FHL5

Summary

Gene Symbol: FHL5
Description: four and a half LIM domains 5
Alias: 1700027G07Rik, ACT, FHL-5, dJ393D12.2, four and a half LIM domains protein 5, LIM protein ACT, activator of cAMP-responsive element modulator (CREM) in testis, activator of cAMP-responsive element modulator in testis
Species: human
Products:     FHL5

Top Publications

  1. Zhang M, Zhu X, Zhang Y, Cai Y, Chen J, Sivaprakasam S, et al. RCAD/Ufl1, a Ufm1 E3 ligase, is essential for hematopoietic stem cell function and murine hematopoiesis. Cell Death Differ. 2015;22:1922-34 pubmed publisher
    ..The finding of RCAD/Ufl1 as a key regulator of cellular stress response sheds a light into the role of a novel protein network including RCAD/Ufl1 and its associated proteins in regulating cellular homeostasis. ..
  2. Hackmann Y, Graham S, Ehl S, Höning S, Lehmberg K, Aricò M, et al. Syntaxin binding mechanism and disease-causing mutations in Munc18-2. Proc Natl Acad Sci U S A. 2013;110:E4482-91 pubmed publisher
    ..and natural killer cell (NK) cytotoxicity, and give rise to familial hemophagocytic lymphohistiocytosis (FHL4 or FHL5, respectively)...
  3. Cetica V, Santoro A, Gilmour K, Sieni E, Beutel K, Pende D, et al. STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis type 5. J Med Genet. 2010;47:595-600 pubmed publisher
    ..Additional polymorphisms are also described. These data expand current knowledge on the genetic heterogeneity of FHL and suggest that patients with FHL5 may have different results in degranulation assays under different conditions.
  4. Esmaeilzadeh H, Bemanian M, Nabavi M, Arshi S, Fallahpour M, Fuchs I, et al. Novel Patient with Late-Onset Familial Hemophagocytic Lymphohistiocytosis with STXBP2 Mutations Presenting with Autoimmune Hepatitis, Neurological Manifestations and Infections Associated with Hypogammaglobulinemia. J Clin Immunol. 2015;35:22-5 pubmed publisher
    ..Herein, a patient is presented who suffered from hepatitis and atypical brain lesions. Genetic studies revealed a homozygous mutation in the STXP2 gene; and thus, the diagnosis of FHL5 was confirmed.
  5. Seo J, Lee K, Yoo K, Sung K, Koo H, Kim S, et al. Prevalence of type 5 familial hemophagocytic lymphohistiocytosis in Korea and novel mutations in STXBP2. Clin Genet. 2016;89:222-7 pubmed publisher
    ..Most recently, STXBP2 has been identified as the causative gene of type 5 FHL (FHL5) with a worldwide distribution. In this study, we investigated the prevalence of FHL5 in Korea...
  6. Dieckmann N, Hackmann Y, Aricò M, Griffiths G. Munc18-2 is required for Syntaxin 11 Localization on the Plasma Membrane in Cytotoxic T-Lymphocytes. Traffic. 2015;16:1330-41 pubmed publisher
    ..Using a novel FHL5 Munc18-2 mutation that results in loss of protein, cytotoxicity and degranulation together with CTL from an FHL4 ..
  7. Palermo I, Litrico L, Emmanuele G, Giuffrida V, Sassone Corsi P, De Cesare D, et al. Cloning and expression of activator of CREM in testis in human testicular tissue. Biochem Biophys Res Commun. 2001;283:406-11 pubmed
    Activator of cAMP-responsive element modulator (CREM) in testis (ACT) has recently been found in the mouse testis where it activates CREM, a transcription factor essential for the differentiation of spermatids into mature spermatozoa...
  8. Christensen G, Wooding S, Ivanov I, Atkins J, Carrell D. Sequencing and haplotype analysis of the activator of CREM in the testis (ACT) gene in populations of fertile and infertile males. Mol Hum Reprod. 2006;12:257-62 pubmed
    ..During spermiogenesis, CREM is regulated in part by activator of CREM in the testis (ACT), which activates CREM in a phosphorylation-independent fashion...
  9. Lin Q, Fu X, Yao L, Yang J, Cao L, Xin Y, et al. Association of genetic loci for migraine susceptibility in the she people of China. J Headache Pain. 2015;16:553 pubmed publisher
    ..gene; rs12134493 is upstream of the tetraspanin 2 (TSPAN2) gene; and rs13208321 is within the four and a half LIM domains protein 5 (FHL5) gene. This was a case-controlled study conducted in She people of Fujian province in China...

More Information

Publications28

  1. Krausz C, Sassone Corsi P. Genetic control of spermiogenesis: insights from the CREM gene and implications for human infertility. Reprod Biomed Online. 2005;10:64-71 pubmed
    ..Targeted inactivation of the genes encoding CREM and ACT has been achieved. ACT selectively associates with KIF17b, a kinesin motor protein highly expressed in germ cells...
  2. Fimia G, Morlon A, Macho B, De Cesare D, Sassone Corsi P. Transcriptional cascades during spermatogenesis: pivotal role of CREM and ACT. Mol Cell Endocrinol. 2001;179:17-23 pubmed
    ..The molecular mechanism by which CREM elicits its regulatory function involves ACT (Activator of CREM in Testis), a testis-specific coactivator constituted by a repeat of four and half LIM domains...
  3. Hogeveen K, Sassone Corsi P. Regulation of gene expression in post-meiotic male germ cells: CREM-signalling pathways and male fertility. Hum Fertil (Camb). 2006;9:73-9 pubmed
    ..a germ cell-specific, CREM phosphorylation-independent transcriptional co-activator, activator of CREM in testis (ACT)...
  4. Steger K, Behr R, Kleiner I, Weinbauer G, Bergmann M. Expression of activator of CREM in the testis (ACT) during normal and impaired spermatogenesis: correlation with CREM expression. Mol Hum Reprod. 2004;10:129-35 pubmed
    ..Transcriptional activity of the CREM protein is thought to be regulated by activator of CREM in the testis (ACT)...
  5. Macho B, Brancorsini S, Fimia G, Setou M, Hirokawa N, Sassone Corsi P. CREM-dependent transcription in male germ cells controlled by a kinesin. Science. 2002;298:2388-90 pubmed
    b>ACT is a LIM-only protein expressed exclusively in round spermatids, where it cooperates with transcriptional activator CREM in regulating various postmeiotic genes...
  6. Stoffregen E, Donley N, Stauffer D, Smith L, Thayer M. An autosomal locus that controls chromosome-wide replication timing and mono-allelic expression. Hum Mol Genet. 2011;20:2366-78 pubmed publisher
    ..Taken together, these observations indicate that human autosomes contain discrete cis-acting loci that control chromosome-wide replication timing, mono-allelic expression and the stability of entire chromosomes. ..
  7. Freilinger T, Anttila V, de Vries B, Malik R, Kallela M, Terwindt G, et al. Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nat Genet. 2012;44:777-82 pubmed publisher
    ..This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder. ..
  8. Philippar U, Schratt G, Dieterich C, Müller J, Galgoczy P, Engel F, et al. The SRF target gene Fhl2 antagonizes RhoA/MAL-dependent activation of SRF. Mol Cell. 2004;16:867-80 pubmed
    ..Our findings identify an autoregulatory mechanism to selectively regulate subsets of RhoA-activated SRF target genes. ..
  9. Belbin O, Dunn J, Chappell S, Ritchie A, Ling Y, Morgan L, et al. A SNP in the ACT gene associated with astrocytosis and rapid cognitive decline in AD. Neurobiol Aging. 2008;29:1167-76 pubmed
    There is biochemical and animal model evidence supporting a pathological role of the ACT gene in AD...
  10. Davies R, Wells G, Stewart A, Erdmann J, Shah S, Ferguson J, et al. A genome-wide association study for coronary artery disease identifies a novel susceptibility locus in the major histocompatibility complex. Circ Cardiovasc Genet. 2012;5:217-25 pubmed publisher
    ..Further laboratory studies will be required to understand the biological basis of this association and identify the causative allele(s). ..
  11. Fimia G, De Cesare D, Sassone Corsi P. A family of LIM-only transcriptional coactivators: tissue-specific expression and selective activation of CREB and CREM. Mol Cell Biol. 2000;20:8613-22 pubmed
    ..We have recently described the first tissue-specific coactivator of CREB family transcription factors, ACT (activator of CREM in testis)...
  12. Wu H, Chen Y, Miao S, Zhang C, Zong S, Koide S, et al. Sperm associated antigen 8 (SPAG8), a novel regulator of activator of CREM in testis during spermatogenesis. FEBS Lett. 2010;584:2807-15 pubmed publisher
    ..CREM and its coactivator in testis, ACT, activate the transcription of many essential genes for spermatogenesis...
  13. Sassone Corsi P. Transcription factors governing male fertility. Andrologia. 2005;37:228-9 pubmed
  14. Kimmins S, Kotaja N, Fienga G, Kolthur U, Brancorsini S, Hogeveen K, et al. A specific programme of gene transcription in male germ cells. Reprod Biomed Online. 2004;8:496-500 pubmed
    ..In testis, CREM transcriptional activity is controlled through interaction with a tissue-specific partner, ACT, which confers a powerful, phosphorylation-independent activation capacity...
  15. Peri A, Luciani P, Tonacchera M, Agretti P, Baglioni Peri S, Buci L, et al. Expression of cAMP-responsive element binding protein and inducible cAMP early repressor in hyperfunctioning thyroid adenomas. Eur J Endocrinol. 2002;146:759-66 pubmed
  16. Fimia G, De Cesare D, Sassone Corsi P. CBP-independent activation of CREM and CREB by the LIM-only protein ACT. Nature. 1999;398:165-9 pubmed
    ..Using a two-hybrid screen, we have isolated a testis-derived complementary DNA encoding a protein that we term ACT (for activator of CREM in testis), a LIM-only protein which specifically associates with CREM...
  17. Nakanishi K, Saito Y, Azuma N, Sasajima T. Cyclic adenosine monophosphate response-element binding protein activation by mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half LIM domains 5 plays a key role for vein graft intimal hyperplasia. J Vasc Surg. 2013;57:182-93, 193.e1-10 pubmed publisher
    ..genes, mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3) and four-and-a-half LIM domains 5 (FHL5)...
  18. Zhao H, Eising E, de Vries B, Vijfhuizen L, Anttila V, Winsvold B, et al. Gene-based pleiotropy across migraine with aura and migraine without aura patient groups. Cephalalgia. 2016;36:648-57 pubmed publisher
    ..Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while ..
  19. Vogel G, van Rijn J, Krainer I, Janecke A, Posovszky C, Cohen M, et al. Disrupted apical exocytosis of cargo vesicles causes enteropathy in FHL5 patients with Munc18-2 mutations. JCI Insight. 2017;2: pubmed publisher
    Familial hemophagocytic lymphohistiocytosis 5 (FHL5) is an autosomal recessive disease caused by mutations in STXBP2, coding for Munc18-2, which is required for SNARE-mediated membrane fusion...