| IED ID | IndEnz0002003646 |
| Enzyme Type ID | protease003646 |
| Protein Name |
Adenomatous polyposis coli protein Protein APC |
| Gene Name | Apc |
| Organism | Rattus norvegicus (Rat) |
| 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 Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MAAASYDQLLKQVEALKMENSNLRQELEDNSNHLTELETEASNMKEVLKQLQGSIEDETMTSGQIDLLERLKEFNLDSNFPGVKLRSKMSLRSYGSREGSVSSRSGECSPVPMGSFPRRAFVNGSRESTGYLEELEKERSLLLADLDKEEKEKDWYYAQLQNLTKRIDSLPLTENFSLQTDMTRRQLEYEARQIRAAMEEQLGTCQDMEKRAQRRIARIQQIEKDILRVRQLLQSQAAEAERSSQSKHETASHEAERQLEGQGVAESNLATSGSGQSSAARVDHETAGVLSSSGTHSAPRRLTSHLGTKVEMVYSLLSMLGTHDKDDMSRTLLAMSSSQDSCISMRQSGCLPLLIQLLHGNDKDSVLLGNSRGSKEARARASAALHNIIHSQPDDKRGRREIRVLHLLEQIRAYCETCWEWQEAHEQGMDQDKNPMPAPVEHQICPAVCVLMKLSFDEEHRHAMNELGGLQAIAELLQVDCEMHGLTDDHYSVTLRRYAGMALTNLTFGDVANKATLCSMKGCMRALVAQLKSESEDLQQVIASVLRNLSWRADVNSKKTLREVGSVKALMECALEVKKESTLKSVLSALWNLSAHCTENKADICAVDGALAFLVGTLTYRSQTNTLAIIESGGGILRNVSSLIATNEDHRQILRENNCLQTLLQHLKSHSLTIVSNACGTLWNLSARNPKDQEALWDMGAVSMLKNLIHSKHKMIAMGSAAALRNLMANRPAKYKDANIMSPGSSLPSLHVRKQKALEAELDAQHLSETFDNIDNLSPKASHRSKQRHKQNLYGDYVFDASRHDDNRSDNFNTGNMTVLSPYLNTTVLPSSSSSRGSLDSSRSEKDRSLERERGIGLSTYHSATENPGTSSKRGLQLSATAAQIAKVMEEVSALHTSQDDRSPASAAELHCVAEERTAARRSSASHTHPNTHNFAKSESSNRTCSMPYAKVEYKRSSNDSLNSVTSSDGYGKRGQMKPSVESYSEDDEGKFCSYGQYPADLAHKIHSANHMDDNGGELDTPINYSLKYSDEQLNSGRQSPSQNERWARPKHVIEDEIKQNEQRQSRSQNTNFPVYSENTDDKHLKFQQHFGQQECVSPYRSRGTNGSETNRMGSSHAVNQNVNQSLCQEDDYEDDKPTNYSERYSEEEQHEEEERPTNYSIKYNEEKHHVDQPIDYSLKYATDISSSQKPSFSFSKTPSVQGTKTEHNSPSSEAASAPSSNAKRQSQLHPSSAQRNGQTPKGTACKVPSINQETMQTYCVEDTPICFSRCSSLSSLSSAEDEIGCDQTTQEADSANTLQIAEIKENDVTRSAQDPASDVPAVSQSTRTKPSRLQASGLASESARHKAVEFSSGAKSPSKSGAQTPKSPPEHYVQETPLVFSRCTSVSSLDSFESRSIASSVQSEPCSGMVSGIVSPSDLPDSPGQTMPPSRSKTPPPPPPPQPVQTKREVPKTKVPAAEQREGGPKQTAVSAAVQRVQVLPDADTLLHFATESTPDGFSCSSSLSALSLDEPFIQKDVELRIMPPVQENDNGNETEPEQPEESNENQDKEVEKPDSEKDLLDDSDDDDIEILEECIISAMPTKSSRKAKKLAQTASKLPPPVARKPSQLPVYKLLPSQSRLQAQKHVSFTPGDDVPRVYCVEGTPINFSTATSLSDLTIESPPNELAAGDGVRASVQSGEFEKRDTIPTEGRSTDEAQRGKVSSIAIPDLDGSKAEEGDILAECINSALPKGRSHKPFRVKKIMDQVQQASMTSSGTNKNQIDTKKKKPTSPVKPMPQNTEYRTRVRKNTDSKVNVNTEETFSDNKDSKKQSLKNNPKDLNDKLPDNEDRVRGGFTFDSPHHYAPIEGTPYCFSRNDSLSSLDFDDDDVDLSREKAELRKGKESKDSEAKVTCHTEPSSSQQSARKAQASTKHPVNRGPSKPLLQEQPTFPQSSKDVPDRGAATDEKLQNFAIENTPVCFSRNSSLSSLSDVDQENNNNEETGPVRDAEPANAQGQPGKPQASGYAPKSFHVEDTPVCFSRNSSLSSLSIDSEDDLLRECISSAMPKKRRPSRLKGEGEWQSPRKVGSVLAEDLTLDLKDIQRPESEHGLSPDSENFDWKAIQEGANSIVSSLHQAAAAAACLSRQASSDSDSILSLKSGVSLGSPFHLTPDQEEKPFTSHKGPRILKPGEKSTLEAKKIESENKGIKGGKKVYKSLITGKIRSNSEISSQMKQPLQTNMPSISRGRTMIHIPGVRNSSSSTSPVSKKGPPLKTPASKSPSEGPVATTSPRGTKPAVKSELSPITRQTSHISGSNKGPSRSGSRDSTPSRPTQQPLSRPMQSPGRNSISPGRNGISTPNKLSQLPRTSSPSTASTKSSGSGKMSYTSPGRQLSQQNLSKQTGLSKNASSIPRSESASKGLNQMNNSNGSNKKVELSRMSSTKSSGSESDRSERPALVRQSTFIKEAPSPTLRRKLEESASFESLSPSSRPDSPTRSQAQTPVLSPSLPDMSLSTHPSVQAGGWRKLPPNLSPTIEYSDGRPSKRHDIARSHSESPSRLPVNRAGTWKREHSKHSSSLPRVSTWRRTGSSSSILSASSESSEKAKSEDEKHVNSVPGPRQMKENQVPTKGTWRKIKESEISPTNTVSQTTSSGAASGAESKTLIYQMAPAVSRTEDVWVRIEDCPINNPRSGRSPTGNTPPVIDSISEKGNPSIKDSKDTQGKQSVGSGSPVQTVGLENRLNSFIQVEAPEQKGTETKAGQGSPAPVAETGETCMAERTPFSSSSSSKHSSPSGTVAARVTPFNYNPSPRKSSADSTSARPSQIPTPVGSSTKKRDSKTDSTESSGAQSPKRHSGSYLVTSV |
| Enzyme Length | 2842 |
| Uniprot Accession Number | P70478 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization (By similarity). {ECO:0000250|UniProtKB:P25054, ECO:0000250|UniProtKB:Q61315}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Chain (1); Coiled coil (2); Compositional bias (32); Initiator methionine (1); Modified residue (43); Motif (2); Mutagenesis (1); Region (19); Repeat (7) |
| Keywords | Acetylation;Cell junction;Cell membrane;Cell projection;Coiled coil;Cytoplasm;Cytoskeleton;Membrane;Microtubule;Phosphoprotein;Reference proteome;Repeat;Tumor suppressor;Ubl conjugation;Wnt signaling pathway |
| Interact With | P31016 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell junction, adherens junction {ECO:0000250|UniProtKB:P25054}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P25054}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:P25054}. Cell projection, ruffle membrane {ECO:0000250|UniProtKB:P25054}. Cytoplasm {ECO:0000250|UniProtKB:P25054}. Cell membrane {ECO:0000250|UniProtKB:P25054}. Note=Associated with the microtubule network at the growing distal tip of microtubules. Accumulates in the lamellipodium and ruffle membrane in response to hepatocyte growth factor (HGF) treatment. The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosphorylated form to the cell membrane. {ECO:0000250|UniProtKB:P25054}. |
| Modified Residue | MOD_RES 2; /note=N-acetylalanine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 105; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q61315; MOD_RES 109; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q61315; MOD_RES 742; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 746; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 778; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 906; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 985; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 1036; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q61315; MOD_RES 1040; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 1357; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 1368; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 1382; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 1389; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q61315; MOD_RES 1392; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q61315; MOD_RES 1435; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 1565; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 1714; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:16641100; MOD_RES 1772; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 1859; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 1861; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 1862; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 1969; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q61315; MOD_RES 1971; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q61315; MOD_RES 2087; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 2092; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 2125; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q61315; MOD_RES 2129; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 2130; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 2132; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 2151; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 2260; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 2270; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 2283; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 2473; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 2535; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 2569; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 2671; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 2674; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 2679; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 2710; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 2723; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054; MOD_RES 2788; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P25054 |
| Post Translational Modification | PTM: Phosphorylated by GSK3B. {ECO:0000250}.; PTM: Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is facilitated by Axin. Deubiquitinated by ZRANB1/TRABID (By similarity). {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11689703; 12610628; 15670646; 16303851; 16688812; 16767746; 17360473; 17507554; 18042042; 18945221; 19694754; 19858196; 22399805; 23001297; 28948298; 8638125; 9786987; |
| Motif | MOTIF 2802..2805; /note=Microtubule tip localization signal; MOTIF 2840..2842; /note=PDZ-binding; /evidence=ECO:0000250 |
| Gene Encoded By | |
| Mass | 310,533 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |