Description: Homo sapiens axin 1 (AXIN1), transcript variant 1, mRNA. RefSeq Summary (NM_003502): 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 beta-1, glycogen synthase kinase 3 beta, protein phosphate 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 medullablastomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]. Transcript (Including UTRs) Position: hg19 chr16:337,440-402,676 Size: 65,237 Total Exon Count: 11 Strand: - Coding Region Position: hg19 chr16:338,122-397,025 Size: 58,904 Coding Exon Count: 10
ID:AXIN1_HUMAN DESCRIPTION: RecName: Full=Axin-1; AltName: Full=Axis inhibition protein 1; Short=hAxin; FUNCTION: Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt- independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7. Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development. SUBUNIT: Homodimer (By similarity). Component of the beta-catenin destruction complex, containing at least, CTNNB1, an axin and GSK3B, that regulates CTNNB1 protein levels through phosphorylation and ubiquitination. Interacts with CTNNB1 (via the armadillo repeats 2-7). Interacts with GSK3B; the interaction hyperphosphorylates CTNNB1 leading to its ubiquitination and destruction. Component of the AXIN1-HIPK2-TP53 complex. Interacts directly in the complex with TP53 and HIPK2. Interacts with DAXX; the interaction stimulates the interaction of DAXX with TP53, stimulates 'Ser-46' phosphorylation of TP53 and induces cell death on UV irradiation. Also binds APC, SMAD6, SMAD7 and RNF111. Interacts with DIXDC1; prevents interaction with MAP3K1. Interacts with MAP3K4. Interacts with ANKRD6 and AIDA (By similarity). Interacts with MDFI; the interaction decreases AXIN1-mediated JUN N-terminal kinase (JNK) activation. Interacts with MDFIC; the interaction inhibits beta-cateninin-mediated signaling and AXIN1- mediated JUN N-terminal kinase (JNK) activation. Interacts with LRP5 (via its phosphorylated PPPSP motifs); the interaction is stimulated by WNT1 and GSK3B and activates beta-catenin signaling. Interacts (via the C-terminal) with PPP1CA; the interaction dephosphorylates AXIN1 and regulates interaction with GSK3B. Interacts with PPP2CA; the interaction dephosphorylates AXIN1. Interacts with MACF1 (By similarity). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). Interacts with TNKS. Interacts with DAB2; the interaction is mutually exclusive with the AXIN1:PPP1CA interaction. INTERACTION: P39687:ANP32A; NbExp=2; IntAct=EBI-710484, EBI-359234; Q14194:CRMP1; NbExp=2; IntAct=EBI-710484, EBI-473101; P49674:CSNK1E; NbExp=4; IntAct=EBI-710484, EBI-749343; P35222:CTNNB1; NbExp=20; IntAct=EBI-710484, EBI-491549; Q02248:Ctnnb1 (xeno); NbExp=5; IntAct=EBI-710484, EBI-397872; Q9UKB1:FBXW11; NbExp=4; IntAct=EBI-710484, EBI-355189; P49841:GSK3B; NbExp=26; IntAct=EBI-710484, EBI-373586; Q9H2K2:TNKS2; NbExp=2; IntAct=EBI-710484, EBI-4398527; P04637:TP53; NbExp=4; IntAct=EBI-710484, EBI-366083; Q14134:TRIM29; NbExp=2; IntAct=EBI-710484, EBI-702370; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane (By similarity). Note=MACF1 is required for its translocation to cell membrane (By similarity). On UV irradiation, translocates to the nucleus and colocalizes with DAAX. TISSUE SPECIFICITY: Ubiquitously expressed. DOMAIN: The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2. PTM: Phosphorylation and dephosphorylation of AXIN1 regulates assembly and function of the beta-catenin complex. Phosphorylated by CK1 and GSK3B. Dephosphorylated by PPP1CA and PPP2CA. Phosphorylation by CK1 enhances binding of GSK3B to AXIN1. PTM: ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP- ribosylated protein is recognized by RNF146, followed by ubiquitination at 'Lys-48' and subsequent activation of the Wnt signaling pathway. PTM: Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation and subsequent activation of the Wnt signaling pathway. Sumoylation at Lys-857 and Lys-860 prevents ubiquitination and degradation. Sumoylation is required for AXIN1- mediated JNK activation. Deubiquitinated by USP34, deubiquitinated downstream of beta-catenin stabilization step: deubiquitination is important for nuclear accumulation during Wnt signaling to positively regulate beta-catenin (CTNBB1)-mediated transcription. DISEASE: Defects in AXIN1 are involved in hepatocellular carcinoma (HCC) [MIM:114550]. DISEASE: Defects in AXIN1 are a cause of caudal duplication anomaly (CADUA) [MIM:607864]. Caudal duplication anomaly is characterized by the occurrence of duplications of different organs in the caudal region. Note=Caudal duplication anomaly is associated with hypermethylation of the AXIN1 promoter. SIMILARITY: Contains 1 DIX domain. SIMILARITY: Contains 1 RGS domain. SEQUENCE CAUTION: Sequence=AAC51624.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O15169
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AB208876 - Homo sapiens mRNA for axin 1 isoform a variant protein. BC035872 - Homo sapiens, clone IMAGE:5309734, mRNA. KF615850 - Homo sapiens clone WBr-AK2013F1 axin-1 variant-like (AXIN1) mRNA, complete sequence, alternatively spliced. KF615851 - Homo sapiens clone WBr-AK2013F2 axin-1 variant-like (AXIN1) mRNA, complete sequence, alternatively spliced. KF615852 - Homo sapiens clone WBr-AK2013F3 axin-1 variant-like (AXIN1) mRNA, complete sequence, alternatively spliced. KF615847 - Homo sapiens clone WBr-AK2013A1 axin-1 variant-like (AXIN1) mRNA, complete sequence, alternatively spliced. KF615848 - Homo sapiens clone WBr-AK2013A2 axin-1 variant-like (AXIN1) mRNA, complete sequence, alternatively spliced. KF615849 - Homo sapiens clone WBr-AK2013A3 axin-1 variant-like (AXIN1) mRNA, complete sequence, alternatively spliced. KF615853 - Homo sapiens clone WBr-AK2013A4 axin-1 variant-like (AXIN1) mRNA, complete sequence, alternatively spliced. KF615854 - Homo sapiens clone WBr-AK2013A5 axin-1 variant-like (AXIN1) mRNA, complete sequence, alternatively spliced. AF009674 - Homo sapiens axin (AXIN) mRNA, partial cds. BC044648 - Homo sapiens axin 1, mRNA (cDNA clone MGC:52315 IMAGE:5809104), complete cds. KU178413 - Homo sapiens axin 1 isoform 1 (AXIN1) mRNA, partial cds. KU178414 - Homo sapiens axin 1 isoform 2 (AXIN1) mRNA, partial cds. KU178415 - Homo sapiens axin 1 isoform 3 (AXIN1) mRNA, partial cds, alternatively spliced. BC017447 - Homo sapiens, clone IMAGE:3506533, mRNA, partial cds. BX648449 - Homo sapiens mRNA; cDNA DKFZp686J15273 (from clone DKFZp686J15273). JD383178 - Sequence 364202 from Patent EP1572962. JD162324 - Sequence 143348 from Patent EP1572962. JD155714 - Sequence 136738 from Patent EP1572962. JD367549 - Sequence 348573 from Patent EP1572962. JD452077 - Sequence 433101 from Patent EP1572962. JD050543 - Sequence 31567 from Patent EP1572962. JD201897 - Sequence 182921 from Patent EP1572962. JD537556 - Sequence 518580 from Patent EP1572962. JD258602 - Sequence 239626 from Patent EP1572962. JD058422 - Sequence 39446 from Patent EP1572962. JD547469 - Sequence 528493 from Patent EP1572962. JD255116 - Sequence 236140 from Patent EP1572962. JD209478 - Sequence 190502 from Patent EP1572962. JD532879 - Sequence 513903 from Patent EP1572962. JD126983 - Sequence 108007 from Patent EP1572962. JD473778 - Sequence 454802 from Patent EP1572962. JD178742 - Sequence 159766 from Patent EP1572962. JD384632 - Sequence 365656 from Patent EP1572962. JD143122 - Sequence 124146 from Patent EP1572962. JD451409 - Sequence 432433 from Patent EP1572962. JD099873 - Sequence 80897 from Patent EP1572962. JD389969 - Sequence 370993 from Patent EP1572962. JD129242 - Sequence 110266 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04310 - Wnt signaling pathway hsa05200 - Pathways in cancer hsa05210 - Colorectal cancer hsa05213 - Endometrial cancer hsa05217 - Basal cell carcinoma
BioCarta from NCI Cancer Genome Anatomy Project h_alkPathway - ALK in cardiac myocytes h_ps1Pathway - Presenilin action in Notch and Wnt signaling h_gsk3Pathway - Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages h_wntPathway - WNT Signaling Pathway h_pitx2Pathway - Multi-step Regulation of Transcription by Pitx2
Reactome (by CSHL, EBI, and GO)
Protein O15169 (Reactome details) participates in the following event(s):
R-HSA-195251 Assembly of the destruction complex R-HSA-5229343 AXIN is phosphorylated in the destruction complex R-HSA-1504186 DVL recruits GSK3beta:AXIN1 to the receptor complex R-HSA-201685 Beta-catenin is released from the destruction complex R-HSA-3640862 Tankyrase binds AXIN R-HSA-4641134 SMURF2 binds AXIN R-HSA-195280 Dissociation of beta-catenin from Axin and association of beta catenin with phospho-(20 aa) APC in the detruction complex R-HSA-195275 Phosphorylation of APC component of the destruction complex R-HSA-2130279 Association of beta-catenin with the RBX1:SCF(beta-TrCP1) ubiquitin ligase complex R-HSA-195304 Association of beta-catenin with the destruction complex R-HSA-201691 Phosphorylation of LRP5/6 cytoplasmic domain by CSNKI R-NUL-1458902 frog CK1gamma phosphorylates LRP5/6 R-HSA-201677 Phosphorylation of LRP5/6 cytoplasmic domain by membrane-associated GSK3beta R-HSA-3640858 Tankyrase ADP-ribosylates AXIN R-HSA-4641129 AXIN is ubiquitinated by SMURF2 R-HSA-2130286 Multi-ubiquitination of phospho-beta-catenin by RBX1:SCF(beta-TrCP1) R-HSA-195287 Phosphorylation of phospho-(Ser45 ) at Thr 41 by GSK-3 R-HSA-195318 Phosphorylation of beta-catenin at Ser45 by CK1 alpha R-HSA-195300 Phosphorylation of phospho-(Ser45,Thr41,Ser37) at Ser33 by GSK-3 R-HSA-195283 Phosphorylation of phospho- (Ser45, Thr41) beta-catenin at Ser37 by GSK-3 R-HSA-3640844 RNF146 binds RibC-AXIN:TNKS complex R-HSA-3640872 USP34 deubiquitinates AXIN1,AXIN2 R-HSA-3640861 RNF146 ubiquitinates ADP-ribosylated AXIN R-HSA-195253 Degradation of beta-catenin by the destruction complex R-HSA-5467337 APC truncation mutants have impaired AXIN binding R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex R-HSA-8931987 RUNX1 regulates estrogen receptor mediated transcription R-HSA-8939256 RUNX1 regulates transcription of genes involved in WNT signaling R-HSA-9018519 Estrogen-dependent gene expression R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane R-HSA-4641257 Degradation of AXIN R-HSA-195721 Signaling by WNT R-HSA-4839744 truncated APC mutants destabilize the destruction complex R-HSA-4839748 AMER1 mutants destabilize the destruction complex R-HSA-8878171 Transcriptional regulation by RUNX1 R-HSA-8939211 ESR-mediated signaling R-HSA-5467340 AXIN missense mutants destabilize the destruction complex R-HSA-5358751 S45 mutants of beta-catenin aren't phosphorylated R-HSA-5358752 T41 mutants of beta-catenin aren't phosphorylated R-HSA-5358749 S37 mutants of beta-catenin aren't phosphorylated R-HSA-5358747 S33 mutants of beta-catenin aren't phosphorylated R-HSA-201681 TCF dependent signaling in response to WNT R-HSA-162582 Signal Transduction R-HSA-4791275 Signaling by WNT in cancer R-HSA-212436 Generic Transcription Pathway R-HSA-9006931 Signaling by Nuclear Receptors R-HSA-196299 Beta-catenin phosphorylation cascade R-HSA-5339716 Misspliced GSK3beta mutants stabilize beta-catenin R-HSA-5689880 Ub-specific processing proteases R-HSA-4839735 AXIN mutants destabilize the destruction complex, activating WNT signaling R-HSA-4839743 phosphorylation site mutants of CTNNB1 are not targeted to the proteasome by the destruction complex R-HSA-5663202 Diseases of signal transduction R-HSA-73857 RNA Polymerase II Transcription R-HSA-5688426 Deubiquitination R-HSA-1643685 Disease R-HSA-74160 Gene expression (Transcription) R-HSA-597592 Post-translational protein modification R-HSA-392499 Metabolism of proteins
US Server
