AXIN1

AXIN1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1DK8, 1EMU, 1O9U, 3ZDI, 4B7T, 4NM0, 4NM3, 4NM5, 4NM7, 4NU1
Identifiers
Aliases	AXIN1, AXIN, PPP1R49, axin 1
External IDs	OMIM: 603816 MGI: 1096327 HomoloGene: 2614 GeneCards: AXIN1
Gene location (Human)
Chr.	Chromosome 16 (human)[1]
End	352,723 bp[1]
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)[2]
End	26,195,811 bp[2]
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• beta-catenin binding; • protein homodimerization activity; • I-SMAD binding; • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity; • GO:0001948 protein binding; • enzyme binding; • receptor signaling complex scaffold activity; • SMAD binding; • ubiquitin protein ligase binding; • GO:0032947 molecular adaptor activity; • protein kinase binding; • armadillo repeat domain binding; • identical protein binding; • signaling adaptor activity;
Cellular component	• cytoplasm; • cytosol; • lateral plasma membrane; • membrane; • cell membrane; • perinuclear region of cytoplasm; • cytoplasmic vesicle; • cell nucleus; • beta-catenin destruction complex; • cell periphery;
Biological process	• forebrain anterior/posterior pattern specification; • negative regulation of fat cell differentiation; • positive regulation of protein phosphorylation; • olfactory placode formation; • positive regulation of protein catabolic process; • activation of JUN kinase activity; • positive regulation of canonical Wnt signaling pathway; • embryonic eye morphogenesis; • negative regulation of Wnt signaling pathway; • positive regulation of JNK cascade; • negative regulation of transcription elongation from RNA polymerase II promoter; • positive regulation of peptidyl-serine phosphorylation; • positive regulation of transcription, DNA-templated; • multicellular organism development; • optic placode formation; • determination of left/right symmetry; • canonical Wnt signaling pathway involved in neural plate anterior/posterior pattern formation; • positive regulation of ubiquitin-protein transferase activity; • positive regulation of peptidyl-threonine phosphorylation; • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process; • cytoplasmic microtubule organization; • canonical Wnt signaling pathway; • embryonic skeletal joint morphogenesis; • axial mesoderm formation; • positive regulation of protein ubiquitination; • activation of protein kinase activity; • muscle cell development; • Wnt-activated signaling pathway involved in forebrain neuron fate commitment; • negative regulation of canonical Wnt signaling pathway; • signal transduction; • apoptotic process; • beta-catenin destruction complex disassembly; • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity; • Wnt signaling pathway; • beta-catenin destruction complex assembly; • regulation of Wnt signaling pathway; • regulation of intracellular estrogen receptor signaling pathway; • cellular macromolecular complex assembly;
	Sources:Amigo / QuickGO
Orthologs
	8312
	12005
	ENSG00000103126
	ENSMUSG00000024182
	O15169
	O35625
	NM_003502; NM_181050
	NM_001159598; NM_009733
	NP_003493; NP_851393
	NP_001153070; NP_033863
	Wikidata
View/Edit Human	View/Edit Mouse

Axin-1 is a protein that in humans is encoded by the AXIN1 gene.[5]

Function

This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin (cadherin-associated protein) beta 1, glycogen synthase kinase 3 beta, protein phosphatase 2, and itself. This protein functions as a negative regulator of the wingless-type MMTV integration site family, member 1 (WNT) signaling pathway and can induce apoptosis. The crystal structure of a portion of this protein, alone and in a complex with other proteins, has been resolved. Mutations in this gene have been associated with hepatocellular carcinoma, hepatoblastomas, ovarian endometrioid adenocarcinomas, and medulloblastomas. Two transcript variants encoding distinct isoforms have been identified for this gene.[6]

Structure

The full-length human protein comprises 862 amino acids with a (predicted) molecular mass of 96 kDa. The N-terminal RGS domain, a GSK3 kinase interacting peptide of Axin1 and homologs of the C-terminal DIX domains have been solved at atomic resolution. Large WNT-downregulating central regions have been characterized as intrinsically disordered by biophysical experiments and bioinformatic analysis.[7] Biophysical destabilization of the folded RGS domain induces formation of nanoaggregates that expose and locally concentrate intrinsically disordered regions, which in turn misregulate Wnt signalling. Many other large IDPs (Intrinsically Disordered Proteins) are affected by missense mutations, such as BRCA1, Adenomatous polyposis coli, CREB-binding protein/(CBP) and might be affected in similar ways by missense mutations of their folded domains.[8]

Interactions

AXIN1 has been shown to interact with:

References

GRCh38: Ensembl release 89: ENSG00000103126 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000024182 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL, Lee JJ, Tilghman SM, Gumbiner BM, Costantini F (August 1997). "The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation". Cell. 90 (1): 181–92. doi:10.1016/S0092-8674(00)80324-4. PMID 9230313. S2CID 10565695.
"Entrez Gene: AXIN1 axin 1".
Noutsou M, Duarte AM, Anvarian Z, Didenko T, Minde DP, Kuper I, de Ridder I, Oikonomou C, Friedler A, Boelens R, Rüdiger SG, Maurice MM (2011). "Critical scaffolding regions of the tumor suppressor Axin1 are natively unfolded". J Mol Biol. 405 (3): 773–86. doi:10.1016/j.jmb.2010.11.013. PMID 21087614.
Anvarian Z, Nojima H, van Kappel EC, Madl T, Spit M, Viertler M, Jordens I, Low TY, van Scherpenzeel RC, Kuper I, Richter K, Heck AJ, Boelens R, Vincent JP, Rüdiger SG, Maurice MM (2016). "Axin cancer mutants form nanoaggregates to rewire the Wnt signaling network". Nat Struct Mol Biol. 23 (4): 324–32. doi:10.1038/nsmb.3191. PMID 26974125. S2CID 30761541.
Nakamura T, Hamada F, Ishidate T, Anai K, Kawahara K, Toyoshima K, Akiyama T (June 1998). "Axin, an inhibitor of the Wnt signalling pathway, interacts with beta-catenin, GSK-3beta and APC and reduces the beta-catenin level". Genes Cells. 3 (6): 395–403. doi:10.1046/j.1365-2443.1998.00198.x. PMID 9734785. S2CID 10875463.
Hocevar BA, Mou F, Rennolds JL, Morris SM, Cooper JA, Howe PH (June 2003). "Regulation of the Wnt signaling pathway by disabled-2 (Dab2)". EMBO J. 22 (12): 3084–94. doi:10.1093/emboj/cdg286. PMC 162138. PMID 12805222.
Zhang Y, Qiu WJ, Chan SC, Han J, He X, Lin SC (May 2002). "Casein kinase I and casein kinase II differentially regulate axin function in Wnt and JNK pathways". J. Biol. Chem. 277 (20): 17706–12. doi:10.1074/jbc.M111982200. PMID 11884395.
Kim MJ, Chia IV, Costantini F (November 2008). "SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability". FASEB J. 22 (11): 3785–94. doi:10.1096/fj.08-113910. PMC 2574027. PMID 18632848.
Li L, Yuan H, Weaver CD, Mao J, Farr GH, Sussman DJ, Jonkers J, Kimelman D, Wu D (August 1999). "Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1". EMBO J. 18 (15): 4233–40. doi:10.1093/emboj/18.15.4233. PMC 1171499. PMID 10428961.
Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS (February 2003). "The tuberin-hamartin complex negatively regulates beta-catenin signaling activity". J. Biol. Chem. 278 (8): 5947–51. doi:10.1074/jbc.C200473200. PMID 12511557.
Mao J, Wang J, Liu B, Pan W, Farr GH, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D (April 2001). "Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway". Mol. Cell. 7 (4): 801–9. doi:10.1016/S1097-2765(01)00224-6. PMID 11336703.
Zhang Y, Neo SY, Han J, Lin SC (August 2000). "Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase". J. Biol. Chem. 275 (32): 25008–14. doi:10.1074/jbc.M002491200. PMID 10829020.
Yamamoto H, Hinoi T, Michiue T, Fukui A, Usui H, Janssens V, Van Hoof C, Goris J, Asashima M, Kikuchi A (July 2001). "Inhibition of the Wnt signaling pathway by the PR61 subunit of protein phosphatase 2A". J. Biol. Chem. 276 (29): 26875–82. doi:10.1074/jbc.M100443200. PMID 11297546.

External links

Human AXIN1 genome location and AXIN1 gene details page in the UCSC Genome Browser.
Overview of all the structural information available in the PDB for UniProt: O15169 (Axin-1) at the PDBe-KB.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000103126 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000024182 - Ensembl, 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.

[pmid9230313-5] Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL, Lee JJ, Tilghman SM, Gumbiner BM, Costantini F (August 1997). "The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation". Cell. 90 (1): 181–92. doi:10.1016/S0092-8674(00)80324-4. PMID 9230313. S2CID 10565695.

[6] "Entrez Gene: AXIN1 axin 1".

[pmid21859464-7] Noutsou M, Duarte AM, Anvarian Z, Didenko T, Minde DP, Kuper I, de Ridder I, Oikonomou C, Friedler A, Boelens R, Rüdiger SG, Maurice MM (2011). "Critical scaffolding regions of the tumor suppressor Axin1 are natively unfolded". J Mol Biol. 405 (3): 773–86. doi:10.1016/j.jmb.2010.11.013. PMID 21087614.

[pmid26974125-8] Anvarian Z, Nojima H, van Kappel EC, Madl T, Spit M, Viertler M, Jordens I, Low TY, van Scherpenzeel RC, Kuper I, Richter K, Heck AJ, Boelens R, Vincent JP, Rüdiger SG, Maurice MM (2016). "Axin cancer mutants form nanoaggregates to rewire the Wnt signaling network". Nat Struct Mol Biol. 23 (4): 324–32. doi:10.1038/nsmb.3191. PMID 26974125. S2CID 30761541.

[pmid9734785-9] Nakamura T, Hamada F, Ishidate T, Anai K, Kawahara K, Toyoshima K, Akiyama T (June 1998). "Axin, an inhibitor of the Wnt signalling pathway, interacts with beta-catenin, GSK-3beta and APC and reduces the beta-catenin level". Genes Cells. 3 (6): 395–403. doi:10.1046/j.1365-2443.1998.00198.x. PMID 9734785. S2CID 10875463.

[pmid12805222-10] Hocevar BA, Mou F, Rennolds JL, Morris SM, Cooper JA, Howe PH (June 2003). "Regulation of the Wnt signaling pathway by disabled-2 (Dab2)". EMBO J. 22 (12): 3084–94. doi:10.1093/emboj/cdg286. PMC 162138. PMID 12805222.

[pmid11884395-11] Zhang Y, Qiu WJ, Chan SC, Han J, He X, Lin SC (May 2002). "Casein kinase I and casein kinase II differentially regulate axin function in Wnt and JNK pathways". J. Biol. Chem. 277 (20): 17706–12. doi:10.1074/jbc.M111982200. PMID 11884395.

[pmid18632848-12] Kim MJ, Chia IV, Costantini F (November 2008). "SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability". FASEB J. 22 (11): 3785–94. doi:10.1096/fj.08-113910. PMC 2574027. PMID 18632848.

[pmid10428961-13] Li L, Yuan H, Weaver CD, Mao J, Farr GH, Sussman DJ, Jonkers J, Kimelman D, Wu D (August 1999). "Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1". EMBO J. 18 (15): 4233–40. doi:10.1093/emboj/18.15.4233. PMC 1171499. PMID 10428961.

[pmid12511557-14] Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS (February 2003). "The tuberin-hamartin complex negatively regulates beta-catenin signaling activity". J. Biol. Chem. 278 (8): 5947–51. doi:10.1074/jbc.C200473200. PMID 12511557.

[pmid11336703-15] Mao J, Wang J, Liu B, Pan W, Farr GH, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D (April 2001). "Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway". Mol. Cell. 7 (4): 801–9. doi:10.1016/S1097-2765(01)00224-6. PMID 11336703.

[pmid10829020-16] Zhang Y, Neo SY, Han J, Lin SC (August 2000). "Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase". J. Biol. Chem. 275 (32): 25008–14. doi:10.1074/jbc.M002491200. PMID 10829020.

[pmid11297546-17] Yamamoto H, Hinoi T, Michiue T, Fukui A, Usui H, Janssens V, Van Hoof C, Goris J, Asashima M, Kikuchi A (July 2001). "Inhibition of the Wnt signaling pathway by the PR61 subunit of protein phosphatase 2A". J. Biol. Chem. 276 (29): 26875–82. doi:10.1074/jbc.M100443200. PMID 11297546.