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Gene Review

ACVR1  -  activin A receptor, type I

Homo sapiens

Synonyms: ACTR-I, ACTRI, ACVR1A, ACVRLK2, ALK-2, ...
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Disease relevance of ACVR1

  • Activin type I receptors, SKR1 and SKR2, were first cloned from well differentiated human hepatoma cells (HepG2) [1].
  • The median ED50 of Viracea for the ten ACV-R strains of HSV-2 was 1:200 with a range of 1:50-1:3200 [2].
  • The median ED50 of Viracea for the five ACV-R strains of HSV-1 was a 1:100 dilution of the drug with a range of 1:50-1:400 [2].
  • To address this question, mixed infections followed by multiple passages were performed with a reassortant SA11-L2/KU-R1 (SKR1) (which possesses VP7 gene derived from G1 human rotavirus KU and other 10 genes of SA11 origin) and one of the five G3-rotaviruses, RRV, K9, YO, AK35, and S3 [3].
  • The acyclovir resistant mutant of varicella-zoster virus ACV-R (A 8) induced the same level of thymidine kinase activity in infected cells as the parent Kawaguchi strain [4].

High impact information on ACVR1

  • In the normal colon a low concentration of SP receptor binding sites is expressed by submucosal arterioles and venules and a moderate concentration is expressed by the external circular muscle, whereas SK receptor binding sites are expressed in low concentrations by the external circular and longitudinal muscle [5].
  • Alk2-specific small interfering RNA (siRNA) blocks both the transition of MISRII expression from the coelomic epithelium to the mesenchyme and Müllerian duct regression in organ culture [6].
  • Conversely, BMP signaling leading to Smad1/5/8 activation via ALK2/3/6 is blocked in undifferentiated cells and becomes activated upon differentiation [7].
  • CUL-1 was found to interact with SKR-1, -2, -3, -7, -8, and -10 in the yeast two-hybrid system [8].
  • Constitutively active activin receptor-like kinase 2 inhibited Galpha(i2) promoter activity, whereas constitutively active activin receptor-like kinase 5 stimulated Galpha(i2) promoter activity independent of embryonic age [9].

Biological context of ACVR1


Anatomical context of ACVR1


Associations of ACVR1 with chemical compounds

  • Tailed cDNA is then amplified by PCR using a nested gene-specific primer (ALK2), which anneals 3' to ALK1, and a complementary homopolymer containing an anchor primer (i.e., AAP), which permits amplification from the homopolymeric tail [16].
  • The increased expression of SKR1 mRNA in the cells was actinomycin D-sensitive and was not dependent on new protein synthesis [10].
  • These antibodies were then tested for both structural and functional recognition of epitopes on the substance P (SP) receptor on rat AR42J pancreatic cells and human IM9 lymphoblasts, which express the SP receptor, but not the SK receptor [17].
  • The altered substrate specificity of thymidine kinase induced by ACV-R (A 8) is concluded to confer resistance to acyclovir on ACV-R (A 8) [4].

Regulatory relationships of ACVR1

  • The results indicate that TGF-beta 1 selectively induces SKR1 message at a transcriptional level by a positive regulator [10].
  • Both ALK2 and ALK5 are expressed throughout the heart with ALK2 expressed abundantly in endocardial cells of the outflow tract (OFT), ventricle, and AV cushion [18].
  • These data suggest that ALK2 activation may stimulate EMT in the AV cushion and that Smad6 may act downstream of ALK2 to negatively regulate EMT [18].
  • Surprisingly, although parathyroid hormone-related peptide (PTHrP) strongly inhibited CA ALK2 mediated chondrocyte differentiation, Ihh expression was minimally decreased [15].

Other interactions of ACVR1

  • The reamplification is achieved by using a nested gene-specific primer (ALK3), which anneals 3' to ALK2, and a universal amplification primer, which anneals to the 5' sequence previously introduced by the AAP primer [16].
  • ALK5 and SKR1 mRNA levels were 6.8- and 9-fold greater in the pancreatic tumors in comparison with the corresponding levels in the normal pancreas [19].
  • This increase of SKR1 mRNA in Hep 3B-TS cells could be detected by Northern blot analysis within 3 h of addition of TGF-beta 1 to the cells, and enhanced message levels peaked at 12 h as long as TGF-beta 1 was present in the culture medium [10].
  • Activin receptor-like kinase 2 and Smad6 regulate epithelial-mesenchymal transformation during cardiac valve formation [18].
  • There were no apparent differences in the distribution of the beta(A) subunit and receptors Alk2, ActRII and ActRIIB between control and preeclamptic tissues [20].

Analytical, diagnostic and therapeutic context of ACVR1

  • Altogether, these functional, gene mapping and phylogenetic analyses suggest that alk8 may be the zebrafish orthologue to human ACVRI (alk2), and therefore extend previous studies of Alk2 conducted in Xenopus [21].


  1. Inhibin antagonizes inhibition of liver cell growth by activin by a dominant-negative mechanism. Xu, J., McKeehan, K., Matsuzaki, K., McKeehan, W.L. J. Biol. Chem. (1995) [Pubmed]
  2. Antiviral activity of Viracea against acyclovir susceptible and acyclovir resistant strains of herpes simplex virus. Thompson, K.D. Antiviral Res. (1998) [Pubmed]
  3. G (VP7) serotype-dependent preferential VP7 gene selection detected in the genetic background of simian rotavirus SA11. Kobayashi, N., Taniguchi, K., Kojima, K., Urasawa, T., Urasawa, S. Arch. Virol. (1996) [Pubmed]
  4. Thymidine kinase with altered substrate specificity of acyclovir resistant varicella-zoster virus. Shiraki, K., Ogino, T., Yamanishi, K., Takahashi, M. Biken journal. (1986) [Pubmed]
  5. Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease. Mantyh, C.R., Gates, T.S., Zimmerman, R.P., Welton, M.L., Passaro, E.P., Vigna, S.R., Maggio, J.E., Kruger, L., Mantyh, P.W. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  6. Müllerian inhibiting substance regulates its receptor/SMAD signaling and causes mesenchymal transition of the coelomic epithelial cells early in Müllerian duct regression. Zhan, Y., Fujino, A., MacLaughlin, D.T., Manganaro, T.F., Szotek, P.P., Arango, N.A., Teixeira, J., Donahoe, P.K. Development (2006) [Pubmed]
  7. Expression of nodal, lefty-a, and lefty-B in undifferentiated human embryonic stem cells requires activation of Smad2/3. Besser, D. J. Biol. Chem. (2004) [Pubmed]
  8. The Caenorhabditis elegans Skp1-related gene family: diverse functions in cell proliferation, morphogenesis, and meiosis. Nayak, S., Santiago, F.E., Jin, H., Lin, D., Schedl, T., Kipreos, E.T. Curr. Biol. (2002) [Pubmed]
  9. Transforming growth factor beta (TGFbeta ) signaling via differential activation of activin receptor-like kinases 2 and 5 during cardiac development. Role in regulating parasympathetic responsiveness. Ward, S.M., Desgrosellier, J.S., Zhuang, X., Barnett, J.V., Galper, J.B. J. Biol. Chem. (2002) [Pubmed]
  10. Transforming growth factor beta 1 selectively increases gene expression of the serine/threonine kinase receptor 1 (SKR1) in human hepatoma cell lines. Inagaki, M., Wang, Z., Carr, B.I. Cell Struct. Funct. (1994) [Pubmed]
  11. Alk1 and Alk2 are two new cell cycle-regulated haspin-like proteins in budding yeast. Nespoli, A., Vercillo, R., di Nola, L., Diani, L., Giannattasio, M., Plevani, P., Muzi-Falconi, M. Cell Cycle (2006) [Pubmed]
  12. Functional roles of the bone morphogenetic protein system in thyrotropin signaling in porcine thyroid cells. Suzuki, J., Otsuka, F., Takeda, M., Inagaki, K., Miyoshi, T., Mimura, Y., Ogura, T., Doihara, H., Makino, H. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  13. A widely expressed transmembrane serine/threonine kinase that does not bind activin, inhibin, transforming growth factor beta, or bone morphogenic factor. Matsuzaki, K., Xu, J., Wang, F., McKeehan, W.L., Krummen, L., Kan, M. J. Biol. Chem. (1993) [Pubmed]
  14. Expression of osteogenic protein-1 mRNA in cultured kidney cells. Kitten, A.M., Kreisberg, J.I., Olson, M.S. J. Cell. Physiol. (1999) [Pubmed]
  15. ALK2 functions as a BMP type I receptor and induces Indian hedgehog in chondrocytes during skeletal development. Zhang, D., Schwarz, E.M., Rosier, R.N., Zuscik, M.J., Puzas, J.E., O'Keefe, R.J. J. Bone Miner. Res. (2003) [Pubmed]
  16. Identification of anaplastic lymphoma kinase variant translocations using 5'RACE. Hernández, L., Campo, E. Methods Mol. Med. (2005) [Pubmed]
  17. Tachykinin receptor cross-talk. Immunological cross-reactivity between the external domains of the substance K and substance P receptors. Parnet, P., Mitsuhashi, M., Turck, C.W., Kerdelhue, B., Payan, D.G. Brain Behav. Immun. (1991) [Pubmed]
  18. Activin receptor-like kinase 2 and Smad6 regulate epithelial-mesenchymal transformation during cardiac valve formation. Desgrosellier, J.S., Mundell, N.A., McDonnell, M.A., Moses, H.L., Barnett, J.V. Dev. Biol. (2005) [Pubmed]
  19. Attenuated ALK5 receptor expression in human pancreatic cancer: correlation with resistance to growth inhibition. Baldwin, R.L., Friess, H., Yokoyama, M., Lopez, M.E., Kobrin, M.S., Büchler, M.W., Korc, M. Int. J. Cancer (1996) [Pubmed]
  20. Activin A and activin receptors in gestational tissue from preeclamptic pregnancies. Manuelpillai, U., Schneider-Kolsky, M., Dole, A., Wallace, E.M. J. Endocrinol. (2001) [Pubmed]
  21. Functional characterization and genetic mapping of alk8. Payne, T.L., Postlethwait, J.H., Yelick, P.C. Mech. Dev. (2001) [Pubmed]
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