Reactome | UniProt:Q8IVT5 KSR1

Schema > ReferenceGeneProduct > Entries

UniProt:Q8IVT5 KSR1 Show undefined attributes

chain	chain:1-923
checksum	61BF0F1598349540
comment	FUNCTION Part of a multiprotein signaling complex which promotes phosphorylation of Raf family members and activation of downstream MAP kinases (By similarity). Independently of its kinase activity, acts as MAP2K1/MEK1 and MAP2K2/MEK2-dependent allosteric activator of BRAF; upon binding to MAP2K1/MEK1 or MAP2K2/MEK2, dimerizes with BRAF and promotes BRAF-mediated phosphorylation of MAP2K1/MEK1 and/or MAP2K2/MEK2 (PubMed:29433126). Promotes activation of MAPK1 and/or MAPK3, both in response to EGF and to cAMP (By similarity). Its kinase activity is unsure (By similarity). Some protein kinase activity has been detected in vitro, however the physiological relevance of this activity is unknown (By similarity).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(+)SUBUNIT Homodimer (PubMed:29433126). Heterodimerizes (via N-terminus) with BRAF (via N-terminus) in a MAP2K1/MEK1 or MAP2K2/MEK2-dependent manner (PubMed:29433126). Interacts with MAP2K1/MEK1 and MAP2K2/MEK2 (PubMed:10409742, PubMed:29433126). Binding to MAP2K1/MEK1 releases the intramolecular inhibitory interaction between KSR1 N-terminus and kinase domains which is required for the subsequent RSK1 dimerization with BRAF (PubMed:29433126). Identified in a complex with AKAP13, MAP2K1 and BRAF (By similarity). Interacts with AKAP13 and BRAF (PubMed:21102438). Interacts with RAF and MAPK/ERK, in a Ras-dependent manner (By similarity). Interacts with 14-3-3 proteins including YWHAB (By similarity). Interacts with HSP90AA1/HSP90, YWHAE/14-3-3 and CDC37 (PubMed:10409742, PubMed:29433126). The binding of 14-3-3 proteins to phosphorylated KSR1 prevents the membrane localization (By similarity). Interacts with MARK3/C-TAK1 (PubMed:12941695). Interacts with PPP2R1A and PPP2CA (By similarity). Interacts with isoform 1 of VRK2 (PubMed:20679487).INTERACTION In unstimulated cells, where the phosphorylated form is bound to a 14-3-3 protein, sequestration in the cytoplasm occurs. Following growth factor treatment, the protein is free for membrane translocation, and it moves from the cytoplasm to the cell periphery.ALTERNATIVE PRODUCTS The protein kinase domain is predicted to be catalytically inactive. The domain is sufficient for KSR1 and KSR1-mediated MAP2K1 and MAP2K2 membrane localization. The domain is required but not sufficient for MAP kinase-mediated inhibition of ELK1 phosphorylation (PubMed:10409742).DOMAIN The N-terminal region mediates interaction with BRAF (PubMed:29433126). Also mediates membrane localization (By similarity).PTM Phosphorylated on Ser-311 and, to a higher extent, on Ser-406 by MARK3. Dephosphorylated on Ser-406 by PPP2CA. In resting cells, phosphorylated KSR1 is cytoplasmic and in stimulated cells, dephosphorylated KSR1 is membrane-associated. Phosphorylated by PKA at Ser-888. Phosphorylation at Ser-888 is required for cAMP-dependent activation of MAPK1 and/or MAPK3 (By similarity).SIMILARITY Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.CAUTION Although it belongs to the protein kinase superfamily, the ATP-binding motif VAIK has an arginine instead of a lysine residue suggesting that KSR1 cannot bind ATP and therefore lacks protein kinase activity. However, KSR1 is capable of binding ATP (PubMed:29433126). Has protein kinase activity towards MAP2K1 in the presence of RAF1/c-RAF in vitro (By similarity).
created	[InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
crossReference	[DatabaseIdentifier:11470551] ENSEMBL:ENSG00000141068 [DatabaseIdentifier:11567445] ENSEMBL:ENSP00000381958 [DatabaseIdentifier:11690144] ENSEMBL:ENST00000398988 [DatabaseIdentifier:11779801] Guide to Pharmacology - Targets:2051 [DatabaseIdentifier:11786685] GeneCards:KSR1 [DatabaseIdentifier:11830220] HMDB Protein:HMDBP10939 [DatabaseIdentifier:11839764] HPA:ENSG00000141068-KSR1 [DatabaseIdentifier:12124292] OpenTargets:ENSG00000141068 [DatabaseIdentifier:12148864] PDB:5VYK [DatabaseIdentifier:12155369] PDB:9AXH [DatabaseIdentifier:12172032] PDB:7JV1 [DatabaseIdentifier:12172035] PDB:7JUY [DatabaseIdentifier:12172033] PDB:7JV0 [DatabaseIdentifier:12172036] PDB:7JUW [DatabaseIdentifier:12172034] PDB:7JUX [DatabaseIdentifier:12172031] PDB:7JUZ [DatabaseIdentifier:12263259] PRO:Q8IVT5 [DatabaseIdentifier:12284604] Pharos - Targets:Q8IVT5
databaseName	UniProt
dbId	234680
description	recommendedName: Kinase suppressor of Ras 1 ecNumber evidence="1"2.7.11.1
displayName	UniProt:Q8IVT5 KSR1
geneName	KSR1 KSR
identifier	Q8IVT5
isSequenceChanged	false
keyword	3D-structure Alternative splicing ATP-binding Cell membrane Cell projection Cytoplasm Endoplasmic reticulum Kinase Membrane Metal-binding Nucleotide-binding Phosphoprotein Proteomics identification Reference proteome Serine/threonine-protein kinase Transferase Zinc Zinc-finger
modified	[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType	Protein
name	KSR1
otherIdentifier	11740384_a_at 16832350 1716_at 213767_PM_at 213767_at 213769_PM_at 213769_at 235252_PM_at 235252_at 3005002 3715197 3715198 3715200 3715203 3715211 3715215 3715219 3715220 3715222 3715223 3715226 3715227 3715228 3715229 3715231 3715232 3715234 3715235 3715236 3715237 3715239 3715242 3715243 3715244 3715245 3715246 3715247 3715248 3715249 3715250 3715251 3715252 3715253 3715254 3715257 3715259 3715260 3715261 3715262 3715263 3715264 3715265 3715266 3715267 3715272 3715273 3715275 8005785 80554_s_at 84487_at 8844 92089_at A_14_P114125 A_23_P207774 A_24_P255483 A_24_P911112 A_32_P66091 GE80370 GE87872 GO:0000165 GO:0000166 GO:0003824 GO:0004672 GO:0004674 GO:0005078 GO:0005515 GO:0005524 GO:0005737 GO:0005783 GO:0005789 GO:0005829 GO:0005886 GO:0006468 GO:0007265 GO:0008270 GO:0016020 GO:0016301 GO:0016740 GO:0019901 GO:0031434 GO:0032587 GO:0032991 GO:0042127 GO:0042995 GO:0043405 GO:0043410 GO:0046872 GO:0051087 GO:0051879 GO:0060090 GO:0071889 GO:0106310 GO:0140096 HMNXSV003005518 HMNXSV003015816 HMNXSV003023535 Hs.152094.0.A1_3p_at Hs.152094.0.A2_3p_at Hs.169061.0.A1_3p_at ILMN_1754798 PH_hs_0023378 TC17000311.hg U43586_at p26022
physicalEntity	[EntityWithAccessionedSequence:R-HSA-5672656] p-S311,Y602 KSR1 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5672659] p-S311,Y602 KSR1 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5672652] p-S311 KSR1 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5672587] KSR1 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5672654] p-S311,S406 KSR1 [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000141068] ENSEMBL:ENSG00000141068 KSR1 [ReferenceDNASequence:12685396] UCSC:Q8IVT5 KSR1 [ReferenceDNASequence:11335528] BioGPS Gene:8844 KSR1 [ReferenceDNASequence:11392516] COSMIC - genes:KSR1 KSR1 [ReferenceDNASequence:11411927] CTD Gene:8844 KSR1 [ReferenceDNASequence:11428318] dbSNP Gene:8844 KSR1 [ReferenceDNASequence:11818324] HGNC:6465 KSR1 [ReferenceDNASequence:11876722] KEGG:hsa:8844 KSR1 [ReferenceDNASequence:11965317] Monarch:8844 KSR1 [ReferenceDNASequence:12049410] NCBI Gene:8844 KSR1 [ReferenceDNASequence:12109713] OMIM:601132 KSR1
referenceTranscript	[ReferenceRNASequence:12545791] RefSeq:XM_054317665.1 KSR1 [ReferenceRNASequence:12545787] RefSeq:NM_014238.2 KSR1 [ReferenceRNASequence:12545789] RefSeq:XM_011525429.3 KSR1 [ReferenceRNASequence:12545790] RefSeq:XM_047436987.1 KSR1 [ReferenceRNASequence:12545788] RefSeq:XM_054317669.1 KSR1
schemaClass	ReferenceGeneProduct
secondaryIdentifier	KSR1_HUMAN F8WEA9 H7BYU0 Q13476
sequenceLength	923
species	[Species:48887] Homo sapiens
stId	uniprot:Q8IVT5
url	http://purl.uniprot.org/uniprot/Q8IVT5

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-5672656] p-S311,Y602 KSR1 [cytosol] [EntityWithAccessionedSequence:R-HSA-5672659] p-S311,Y602 KSR1 [plasma membrane] [EntityWithAccessionedSequence:R-HSA-5672652] p-S311 KSR1 [cytosol] [EntityWithAccessionedSequence:R-HSA-5672587] KSR1 [cytosol] [EntityWithAccessionedSequence:R-HSA-5672654] p-S311,S406 KSR1 [cytosol]
(referenceSequence)	[ModifiedResidue:5672657] O4'-phospho-L-tyrosine at 602 [ModifiedResidue:5672650] O-phospho-L-serine at 311 [ModifiedResidue:5672655] O-phospho-L-serine at 406
(interactor)	[UndirectedInteraction:11139109] UniProt:P31946 <-> UniProt:Q8IVT5 (IntAct) [UndirectedInteraction:11202975] UniProt:P31947 <-> UniProt:Q8IVT5 (IntAct) [UndirectedInteraction:11208833] UniProt:P63151 <-> UniProt:Q8IVT5 (IntAct) [UndirectedInteraction:11230337] UniProt:P36507 <-> UniProt:Q8IVT5 (IntAct) [UndirectedInteraction:11235643] UniProt:P04049 <-> UniProt:Q8IVT5 (IntAct) [UndirectedInteraction:11243393] UniProt:P61981 <-> UniProt:Q8IVT5 (IntAct) [UndirectedInteraction:11264751] UniProt:P62258 <-> UniProt:Q8IVT5 (IntAct) [UndirectedInteraction:11285407] UniProt:Q02750 <-> UniProt:Q8IVT5 (IntAct) [UndirectedInteraction:11288213] UniProt:P63104 <-> UniProt:Q8IVT5 (IntAct)

Cite Us!