[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH HSPCA; YWHAB; CDC37 AND MAP2K. DOI=10.1016/0092-8674(95)90204-X; PubMed=8521512 [NCBI, ExPASy, EBI, Israel, Japan] Therrien M., Chang H.C., Solomon N.M., Karim F.D., Wassarman D.A., Rubin G.M.; "KSR, a novel protein kinase required for RAS signal transduction."; Cell 83:879-888(1995).
[2]	NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2), INTERACTION WITH MAPK, MUTAGENESIS OF GLY-572; ARG-589; ARG-615; ASP-700 AND CYS-809, AND TISSUE SPECIFICITY. TISSUE=Brain; DOI=10.1128/MCB.20.15.5529-5539.2000; PubMed=10891492 [NCBI, ExPASy, EBI, Israel, Japan] Mueller J., Cacace A.M., Lyons W.E., McGill C.B., Morrison D.K.; "Identification of B-KSR1, a novel brain-specific isoform of KSR1 that functions in neuronal signaling."; Mol. Cell. Biol. 20:5529-5539(2000).
[3]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Pelan S.; Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
[4]	NUCLEOTIDE SEQUENCE [MRNA] OF 49-474 (ISOFORMS 1/2). STRAIN=BALB/c; DOI=10.1007/BF00364794; PubMed=7626882 [NCBI, ExPASy, EBI, Israel, Japan] Nehls M., Luno K., Schorpp M., Pfeifer D., Krause S., Matysiak-Scholze U., Dierbach H., Boehm T.; "YAC/P1 contigs defining the location of 56 microsatellite markers and several genes across a 3.4cM interval on mouse chromosome 11."; Mamm. Genome 6:321-331(1995).
[5]	INTERACTION WITH MARK3, PHOSPHORYLATION AT SER-297 AND SER-392, AND MUTAGENESIS OF SER-297; SER-392; ILE-397 AND VAL-401. DOI=10.1016/S1097-2765(01)00383-5; PubMed=11741534 [NCBI, ExPASy, EBI, Israel, Japan] Mueller J., Ory S., Copeland T., Piwnica-Worms H., Morrison D.K.; "C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1."; Mol. Cell 8:983-993(2001).
[6]	INTERACTION WITH PPP2R1A AND PPP2CA, AND DEPHOSPHORYLATION BY PPP2CA. DOI=10.1016/S0960-9822(03)00535-9; PubMed=12932319 [NCBI, ExPASy, EBI, Israel, Japan] Ory S., Zhou M., Conrads T.P., Veenstra T.D., Morrison D.K.; "Protein phosphatase 2A positively regulates Ras signaling by dephosphorylating KSR1 and Raf-1 on critical 14-3-3 binding sites."; Curr. Biol. 13:1356-1364(2003).
[7]	REVIEW. DOI=10.1016/S0960-9822(02)00831-X; PubMed=12007434 [NCBI, ExPASy, EBI, Israel, Japan] Roy F., Therrien M.; "MAP kinase module: the Ksr connection."; Curr. Biol. 12:R325-R327(2002).
[8]	STRUCTURE BY NMR OF 331-378 IN COMPLEX WITH ZINC. DOI=10.1006/jmbi.2001.5263; PubMed=11786023 [NCBI, ExPASy, EBI, Israel, Japan] Zhou M., Horita D.A., Waugh D.S., Byrd R.A., Morrison D.K.; "Solution structure and functional analysis of the cysteine-rich C1 domain of kinase suppressor of Ras (KSR)."; J. Mol. Biol. 315:435-446(2002).

Comments

FUNCTION: Location-regulated scaffolding protein connecting MEK to RAF. Promotes MEK and RAF phosphorylation and activity through assembly of an activated signaling complex. By itself, it has no demonstrated kinase activity.
SUBUNIT: Interacts with HSPCA/HSP90, YWHAB/14-3-3, CDC37, MAP2K/MEK, MARK3, PPP2R1A and PPP2CA. Also interacts with RAF and MAPK/ERK, in a Ras-dependent manner. The binding of 14-3-3 proteins to phosphorylated KSR prevents the membrane localization.
INTERACTION:
P15531:NME1 (xeno); NbExp=2; IntAct=EBI-1536336, EBI-741141;
SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein. Note=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: 2 named isoforms [FASTA] produced by alternative splicing.

Name	1
Isoform ID	Q61097-1
This is the isoform sequence displayed in this entry.

Name	2
Synonyms	B-KSR1
Isoform ID	Q61097-2
Features which should be applied to build the isoform sequence: VSP_012232, VSP_012233.

TISSUE SPECIFICITY: Expressed in brain, spleen and testis. Isoform 1 is highly expressed spleen and weakly in testis, and isoform 2 is highly expressed in brain and weakly in testis.
PTM: Phosphorylated on Ser-297 and, to a higher extent, on Ser-392 by MARK3. Dephosphorylated on Ser-392 by PPP2CA. Phosphorylated KSR is cytoplasmic and dephosphorylated KSR is membrane-associated.
SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger.
SIMILARITY: Contains 1 protein kinase domain.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

U43585; AAC52382.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL592551; CAI24047.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X81634; CAA57288.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

I48379; I48379.

NP_038599.1; -.

3D structure databases

PDB

1KBE; NMR; -; A=331-378.	[ExPASy / RCSB / EBI]
1KBF; NMR; -; A=331-378.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1KBE; -.
1KBF; -.

ModBase

Q61097.

Protein-protein interaction databases

IntAct

Q61097; -.

PTM databases

PhosphoSite

Q61097; -.

Organism-specific databases

MGI

MGI:105051; Ksr1.

GeneLynx

Ksr1; Mus musculus.

Gene expression databases

ArrayExpress

Q61097; -.

CleanEx

MM_KSR1; -.

GermOnline

ENSMUSG00000018334; Mus musculus.

Ontologies

GO:0005515;	Molecular function: protein binding (inferred from physical interaction from IntAct).
QuickGo view.

Family and domain databases

InterPro

IPR002219; DAG_PE_bd.
IPR000719; Prot_kinase_core.
IPR008271; Ser_thr_pkin_AS.
IPR001245; Tyr_pkinase.
Graphical view of domain structure.

Pfam

PF00130; C1_1; 1.
PF07714; Pkinase_Tyr; 1.
Pfam graphical view of domain structure.

ProDom

PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00109; C1; 1.
SMART graphical view of domain structure.

PROSITE

PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
PS00479; ZF_DAG_PE_1; 1.
PS50081; ZF_DAG_PE_2; 1.
PROSITE graphical view of domain structure (profiles).

BLOCKS

Q61097.

Genome annotation databases

Ensembl

ENSMUSG00000018334; Mus musculus. [Contig view]

GeneID

16706; -.

KEGG

mmu:16706; -.

Phylogenomic databases

HOGENOM

Q61097; -.

HOVERGEN

Q61097; -.

Other

Ksr1; Mus musculus.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Alternative splicing; Cytoplasm; Membrane; Metal-binding; Phorbol-ester binding; Phosphoprotein; Zinc; Zinc-finger.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 873`	`873`	`Kinase suppressor of Ras 1.`	`PRO_0000086230`
`DOMAIN`	`563 833`	`271`	`Protein kinase.`
`ZN_FING`	`333 377`	`45`	`Phorbol-ester/DAG-type.`
`COMPBIAS`	`17 21`	`5`	`Poly-Gly.`
`COMPBIAS`	`275 278`	`4`	`Poly-Pro.`
`COMPBIAS`	`429 491`	`63`	`Ser-rich.`
`METAL`	`334 334`		`Zinc 1.`
`METAL`	`346 346`		`Zinc 2.`
`METAL`	`349 349`		`Zinc 2.`
`METAL`	`359 359`		`Zinc 1.`
`METAL`	`362 362`		`Zinc 1.`
`METAL`	`367 367`		`Zinc 2.`
`METAL`	`370 370`		`Zinc 2.`
`METAL`	`377 377`		`Zinc 1.`
`MOD_RES`	`256 256`		`Phosphothreonine (By similarity).`
`MOD_RES`	`260 260`		`Phosphothreonine (By similarity).`
`MOD_RES`	`297 297`		`Phosphoserine; by MARK3.`
`MOD_RES`	`320 320`		`Phosphoserine (By similarity).`
`MOD_RES`	`392 392`		`Phosphoserine; by MARK3.`
`VAR_SEQ`	`474 474`		`P -> PAAYFIHHRQQFIFP (in isoform 2).`	`VSP_012232`
`VAR_SEQ`	`848 873`		`DINSSKVMPRFERFGLGTLESGNPKM -> EL (in isoform 2).`	`VSP_012233`
`MUTAGEN`	`297 297`		`S->A: Constitutive targeting to the plasma membrane; when associated with A-392.`
`MUTAGEN`	`392 392`		`S->A: Constitutive targeting to the plasma membrane; when associated with A-297.`
`MUTAGEN`	`397 397`		`I->A: Decrease in MARK3 binding; when associated with A-401.`
`MUTAGEN`	`401 401`		`V->A: Decrease in MARK3 binding; when associated with A-397.`
`MUTAGEN`	`572 572`		`G->E: Decrease in MEK binding.`
`MUTAGEN`	`589 589`		`R->M: Almost no MEK binding.`
`MUTAGEN`	`615 615`		`R->H: Decrease in MEK binding.`
`MUTAGEN`	`700 700`		`D->V: Decrease in MEK binding.`
`MUTAGEN`	`809 809`		`C->Y: No MEK binding.`
`STRAND`	`336 339`	`4`
`STRAND`	`347 349`	`3`
`STRAND`	`356 359`	`4`
`TURN`	`360 363`	`4`
`STRAND`	`364 369`	`6`
`TURN`	`371 373`	`3`

Sequence information

Length: 873 AA [This is the length of the unprocessed precursor]

Molecular weight: 96755 Da [This is the MW of the unprocessed precursor]

CRC64: EAEEB23FAE715D94 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MDRAALRAAA MGEKKEGGGG GAAADGGAGA AVSRALQQCG QLQKLIDISI GSLRGLRTKC 

        70         80         90        100        110        120 
SVSNDLTQQE IRTLEAKLVK YICKQQQSKL SVTPSDRTAE LNSYPRFSDW LYIFNVRPEV 

       130        140        150        160        170        180 
VQEIPQELTL DALLEMDEAK AKEMLRRWGA STEECSRLQQ ALTCLRKVTG LGGEHKMDSG 

       190        200        210        220        230        240 
WSSTDARDSS LGPPMDMLSS LGRAGASTQG PRSISVSALP ASDSPVPGLS EGLSDSCIPL 

       250        260        270        280        290        300 
HTSGRLTPRA LHSFITPPTT PQLRRHAKLK PPRTPPPPSR KVFQLLPSFP TLTRSKSHES 

       310        320        330        340        350        360 
QLGNRIDDVT PMKFELPHGS PQLVRRDIGL SVTHRFSTKS WLSQVCNVCQ KSMIFGVKCK 

       370        380        390        400        410        420 
HCRLKCHNKC TKEAPACRIT FLPLARLRRT ESVPSDINNP VDRAAEPHFG TLPKALTKKE 

       430        440        450        460        470        480 
HPPAMNLDSS SNPSSTTSST PSSPAPFLTS SNPSSATTPP NPSPGQRDSR FSFPDISACS 

       490        500        510        520        530        540 
QAAPLSSTAD STRLDDQPKT DVLGVHEAEA EEPEAGKSEA EDDEEDEVDD LPSSRRPWRG 

       550        560        570        580        590        600 
PISRKASQTS VYLQEWDIPF EQVELGEPIG QGRWGRVHRG RWHGEVAIRL LEMDGHNQDH 

       610        620        630        640        650        660 
LKLFKKEVMN YRQTRHENVV LFMGACMNPP HLAIITSFCK GRTLHSFVRD PKTSLDINKT 

       670        680        690        700        710        720 
RQIAQEIIKG MGYLHAKGIV HKDLKSKNVF YDNGKVVITD FGLFGISGVV REERRENQLK 

       730        740        750        760        770        780 
LSHDWLCYLA PEIVREMIPG RDEDQLPFSK AADVYAFGTV WYELQARDWP FKHQPAEALI 

       790        800        810        820        830        840 
WQIGSGEGVR RVLASVSLGK EVGEILSACW AFDLQERPSF SLLMDMLERL PKLNRRLSHP 

       850        860        870 
GHFWKSADIN SSKVMPRFER FGLGTLESGN PKM

Q61097 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools