantly lower compared with the age-matched Cbl-sufficient control rats [1].
  • These results suggest that B61 is an autocrine growth factor for melanomas but not normal melanocytes [2].
  • Expression and regulation of Eck and its cognate ligand B61 were analyzed in the human colonic adenocarcinoma cell line Caco-2 [3].
  • Shaky-leg syndrome and vitamin B12 deficiency [4].
  • Homocystinuria and megaloblastic anemia responsive to vitamin B12 therapy. An inborn error of metabolism due to a defect in cobalamin metabolism [5].

Psychiatry related information on TNFAIP1


High impact information on TNFAIP1

  • New B12 coenzyme-dependent enzymes that catalyzed intermediate steps in the anaerobic conversion of lysine to fatty acids and ammonia were isolated from C. sticklandii and characterized [11].
  • These structures reveal that the B12 cofactor undergoes a major conformational change on binding to the apoenzymes of methionine synthase and methylmalonyl-coenzyme A mutase: The dimethylbenzimidazole ligand to the cobalt is displaced by a histidine residue from the protein [12].
  • The best-characterized B12-dependent mutases that catalyze carbon skeleton rearrangement, for which methylmalonyl-coenzyme A mutase is the prototype, also bind cobalamin cofactors with histidine as the cobalt ligand, although other cobalamin-dependent mutases do not appear to utilize histidine ligation [12].
  • CONCLUSIONS: Treatment with a combination of folic acid, vitamin B12, and pyridoxine significantly reduces homocysteine levels and decreases the rate of restenosis and the need for revascularization of the target lesion after coronary angioplasty [13].
  • METHODS: A combination of folic acid (1 mg), vitamin B12 (400 microg), and pyridoxine (10 mg)--referred to as folate treatment--or placebo was administered to 205 patients (mean [+/-SD] age, 61+/-11 years) for six months after successful coronary angioplasty in a prospective, double-blind, randomized trial [13].

Chemical compound and disease context of TNFAIP1


Biological context of TNFAIP1

  • The rat TNFAIP1 gene is mapped to chromosome 10q25 cM, spans approximately 12.9 kb, and is composed of seven exons [19].
  • The open reading frame of B12 predicts a 316-amino acid sequence rich in charged residues, particularly at the carboxyl terminus, and has neither significant homology to other known proteins nor to any extent sequence motifs [20].
  • B12 is found to be a highly conserved single-copy gene which is located in the q22----q23 region of human chromosome 17 [20].
  • Transcript expression is found to be developmentally regulated in a tissue-specific manner, with B12 message being differentially expressed in the heart and liver during mouse embryogenesis [20].
  • Protein B61 as a new growth factor: expression of B61 and up-regulation of its receptor epithelial cell kinase during melanoma progression [2].

Anatomical context of TNFAIP1


Associations of TNFAIP1 with chemical compounds

  • Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis [21].
  • There was no evidence of methylmalonic aciduria or deficiency of folate or vitamin B12 [5].
  • METHODS: To test this hypothesis, we assessed the effects of breakfast cereals fortified with three levels of folic acid, and also containing the recommended dietary allowances of vitamins B6 and B12, in a randomized, double-blind, placebo-controlled, crossover trial in 75 men and women with coronary artery disease [24].
  • Two brothers 62 and 70 years old, without evidence of vitamin B12 lack, excreted 12 to 115 mg of methylmalonic acid daily (normal, less than 9 mg per day) [25].
  • These children have no evidence of a deficiency of vitamin B12, which acts as a cofactor with methylmalonyl-CoA mutase, and they did not respond to the administration of vitamin B12 [26].

Regulatory relationships of TNFAIP1


Other interactions of TNFAIP1

  • Both CRYAB and TNFAIP1 show increased transcript levels in AD brains, supporting the validity of this approach [27].
  • The deduced proteins of rat PDIP1 and rat TNFAIP1 share 63.1% sequence identity with each other and are highly conserved in the majority of the middle portion of the two proteins, which encode a BTB/POZ domain at the N-terminus and a PCNA binding motif (QTKV-EFP) at the C-terminus, respectively [19].
  • MNCs from obese subjects have higher IKBKB expression, increased nuclear factor kappa B (NFkappaB) binding and higher mRNA expression of TNFAIP1 and IL6 genes [28].

Analytical, diagnostic and therapeutic context of TNFAIP1

  • Sequence analysis of cDNA clones encoding B61 revealed that its protein product has no significant homology to previously described proteins [22].
  • B61 was also identified by Western blotting and ECK binding activity with the use of a BIAcore binding assay in melanoma cell-conditioned media [2].
  • Examination of B61 mRNA expression by in situ hybridization analysis revealed tight association of B61 with endothelial cells at an early stage and epithelial cells in various tissues including lung, kidney, intestine, skin at later stage of organogenesis [23].
  • The results should not be construed as pointing to a potential way of preventing lung cancer in individuals who continue to smoke or as supporting self-medication with large doses of folate or B12 by smokers [14].
  • Two sandwich immunoassays were evaluated, one which used the mAb G5 for capture, the other which used B12 for capture [29].


  1. Abnormal increase in the expression level of proliferating cell nuclear antigen (PCNA) in the liver and hepatic injury in rats with dietary cobalamin deficiency. Nakao, M., Kono, N., Adachi, S., Ebara, S., Adachi, T., Miura, T., Yamaji, R., Inui, H., Nakano, Y. J. Nutr. Sci. Vitaminol. (2006) [Pubmed]
  2. Protein B61 as a new growth factor: expression of B61 and up-regulation of its receptor epithelial cell kinase during melanoma progression. Easty, D.J., Guthrie, B.A., Maung, K., Farr, C.J., Lindberg, R.A., Toso, R.J., Herlyn, M., Bennett, D.C. Cancer Res. (1995) [Pubmed]
  3. Epithelial cell kinase-B61: an autocrine loop modulating intestinal epithelial migration and barrier function. Rosenberg, I.M., Göke, M., Kanai, M., Reinecker, H.C., Podolsky, D.K. Am. J. Physiol. (1997) [Pubmed]
  4. Shaky-leg syndrome and vitamin B12 deficiency. Benito-León, J., Porta-Etessam, J. N. Engl. J. Med. (2000) [Pubmed]
  5. Homocystinuria and megaloblastic anemia responsive to vitamin B12 therapy. An inborn error of metabolism due to a defect in cobalamin metabolism. Schuh, S., Rosenblatt, D.S., Cooper, B.A., Schroeder, M.L., Bishop, A.J., Seargeant, L.E., Haworth, J.C. N. Engl. J. Med. (1984) [Pubmed]
  6. Yield of psychiatric consultants' recommendations for diagnostic action. Popkin, M.K., Mackenzie, T.B., Callies, A.L., Hall, R.C. Arch. Gen. Psychiatry (1982) [Pubmed]
  7. Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. Wainfan, E., Poirier, L.A. Cancer Res. (1992) [Pubmed]
  8. Low serum cobalamin levels in primary degenerative dementia. Do some patients harbor atypical cobalamin deficiency states? Karnaze, D.S., Carmel, R. Arch. Intern. Med. (1987) [Pubmed]
  9. B12 deficiency in presenile dementia. Abalan, F., Delile, J.M. Biol. Psychiatry (1985) [Pubmed]
  10. Vitamin B12 and folate levels and lithium administration in patients with affective disorders. Cervantes, P., Ghadirian, A.M., Vida, S. Biol. Psychiatry (1999) [Pubmed]
  11. Discoveries of vitamin B12 and selenium enzymes. Stadtman, T.C. Annu. Rev. Biochem. (2002) [Pubmed]
  12. Structure-based perspectives on B12-dependent enzymes. Ludwig, M.L., Matthews, R.G. Annu. Rev. Biochem. (1997) [Pubmed]
  13. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. Schnyder, G., Roffi, M., Pin, R., Flammer, Y., Lange, H., Eberli, F.R., Meier, B., Turi, Z.G., Hess, O.M. N. Engl. J. Med. (2001) [Pubmed]
  14. Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12. Report of a preliminary randomized, double-blind intervention trial. Heimburger, D.C., Alexander, C.B., Birch, R., Butterworth, C.E., Bailey, W.C., Krumdieck, C.L. JAMA (1988) [Pubmed]
  15. Folic acid fortification of the food supply. Potential benefits and risks for the elderly population. Tucker, K.L., Mahnken, B., Wilson, P.W., Jacques, P., Selhub, J. JAMA (1996) [Pubmed]
  16. Letter: Ascorbic acid and vitamin B12 deficiency. Hines, J.D. JAMA (1975) [Pubmed]
  17. Urinary methylmalonic acid to detect vitamin B12 deficiency. Norman, E.J. JAMA (1995) [Pubmed]
  18. Gastrointestinal dysfunction in immunoglobulin deficiency. Effect of corticosteroids and tetracycline. Diaz-Buxo, J.A., Hermans, P.E., Huizenga, K.A. JAMA (1975) [Pubmed]
  19. Cloning of two rat PDIP1 related genes and their interactions with proliferating cell nuclear antigen. Zhou, J., Hu, X., Xiong, X., Liu, X., Liu, Y., Ren, K., Jiang, T., Hu, X., Zhang, J. J. Exp. Zoolog. Part A Comp. Exp. Biol. (2005) [Pubmed]
  20. Characterization of a novel tumor necrosis factor-alpha-induced endothelial primary response gene. Wolf, F.W., Marks, R.M., Sarma, V., Byers, M.G., Katz, R.W., Shows, T.B., Dixit, V.M. J. Biol. Chem. (1992) [Pubmed]
  21. Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis. Pandey, A., Shao, H., Marks, R.M., Polverini, P.J., Dixit, V.M. Science (1995) [Pubmed]
  22. A novel immediate-early response gene of endothelium is induced by cytokines and encodes a secreted protein. Holzman, L.B., Marks, R.M., Dixit, V.M. Mol. Cell. Biol. (1990) [Pubmed]
  23. Molecular cloning and expression of rat and mouse B61 gene: implications on organogenesis. Takahashi, H., Ikeda, T. Oncogene (1995) [Pubmed]
  24. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. Malinow, M.R., Duell, P.B., Hess, D.L., Anderson, P.H., Kruger, W.D., Phillipson, B.E., Gluckman, R.A., Block, P.C., Upson, B.M. N. Engl. J. Med. (1998) [Pubmed]
  25. Methylmalonic aciduria without vitamin B12 deficiency in an adult sibship. Giorgio, A.J., Trowbridge, M., Boone, A.W., Patten, R.S. N. Engl. J. Med. (1976) [Pubmed]
  26. Benign methylmalonic aciduria. Ledley, F.D., Levy, H.L., Shih, V.E., Benjamin, R., Mahoney, M.J. N. Engl. J. Med. (1984) [Pubmed]
  27. Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer's disease model. Link, C.D., Taft, A., Kapulkin, V., Duke, K., Kim, S., Fei, Q., Wood, D.E., Sahagan, B.G. Neurobiol. Aging (2003) [Pubmed]
  28. Role of inflammatory mediators in the suppression of insulin receptor phosphorylation in circulating mononuclear cells of obese subjects. Ghanim, H., Aljada, A., Daoud, N., Deopurkar, R., Chaudhuri, A., Dandona, P. Diabetologia (2007) [Pubmed]
  29. The alpha form of human tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in those with systemic mastocytosis. Schwartz, L.B., Sakai, K., Bradford, T.R., Ren, S., Zweiman, B., Worobec, A.S., Metcalfe, D.D. J. Clin. Invest. (1995) [Pubmed]
WikiGenes - Universities