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ACVR1B

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(Redirected from ALK4)
ACVR1B
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesACVR1B, ACTRIB, ACVRLK4, ALK4, SKR2, activin A receptor type 1B
External IDsOMIM: 601300; MGI: 1338944; HomoloGene: 20906; GeneCards: ACVR1B; OMA:ACVR1B - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004302
NM_020327
NM_020328

NM_007395

RefSeq (protein)

NP_004293
NP_064732
NP_064733

NP_031421

Location (UCSC)Chr 12: 51.95 – 52 MbChr 15: 101.07 – 101.11 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Activin receptor type-1B is a protein that in humans is encoded by the ACVR1B gene.[5][6]

ACVR1B or ALK-4 acts as a transducer of activin or activin-like ligands (e.g., inhibin) signals. Activin binds to either ACVR2A or ACVR2B and then forms a complex with ACVR1B. These go on to recruit the R-SMADs SMAD2 or SMAD3.[7] ACVR1B also transduces signals of nodal, GDF-1, and Vg1; however, unlike activin, they require other coreceptor molecules such as the protein Cripto.[8]

Function

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Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I (I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with a cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling, and type II receptors are required for binding ligands and expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. This gene encodes activin A type IB receptor, composed of 11 exons. Alternative splicing and alternative polyadenylation result in 3 fully described transcript variants. The mRNA expression of variants 1, 2, and 3 is confirmed, and a potential fourth variant contains an alternative exon 8 and lacks exons 9 through 11, but its mRNA expression has not been confirmed.[6]

Interactions

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ACVR1B has been shown to interact with

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000135503Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000532Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ ten Dijke P, Ichijo H, Franzén P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K (October 1993). "Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity". Oncogene. 8 (10): 2879–87. PMID 8397373.
  6. ^ a b "Entrez Gene: ACVR1B activin A receptor, type IB".
  7. ^ Inman GJ, Nicolás FJ, Callahan JF, Harling JD, Gaster LM, Reith AD, Laping NJ, Hill CS (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". Mol. Pharmacol. 62 (1): 65–74. doi:10.1124/mol.62.1.65. PMID 12065756. S2CID 15185199.
  8. ^ Harrison CA, Gray PC, Koerber SC, Fischer W, Vale W (2003). "Identification of a functional binding site for activin on the type I receptor ALK4". J. Biol. Chem. 278 (23): 21129–35. doi:10.1074/jbc.M302015200. PMID 12665502.
  9. ^ a b De Winter JP, De Vries CJ, Van Achterberg TA, Ameerun RF, Feijen A, Sugino H, De Waele P, Huylebroeck D, Verschueren K, Van Den Eijden-Van Raaij AJ (May 1996). "Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors". Exp. Cell Res. 224 (2): 323–34. doi:10.1006/excr.1996.0142. PMID 8612709.
  10. ^ Lebrun JJ, Takabe K, Chen Y, Vale W (January 1999). "Roles of pathway-specific and inhibitory Smads in activin receptor signaling". Mol. Endocrinol. 13 (1): 15–23. doi:10.1210/mend.13.1.0218. PMID 9892009. S2CID 26825706.
  11. ^ Attisano L, Wrana JL, Montalvo E, Massagué J (March 1996). "Activation of signalling by the activin receptor complex". Mol. Cell. Biol. 16 (3): 1066–73. doi:10.1128/MCB.16.3.1066. PMC 231089. PMID 8622651.
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Further reading

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