| IED ID | IndEnz0002016547 |
| Enzyme Type ID | protease016547 |
| Protein Name |
Axin-1 Axis inhibition protein 1 hAxin |
| Gene Name | AXIN1 AXIN |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MNIQEQGFPLDLGASFTEDAPRPPVPGEEGELVSTDPRPASYSFCSGKGVGIKGETSTATPRRSDLDLGYEPEGSASPTPPYLKWAESLHSLLDDQDGISLFRTFLKQEGCADLLDFWFACTGFRKLEPCDSNEEKRLKLARAIYRKYILDNNGIVSRQTKPATKSFIKGCIMKQLIDPAMFDQAQTEIQATMEENTYPSFLKSDIYLEYTRTGSESPKVCSDQSSGSGTGKGISGYLPTLNEDEEWKCDQDMDEDDGRDAAPPGRLPQKLLLETAAPRVSSSRRYSEGREFRYGSWREPVNPYYVNAGYALAPATSANDSEQQSLSSDADTLSLTDSSVDGIPPYRIRKQHRREMQESVQVNGRVPLPHIPRTYRVPKEVRVEPQKFAEELIHRLEAVQRTREAEEKLEERLKRVRMEEEGEDGDPSSGPPGPCHKLPPAPAWHHFPPRCVDMGCAGLRDAHEENPESILDEHVQRVLRTPGRQSPGPGHRSPDSGHVAKMPVALGGAASGHGKHVPKSGAKLDAAGLHHHRHVHHHVHHSTARPKEQVEAEATRRAQSSFAWGLEPHSHGARSRGYSESVGAAPNASDGLAHSGKVGVACKRNAKKAESGKSASTEVPGASEDAEKNQKIMQWIIEGEKEISRHRRTGHGSSGTRKPQPHENSRPLSLEHPWAGPQLRTSVQPSHLFIQDPTMPPHPAPNPLTQLEEARRRLEEEEKRASRAPSKQRYVQEVMRRGRACVRPACAPVLHVVPAVSDMELSETETRSQRKVGGGSAQPCDSIVVAYYFCGEPIPYRTLVRGRAVTLGQFKELLTKKGSYRYYFKKVSDEFDCGVVFEEVREDEAVLPVFEEKIIGKVEKVD |
| Enzyme Length | 862 |
| Uniprot Accession Number | O15169 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (PubMed:12192039, PubMed:27098453). 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 (PubMed:12192039). In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B (PubMed:12192039). Likely to function as a tumor suppressor. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (PubMed:16601693). Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development (PubMed:17210684). Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation (PubMed:17210684). {ECO:0000269|PubMed:12192039, ECO:0000269|PubMed:16601693, ECO:0000269|PubMed:17210684, ECO:0000269|PubMed:27098453}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (1); Beta strand (6); Chain (1); Compositional bias (2); Cross-link (2); Domain (2); Erroneous initiation (1); Helix (13); Modified residue (9); Motif (1); Natural variant (5); Region (13); Sequence conflict (3); Turn (3) |
| Keywords | 3D-structure;ADP-ribosylation;Alternative splicing;Apoptosis;Cell membrane;Cytoplasm;Developmental protein;Disease variant;Isopeptide bond;Membrane;Nucleus;Phosphoprotein;Reference proteome;Tumor suppressor;Ubl conjugation;Wnt signaling pathway |
| Interact With | Q5JTC6; P39687; P25054; P49407; Itself; Q13137; Q9H257-2; Q2TAC2-2; Q14194; P49674; P35222; Q5VWQ8-2; O14641; Q9UKB1; Q08379; P49840; P49841; P14923; Q6A162; Q9BQ66; Q9BYR5; Q969G2; Q99750; Q6FHY5; Q9UJV3-2; Q5JR59-3; P01106; P35813; P62136; O43586; Q6ZNA4; Q96KG9-4; O15105; Q7Z699; O75558; P63165; G2XKQ0; Q9UBB9; Q15583; Q9H2K2; P04637; Q12933; Q9C019; P14373; Q14134; O94972; Q15654; P23258; Q9H7D7; P46937; Q9HCK0; Q96K21-3; P70039; Q02248; G1T8E2; Q99ML9; O75581 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16601693}. Nucleus {ECO:0000269|PubMed:17210684}. Membrane {ECO:0000250|UniProtKB:O35625}. Cell membrane {ECO:0000250|UniProtKB:O35625}. Note=MACF1 is required for its translocation to cell membrane (By similarity). On UV irradiation, translocates to the nucleus and colocalizes with DAAX (PubMed:17210684). {ECO:0000250|UniProtKB:O35625, ECO:0000269|PubMed:17210684}. |
| Modified Residue | MOD_RES 75; /note="Phosphoserine; by CK1"; /evidence="ECO:0000269|PubMed:17318175"; MOD_RES 77; /note="Phosphoserine; by CK1"; /evidence="ECO:0000269|PubMed:17318175, ECO:0007744|PubMed:23186163"; MOD_RES 217; /note="Phosphoserine; by CK1"; /evidence="ECO:0000269|PubMed:17318175"; MOD_RES 469; /note="Phosphoserine; by CK1"; /evidence="ECO:0000269|PubMed:17318175"; MOD_RES 481; /note="Phosphothreonine; by GSK3-beta"; /evidence="ECO:0000250|UniProtKB:O35625"; MOD_RES 486; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 493; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:O35625"; MOD_RES 511; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 581; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163" |
| Post Translational Modification | 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. {ECO:0000269|PubMed:17318175, ECO:0000269|PubMed:9920888}.; 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. {ECO:0000269|PubMed:21383061}.; 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. {ECO:0000269|PubMed:18632848, ECO:0000269|PubMed:21383061}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (12) |
| Cross Reference PDB | 1DK8; 1EMU; 1O9U; 3ZDI; 4B7T; 4NM0; 4NM3; 4NM5; 4NM7; 4NU1; 5WZZ; 6JCK; |
| Mapped Pubmed ID | 10023660; 10092233; 10196136; 10421629; 10487827; 10581160; 10644691; 10698523; 10749138; 10862053; 10921899; 11375957; 11522655; 11746989; 11955436; 12000790; 12036951; 12067995; 12209999; 12439748; 12474228; 12555076; 12717450; 12771989; 12820959; 12883680; 14534723; 14566817; 14630927; 14731402; 14970870; 15063782; 15064706; 15084453; 15306667; 15327769; 15355978; 15520370; 15526030; 15579909; 15698401; 15735151; 15981102; 16163548; 16169070; 16293619; 16341016; 16341017; 16753179; 16772034; 16868183; 16884355; 16890161; 17018282; 17143292; 17143297; 17183061; 17318191; 17353931; 17418091; 17510365; 17529994; 17569865; 17601533; 17768662; 18077588; 18171349; 18311776; 18330950; 18339531; 18362152; 18514389; 18606139; 18708403; 18757411; 18786926; 18985028; 19061640; 19107203; 19125156; 19131971; 19141611; 19166851; 19237556; 19249679; 19303846; 19331826; 19367725; 19390532; 19453261; 19513548; 19582507; 19619488; 19633924; 19731416; 19760609; 19778269; 19913121; 20080667; 20098615; 20122174; 20128690; 20379614; 20628086; 20711500; 20844743; 20846493; 20858899; 21057547; 21087614; 21183070; 21183076; 21242974; 21248786; 21252990; 21304492; 21769465; 21808024; 21902576; 21940452; 21988832; 22014111; 22101459; 22153077; 22234612; 22438566; 22440753; 22470507; 22524844; 22575643; 22614067; 22682247; 22773187; 22933777; 22998443; 23110995; 23135750; 23144924; 23155463; 23192643; 23214499; 23256519; 23277359; 23278310; 23455922; 23525311; 23579495; 23602568; 23879168; 23915259; 24011952; 24419084; 24642411; 24722208; 24846767; 24976009; 25241761; 25355064; 25735981; 25802106; 25873176; 26393419; 26496610; 26894286; 26916619; 26968103; 26974125; 27068743; 27138857; 27530555; 27594684; 27601169; 27630299; 28055379; 28100566; 28107521; 28546513; 28694499; 28731177; 28754688; 29053018; 29525529; 29531269; 29737091; 29923028; 30166345; 30621017; 30810360; 30825236; 30844369; 30929455; 31143301; 31514071; 31524541; 31723073; 31786079; 31822591; 32005247; 32125723; 32213661; 32285989; 32930707; 33096676; 33506901; 33811251; 34352208; 8259518; 8259519; 8638126; 8757136; 9065402; 9482734; 9556553; 9601641; 9990852; |
| Motif | MOTIF 20..29; /note=Tankyrase-binding motif |
| Gene Encoded By | |
| Mass | 95,635 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |