Property Summary

NCBI Gene PubMed Count 100
PubMed Score 355.24
PubTator Score 111.07

Knowledge Summary


No data available


  Differential Expression (22)

Disease log2 FC p
hepatocellular carcinoma 1.100 1.1e-03
malignant mesothelioma -3.700 1.6e-09
astrocytic glioma -1.900 2.9e-03
ependymoma -2.400 5.7e-03
oligodendroglioma -1.900 8.8e-03
adrenocortical carcinoma -1.190 3.7e-02
primary pancreatic ductal adenocarcinoma 3.063 1.4e-03
non-small cell lung cancer 1.172 1.6e-07
intraductal papillary-mucinous adenoma (... 1.900 4.4e-03
intraductal papillary-mucinous carcinoma... 2.000 1.0e-02
intraductal papillary-mucinous neoplasm ... 2.800 6.1e-03
lung cancer 2.100 5.7e-04
active ulcerative colitis 1.259 3.5e-02
pancreatic cancer 2.500 2.4e-03
sonic hedgehog group medulloblastoma 1.400 2.3e-02
lung adenocarcinoma 1.400 4.6e-04
nasopharyngeal carcinoma -1.300 3.9e-05
spina bifida -1.686 3.6e-02
Pick disease -1.200 1.2e-03
Breast cancer -1.500 4.4e-04
ovarian cancer -1.900 1.2e-03
pituitary cancer -1.800 6.0e-04

Gene RIF (69)

26759260 FHL2 overexpression could contribute to the growth, proliferation, invasiveness, and metastasis of human tongue squamous cell carcinoma.
26759258 FHL2 might interact with Runx2 to mediate mesenchymal cell differentiation at the early stages of tooth development and human dental pulp cell differentiation.
26548523 Studies indicate that the LIM-only protein FHL2 interactome is functionally involved in the cardiovascular system.
26320172 KLF8-induced FHL2 activation is a novel and critical signaling mechanism underlying human colorectal cancer invasion and metastasis.
26222912 These results identify FHL2 as a novel gene associated with asthma severity in human.
26211626 Describe the molecular network governing FHL2 expression, and FHL2-linked cancers and the underlying molecular machinery. Review.
25917075 results provide evidence for the importance of the focal adhesion protein FHL2 in pancreatic cancer cell survival, proliferation and radiosensitivity
25855776 we conclude that FHL2 has both structural and functional protein-protein interactions with b-catenin in the podocyte nucleus and that FHL2 protein inhibition can mitigate Wnt/b-catenin-induced podocytopathy.
25596251 Enhanced FHL2 and TGF-beta1 expression is correlated with poor survival in human malignant melanoma
25554651 Tumoral expression of nuclear cofactor FHL2 is associated with lymphatic metastasis in sporadic but not in hereditary nonpolyposis colorectal cancer-associated colorectal cancer.
25540819 HPV16 E6 oncoprotein interacted and impaired the subcellular distribution of FHL2.
25477051 tumoural TGF-beta1 secretion seems to induce nuclear translocation of co-factor FHL2 mediating progressive keratin expression in pilomatricoma.
25358972 FHL2 is down-regulated in HCM; both FHL2 wild type and variants partially protected phenylephrine- or endothelin-1-induced hypertrophy in cardiac myocytes
25332231 FHL2 is a transcriptional coactivator of LXRs and may be an important determinant of cholesterol metabolism in SMCs
25179730 FHL2 downregulation has a role in the pathogenesis of myeloid malignancies.
24219103 Data suggest Fhl1 (four-and-a-half LIM domains protein 1) and FHL2 (four-and-a-half LIM domains protein 2) bind to and regulate activity of Prkd1 (protein kinase D 1) in cardiac/ventricular myocytes; knockdown of FHL2 down-regulates Prkd1 activation.
24008552 High FHL2 expression is associated with colon cancer.
23801747 The calpain-cleaved filamin fragment and FHL2 are present in the nucleus only in CRPC.
23756870 higher FHL2 expression in malignant epithelial cells correlates with progressive disease in patients with colorectal cancer, suggesting that FHL2 is a prognostic indicator for the development of metachronous metastases and for overall survival
23585479 PCBP2 is an RNA-binding protein that modulates glioma growth by regulating FHL3
23413425 Deletion of FHL2 protein by FHL2 small interfering RNA impaired VEGF production under hypoxia conditions, and also suppressed endothelial progenitor cell angiogenic functions.
23383046 FHL2 acts as an oncogene in osteosarcoma cells and contributes to tumorigenesis through Wnt signaling
23212909 FHL2 increases the stability of the TGF-beta pathway positive regulator Arkadia by inhibiting its ubiquitination and cooperates with Arkadia to activate TGF-beta signaling.
22882857 Overexpression of Id3 markedly promoted the proliferation and invasive capacity of MCF-7 cells; however, these effects were significantly suppressed by the overexpression of FHL2.
22851699 FHL2 modulates calcineurin-dependent activation of NFAT target genes.
22796152 The four and a half LIM-only protein 2 regulates liver homeostasis and contributes to carcinogenesis.
22417706 On influenza A virus infection FHL2 translocates into the nucleus, potentiating the IRF-3-dependent transcription of the IFNbeta gene.
22219185 FHL2 directly interacts with HIF-1alpha to repress transcriptional activity.
22049082 association of FHL2 with Nur77 plays a pivotal role in vascular disease.
21826055 Overexpression of FHL2 in peritumoural myofibroblasts correlated to lymphatic metastasis in sporadic colon cancer but not in hereditary non-polyposis colorectal cancer.
21377781 our results indicate FHL2 could exert anti-apoptotic effect independent of tumor growth suppression
21308406 Our data suggest a role of FHL2 in odontoblast differentiation and dentin formation both in normal and in carious teeth
20734429 cooperative regulation of estrogen signaling by FHL2 and Smad4 in breast cancer cells, and might provide a new regulation mechanism underlying breast cancer development and progression
20607723 Sp1 up-regulates FHL2 expression in gastrointestinal cancers through transcription regulation.
20592280 In the absence of transgenic FHL2, CCL19-induced bone marrow-derived dendritic cell migratory speed, persistence, and directionality were markedly increased in vitro and in vivo.
20460358 FHL2 is a potent epithelial-mesenchymal transition (EMT) inducer and might be an important mediator for invasion and/or metastasis of colon cancer.
20442768 In human colorectal carcinoma but not in low-grade dysplasia, we detected up-regulation and enhanced nuclear localization of FHL2, indicating the activation of FHL2 during the development of malignancy
19815066 Aryl hydrocarbon receptor (AhR) modulation of androgen receptor activity is differentially altered by the level of FHL2 and AhR present in the cell.
19465923 Data suggest that in the absence of its ligand Shh the dependence receptor Patched serves as the anchor for a caspase-activating complex that includes DRAL, and caspase-9.
19417068 Ectopic FHL2 expression in neuroblastoma cells markedly reduces the transcriptional and cell-cycle promoting functions of Id2.
19325137 FHL-2 suppresses VEGF-induced phosphatidylinositol 3-kinase/Akt activation via interaction with sphingosine kinase-1.
19139564 Human four-and-a-half LIM family members suppress tumor cell growth through a TGF-beta-like signaling pathway.
18680509 The physiological implication of HERG-FHL2 interaction showed a significant increase in the HERG current amplitude and a faster deactivation of the tail current in human embryonic kidney 293 cells co-expressing HERG and FHL2.
18653765 FHL2-beta-catenin interaction potentiates beta-catenin nuclear translocation and TCF/LEF transcription, resulting in increased Runx2 and alkaline phosphatase expression, which was inhibited by the Wnt inhibitor DKK1.
18615633 Overexpression of FHL2 increases the tumorigenicity of glioblastoma cells in nude mice and decreases the mRNA levels of p53.
18356303 Role of FHL2 in bundling of focal adhesion structures, in integrin-mediated ERK activation, and subsequently in proper allocation of matrix proteins on the cell surface.
18224250 Data suggest that IL-1beta is involved in the regulation of various cytoskeletal components in human chondrocytes including the multifunctional protein FHL2, which might be relevant for the pathogenesis of osteoarthritis.
17975004 These results suggest a novel indirect mechanism of androgen action on FHL2 expression and provide evidence that SRF is an important determinant of AR action in prostate cancer cells.
17682292 Data indicate that overexpression of the transcriptional cofactor FHL2 contributes to breast cancer development by mediating transcriptional activation of MAPK target genes known to be involved in cancer progression, such as p21.
17416352 Functional analysis demonstrated that the FHL2 mutation affected the binding to titin/connectin.
17383428 Suppression of FHL2 induces cell differentiation and inhibits tumorigenesis in gastrointestinal cancers.
17192406 PELP1 functions as a molecular adaptor, coupling FHL2 with nuclear receptors, and PELP1-FHL2 interactions may have a role in prostate cancer progression.
17145880 Data suggest that nuclear FHL2 may serve as a novel biomarker predictive for prostate cancer with aggressive biology and point to a role of FHL2 in constitutive activation of AR-mediated growth signals.
17093190 the interaction of FHL2 with HPV-16 E7 leads to a promoter-specific impairment of FHL2 function and this may contribute to cell transformation.
16652157 findings show that full-length E4F1 protein but not its E1A-activated & truncated form interacts in vitro & in vivo with FHL2; this E4F1-FHL2 association occurs in the nuclear compartment & inhibits the capacity of E4F1 to block cell proliferation
16378916 specific expression in tumor tissue points to an important functional role of FHL2 in human breast cancer
16355270 FHL2 plays an important role in osteoblast differentiation and bone formation.
16343438 Overall, our findings indicate that FHL2 can also regulate p53 via a direct association with HIPK2.
16311053 In conclusion, our findings are consistent with the hypothesis that FHL-2 and ADAM-9 are important modulators of IGFBP-5 actions and are, in part, regulated in a coordinated manner in bone.
15692560 FHL2 inhibits FOXO1 activity in prostate cancer cells by promoting the deacetylation of FOXO1 by SIRT1
15572674 The interaction and functional cooperation between FHL2, CITED4, and CTNNB were studied.
15161045 pp125FAK and FHL2 form a protein complex in human ovarian carcinoma.
15117962 FHL2 and FHL3, respectively, are colocalized with alpha(7)beta(1) integrin receptor at the periphery of Z-discs, suggesting a role in mechanical stabilization of muscle cells
14680945 both the recombinant and the natural proteins are post-translationally modified and indicate that such modifications may lead to an abnormal electrophoretic behavior of natural human FHL2
14550570 -FHL2 interaction may be involved in transcriptional regulation and play a significant role in cancer cell growth
12466281 FHL2 might enforce beta-catenin transactivation activity in cancer cells
12145280 evidence of a functional interaction between the promyelocytic leukemia zinc finger protein (PLZF) and DRAL/FHL2
12067710 TUCAN/CARDINAL and DRAL participate in a common pathway for modulation of NF-kappaB activation.
11821401 Insulin-like growth factor-binding protein 5 (IGFBP-5) interacts with a four and a half LIM protein 2 (FHL2).

AA Sequence


Text Mined References (105)

PMID Year Title
26759260 2016 Four and a half LIM domains 2 contributes to the development of human tongue squamous cell carcinoma.
26759258 2016 FHL2 mediates tooth development and human dental pulp cell differentiation into odontoblasts, partially by interacting with Runx2.
26548523 2016 Protein-protein interactions of the LIM-only protein FHL2 and functional implication of the interactions relevant in cardiovascular disease.
26320172 2015 KLF8 promotes tumorigenesis, invasion and metastasis of colorectal cancer cells by transcriptional activation of FHL2.
26222912 2015 Deficiency of FHL2 attenuates airway inflammation in mice and genetic variation associates with human bronchial hyper-responsiveness.
26211626 2015 The FHL2 regulation in the transcriptional circuitry of human cancers.
25917075 2015 LIM-only protein FHL2 critically determines survival and radioresistance of pancreatic cancer cells.
25855776 2015 Four-and-a-Half LIM Domains Protein 2 Is a Coactivator of Wnt Signaling in Diabetic Kidney Disease.
25596251 2015 Enhanced FHL2 and TGF-?1 Expression Is Associated With Invasive Growth and Poor Survival in Malignant Melanomas.
25554651 2015 Tumoral expression of nuclear cofactor FHL2 is associated with lymphatic metastasis in sporadic but not in HNPCC-associated colorectal cancer.
25540819 2015 High risk HPV E6 oncoproteins impair the subcellular distribution of the four and a half LIM-only protein 2 (FHL2).
25477051 2015 TGF-?1-dependent induction and nuclear translocation of FHL2 promotes keratin expression in pilomatricoma.
25416956 2014 A proteome-scale map of the human interactome network.
25358972 2014 FHL2 expression and variants in hypertrophic cardiomyopathy.
25332231 2015 LIM-only protein FHL2 is a positive regulator of liver X receptors in smooth muscle cells involved in lipid homeostasis.
25218447 2014 Uncovering global SUMOylation signaling networks in a site-specific manner.
25179730 2015 FHL2 regulates hematopoietic stem cell functions under stress conditions.
24219103 2014 Four-and-a-half LIM domains proteins are novel regulators of the protein kinase D pathway in cardiac myocytes.
24008552 2013 A novel colon cancer gene therapy using rAAV?mediated expression of human shRNA-FHL2.
23801747 2013 Regulation of the transcriptional coactivator FHL2 licenses activation of the androgen receptor in castrate-resistant prostate cancer.
23756870 2013 Epithelial expression of FHL2 is negatively associated with metastasis-free and overall survival in colorectal cancer.
23585479 2013 RNA-binding protein PCBP2 modulates glioma growth by regulating FHL3.
23413425 2013 Deletion of FHL2 gene impaired ischemia-induced blood flow recovery by modulating circulating proangiogenic cells.
23383046 2013 FHL2 silencing reduces Wnt signaling and osteosarcoma tumorigenesis in vitro and in vivo.
23212909 2013 The four and a half LIM-only protein 2 (FHL2) activates transforming growth factor ? (TGF-?) signaling by regulating ubiquitination of the E3 ligase Arkadia.
22882857 2012 FHL2 inhibits the Id3-promoted proliferation and invasive growth of human MCF-7 breast cancer cells.
22851699 2012 FHL2 binds calcineurin and represses pathological cardiac growth.
22796152 2012 The four and a half LIM-only protein 2 regulates liver homeostasis and contributes to carcinogenesis.
22417706 2012 The adaptor protein FHL2 enhances the cellular innate immune response to influenza A virus infection.
22219185 2012 Four-and-a-half LIM domain proteins inhibit transactivation by hypoxia-inducible factor 1.
22049082 2011 FHL2 protein is a novel co-repressor of nuclear receptor Nur77.
21988832 2011 Toward an understanding of the protein interaction network of the human liver.
21826055 2011 FHL2 expression in peritumoural fibroblasts correlates with lymphatic metastasis in sporadic but not in HNPCC-associated colon cancer.
21516116 2011 Next-generation sequencing to generate interactome datasets.
21423176 2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for ?-Pix in negative regulation of focal adhesion maturation.
21377781 2011 FHL2 exhibits anti-proliferative and anti-apoptotic activities in liver cancer cells.
21308406 2011 Immunohistochemical localization of four and a half LIM domains 2 in the odontoblasts of mature human teeth.
21269460 2011 Initial characterization of the human central proteome.
20734429 2010 Synergistic repression of estrogen receptor transcriptional activity by FHL2 and Smad4 in breast cancer cells.
20607723 2010 Sp1 upregulates the four and half lim 2 (FHL2) expression in gastrointestinal cancers through transcription regulation.
20592280 2010 Four-and-a-half LIM domain protein 2 is a novel regulator of sphingosine 1-phosphate receptor 1 in CCL19-induced dendritic cell migration.
20460358 2010 Four-and-a-half LIM protein 2 promotes invasive potential and epithelial-mesenchymal transition in colon cancer.
20442768 2010 Deficiency of the LIM-only protein FHL2 reduces intestinal tumorigenesis in Apc mutant mice.
19815066 2010 Four and a half LIM domain 2 alters the impact of aryl hydrocarbon receptor on androgen receptor transcriptional activity.
19608030 2009 ANKRD1, the gene encoding cardiac ankyrin repeat protein, is a novel dilated cardiomyopathy gene.
19465923 2009 The Patched dependence receptor triggers apoptosis through a DRAL-caspase-9 complex.
19417068 2009 FHL2 interacts with and acts as a functional repressor of Id2 in human neuroblastoma cells.
19369964 2009 Enhanced expression of FHL2 leads to abnormal myelopoiesis in vivo.
19325137 2009 FHL-2 suppresses VEGF-induced phosphatidylinositol 3-kinase/Akt activation via interaction with sphingosine kinase-1.
19139564 2009 Human four-and-a-half LIM family members suppress tumor cell growth through a TGF-beta-like signaling pathway.
18853468 The cell migration protein Grb7 associates with transcriptional regulator FHL2 in a Grb7 phosphorylation-dependent manner.
18680509 2008 The four and a half LIM domain protein 2 interacts with and regulates the HERG channel.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18653765 2008 FHL2 mediates dexamethasone-induced mesenchymal cell differentiation into osteoblasts by activating Wnt/beta-catenin signaling-dependent Runx2 expression.
18615633 2008 The four-and-a-half-LIM protein 2 (FHL2) is overexpressed in gliomas and associated with oncogenic activities.
18356303 2008 Deficiency in the LIM-only protein FHL2 impairs assembly of extracellular matrix proteins.
18255255 2008 A protein-protein interaction network of transcription factors acting during liver cell proliferation.
18224250 IL-1beta regulates FHL2 and other cytoskeleton-related genes in human chondrocytes.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17975004 2007 Androgen induction of the androgen receptor coactivator four and a half LIM domain protein-2: evidence for a role for serum response factor in prostate cancer.
17682292 2007 FHL2 regulates cell cycle-dependent and doxorubicin-induced p21Cip1/Waf1 expression in breast cancer cells.
17416352 2007 Structural analysis of four and half LIM protein-2 in dilated cardiomyopathy.
17383428 2007 Suppression of FHL2 expression induces cell differentiation and inhibits gastric and colon carcinogenesis.
17192406 2007 Proline-, glutamic acid-, and leucine-rich protein-1/modulator of nongenomic activity of estrogen receptor enhances androgen receptor functions through LIM-only coactivator, four-and-a-half LIM-only protein 2.
17145880 2006 Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence.
17093190 2007 Identification of the FHL2 transcriptional coactivator as a new functional target of the E7 oncoprotein of human papillomavirus type 16.
16888242 2006 FHL2/SLIM3 decreases cardiomyocyte survival by inhibitory interaction with sphingosine kinase-1.
16652157 2006 The LIM-only protein FHL2 is a negative regulator of E4F1.
16378916 2006 Expression of the transcriptional coregulator FHL2 in human breast cancer: a clinicopathologic study.
16355270 2006 Four and half lim protein 2 (FHL2) stimulates osteoblast differentiation.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16343438 2006 FHL2 mediates p53-induced transcriptional activation through a direct association with HIPK2.
16341674 2005 Transcriptome analysis of human gastric cancer.
16311053 2006 Regulation of insulin-like growth factor binding protein-5, four and a half lim-2, and a disintegrin and metalloprotease-9 expression in osteoblasts.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15692560 2005 Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation.
15572674 2004 Interaction and functional cooperation between the LIM protein FHL2, CBP/p300, and beta-catenin.
15572661 2004 Negative modulation of androgen receptor transcriptional activity by Daxx.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15453830 2005 FHL3 negatively regulates human high-affinity IgE receptor beta-chain gene expression by acting as a transcriptional co-repressor of MZF-1.
15342556 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.
15161045 Focal adhesion kinase interacts with the transcriptional coactivator FHL2 and both are overexpressed in epithelial ovarian cancer.
15117962 2004 The LIM-only proteins FHL2 and FHL3 interact with alpha- and beta-subunits of the muscle alpha7beta1 integrin receptor.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14680945 2003 Characterization of recombinant and natural forms of the human LIM domain-containing protein FHL2.
14550570 2003 BRCA1 interacts with FHL2 and enhances FHL2 transactivation function.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12466281 2003 Identification of the LIM protein FHL2 as a coactivator of beta-catenin.
12432079 2002 Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2.
12145280 2002 The LIM-only protein DRAL/FHL2 interacts with and is a corepressor for the promyelocytic leukemia zinc finger protein.
12067710 2002 TUCAN/CARDINAL and DRAL participate in a common pathway for modulation of NF-kappaB activation.
11821401 2002 Insulin-like growth factor-binding protein 5 (IGFBP-5) interacts with a four and a half LIM protein 2 (FHL2).
11813260 2002 Interaction of the heart-specific LIM domain protein, FHL2, with DNA-binding nuclear protein, hNP220.
11161712 2001 An RNA recognition motif (RRM) is required for the localization of PTB-associated splicing factor (PSF) to subnuclear speckles.
11135358 2001 Protein-protein interaction of FHL3 with FHL2 and visualization of their interaction by green fluorescent proteins (GFP) two-fusion fluorescence resonance energy transfer (FRET).
11124707 2001 Translocation of a human focal adhesion LIM-only protein, FHL2, during myofibrillogenesis and identification of LIM2 as the principal determinants of FHL2 focal adhesion localization.
11062252 2000 DRAL is a p53-responsive gene whose four and a half LIM domain protein product induces apoptosis.
11046156 2000 A family of LIM-only transcriptional coactivators: tissue-specific expression and selective activation of CREB and CREM.
11001931 2000 Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein.
10906324 2000 The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes.
10654935 2000 FHL2, a novel tissue-specific coactivator of the androgen receptor.
10649446 2000 Protein-protein interaction of FHL2, a LIM domain protein preferentially expressed in human heart, with hCDC47.
9573400 1998 Molecular cloning and characterization of FHL2, a novel LIM domain protein preferentially expressed in human heart.
9150430 1997 Subtractive cloning and characterization of DRAL, a novel LIM-domain protein down-regulated in rhabdomyosarcoma.
8753811 1996 Slim defines a novel family of LIM-proteins expressed in skeletal muscle.