Reactome | UniProt:Q16513 PKN2

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UniProt:Q16513 PKN2 Show undefined attributes

chain	chain:1-984
checksum	687EC417A0F51C1D
comment	FUNCTION PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Involved in the negative regulation of ciliogenesis (PubMed:27104747).FUNCTION (Microbial infection) Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)ACTIVITY REGULATION Kinase activity is activated upon binding to GTP-bound Rhoa/Rac1 GTPases. Activated by caspase-3 (CASP3) cleavage during apoptosis. Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids. Two specific sites, Thr-816 (activation loop of the kinase domain) and Thr-958 (turn motif), need to be phosphorylated for its full activation.BIOPHYSICOCHEMICAL PROPERTIES Interacts (via the REM repeats) with RHOA (GTP-bound form preferentially) and interacts (via the REM repeats) with RAC1 (GTP-bound form preferentially); the interactions induce its autophosphorylation (PubMed:20974804, PubMed:9121475). Interacts with RHOC (PubMed:20974804). Interacts with NCK1 and NCK2 (PubMed:10026169). Interacts with NCK1 (via SH3 domains) (By similarity). Interacts with CD44 (PubMed:15123640). Interacts (via C-terminal kinase domain) with PDPK1; the interaction stimulates PDPK1 kinase activity (PubMed:10226025, PubMed:10792047, PubMed:11781095, PubMed:18835241). Interacts with MAP3K2; the interaction activates PRK2 kinase activity in a MAP3K2-independent kinase activity (PubMed:10818102). Interacts (via C-terminal domain) with AKT1; the interaction occurs with the C-terminal cleavage product of PRK2 in apoptotic cells (PubMed:10926925). Interacts (via C-terminus) with PTPN13 (via PDZ 3 domain) (PubMed:11356191). Interacts with CDK10 (PubMed:27104747).SUBUNIT (Microbial infection) Interacts with HCV NS5B (via N-terminal finger domain).INTERACTION Colocalizes with PTPN13 in lamellipodia-like structures, regions of large actin turnover. Accumulates during telophase at the cleavage furrow and concentrates finally around the midbody in cytokinesis. Recruited to nascent cell-cell contacts at the apical surface of cells. In the course of viral infection, colocalizes with HCV NS5B at perinuclear region in the cytoplasm.ALTERNATIVE PRODUCTS Ubiquitous. Expressed in numerous tumor cell lines, especially in bladder tumor cells.INDUCTION Up-regulated during keratinocyte differentiation.DOMAIN The N-terminal regioninterferes with the interaction between AKT1 and the C-terminal regionof PKN2.DOMAIN The C1 domain does not bind the diacylglycerol (DAG).DOMAIN The apoptotic C-terminal cleavage product inhibits EGF-induced kinase activity of AKT1 phosphorylation at 'Thr-308' and 'Ser-473' sites, PDPK1 autophosphorylation and kinases PRKCD and PRKCZ phosphorylations.PTM Autophosphorylated. Phosphorylated during mitosis. Phosphorylated by CDK10 (PubMed:27104747).PTM Activated by limited proteolysis with trypsin (By similarity). Proteolytically cleaved by caspase-3 during the induction of apoptotic cell death.SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
crossReference	[DatabaseIdentifier:12388985] RefSeq:NP_001307636.1 [DatabaseIdentifier:12818559] ZINC - World Drugs:PKN2_HUMAN [DatabaseIdentifier:12815672] ZINC target:Q16513 [DatabaseIdentifier:12812309] ZINC - Substances:PKN2_HUMAN [DatabaseIdentifier:12810529] ZINC - Predictions - Purchasable:PKN2_HUMAN [DatabaseIdentifier:12807003] ZINC - Investigational:PKN2_HUMAN [DatabaseIdentifier:12805920] ZINC - FDA approved:PKN2_HUMAN [DatabaseIdentifier:12804841] ZINC - Biogenic:PKN2_HUMAN [DatabaseIdentifier:12388989] RefSeq:NP_001307638.1 [DatabaseIdentifier:12388988] RefSeq:XP_011540074.1 [DatabaseIdentifier:12388986] RefSeq:NP_001307637.1 [DatabaseIdentifier:11481969] ENSEMBL:ENSG00000065243 [DatabaseIdentifier:11583322] ENSEMBL:ENSP00000359544 [DatabaseIdentifier:11583321] ENSEMBL:ENSP00000359552 [DatabaseIdentifier:11706020] ENSEMBL:ENST00000370513 [DatabaseIdentifier:11706021] ENSEMBL:ENST00000370521 [DatabaseIdentifier:11780952] Guide to Pharmacology - Targets:1521 [DatabaseIdentifier:11794397] GeneCards:PKN2 [DatabaseIdentifier:11810344] GlyGen:Q16513 [DatabaseIdentifier:11831413] HMDB Protein:HMDBP01198 [DatabaseIdentifier:11847370] HPA:ENSG00000065243-PKN2 [DatabaseIdentifier:11850277] IntEnz:2.7.11.13 [DatabaseIdentifier:12132045] OpenTargets:ENSG00000065243 [DatabaseIdentifier:12213799] PDB:6GBE [DatabaseIdentifier:12181734] PDB:4RRV [DatabaseIdentifier:12221997] PDB:6CCY [DatabaseIdentifier:12221996] PDB:4CRS [DatabaseIdentifier:12275181] PRO:Q16513 [DatabaseIdentifier:12292229] Pharos - Targets:Q16513 [DatabaseIdentifier:12388990] RefSeq:XP_054193640.1 [DatabaseIdentifier:12388987] RefSeq:NP_006247.1
databaseName	UniProt
dbId	61784
description	recommendedName: Serine/threonine-protein kinase N2 ecNumber: 2.7.11.13 alternativeName: PKN gamma alternativeName: Protein kinase C-like 2 alternativeName: Protein-kinase C-related kinase 2
displayName	UniProt:Q16513 PKN2
geneName	PKN2 PRK2 PRKCL2
identifier	Q16513
isSequenceChanged	false
keyword	3D-structure Acetylation Alternative splicing Apoptosis ATP-binding Cell adhesion Cell cycle Cell division Cell junction Cell projection Cilium biogenesis/degradation Coiled coil Cytoplasm Cytoskeleton Host-virus interaction Kinase Membrane Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Serine/threonine-protein kinase Transcription Transcription regulation Transferase
modified	[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType	Protein
name	PKN2
otherIdentifier	11724840_at 11724841_a_at 11758207_s_at 16666896 199_s_at 210969_3p_at 210969_PM_at 210969_at 212628_PM_at 212628_at 212629_PM_s_at 212629_s_at 2345621 2345622 2345623 2345624 2345633 2345634 2345642 2345647 2345648 2345649 2345650 2345651 2345652 2345655 2345656 2345657 2345665 2345666 2345667 2345668 2345669 2345670 2345671 2345672 2345673 2345675 2345676 2345677 2345680 2345687 2345689 2345690 2345691 2345693 2345697 2345698 2345699 2345700 2345701 2345702 2345703 2345704 2345705 2345706 2345708 2345711 2345713 2345715 3140847 3590502 36835_at 54121_at 55492_at 5586 7902822 A_14_P100308 A_14_P105176 A_14_P113677 A_23_P23227 A_24_P387869 A_32_P226918 A_33_P3242829 A_33_P3242833 GE59090 GO:0000166 GO:0003723 GO:0003824 GO:0004672 GO:0004674 GO:0004697 GO:0004713 GO:0005515 GO:0005524 GO:0005634 GO:0005654 GO:0005737 GO:0005813 GO:0005815 GO:0005829 GO:0005856 GO:0005886 GO:0006468 GO:0006915 GO:0007155 GO:0007165 GO:0010631 GO:0016020 GO:0016301 GO:0016604 GO:0016740 GO:0030027 GO:0030030 GO:0030496 GO:0031267 GO:0032154 GO:0032467 GO:0032991 GO:0034330 GO:0035556 GO:0042826 GO:0042995 GO:0043296 GO:0043297 GO:0045070 GO:0045111 GO:0045296 GO:0045931 GO:0048471 GO:0048870 GO:0051301 GO:0070063 GO:0070161 GO:0097700 GO:0106310 GO:0140096 GO:2000145 HMNXSV003045848 HMNXSV003048860 Hs.69171.2.S1_3p_a_at Hs.69171.2.S2_3p_at ILMN_1706825 PH_hs_0004094 TC01000831.hg U33052_s_at g6650823_RC_3p_a_at g6650823_RC_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-5623612] PKN2 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5623652] p-T816-PKN2 [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000065243] ENSEMBL:ENSG00000065243 PKN2 [ReferenceDNASequence:12693819] UCSC:Q16513 PKN2 [ReferenceDNASequence:11347410] BioGPS Gene:5586 PKN2 [ReferenceDNASequence:11393216] COSMIC - genes:PKN2 PKN2 [ReferenceDNASequence:11423137] CTD Gene:5586 PKN2 [ReferenceDNASequence:11429153] dbSNP Gene:5586 PKN2 [ReferenceDNASequence:11826093] HGNC:9406 PKN2 [ReferenceDNASequence:11887437] KEGG:hsa:5586 PKN2 [ReferenceDNASequence:11977199] Monarch:5586 PKN2 [ReferenceDNASequence:12061292] NCBI Gene:5586 PKN2 [ReferenceDNASequence:12116440] OMIM:602549 PKN2
referenceTranscript	[ReferenceRNASequence:12570770] RefSeq:NM_001320707.2 PKN2 [ReferenceRNASequence:12570775] RefSeq:NM_006256.4 PKN2 [ReferenceRNASequence:12570771] RefSeq:NM_001320708.2 PKN2 [ReferenceRNASequence:12570774] RefSeq:XM_011541772.3 PKN2 [ReferenceRNASequence:12570773] RefSeq:NM_001320709.2 PKN2 [ReferenceRNASequence:12570772] RefSeq:XM_054337665.1 PKN2
schemaClass	ReferenceGeneProduct
secondaryIdentifier	PKN2_HUMAN B4DQ21 B4DTP5 B4DVG1 D3DT24 Q08AF4 Q9H1W4
sequenceLength	984
species	[Species:48887] Homo sapiens
stId	uniprot:Q16513
url	http://purl.uniprot.org/uniprot/Q16513

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-5623612] PKN2 [cytosol] [EntityWithAccessionedSequence:R-HSA-5623652] p-T816-PKN2 [cytosol]
(referenceSequence)	[ModifiedResidue:5623653] O-phospho-L-threonine at 816
(interactor)	[UndirectedInteraction:11138691] UniProt:P37173 <-> UniProt:Q16513 (IntAct) [UndirectedInteraction:11190069] UniProt:P41208 <-> UniProt:Q16513 (IntAct) [UndirectedInteraction:11202549] UniProt:O76075 <-> UniProt:Q16513 (IntAct) [UndirectedInteraction:11204541] UniProt:Q8TDQ0 <-> UniProt:Q16513 (IntAct) [UndirectedInteraction:11257323] UniProt:P61586 <-> UniProt:Q16513 (IntAct) [UndirectedInteraction:11280903] UniProt:Q16513 <-> UniProt:Q12923 (IntAct) [UndirectedInteraction:11280907] UniProt:Q16513 <-> UniProt:O92972-PRO_0000278753 (IntAct) [UndirectedInteraction:11280909] UniProt:Q16513 <-> UniProt:Q12798 (IntAct) [UndirectedInteraction:11280911] UniProt:Q16513 <-> UniProt:Q9UL42 (IntAct) [UndirectedInteraction:11280913] UniProt:Q16513 <-> UniProt:Q9HD26 (IntAct) [UndirectedInteraction:11280917] UniProt:Q16513 <-> UniProt:Q68DX3 (IntAct) [UndirectedInteraction:11280919] UniProt:Q16513 <-> UniProt:Q9BV97 (IntAct) [UndirectedInteraction:11280923] UniProt:Q16513 <-> UniProt:P0DN37 (IntAct) [UndirectedInteraction:11280925] UniProt:Q16513 <-> UniProt:P47929 (IntAct)

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