Reactome | UniProt:O35625 Axin1

Schema > ReferenceGeneProduct > Entries

UniProt:O35625 Axin1 Show undefined attributes

chain	chain:1-863
checksum	2216D66E92387B81
comment	FUNCTION Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (By similarity). 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 (By similarity). Also a component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development.SUBUNIT Homodimer (PubMed:17681137). Component of the beta-catenin destruction complex, containing at least CTNNB1, an axin and GSK3B, that regulates CTNNB1 protein levels through phosphorylation and ubiquitination (By similarity). Interacts with GSK3B; the interaction hyperphosphorylates CTNNB1 leading to its ubiquitination and destruction (By similarity). 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 (By similarity). Also interacts with APC, RNF111, SMAD6 and SMAD7 (By similarity). Interacts (via the C-terminal) with PPP1CA; the interaction dephosphorylates AXIN1 and regulates interaction with GSK3B (By similarity). Interacts with PPP2CA; the interaction dephosphorylates AXIN1 (By similarity). Interacts with MDFI; the interaction decreases AXIN1-mediated JUN N-terminal kinase (JNK) activation (By similarity). Interacts with MDFIC; the interaction inhibits beta-cateninin-mediated signaling and AXIN1-mediated JUN N-terminal kinase (JNK) activation (By similarity). Binds ANKRD6, PIAS1, PIAS2, PIAS4, SUMO1, MAP3K1 and MAP3K4 (PubMed:12183362, PubMed:12223491). Component of the AXIN1-HIPK2-TP53 complex (PubMed:15526030). Interacts directly in the complex with TP53 and HIPK2 (PubMed:15526030). Interacts with DIXDC1; the interaction prevents interaction with MAP3K1 (PubMed:15262978). Interacts with AIDA; the interaction blocks the AXIN1-mediated JNK activation through disrupting AXIN1 homodimerization and Wnt signaling (PubMed:17681137). Interacts with LRP5 (via its phosphorylated PPPSP motifs); the interaction is stimulated by WNT1 and GSK3B and activates beta-catenin signaling (PubMed:11336703). Interacts with CTNNB1 (via the armadillo repeats 2-7) (PubMed:10581160, PubMed:15063782). Interacts with MACF1 (By similarity). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). Interacts with TNKS (By similarity). Interacts with DAB2; the interaction is mutually exclusive with the AXIN1:PPP1CA interaction (PubMed:19581931). Interacts with ZBED3 (via PPPSP motif); the interaction is direct, enhanced by protein kinase GSK3B and casein kinase CSNK1E activities and decreases GSK3B-induced beta-catenin serine and threonine phosphorylations (PubMed:19141611). Interacts with WDR26 (By similarity). Interacts with GID8 (By similarity). Interacts with SIAH1 and SIAH2; both probably catalyze AXIN1 ubiquitination and subsequent proteasome-mediated ubiquitin-dependent degradation. Interaction with GSK3B and AXIN1 is competitive (By similarity).INTERACTION On UV irradiation, translocates to the nucleus and colocalizes with DAAX (By similarity). MACF1 is required for its translocation to cell membrane (PubMed:16815997).ALTERNATIVE PRODUCTS Expressed in embryonic stem cells.DEVELOPMENTAL STAGE Widely expressed at 10.5 dpc to 16.5 dpc.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 (By similarity). Also phosphorylated by CDK2 which regulates interaction with CTNBB1.PTM ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination and subsequent activation of the Wnt signaling pathway (By similarity).PTM Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation and subsequent activation of the Wnt signaling pathway. 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 (By similarity). Sumoylation at Lys-858 and Lys-861 prevents ubiquitination and degradation. Sumoylation is required for AXIN1-mediated JNK activation. Ubiquitination by SIAH1 and SIAH2 induces its proteasomal degradation as part of the activation of the Wnt signaling pathway (By similarity).SEQUENCE CAUTION Extended N-terminus.
crossReference	[DatabaseIdentifier:12393264] RefSeq:NP_001381310.1 [DatabaseIdentifier:11483874] ENSEMBL:ENSMUSG00000024182 [DatabaseIdentifier:11586172] ENSEMBL:ENSMUSP00001091662 [DatabaseIdentifier:11586173] ENSEMBL:ENSMUSP00000073974 [DatabaseIdentifier:11708872] ENSEMBL:ENSMUST00020183805 [DatabaseIdentifier:11708871] ENSEMBL:ENSMUST00000074370 [DatabaseIdentifier:11935971] MGI:1096327 [DatabaseIdentifier:12162118] PDB:8VMF [DatabaseIdentifier:12162117] PDB:8VME [DatabaseIdentifier:12214493] PDB:3UTM [DatabaseIdentifier:12277512] PRO:O35625 [DatabaseIdentifier:12393266] RefSeq:NP_033863.3 [DatabaseIdentifier:12393265] RefSeq:NP_001381311.1 [DatabaseIdentifier:12393268] RefSeq:NP_001381318.1 [DatabaseIdentifier:12393267] RefSeq:NP_001153070.2
databaseName	UniProt
dbId	85717
description	recommendedName: Axin-1 alternativeName: Axis inhibition protein 1 alternativeName: Protein Fused
displayName	UniProt:O35625 Axin1
geneName	Axin1 Axin Fu
identifier	O35625
isSequenceChanged	false
keyword	3D-structure ADP-ribosylation Alternative splicing Apoptosis Cell membrane Cytoplasm Developmental protein Isopeptide bond Membrane Nucleus Phosphoprotein Reference proteome Tumor suppressor Ubl conjugation Wnt signaling pathway
modified	[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
moleculeType	Protein
name	Axin1
otherIdentifier	10442954 114132_f_at 12005 1426966_at 1426967_at 160701_at 17334869 4348244 4391916 4563112 4580430 4636102 4671161 4779344 4800534 4817887 4880203 5179162 5238929 5249717 5429476 5433268 5548527 AF009011_s_at A_52_P197007 A_55_P2143209 GE33184 GO:0000209 GO:0001701 GO:0002039 GO:0005515 GO:0005634 GO:0005730 GO:0005737 GO:0005829 GO:0005856 GO:0005886 GO:0005938 GO:0006325 GO:0006355 GO:0006913 GO:0006915 GO:0007010 GO:0007605 GO:0008013 GO:0009950 GO:0009953 GO:0010629 GO:0015630 GO:0016020 GO:0016055 GO:0016328 GO:0019899 GO:0019901 GO:0019904 GO:0030163 GO:0030178 GO:0030511 GO:0030877 GO:0031122 GO:0031398 GO:0031410 GO:0031625 GO:0032436 GO:0032991 GO:0034244 GO:0035591 GO:0036342 GO:0042802 GO:0042803 GO:0043161 GO:0043539 GO:0044725 GO:0045599 GO:0045732 GO:0045860 GO:0046330 GO:0046332 GO:0048318 GO:0048320 GO:0048468 GO:0048471 GO:0048856 GO:0050877 GO:0051248 GO:0060070 GO:0060090 GO:0060322 GO:0060828 GO:0065003 GO:0070411 GO:0070412 GO:0071944 GO:0090090 GO:0098772 GO:0120283 GO:1904885 GO:1990756 GO:1990909 GO:2000060 ILMN_1217662 ILMN_1246329 mMC008865
physicalEntity	[EntityWithAccessionedSequence:R-MMU-195249] Axin1 [cytosol] - Mus musculus [EntityWithAccessionedSequence:R-MMU-206040] phospho-Axin1 [cytosol] - Mus musculus [EntityWithAccessionedSequence:R-MMU-205737] Phospho (3 sites) Axin1 [cytosol] - Mus musculus [EntityWithAccessionedSequence:R-MMU-205727] Axin1 [cytosol] - Mus musculus [EntityWithAccessionedSequence:R-MMU-3640864] phospho-Axin1 [cytosol] - Mus musculus [EntityWithAccessionedSequence:R-MMU-3640841] phospho-Axin1 [cytosol] - Mus musculus [EntityWithAccessionedSequence:R-MMU-4641133] Axin1 [cytosol] - Mus musculus [EntityWithAccessionedSequence:R-MMU-206175] Phospho Axin1 [cytosol] - Mus musculus
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:11349259] BioGPS Gene:12005 Axin1 [ReferenceDNASequence:12744264] UCSC:O35625 Axin1 [ReferenceDNASequence:11889161] KEGG:mmu:12005 Axin1 [ReferenceDNASequence:11979048] Monarch:12005 Axin1 [ReferenceDNASequence:12063141] NCBI Gene:12005 Axin1
referenceTranscript	[ReferenceRNASequence:12575022] RefSeq:NM_001394381.1 Axin1 [ReferenceRNASequence:12575020] RefSeq:NM_009733.3 Axin1 [ReferenceRNASequence:12575021] RefSeq:NM_001394389.1 Axin1 [ReferenceRNASequence:12575019] RefSeq:NM_001159598.2 Axin1 [ReferenceRNASequence:12575023] RefSeq:NM_001394382.1 Axin1
schemaClass	ReferenceGeneProduct
secondaryIdentifier	AXIN1_MOUSE
sequenceLength	863
species	[Species:48892] Mus musculus
stId	uniprot:O35625
url	http://purl.uniprot.org/uniprot/O35625

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-MMU-195249] Axin1 [cytosol] [EntityWithAccessionedSequence:R-MMU-206040] phospho-Axin1 [cytosol] [EntityWithAccessionedSequence:R-MMU-205737] Phospho (3 sites) Axin1 [cytosol] [EntityWithAccessionedSequence:R-MMU-205727] Axin1 [cytosol] [EntityWithAccessionedSequence:R-MMU-3640864] phospho-Axin1 [cytosol] [EntityWithAccessionedSequence:R-MMU-3640841] phospho-Axin1 [cytosol] [EntityWithAccessionedSequence:R-MMU-4641133] Axin1 [cytosol] [EntityWithAccessionedSequence:R-MMU-206175] Phospho Axin1 [cytosol]
(referenceSequence)	[ModifiedResidue:10002061] O-phospho-L-threonine at 481 (in Homo sapiens) [ModifiedResidue:10002062] O-phospho-L-serine at 486 (in Homo sapiens) [ModifiedResidue:10002063] O-phospho-L-serine at 493 (in Homo sapiens) [ModifiedResidue:205989] O-phospho-L-serine at 614 [ModifiedResidue:205940] O-phospho-L-serine at 621 [ModifiedResidue:205775] O-phospho-L-threonine at 609 [ModifiedResidue:10049080] adenosine diphosphoribosyl (ADP-ribosyl) modified residue at unknown position [GroupModifiedResidue:10049115] ubiquitinylated lysine (K48polyUb [cytosol]) at unknown position [GroupModifiedResidue:10051129] ubiquitinylated lysine (K48polyUb [cytosol]) at 505 (in Homo sapiens)
(interactor)	[UndirectedInteraction:11159527] UniProt:O75581 <-> UniProt:O35625 (IntAct) [UndirectedInteraction:11190925] UniProt:Q9EPK5 <-> UniProt:O35625 (IntAct) [UndirectedInteraction:11193241] UniProt:P49841 <-> UniProt:O35625 (IntAct) [UndirectedInteraction:11238353] UniProt:P98078 <-> UniProt:O35625 (IntAct) [UndirectedInteraction:11247643] UniProt:P46937 <-> UniProt:O35625 (IntAct) [UndirectedInteraction:11257711] UniProt:O35625 <-> UniProt:Q02248 (IntAct) [UndirectedInteraction:11257713] UniProt:O35625 <-> UniProt:P35222 (IntAct) [UndirectedInteraction:11257715] UniProt:O35625 <-> UniProt:Q9WV60 (IntAct) [UndirectedInteraction:11257717] UniProt:O35625 <-> UniProt:O95271 (IntAct) [UndirectedInteraction:11257719] UniProt:O35625 <-> UniProt:Q99ML9 (IntAct) [UndirectedInteraction:11257721] UniProt:O35625 <-> UniProt:O88572 (IntAct) [UndirectedInteraction:11257723] UniProt:O35625 <-> UniProt:Q61062 (IntAct)

Cite Us!