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3  structures 108  species 0  interactions 298  sequences 6  architectures

Family: AXIN1_TNKS_BD (PF16646)

Summary: Axin-1 tankyrase binding domain

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This is the Wikipedia entry entitled "AXIN1". More...

AXIN1 Edit Wikipedia article

AXIN1
Protein AXIN1 PDB 1dk8.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases AXIN1, AXIN, PPP1R49, axin 1
External IDs MGI: 1096327 HomoloGene: 2614 GeneCards: AXIN1
Gene location (Human)
Chromosome 16 (human)
Chr. Chromosome 16 (human)[1]
Chromosome 16 (human)
Genomic location for AXIN1
Genomic location for AXIN1
Band 16p13.3 Start 287,440 bp[1]
End 352,673 bp[1]
RNA expression pattern
PBB GE AXIN1 212849 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003502
NM_181050

NM_001159598
NM_009733

RefSeq (protein)

NP_003493
NP_851393

NP_001153070
NP_033863

Location (UCSC) Chr 16: 0.29 – 0.35 Mb Chr 16: 26.14 – 26.2 Mb
PubMed search [3] [4]
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 endometriod 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 are affected by missense mutations, such as BRCA1, Adenomatous polyposis coli(APC), 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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000103126 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024182 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  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. 
  6. ^ "Entrez Gene: AXIN1 axin 1". 
  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" (PDF). J Mol Biol. 405 (3): 773–86. doi:10.1016/j.jmb.2010.11.013. PMID 21087614. 
  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: 324–32. doi:10.1038/nsmb.3191. PMID 26974125. 
  9. ^ a b c 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. 
  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 162138Freely accessible. PMID 12805222. 
  11. ^ a b c 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. 
  12. ^ a b 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 2574027Freely accessible. PMID 18632848. 
  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 1171499Freely accessible. PMID 10428961. 
  14. ^ a b 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. 
  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. 
  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. 
  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. 

Further reading

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Axin-1 tankyrase binding domain Provide feedback

This is the N-terminal domain tankyrase binding domain of Axin-1 [1].

Literature references

  1. Morrone S, Cheng Z, Moon RT, Cong F, Xu W;, Proc Natl Acad Sci U S A. 2012;109:1500-1505.: Crystal structure of a Tankyrase-Axin complex and its implications for Axin turnover and Tankyrase substrate recruitment. PUBMED:22307604 EPMC:22307604


This tab holds annotation information from the InterPro database.

InterPro entry IPR032101

This is the N-terminal tankyrase binding domain described for Axin-1 [PUBMED:22307604].

Axin (axis inhibition protein) is a scaffold protein that is involved in many signalling pathways, including the Wnt, transforming growth factor-beta, MAP kinase pathways, as well as p53 activation cascades [PUBMED:18316368, PUBMED:15067197]. It controls many biological processes ranging from sugar intake, cell proliferation, and organ development to cell death [PUBMED:15067197].

Domain organisation

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Alignments

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(24)
Full
(298)
Representative proteomes UniProt
(513)
NCBI
(1086)
Meta
(0)
RP15
(27)
RP35
(96)
RP55
(188)
RP75
(234)
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Key: ✓ available, x not generated, not available.

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  Seed
(24)
Full
(298)
Representative proteomes UniProt
(513)
NCBI
(1086)
Meta
(0)
RP15
(27)
RP35
(96)
RP55
(188)
RP75
(234)
Alignment:
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  Seed
(24)
Full
(298)
Representative proteomes UniProt
(513)
NCBI
(1086)
Meta
(0)
RP15
(27)
RP35
(96)
RP55
(188)
RP75
(234)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: PDB:3utm
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Eberhardt R
Number in seed: 24
Number in full: 298
Average length of the domain: 70.60 aa
Average identity of full alignment: 58 %
Average coverage of the sequence by the domain: 9.20 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 29.9 29.9
Trusted cut-off 30.6 30.6
Noise cut-off 28.5 29.7
Model length: 75
Family (HMM) version: 5
Download: download the raw HMM for this family

Species distribution

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the AXIN1_TNKS_BD domain has been found. There are 3 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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