Property Summary

NCBI Gene PubMed Count 60
PubMed Score 76.38
PubTator Score 61.62

Knowledge Summary

Patent (13,317)


  Differential Expression (10)

Disease log2 FC p
malignant mesothelioma -1.300 1.8e-04
astrocytic glioma -1.100 3.5e-03
psoriasis -1.200 2.4e-02
osteosarcoma 1.382 1.7e-06
atypical teratoid / rhabdoid tumor -1.400 1.8e-06
glioblastoma -1.100 6.8e-04
interstitial cystitis -1.200 3.9e-04
adult high grade glioma -1.200 8.8e-06
ulcerative colitis -1.300 1.6e-05
ovarian cancer 1.300 5.9e-04

 OMIM Phenotype (1)

Protein-protein Interaction (9)

MLP Assay (2)

AID Type Active / Inconclusive / Inactive Description
1982 other 0 / 0 / 0 Kinase inhibition selectivity assay for compound SID-48409448
686923 other 8 / 0 / 2 In vitrocounter assay of key BMP4 Inhibitors

Gene RIF (26)

26305619 Data suggest that activin A up-regulates SNAIL expression via ALK4/ACVR1B-induced SMAD signaling in trophoblast cells; elevated SNAIL contributes to up-regulation of MMP2 expression which plays key role in promoting trophoblast cell invasion.
26289399 ALK4 is expressed in male germ cells and Sertoli cells.
26149389 This study demonstrated positive regulation of monocyte/macrophage differentiation by lnc-MC and uncovered an elaborate regulation mechanism composed of PU.1, lnc-MC, miR-199a-5p, and ACVR1B.
25258381 ACVR1B functions as a positive regulator of monocyte/macrophage differentiation. ACVR1B knockdown promoted THP-1 proliferation by increasing Rb phosphorylation. Down-regulation reduced p-Smad2/3 and C/EBPalpha, inhibiting monocyte/macrophage differentiation.
24886203 The deletion of the ACVR1B gene may mediate an aggressive cancer phenotype in pancreatic cancer.
23211491 Findings define a regulatory role of miR-98 in tumor angiogenesis and invasion through repressed ALK4 and MMP11 expression.
23159635 ActRIBCA signaling can promote cell migration in prostate cancer cells via a network of signaling molecules that work together to trigger the process of EMT, and thereby aid in the aggressiveness and progression of prostate cancers.
23010638 Act A protein levels were significantly higher in NTM tissues compared to GTM tissues.
22267736 Inhibin alpha-subunit N terminus interacts with activin type IB receptor to disrupt activin signaling.
21377836 Activin A-ACVRIB/ALK4-Smad-dependent collagen production was augmented in SSc fibroblasts, suggesting the involvement of this signaling mechanism in systemic sclerosis.
21063444 We applied a two-stage fine mapping approach, and are the first to identify and partially replicate genetic variants in the ACVR1B gene that account for genetic variation in human muscle strength.
21063444 Observational study of gene-disease association. (HuGE Navigator)
20819778 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20734064 Observational study of gene-disease association. (HuGE Navigator)
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20347265 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20226172 activin A signal is transduced through the activin A type 1 receptor, ALK4, and transactivates several TGF-beta target genes in a SMAD-independent manner.
19035567 Study indicate that the synthetic h-CFC interacts with the ALK4 receptor with a K(D) in micro M range, that the h-CFC overall topology is determined by the presence of three disulfide bridges.
17906079 a regulation mode of miR-24 on erythropoiesis by impeding ALK4 expression.
16720724 findings indicate a new inhibitory function of FKBP12 as an adaptor molecule for the Smad7-Smurf1 complex to regulate the duration of the activin signal through activin type I receptors
15459392 Dpr2 binds to the TGFbeta receptors ALK5 and ALK4, and accelerates lysosomal degradation of these receptors
15123686 ALK4 binds to activin at a specific site in order to signal via type II receptors
12665502 there is only a partial overlap of the binding sites on ALK4 and ALK3 for activin-A and bone morphogenetic protein-2, respectively
12639945 Activin signaling mediated by ActRIB-Smad2 system in the ovary may thus be essential for the regulation of follicular differentiation.
12364468 data indicate that truncated Alk4 isoforms interfere with activin signaling pathways and thereby may contribute to uncontrolled cell growth
11969340 distribution in gestational tissues across human pregnancy and during labour

AA Sequence

KKTLSQLSVQEDVKI                                                           491 - 505

Text Mined References (64)

PMID Year Title
26305619 2015 Activin A Increases Human Trophoblast Invasion by Inducing SNAIL-Mediated MMP2 Up-Regulation Through ALK4.
26289399 NODAL secreted by male germ cells regulates the proliferation and function of human Sertoli cells from obstructive azoospermia and nonobstructive azoospermia patients.
26149389 2015 PU.1-Regulated Long Noncoding RNA lnc-MC Controls Human Monocyte/Macrophage Differentiation through Interaction with MicroRNA 199a-5p.
25258381 2014 miR-199a-5p inhibits monocyte/macrophage differentiation by targeting the activin A type 1B receptor gene and finally reducing C/EBP? expression.
24939585 2015 Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment.
24886203 2014 Homozygous deletion of the activin A receptor, type IB gene is associated with an aggressive cancer phenotype in pancreatic cancer.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23263486 2013 Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
23211491 2012 MicroRNA miR-98 inhibits tumor angiogenesis and invasion by targeting activin receptor-like kinase-4 and matrix metalloproteinase-11.
23159635 2013 Activin type IB receptor signaling in prostate cancer cells promotes lymph node metastasis in a xenograft model.
23010638 2012 The effects of transforming growth factor-?2 on the expression of follistatin and activin A in normal and glaucomatous human trabecular meshwork cells and tissues.
22939624 2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition.
22267736 2012 Inhibin ?-subunit N terminus interacts with activin type IB receptor to disrupt activin signaling.
21377836 2011 Activation of the activin A-ALK-Smad pathway in systemic sclerosis.
21356369 2011 Nodal signals through activin receptor-like kinase 7 to inhibit trophoblast migration and invasion: implication in the pathogenesis of preeclampsia.
21063444 2011 Comprehensive fine mapping of chr12q12-14 and follow-up replication identify activin receptor 1B (ACVR1B) as a muscle strength gene.
20819778 2010 MicroRNA-related genetic variations as predictors for risk of second primary tumor and/or recurrence in patients with early-stage head and neck cancer.
20734064 2010 A large-scale candidate gene association study of age at menarche and age at natural menopause.
20596523 2010 Development and validation of a method for profiling post-translational modification activities using protein microarrays.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20347265 2010 MicroRNAs and target site screening reveals a pre-microRNA-30e variant associated with schizophrenia.
20226172 2010 Activin A induces neuronal differentiation and survival via ALK4 in a SMAD-independent manner in a subpopulation of human neuroblastomas.
19035567 2009 Structural insights into the interaction between the Cripto CFC domain and the ALK4 receptor.
18039968 2007 Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination.
17906079 2008 MicroRNA miR-24 inhibits erythropoiesis by targeting activin type I receptor ALK4.
17344846 2007 Patterns of somatic mutation in human cancer genomes.
16720724 2006 FKBP12 functions as an adaptor of the Smad7-Smurf1 complex on activin type I receptor.
16541075 2006 The finished DNA sequence of human chromosome 12.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15459392 2004 Zebrafish Dpr2 inhibits mesoderm induction by promoting degradation of nodal receptors.
15196700 2004 Activin isoforms signal through type I receptor serine/threonine kinase ALK7.
15123686 2004 An activin mutant with disrupted ALK4 binding blocks signaling via type II receptors.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14517293 2003 Myostatin signals through a transforming growth factor beta-like signaling pathway to block adipogenesis.
12919325 2003 The CRIPTO/FRL-1/CRYPTIC (CFC) domain of human Cripto. Functional and structural insights through disulfide structure analysis.
12665502 2003 Identification of a functional binding site for activin on the type I receptor ALK4.
12651901 2003 Inhibin, activin, follistatin, activin receptors and beta-glycan gene expression in the placental tissue of patients with pre-eclampsia.
12639945 2003 Activin signaling through type IB activin receptor stimulates aromatase activity in the ovarian granulosa cell-like human granulosa (KGN) cells.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12364468 2002 Overexpression of wild-type activin receptor alk4-1 restores activin antiproliferative effects in human pituitary tumor cells.
12112843 2002 Identification of the phosphotyrosine proteome from thrombin activated platelets.
12065756 2002 SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7.
12052855 2002 Dual roles of Cripto as a ligand and coreceptor in the nodal signaling pathway.
12032389 2002 The physiology and pathophysiology of inhibin, activin and follistatin in female reproduction.
12023024 2002 Phosphorylation regulation of the interaction between Smad7 and activin type I receptor.
11969340 2002 The distribution of activin and activin receptors in gestational tissues across human pregnancy and during labour.
11909953 2002 Cripto-1 activates nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial Cells.
11389842 2001 Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms.
11279102 2001 Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases.
11278302 2001 Transforming growth factor-beta receptor-associated protein 1 is a Smad4 chaperone.
11266516 2001 Modulation of activin signal transduction by inhibin B and inhibin-binding protein (INhBP).
11248065 2001 ACVR1B (ALK4, activin receptor type 1B) gene mutations in pancreatic carcinoma.
11117535 2000 Truncated activin type I receptor Alk4 isoforms are dominant negative receptors inhibiting activin signaling.
10652306 2000 Identification of a binding site on the type II activin receptor for activin and inhibin.
9892009 1999 Roles of pathway-specific and inhibitory Smads in activin receptor signaling.
9884026 1998 The role of activin type I receptors in activin A-induced growth arrest and apoptosis in mouse B-cell hybridoma cells.
9501322 1998 Chromosomal localization of three human genes encoding members of the TGF-beta superfamily of type I serine/threonine kinase receptors.
9032295 1997 Activin and inhibin have antagonistic effects on ligand-dependent heteromerization of the type I and type II activin receptors and human erythroid differentiation.
8622651 1996 Activation of signalling by the activin receptor complex.
8612709 1996 Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors.
8397373 1993 Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity.
8196624 1994 Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin.
8058741 1994 Genomic structure and cloned cDNAs predict that four variants in the kinase domain of serine/threonine kinase receptors arise by alternative splicing and poly(A) addition.
7890768 1995 Inhibin antagonizes inhibition of liver cell growth by activin by a dominant-negative mechanism.