| IED ID | IndEnz0002008190 |
| Enzyme Type ID | protease008190 |
| 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 PKN-alpha Protein-kinase C-related kinase 1 Serine-threonine protein kinase N |
| Gene Name | PKN1 PAK1 PKN PRK1 PRKCL1 |
| 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 | MASDAVQSEPRSWSLLEQLGLAGADLAAPGVQQQLELERERLRREIRKELKLKEGAENLRRATTDLGRSLGPVELLLRGSSRRLDLLHQQLQELHAHVVLPDPAATHDGPQSPGAGGPTCSATNLSRVAGLEKQLAIELKVKQGAENMIQTYSNGSTKDRKLLLTAQQMLQDSKTKIDIIRMQLRRALQAGQLENQAAPDDTQGSPDLGAVELRIEELRHHFRVEHAVAEGAKNVLRLLSAAKAPDRKAVSEAQEKLTESNQKLGLLREALERRLGELPADHPKGRLLREELAAASSAAFSTRLAGPFPATHYSTLCKPAPLTGTLEVRVVGCRDLPETIPWNPTPSMGGPGTPDSRPPFLSRPARGLYSRSGSLSGRSSLKAEAENTSEVSTVLKLDNTVVGQTSWKPCGPNAWDQSFTLELERARELELAVFWRDQRGLCALKFLKLEDFLDNERHEVQLDMEPQGCLVAEVTFRNPVIERIPRLRRQKKIFSKQQGKAFQRARQMNIDVATWVRLLRRLIPNATGTGTFSPGASPGSEARTTGDISVEKLNLGTDSDSSPQKSSRDPPSSPSSLSSPIQESTAPELPSETQETPGPALCSPLRKSPLTLEDFKFLAVLGRGHFGKVLLSEFRPSGELFAIKALKKGDIVARDEVESLMCEKRILAAVTSAGHPFLVNLFGCFQTPEHVCFVMEYSAGGDLMLHIHSDVFSEPRAIFYSACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYVKIADFGLCKEGMGYGDRTSTFCGTPEFLAPEVLTDTSYTRAVDWWGLGVLLYEMLVGESPFPGDDEEEVFDSIVNDEVRYPRFLSAEAIGIMRRLLRRNPERRLGSSERDAEDVKKQPFFRTLGWEALLARRLPPPFVPTLSGRTDVSNFDEEFTGEAPTLSPPRDARPLTAAEQAAFLDFDFVAGGC |
| Enzyme Length | 942 |
| Uniprot Accession Number | Q16512 |
| Absorption | |
| Active Site | ACT_SITE 740; /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-774 (activation loop of the kinase domain) and Ser-916 (turn motif), need to be phosphorylated for its full activation. {ECO:0000269|PubMed:8571126, ECO:0000269|PubMed:9751706}. |
| Binding Site | BINDING 644; /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:18066052}; 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:18066052}; |
| 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. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. 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 (AR)-dependent transcription, by being recruited to AR 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. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 621..629; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Features | Active site (1); Alternative sequence (3); Beta strand (11); Binding site (1); Chain (1); Compositional bias (1); Domain (6); Helix (21); Initiator methionine (1); Modified residue (15); Mutagenesis (10); Natural variant (10); Nucleotide binding (1); Region (4); Sequence conflict (8); Site (3); Turn (8) |
| Keywords | 3D-structure;ATP-binding;Acetylation;Alternative splicing;Cell membrane;Chromatin regulator;Coiled coil;Cytoplasm;Endosome;Kinase;Membrane;Nucleotide-binding;Nucleus;Phosphoprotein;Reference proteome;Repeat;Serine/threonine-protein kinase;Transcription;Transcription regulation;Transferase;Ubl conjugation |
| Interact With | Q6UY14-3; Q9ULX6; Q6PJH3; P05067; P15289; Q14457; Q9H2G9; Q8WU43; Q8IW40; Q96M89-2; Q15834; Q8IV13; Q01850; Q86XR8-3; Q8IYX8-2; Q8NHQ1; A8MQ03; Q9NRI5-2; Q8WWB3; P26641; O00303; Q06547-2; Q08379; A6NEM1; P54257; Q96CS2; Q9NSC5; O75031; Q9UKT9; Q5TA45; Q8N5Z5; Q86T90; P19012; P08779; P08727; Q15323; O76011; Q92764; O76013-2; O76014; Q9BV99; Q9NYL2-1; P53778; O15344; Q9UJV3-2; Q8N108-16; Q8TD10; Q13064; Q5JR59-3; P07196; Q9NRD5; Q8ND90; P78424; P28070; Q96QF0-7; Q9UJW9; Q9H7B4; Q96R06; Q9Y2D8; Q9NZ72; O75558; A1L190; Q8WTV1; Q13077; Q12933; P14373; Q9BZW7; Q8IWV8-2; Q8N6Y0; P08670; Q8TF47; Q9UNY5; Q96MN9-2; Q9P0T4; Q9UGI0; A1JU68 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:9478917}. Nucleus {ECO:0000269|PubMed:12514133}. Endosome {ECO:0000269|PubMed:9478917}. Cell membrane {ECO:0000250|UniProtKB:Q63433}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q63433}. Cleavage furrow {ECO:0000269|PubMed:17332740}. Midbody {ECO:0000269|PubMed:17332740}. Note=Associates with chromatin in a ligand-dependent manner. Localization to endosomes is mediated via its interaction with RHOB. Association to the cell membrane is dependent on Ser-377 phosphorylation. Accumulates during telophase at the cleavage furrow and finally concentrates around the midbody in cytokinesis. {ECO:0000250|UniProtKB:Q63433, ECO:0000269|PubMed:17332740}. |
| Modified Residue | MOD_RES 2; /note="N-acetylalanine"; /evidence="ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22814378"; MOD_RES 69; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 205; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332"; MOD_RES 374; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q63433"; MOD_RES 448; /note="N6-acetyllysine"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES 533; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 537; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 540; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 559; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332"; MOD_RES 562; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"; MOD_RES 608; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 774; /note="Phosphothreonine; by PDPK1"; /evidence="ECO:0000269|PubMed:10792047"; MOD_RES 778; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:18220336"; MOD_RES 914; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:19690332"; MOD_RES 916; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" |
| Post Translational Modification | PTM: Autophosphorylated; preferably on serine. Phosphorylated during mitosis. {ECO:0000269|PubMed:10792047, ECO:0000269|PubMed:17332740}.; PTM: Activated by limited proteolysis with trypsin. {ECO:0000250}.; PTM: (Microbial infection) In case of infection, polyubiquitinated by the bacterial E3 ubiquitin-protein ligase SspH1, leading to its proteasomal degradation. {ECO:0000269|PubMed:24248594}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (2); X-ray crystallography (6) |
| Cross Reference PDB | 1CXZ; 1URF; 2RMK; 4NKG; 4OTD; 4OTG; 4OTH; 4OTI; |
| Mapped Pubmed ID | 10037681; 10467162; 10490598; 10508610; 10699464; 10753910; 10873388; 10873802; 10924361; 10958683; 11134534; 11756552; 11773441; 11803464; 11804587; 12221077; 12480817; 12761180; 12783890; 15003508; 15123640; 15791647; 15866170; 16002401; 16079795; 16189514; 16507994; 16603238; 16630611; 16636067; 16702231; 16762923; 17244649; 17301291; 17583407; 17721511; 18158243; 18218625; 18347018; 18429822; 18519042; 18713748; 18829452; 19427017; 19723632; 19913121; 20030946; 20101212; 20237496; 20460433; 20591975; 20628086; 20660154; 20711500; 21351730; 21516116; 21576392; 21699497; 21730051; 21749319; 21900206; 21988832; 22608513; 22790947; 22893700; 22939624; 22970203; 22992742; 23707487; 24114839; 24128008; 24189400; 25111382; 25416956; 25504435; 26296974; 27919031; 28875501; 29146911; 29358323; 30206226; 30742064; 31045890; 31105010; 31125460; 31871319; 31981797; 32127582; 7559638; 8107774; 8543060; 8617235; 8645157; 8662891; 8756646; 8798539; 8805223; 8816443; 9013646; 9111050; 9418861; 9535835; 9792683; 9822598; 9829970; 9843499; 9988689; |
| Motif | |
| Gene Encoded By | |
| Mass | 103,932 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=20.6 uM for HDAC5 {ECO:0000269|PubMed:20188095}; |
| Metal Binding | |
| Rhea ID | RHEA:17989; RHEA:46608 |
| Cross Reference Brenda | 2.7.11.13; |