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Future edits for AGGF1 article: 1. Write some of the sentences from previous authors more clearly. 2. Expand on the function of the gene and its role in development 3. Add where the gene is expressed and its functional roles 4. Interactions with other proteins 5. Discovery of the gene 6. Clinical implications of mutations 7. Alternate names (name of the gene has been changed in recent years) 8. Protein Interactions

Sources: PMID: 27522498 PMID: 27513923 PMID: 27222614 PMID: 2579650 PMID: 25564648 PMID: 24893993 PMID: 24277077 PMID: 23197652 PMID: 19556247 PMID: 18564129 PMID: 18327598 PMID: 16443853 PMID: 14961121

An Error has occurred retrieving Wikidata item for infobox Angiogenic factor with G patch and FHA domains 1 is a protein that in humans is encoded by the AGGF1 gene.[1][2][3][4]


AGGF1 is a human gene that functions as an angiogenic factor with G-patch and forkhead-associated domain. [5] This gene is predominantly expressed in activated, plump endothelial cells and acts to regulate angiogenesis and vascular development.[6] AGGF1 is known to interact with a wide range of proteins involved in vascular development.[7] Mutations to AGGF1 have been implicated in multiple cancers and is known to causes the rare cogenital condition Klippel-Treanaunay syndrome. [6][8][9]

Gene

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The AGGF1 gene promoter does not contain a TATA box and contains 2 transcription start sites that are -367 and -364 base pairs ahead of the base translation start site.[10] Notably, the gene promoter contains more than 50 CpG islands, which makes it a DNA methylation target.[10] AGGF1 contains 2 repressor sites and 2 activator sites.[10] Expression of AGGF1 is regulated by GATA1 binding upstream of the AGGF1 promoter at -295 and -300.[6][10][11] In order for full gene expression, both of the activator sites must be bound by the transcription factors. [10]

The gene was originally named VG5Q, which indicated that it was a vascular gene on chromosome 5, but the name was changed to more accurately reflect its function, instead of just location. [12]

There are pseudogenes related to AGGF1 located on chromosomes 3, 4, 10 and 16. [13]

This gene is conserved across many species, such as chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and frog. [13] There are 212 organisms that have genes which are orthologs to AGGF1.

Protein

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The mRNA transcript contains 14 exons and 34 807 nucleotides.[2]

The AGGF1 protein contains a coiled coil domain and an OCRE domain at the N terminus.[14] There are 714 amino acids present in the protein.[14] The G-patch domain is located at amino acids 619-663 while the forkhead-associated domain is located at amino acids 435-508. [14]

Expression

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AGGF1 is largely expressed during early embryonic vein specification, and expression is increased when endothelial cells are activated.[14][15] While AGGF1 is largely functional in endothelial, vascular smooth muscle cells, and osteoblasts, it also has activity in mast cells, cardiac cells, Kupffer cells and hematopoietic stem cells. [12] [15] [16][17] AGGF1 mRNA has been detected in the heart, kidneys and limbs. [14] The proliferation of vascular smooth muscle cells is inhibited when AGGF1 is expressed.[18] It has been found that AGGF1 is highly expressed in some malignant tumours.[8] In vitro models have shown that AGGF1 localizes to cell periphery and directly outside of the cell.[17]

Depending on the mutation type, AGGF1 mutations can be lethal in either the heterozygous or homozygous genotype due to its haploinsufficiency. Heterozygous mutations can cause fatality due to hemorrhaging while homozygous mutations can prevent proper stem cell differentiation. [19]

Functions

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AGGF1 functions to regulate angiogenesis and vascular development. [6] Gene ontology has also implicated AGGF1 in cell adhesion, positive regulation of angiogenesis and endothelial cell proliferation.[13] Additionally, AGGF1 has been shown to protect against inflammation and ischemic injuries.[16] During embryongenesis, AGGF1 is required for hematopoietic stem cell specification and the differentiation of hematopoietic and endothelial cell lineages.[19] Specifically, it regulates VE cadherin by inhibiting the phosphorylation of the cadherin and increasing its presence in the plasma membrane of endothelial cells.[6] It has been found that this gene is critical to the specification of veins and multipotent hemanigioblasts, anti-inflammation, tumour angiogenesis, and inhibition of vascular permeability.[20] Additionally, it has been shown to activate autophagy in specific cell types, such as endothelial cells, cardiac HL1 and H9C2 cells, and vascular smooth muscle cells. [14] [6][20]

Interactions

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AGGF1 directly and indirectly interacts with many proteins. There are direct interactions between AGGF1 and TNFSF12, another secreted angiogenic factor, that leads to increased angiogenesis.[21] AGGF1 acts upstream of hemangioblast genes such as scl, fil1, and etsrp. [7] AGGF1 acts similarly to VEGF - another gene implicated in vascular growth. [7] Additionally, AGGF1 is known to activate catalytic and regulatory subunits of PI3K. [6] This leads to downstream activation of AKT, GSK3b and p70S6K signalling pathway which leads to vein specification and angiogenesis. [7][6] AGGF1 also interacts with vein specific markers such at flt4, dab2, and ephB4.[22] Ccl2 has also been shown to interact with AGGF1 in hepatocytes through blocking NF-κB/p65 from binding to Ccl2.[23] AGGF1 activity is eliminated when Elk is overexpressed.[18] AGGF1 regulates autophagy by regulating expression of JNK genes.[18] SMAD7 and Aggf1 directly interact in the liver to inhibit fibrogenesis. [16] The presence of DNMT3b will repress AGGF1 by acting on the promoter region of the gene.[16]

Clinical Relevance

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Heterogenous mutations in this gene causing deregulation of expression can lead to the vascular malformations associated with Klippel-Trenaunay-Weber syndrome.[6][22][10] AGGF1 was the third human haploinsufficient gene identified.[6] This is very significant because this means that individuals who have even one mutant allele may have Klippel-Treanaunay syndrome. Frequent haemorrhages and increased vascular permeability has been seen in individuals who are heterozygous for Aggf1. [6] A translocation between the chromosome 5 q-arm at region 13 in band 3 and the chromosome 11 p-arm at region 15 in band 1 has been implicated in KTS. [2] This translocation affects the AGGF1 promoter so there is a 3 fold increase in protein production. [2] Single nucleotide polymorphisms in intron 11 and exon 7 were associated with KTS susceptibility even though neither of these SNPs resulted in an amino acid change. [2] At one point, the E133K allele was thought to be a mutational hotspot - due to altered phosophorylation - causing KTS, but it has since been found as much as 3.3% of the population are carriers for the mutation. [21][24]

AGGF1 has also been implicated in treatment after vascular smooth muscle cell damage due to coronary artery disease and myocardial infarction. [18] By blocking vascular permeability and regulating vascular smooth muscle cell phenotypic switching, AGGF1 protein therapy is currently being investigated as a new method of treating both of these diseases. [18]

Abberant AGGF1 has been implicated in multiple cancers and functions in tumour initiation and progression.[9] For example, both hepatocellular carcinoma and gastric cancer survivability is related to the levels of AGGF1 expression in tumors. [8][9] AGGF1 has been found to have higher expression in tumours than the surrounding tissues, and higher levels of AGGF1 are associated with a poor patient prognosis.[8][9]

See also

References

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  1. ^ Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA (Dec 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc Natl Acad Sci U S A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
  2. ^ a b c d e Hu Y, Li L, Seidelmann SB, Timur AA, Shen PH, Driscoll DJ, Wang QK (Oct 2008). "Identification of association of common AGGF1 variants with susceptibility for Klippel-Trenaunay syndrome using the structure association program". Ann Hum Genet. 72 (Pt 5): 636–43. doi:10.1111/j.1469-1809.2008.00458.x. PMC 2602961. PMID 18564129.
  3. ^ Gutierrez S, Magano L, Delicado A, Mori MA, de Torres ML, Fernandez L, Palomares M, Fernandez E, Tarduchy GR, Molano J, Gracia R, Pajares IL, Lapunzina P (Nov 2006). "The G397A (E133K) change in the AGGF1 (VG5Q) gene is a single nucleotide polymorphism in the Spanish population". Am J Med Genet A. 140 (24): 2832–3. doi:10.1002/ajmg.a.31532. PMID 17103452.
  4. ^ "Entrez Gene: AGGF1 angiogenic factor with G patch and FHA domains 1".
  5. ^ Zhan, M; Hori, Y; Wada, N; Ikeda, J; Hata, Y; Osuga, K; Morii, E (28 April 2016). "Angiogenic Factor with G-patch and FHA Domain 1 (AGGF1) Expression in Human Vascular Lesions". Acta Histochem Cytochem. 49 (2): 75-81. doi:10.1267/ahc.15035. PMID 27222614. {{cite journal}}: |access-date= requires |url= (help)
  6. ^ a b c d e f g h i j k Zhang, Teng; Yao, Yufeng; Wang, Jingjing; Li, Yong; He, Ping; Pasupuleti, Vinay; Hu, Zhengkun; Jia, Xinzhen; Song, Qixue (2016-12-01). "Haploinsufficiency of Klippel-Trenaunay syndrome gene Aggf1 inhibits developmental and pathological angiogenesis by inactivating PI3K and AKT and disrupts vascular integrity by activating VE-cadherin". Human Molecular Genetics. 25 (23): 5094–5110. doi:10.1093/hmg/ddw273. ISSN 1460-2083. PMID 27522498.
  7. ^ a b c d Li, Lei; Chen, Di; Li, Jia; Wang, Xiaojing; Wang, Nan; Xu, Chengqi; Wang, Qing K. (2014-01-23). "Aggf1 acts at the top of the genetic regulatory hierarchy in specification of hemangioblasts in zebrafish". Blood. 123 (4): 501–508. doi:10.1182/blood-2013-07-514612. ISSN 1528-0020. PMC 3901065. PMID 24277077.{{cite journal}}: CS1 maint: PMC format (link)
  8. ^ a b c d Yao, Han-Hui; Wang, Ben-Jun; Wu, Yang; Huang, Qiang. "High Expression of Angiogenic Factor with G-Patch and FHA Domain1 (AGGF1) Predicts Poor Prognosis in Gastric Cancer". Medical Science Monitor. 23: 1286–1294. doi:10.12659/msm.903248.
  9. ^ a b c d Wang, Wei; Li, Guang-Yao; Zhu, Jian-Yu; Huang, Da-Bing; Zhou, Hang-Cheng; Zhong, Wen; Ji, Chu-Shu (2015-04-01). "Overexpression of AGGF1 is correlated with angiogenesis and poor prognosis of hepatocellular carcinoma". Medical Oncology. 32 (4): 131. doi:10.1007/s12032-015-0574-2. ISSN 1357-0560.
  10. ^ a b c d e f Fan, Chun; Ouyang, Ping; Timur, Ayse A.; He, Ping; You, Sun-Ah; Hu, Ying; Ke, Tie; Driscoll, David J.; Chen, Qiuyun (2009-08-28). "Novel roles of GATA1 in regulation of angiogenic factor AGGF1 and endothelial cell function". The Journal of Biological Chemistry. 284 (35): 23331–23343. doi:10.1074/jbc.M109.036079. ISSN 0021-9258. PMC 2749107. PMID 19556247.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  11. ^ Fan, Chun; Ouyang, Ping; Timur, Ayse A.; He, Ping; You, Sun-Ah; Hu, Ying; Ke, Tie; Driscoll, David J.; Chen, Qiuyun (2009-08-28). "Novel Roles of GATA1 in Regulation of Angiogenic Factor AGGF1 and Endothelial Cell Function". Journal of Biological Chemistry. 284 (35): 23331–23343. doi:10.1074/jbc.m109.036079. ISSN 0021-9258. PMID 19556247.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  12. ^ a b Zhan, Maosheng; Hori, Yumiko; Wada, Naoki; Ikeda, Jun-Ichiro; Hata, Yuuki; Osuga, Keigo; Morii, Eiichi (2016-04-28). "Angiogenic Factor with G-patch and FHA Domain 1 (AGGF1) Expression in Human Vascular Lesions". Acta Histochemica Et Cytochemica. 49 (2): 75–81. doi:10.1267/ahc.15035. ISSN 0044-5991. PMC 4858542. PMID 27222614.{{cite journal}}: CS1 maint: PMC format (link)
  13. ^ a b c "AGGF1 angiogenic factor with G-patch and FHA domains 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-11-26.
  14. ^ a b c d e f Liu, Yu; Yang, Hui; Song, Lina; Li, Nan; Han, Qiu-Yue; Tian, Cui; Gao, Erhe; Du, Jie; Xia, Yun-Long (August 2014). "AGGF1 protects from myocardial ischemia/reperfusion injury by regulating myocardial apoptosis and angiogenesis". Apoptosis: An International Journal on Programmed Cell Death. 19 (8): 1254–1268. doi:10.1007/s10495-014-1001-4. ISSN 1573-675X. PMID 24893993.
  15. ^ a b Zhan, M; Hori, Y; Wada, N; Ikeda, J; Hata, Y; Osuga, K; Morii, E (28 April 2016). "Angiogenic Factor with G-patch and FHA Domain 1 (AGGF1) Expression in Human Vascular Lesions". Acta Histochem Cytochem. 49 (2): 75-81. doi:10.1267/ahc.15035. PMID 27222614. {{cite journal}}: |access-date= requires |url= (help)
  16. ^ a b c d Zhou, Bisheng; Zeng, Sheng; Li, Luyuang; Fan, Zhiwen; Tian, Wenfang; Li, Min; Xu, Huihui; Wu, Xiaoyan; Fang, Mingming. "Angiogenic factor with G patch and FHA domains 1 (Aggf1) regulates liver fibrosis by modulating TGF-β signaling". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1862 (6): 1203–1213. doi:10.1016/j.bbadis.2016.02.002.
  17. ^ a b Tian, Xiao-Li; Kadaba, Rajkumar; You, Sun-Ah; Liu, Mugen; Timur, Ayse Anil; Yang, Lin; Chen, Qiuyun; Szafranski, Przemyslaw; Rao, Shaoqi (2004-02-12). "Identification of an angiogenic factor that when mutated causes susceptibility to Klippel-Trenaunay syndrome". Nature. 427 (6975): 640–645. doi:10.1038/nature02320. ISSN 1476-4687. PMC 1618873. PMID 14961121.{{cite journal}}: CS1 maint: PMC format (link)
  18. ^ a b c d e Yao, Yufeng; Hu, Zhenkun; Ye, Jian; Hu, Changqing; Song, Qixue; Da, Xingwen; Yu, Yubin; Li, Hui; Xu, Chengqi (2017-06-25). "Targeting AGGF1 (angiogenic factor with G patch and FHA domains 1) for Blocking Neointimal Formation After Vascular Injury". Journal of the American Heart Association. 6 (6). doi:10.1161/JAHA.117.005889. ISSN 2047-9980. PMC 5669188. PMID 28649088.{{cite journal}}: CS1 maint: PMC format (link)
  19. ^ a b Liu, Yu; Yang, Hui; Song, Lina; Li, Nan; Han, Qiu-Yue; Tian, Cui; Gao, Erhe; Du, Jie; Xia, Yun-Long (August 2014). "AGGF1 protects from myocardial ischemia/reperfusion injury by regulating myocardial apoptosis and angiogenesis". Apoptosis: An International Journal on Programmed Cell Death. 19 (8): 1254–1268. doi:10.1007/s10495-014-1001-4. ISSN 1573-675X. PMID 24893993.
  20. ^ a b Lu, Qiulun; Yao, Yufeng; Hu, Zhenkun; Hu, Changqing; Song, Qixue; Ye, Jian; Xu, Chengqi; Wang, Annabel Z.; Chen, Qiuyun (August 2016). "Angiogenic Factor AGGF1 Activates Autophagy with an Essential Role in Therapeutic Angiogenesis for Heart Disease". PLoS biology. 14 (8): e1002529. doi:10.1371/journal.pbio.1002529. ISSN 1545-7885. PMC 4981375. PMID 27513923.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  21. ^ a b Tian, Xiao-Li; Kadaba, Rajkumar; You, Sun-Ah; Liu, Mugen; Timur, Ayse Anil; Yang, Lin; Chen, Qiuyun; Szafranski, Przemyslaw; Rao, Shaoqi (2004-02-12). "Identification of an angiogenic factor that when mutated causes susceptibility to Klippel-Trenaunay syndrome". Nature. 427 (6975): 640–645. doi:10.1038/nature02320. ISSN 1476-4687. PMC 1618873. PMID 14961121.{{cite journal}}: CS1 maint: PMC format (link)
  22. ^ a b Chen, Di; Li, Lei; Tu, Xin; Yin, Zhan; Wang, Qing (2013-03-01). "Functional characterization of Klippel-Trenaunay syndrome gene AGGF1 identifies a novel angiogenic signaling pathway for specification of vein differentiation and angiogenesis during embryogenesis". Human Molecular Genetics. 22 (5): 963–976. doi:10.1093/hmg/dds501. ISSN 1460-2083. PMID 23197652.
  23. ^ Xu, Wenping; Zeng, Sheng; Li, Min; Fan, Zhiwen; Zhou, Bisheng (2017-09-26). "Aggf1 attenuates hepatic inflammation and activation of hepatic stellate cells by repressing Ccl2 transcription". Journal of Biomedical Research. 31 (5): 428–436. doi:10.7555/JBR.30.20160046. ISSN 1674-8301. PMID 28958996.
  24. ^ Barker, K. T.; Foulkes, W. D.; Schwartz, C. E.; Labadie, C.; Monsell, F.; Houlston, R. S.; Harper, J. (July 2006). "Is the E133K allele of VG5Q associated with Klippel-Trenaunay and other overgrowth syndromes?". Journal of Medical Genetics. 43 (7): 613–614. doi:10.1136/jmg.2006.040790. ISSN 1468-6244. PMC 2564558. PMID 16443853.{{cite journal}}: CS1 maint: PMC format (link)
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Further reading

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This article on a gene on human chromosome 5 is a stub. You can help Wikipedia by expanding it.

Possible Topics: 1. Aggf1 2. Ced9 3. Chromosome jumping 4. Nucleasome Article Evaluation - Single nucleotide Polymorphism This article has a C rating and it a part of The WikiProjects Genetics, Molecular and Cell Biology and Human Genetic History. The article uses very specific examples that appear biased towards certain areas of research (ex. Alzheimer's research) but these specific examples help to improve the quality of the article because they demonstrate the relevance of SNPs in common diseases. However, the language used in these examples may be too complicated or scientific for the average person reading a Wikipedia article to understand. There is a few grammatical error in the article. There are comma splices which make reading the article choppy and awkward. The article could be improved by adding a section on how SNPs arise in the genome. It focused heavily on the impact of SNPs on human disease but it failed to explain where SNPs come from and why they are present in the genome. The diagram describing the different types of SNPs would be helpful in clarifying the types of SNPs for someone who was unfamiliar with them. When I clicked on citation [5], I found that it was not a primary research article and therefore it should not be used as a citation in a Wikipedia article.

Great evaluation. Keep it up! AdamCF87 (talk) 14:31, 17 October 2017 (UTC)

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