| IED ID | IndEnz0002008457 |
| Enzyme Type ID | protease008457 |
| Protein Name |
SH3 and PX domain-containing protein 2A Adapter protein TKS5 Five SH3 domain-containing protein SH3 multiple domains protein 1 Tyrosine kinase substrate with five SH3 domains |
| Gene Name | SH3PXD2A FISH KIAA0418 SH3MD1 TKS5 |
| 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 | MLAYCVQDATVVDVEKRRNPSKHYVYIINVTWSDSTSQTIYRRYSKFFDLQMQLLDKFPIEGGQKDPKQRIIPFLPGKILFRRSHIRDVAVKRLKPIDEYCRALVRLPPHISQCDEVFRFFEARPEDVNPPKEDYGSSKRKSVWLSSWAESPKKDVTGADATAEPMILEQYVVVSNYKKQENSELSLQAGEVVDVIEKNESGWWFVSTSEEQGWVPATYLEAQNGTRDDSDINTSKTGEVSKRRKAHLRRLDRRWTLGGMVNRQHSREEKYVTVQPYTSQSKDEIGFEKGVTVEVIRKNLEGWWYIRYLGKEGWAPASYLKKAKDDLPTRKKNLAGPVEIIGNIMEISNLLNKKASGDKETPPAEGEGHEAPIAKKEISLPILCNASNGSAVGVPDRTVSRLAQGSPAVARIAPQRAQISSPNLRTRPPPRRESSLGFQLPKPPEPPSVEVEYYTIAEFQSCISDGISFRGGQKAEVIDKNSGGWWYVQIGEKEGWAPASYIDKRKKPNLSRRTSTLTRPKVPPPAPPSKPKEAEEGPTGASESQDSPRKLKYEEPEYDIPAFGFDSEPELSEEPVEDRASGERRPAQPHRPSPASSLQRARFKVGESSEDVALEEETIYENEGFRPYAEDTLSARGSSGDSDSPGSSSLSLTRKNSPKSGSPKSSSLLKLKAEKNAQAEMGKNHSSASFSSSITINTTCCSSSSSSSSSLSKTSGDLKPRSASDAGIRGTPKVRAKKDADANAGLTSCPRAKPSVRPKPFLNRAESQSQEKMDISTLRRQLRPTGQLRGGLKGSKSEDSELPPQTASEAPSEGSRRSSSDLITLPATTPPCPTKKEWEGPATSYMTCSAYQKVQDSEISFPAGVEVQVLEKQESGWWYVRFGELEGWAPSHYLVLDENEQPDPSGKELDTVPAKGRQNEGKSDSLEKIERRVQALNTVNQSKKATPPIPSKPPGGFGKTSGTPAVKMRNGVRQVAVRPQSVFVSPPPKDNNLSCALRRNESLTATDGLRGVRRNSSFSTARSAAAEAKGRLAERAASQGSDSPLLPAQRNSIPVSPVRPKPIEKSQFIHNNLKDVYVSIADYEGDEETAGFQEGVSMEVLERNPNGWWYCQILDGVKPFKGWVPSNYLEKKN |
| Enzyme Length | 1133 |
| Uniprot Accession Number | Q5TCZ1 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Adapter protein involved in invadopodia and podosome formation, extracellular matrix degradation and invasiveness of some cancer cells. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. In association with ADAM12, mediates the neurotoxic effect of amyloid-beta peptide. {ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:15710328, ECO:0000269|PubMed:15710903, ECO:0000269|PubMed:19755710, ECO:0000269|PubMed:20609497}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (2); Beta strand (20); Chain (1); Coiled coil (1); Compositional bias (4); Domain (6); Erroneous initiation (1); Helix (3); Modified residue (16); Mutagenesis (2); Natural variant (3); Region (5); Turn (1) |
| Keywords | 3D-structure;Alternative splicing;Cell junction;Cell projection;Coiled coil;Cytoplasm;Phosphoprotein;Reference proteome;Repeat;SH3 domain |
| Interact With | Q13444; Q07889; P21575 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm. Cell projection, podosome. Note=Cytoplasmic in normal cells and localizes to podosomes in SRC-transformed cells. |
| Modified Residue | MOD_RES 256; /note="Phosphothreonine"; /evidence="ECO:0000250|UniProtKB:O89032"; MOD_RES 406; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 421; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"; MOD_RES 547; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"; MOD_RES 567; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 593; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 644; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 731; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 767; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:O89032"; MOD_RES 769; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:O89032"; MOD_RES 819; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:O89032"; MOD_RES 829; /note="Phosphothreonine"; /evidence="ECO:0000250|UniProtKB:O89032"; MOD_RES 1002; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 1016; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 1017; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 1038; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" |
| Post Translational Modification | PTM: Tyrosine phosphorylated by SRC. Phosphorylation plays a regulatory role in the protein localization. The intramolecular interaction of the PX domain with the third SH3 domain maintains the protein in the cytoplasm and phosphorylation disrupts this interaction, resulting in the redistribution of the protein from cytoplasm to the perimembrane region. Phosphorylated on serine upon DNA damage, probably by ATM or ATR. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (4) |
| Cross Reference PDB | 2DNU; 2EGA; 2EGC; 2EKH; |
| Mapped Pubmed ID | 10490598; 10699464; 10724160; 10873802; 11696321; 11756552; 11773441; 11804587; 11948177; 12464619; 12860998; 12907671; 15260990; 16374509; 16630611; 16964398; 17064668; 17244649; 17440933; 18218625; 19464300; 19540230; 19837132; 20309963; 20379614; 20562859; 21706016; 22249020; 22584907; 22608513; 22970203; 23544093; 23873940; 24174371; 24206842; 24255178; 24584464; 24993883; 25564649; 25826475; 25963737; 26299518; 26334100; 26446840; 26496610; 26598554; 27789576; 27802184; 27835612; 28390157; 28737753; 28825699; 28860633; 30061681; 30439350; 31817908; 31871319; 31999741; 32673397; 33087629; 33414172; 34255789; 34769479; 8662891; 8670801; 8756646; 8798539; 8805223; 8816443; 9013646; 9405671; 9829970; 9843499; |
| Motif | |
| Gene Encoded By | |
| Mass | 125,289 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |