Human Gene AXIN1 (uc002cgp.2) Description and Page Index
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;
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): AXIN1 CDC HuGE Published Literature: AXIN1 Positive Disease Associations: Parkinson Disease Related Studies:
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
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
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