| IED ID | IndEnz0002008672 |
| Enzyme Type ID | protease008672 |
| Protein Name |
Serine/threonine-protein kinase N1 EC 2.7.11.13 Protease-activated kinase 1 PAK-1 Protein kinase C-like 1 Protein kinase C-like PKN Protein-kinase C-related kinase 1 Serine-threonine protein kinase N |
| Gene Name | Pkn1 Pkn Prk1 Prkcl1 |
| 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 | MAGDAVQSEPRSWSLLEQLGLAGADLAAPGVQQQLELERERLKREIRKELKLKEGAENLRRATTDLGRSLAPVELLLRGSARRLDLLHQQLQELHAHVVLPDPTAGSDAPQSLAEGSPVCSSTNLSRVAGLEKQLAIELKVKQGAENMIQTYSNGSTKDRKLLLTAQQMLQDSKTKIDIIRMQLRRALQALQAGQLESQAAPDEAHGDPDLGAVELRIEELRHHFRVEHAVAEGAKNVLRLLSAAKAPDRKAVSEAQEKLTESNQKLGLLRESLERRLGELPADHPKGRLLREELTAASSAAFSAILPGPFPATHYSTLSKPAPLTGTLEVRVVGCKNLPETIPWSPPPSVGASGTPDSRTPFLSRPARGLYNRSGSLSGRSSLKGEAENSTEVSTVLKLDNTVVGQTAWKPCGPNAWDQSFTLELERARELELAVFWRDQRGLCALKFLKLEDFLDNERHEVQLDMEPQGCLVAEVTFRNPIIERIPRLQRQKKIFSKQQGQTFQRARQMNIDVATWVRLLRRLIPNAVATGSFSPNASPGSEIRSTGDISMEKLNLGADSDSSSQKSPAGLPSTSCSLSSPTHESTTSPELPSETQETPGPGLCSPLRKSPLTLEDFKFLAVLGRGHFGKVLLSEFHSSGELFAIKALKKGDIVARDEVESLMCEKRILATVTRAGHPFLVNLFGCFQTPEHVCFVMEYSAGGDLMLHIHSDVFSEPRAVFYSACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYVKIADFGLCKEGMGYGDRTSTFCGTPEFLAPEVLTDTSYTRAVDWWGLGVLLYEMLVGESPFPGDDEEEVFDSIVNDEVRYPRFLSAEAIGIMRRLLRRNPERRLGSTERDAEDVKKQPFFRTLDWDALLARRLPPPFVPTLSGRTDVSNFDEEFTGEAPTLSPPRDARPLTAAEQAAFRDFDFVAGGY |
| Enzyme Length | 946 |
| Uniprot Accession Number | Q63433 |
| Absorption | |
| Active Site | ACT_SITE 744; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU10027" |
| Activity Regulation | ACTIVITY REGULATION: Kinase activity is activated upon binding to Rho proteins (RHOA, RHOB and RAC1). Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids. Activated by caspase-3 (CASP3) cleavage during apoptosis. Two specific sites, Thr-778 (activation loop of the kinase domain) and Ser-920 (turn motif), need to be phosphorylated for its full activation (By similarity). {ECO:0000250}. |
| Binding Site | BINDING 648; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13; Evidence={ECO:0000269|PubMed:8051089}; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.13; Evidence={ECO:0000269|PubMed:8051089}; |
| DNA Binding | |
| EC Number | 2.7.11.13 |
| Enzyme Function | FUNCTION: PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation (PubMed:8051089, PubMed:15375078). Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14 (By similarity). Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro (By similarity). {ECO:0000250|UniProtKB:Q16512, ECO:0000269|PubMed:15375078, ECO:0000269|PubMed:8051089}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 625..633; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Features | Active site (1); Binding site (1); Chain (1); Compositional bias (1); Domain (6); Initiator methionine (1); Modified residue (14); Nucleotide binding (1); Region (3); Sequence conflict (5); Site (3) |
| Keywords | ATP-binding;Acetylation;Cell membrane;Chromatin regulator;Coiled coil;Cytoplasm;Direct protein sequencing;Endosome;Kinase;Membrane;Nucleotide-binding;Nucleus;Phosphoprotein;Reference proteome;Repeat;Serine/threonine-protein kinase;Transcription;Transcription regulation;Transferase |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15375078}. Nucleus {ECO:0000250|UniProtKB:Q16512}. Endosome {ECO:0000250|UniProtKB:Q16512}. Cell membrane {ECO:0000269|PubMed:15375078}; Peripheral membrane protein {ECO:0000269|PubMed:15375078}. Cleavage furrow {ECO:0000250|UniProtKB:Q16512}. Midbody {ECO:0000250|UniProtKB:Q16512}. Note=Associates with chromatin in a ligand-dependent manner (By similarity). Localization to endosomes is mediated via its interaction with RHOB. Accumulates during telophase at the cleavage furrow and finally concentrates around the midbody in cytokinesis (By similarity). Association to the cell membrane is dependent on Ser-377 phosphorylation. {ECO:0000250|UniProtKB:Q16512, ECO:0000269|PubMed:15375078}. |
| Modified Residue | MOD_RES 2; /note=N-acetylalanine; /evidence=ECO:0000250|UniProtKB:Q16512; MOD_RES 69; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q16512; MOD_RES 377; /note=Phosphoserine; /evidence=ECO:0000269|PubMed:15375078; MOD_RES 451; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:Q16512; MOD_RES 536; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q16512; MOD_RES 540; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q16512; MOD_RES 543; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q16512; MOD_RES 562; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q16512; MOD_RES 565; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q16512; MOD_RES 612; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q16512; MOD_RES 778; /note=Phosphothreonine; by PDPK1; /evidence=ECO:0000250|UniProtKB:Q16512; MOD_RES 782; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:Q16512; MOD_RES 918; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:Q16512; MOD_RES 920; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903 |
| Post Translational Modification | PTM: Autophosphorylated; preferably on serine. Phosphorylated during mitosis. {ECO:0000250|UniProtKB:Q16512}.; PTM: Activated by limited proteolysis with trypsin. {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 16427251; 17687038; 22893700; 29045568; |
| Motif | |
| Gene Encoded By | |
| Mass | 104,468 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:17989; RHEA:46608 |
| Cross Reference Brenda | 2.7.11.13; |