Protein: Kinase suppressor of Ras 2 (hKSR2) (EC 2.7.11.1) (Q6VAB6)
Organism: Homo sapiens (Human)
Function: Location-regulated scaffold connecting MEK to RAF. Has very low protein kinase activity and can phosphorylate MAP2K1 at several Ser and Thr residues with very low efficiency (in vitro). Acts as MAP2K1/MEK1-dependent allosteric activator of BRAF; upon binding to MAP2K1/MEK1, dimerizes with BRAF and promotes BRAF-mediated phosphorylation of MAP2K1/MEK1. Interaction with BRAF enhances KSR2-mediated phosphorylation of MAP2K1 (in vitro). Blocks MAP3K8 kinase activity and MAP3K8-mediated signaling. Acts as a negative regulator of MAP3K3-mediated activation of ERK, JNK and NF-kappa-B pathways, inhibiting MAP3K3-mediated interleukin-8 production.
Subcellular location: Cytoplasm {ECO:0000250}. Membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
Sequence: MDEENMTKSEEQQPLSLQKALQQCELVQNMIDLSISNLEGLRTKCATSNDLTQKEIRTLESKLVKYFSRQLSCKKKVALQERNAELDGFPQLRHWFRIVDVRKEVLEEISPGQLSLEDLLEMTDEQVCETVEKYGANREECARLNASLSCLRNVHMSGGNLSKQDWTIQWPTTETGKENNPVCPPEPTPWIRTHLSQSPRVPSKCVQHYCHTSPTPGAPVYTHVDRLTVDAYPGLCPPPPLESGHRSLPPSPRQRHAVRTPPRTPNIVTTVTPPGTPPMRKKNKLKPPGTPPPSSRKLIHLIPGFTALHRSKSHEFQLGHRVDEAHTPKAKKKSKPLNLKIHSSVGSCENIPSQQRSPLLSERSLRSFFVGHAPFLPSTPPVHTEANFSANTLSVPRWSPQIPRRDLGNSIKHRFSTKYWMSQTCTVCGKGMLFGLKCKNCKLKCHNKCTKEAPPCHLLIIHRGDPARLVRTESVPCDINNPLRKPPRYSDLHISQTLPKTNKINKDHIPVPYQPDSSSNPSSTTSSTPSSPAPPLPPSATPPSPLHPSPQCTRQQKNFNLPASHYYKYKQQFIFPDVVPVPETPTRAPQVILHPVTSNPILEGNPLLQIEVEPTSENEEVHDEAEESEDDFEEMNLSLLSARSFPRKASQTSIFLQEWDIPFEQLEIGELIGKGRFGQVYHGRWHGEVAIRLIDIERDNEDQLKAFKREVMAYRQTRHENVVLFMGACMSPPHLAIITSLCKGRTLYSVVRDAKIVLDVNKTRQIAQEIVKGMGYLHAKGILHKDLKSKNVFYDNGKVVITDFGLFSISGVLQAGRREDKLRIQNGWLCHLAPEIIRQLSPDTEEDKLPFSKHSDVFALGTIWYELHAREWPFKTQPAEAIIWQMGTGMKPNLSQIGMGKEISDILLFCWAFEQEERPTFTKLMDMLEKLPKRNRRLSHPGHFWKSAEL
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [642-928]
- IPR046349: C1-like domain superfamily (homologous_superfamily) [388-456]
- IPR046933: Kinase suppressor RAS 1, N-terminal helical hairpin superfamily (homologous_superfamily) [7-84]
- IPR050167: Serine/threonine-protein kinase (family) [516-930]
- IPR046861: Kinase suppressor RAS 1, N-terminal helical hairpin (domain) [24-76]
- IPR013761: Sterile alpha motif/pointed domain superfamily (homologous_superfamily) [85-155]
- IPR008271: Serine/threonine-protein kinase, active site (active_site) [782-794]
- IPR002219: Protein kinase C-like, phorbol ester/diacylglycerol-binding domain (domain) [411-456]
- IPR025561: Kinase suppressor of RAS, SAM-like domain (domain) [90-152]
- IPR001245: Serine-threonine/tyrosine-protein kinase, catalytic domain (domain) [666-928]
- IPR000719: Protein kinase domain (domain) [666-931]
Interaction partners: - Dual specificity mitogen-activated protein kinase kinase 1
- Kinase suppressor of Ras 1
- BRCA1-associated protein
- Serine/threonine-protein kinase B-raf
- Dual specificity mitogen-activated protein kinase kinase 2
- Mitogen-activated protein kinase 3
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0036094 (small molecule binding), GO:1901363 (heterocyclic compound binding), GO:0043167 (ion binding), GO:0097159 (organic cyclic compound binding), GO:0097367 (carbohydrate derivative binding), GO:0005515 (protein binding), GO:1901265 (nucleoside phosphate binding), GO:0043168 (anion binding), GO:0071889 (14-3-3 protein binding), GO:0000166 (nucleotide binding), GO:0032553 (ribonucleotide binding), GO:0035639 (purine ribonucleoside triphosphate binding), GO:0032555 (purine ribonucleotide binding), GO:0017076 (purine nucleotide binding), GO:0005524 (ATP binding), GO:0032559 (adenyl ribonucleotide binding), GO:0030554 (adenyl nucleotide binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0023052 (signaling), GO:0023056 (positive regulation of signaling), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0051240 (positive regulation of multicellular organismal process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0051239 (regulation of multicellular organismal process), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0048522 (positive regulation of cellular process), GO:0009967 (positive regulation of signal transduction), GO:0120161 (regulation of cold-induced thermogenesis), GO:0035556 (intracellular signal transduction), GO:0010646 (regulation of cell communication), GO:0009966 (regulation of signal transduction), GO:0010647 (positive regulation of cell communication), GO:0120162 (positive regulation of cold-induced thermogenesis), GO:1902533 (positive regulation of intracellular signal transduction), GO:1902531 (regulation of intracellular signal transduction), GO:0019932 (second-messenger-mediated signaling), GO:0043408 (regulation of MAPK cascade), GO:0043410 (positive regulation of MAPK cascade), GO:0019722 (calcium-mediated signaling)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0071944 (cell periphery), GO:0098796 (membrane protein complex), GO:0012505 (endomembrane system), GO:0098797 (plasma membrane protein complex), GO:0005783 (endoplasmic reticulum), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0043231 (intracellular membrane-bounded organelle)