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Reviewed, UniProtKB/Swiss-Prot Q61097 (KSR1_MOUSE)

Last modified November 4, 2008. Version 68. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Kinase suppressor of Ras 1
      Short name=mKSR1
Alternative name(s):
    Protein Hb
Gene names
Name: Ksr1
Synonyms: Ksr
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length873 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (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 structure

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.

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.

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.

Post-translational modification

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.

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.

Contains 1 phorbol-ester/DAG-type zinc finger.

Contains 1 protein kinase domain.

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Ontologies

Keywords

   Cellular componentCytoplasm
Membrane
   Coding sequence diversityAlternative splicing
   DomainPhorbol-ester binding
Zinc-finger
   LigandMetal-binding
Zinc
   PTMPhosphoprotein
   Technical term3D-structure

Gene Ontology (GO)

   Molecular functionprotein binding

Inferred from physical interaction. Source: IntAct

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

NME1P155312EBI-1536336,EBI-741141From a different organism.

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q61097-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q61097-2)

Also known as: B-KSR1;

The sequence of this isoform differs from the canonical sequence as follows:
     474-474: P → PAAYFIHHRQQFIFP
     848-873: DINSSKVMPRFERFGLGTLESGNPKM → EL

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 873873Kinase suppressor of Ras 1
PRO_0000086230

Regions

Domain563 – 833271Protein kinase
Zinc finger333 – 37745Phorbol-ester/DAG-type
Compositional bias17 – 215Poly-Gly
Compositional bias275 – 2784Poly-Pro
Compositional bias429 – 49163Ser-rich

Sites

Metal binding3341Zinc 1
Metal binding3461Zinc 2
Metal binding3491Zinc 2
Metal binding3591Zinc 1
Metal binding3621Zinc 1
Metal binding3671Zinc 2
Metal binding3701Zinc 2
Metal binding3771Zinc 1

Amino acid modifications

Modified residue2561Phosphothreonine By similarity
Modified residue2601Phosphothreonine By similarity
Modified residue2971Phosphoserine; by MARK3
Modified residue3201Phosphoserine By similarity
Modified residue3921Phosphoserine; by MARK3

Natural variations

Alternative sequence4741P → PAAYFIHHRQQFIFP in isoform 2.
VSP_012232
Alternative sequence848 – 87326DINSS…GNPKM → EL in isoform 2.
VSP_012233

Experimental info

Mutagenesis2971S → A: Constitutive targeting to the plasma membrane; when associated with A-392
Mutagenesis3921S → A: Constitutive targeting to the plasma membrane; when associated with A-297
Mutagenesis3971I → A: Decrease in MARK3 binding; when associated with A-401
Mutagenesis4011V → A: Decrease in MARK3 binding; when associated with A-397
Mutagenesis5721G → E: Decrease in MEK binding
Mutagenesis5891R → M: Almost no MEK binding
Mutagenesis6151R → H: Decrease in MEK binding
Mutagenesis7001D → V: Decrease in MEK binding
Mutagenesis8091C → Y: No MEK binding

Secondary structure

1 ........... 873
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: EAEEB23FAE715D94

FASTA87396,755
        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

« Hide

Isoform 2 (B-KSR1) [UniParc].

Checksum: CAC9B367C41314FA
Show »

86395,861

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References

« Hide 'large scale' references
[1]"KSR, a novel protein kinase required for RAS signal transduction."
Therrien M., Chang H.C., Solomon N.M., Karim F.D., Wassarman D.A., Rubin G.M.
Cell 83:879-888(1995) [PubMed: 8521512] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH HSPCA; YWHAB; CDC37 AND MAP2K.
[2]"Identification of B-KSR1, a novel brain-specific isoform of KSR1 that functions in neuronal signaling."
Mueller J., Cacace A.M., Lyons W.E., McGill C.B., Morrison D.K.
Mol. Cell. Biol. 20:5529-5539(2000) [PubMed: 10891492] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2), INTERACTION WITH MAPK, MUTAGENESIS OF GLY-572; ARG-589; ARG-615; ASP-700 AND CYS-809, TISSUE SPECIFICITY.
Tissue: Brain.
[3]Pelan S.
Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"YAC/P1 contigs defining the location of 56 microsatellite markers and several genes across a 3.4cM interval on mouse chromosome 11."
Nehls M., Luno K., Schorpp M., Pfeifer D., Krause S., Matysiak-Scholze U., Dierbach H., Boehm T.
Mamm. Genome 6:321-331(1995) [PubMed: 7626882] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 49-474 (ISOFORMS 1/2).
Strain: BALB/c.
[5]"C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1."
Mueller J., Ory S., Copeland T., Piwnica-Worms H., Morrison D.K.
Mol. Cell 8:983-993(2001) [PubMed: 11741534] [Abstract]
Cited for: INTERACTION WITH MARK3, PHOSPHORYLATION AT SER-297 AND SER-392, MUTAGENESIS OF SER-297; SER-392; ILE-397 AND VAL-401.
[6]"Protein phosphatase 2A positively regulates Ras signaling by dephosphorylating KSR1 and Raf-1 on critical 14-3-3 binding sites."
Ory S., Zhou M., Conrads T.P., Veenstra T.D., Morrison D.K.
Curr. Biol. 13:1356-1364(2003) [PubMed: 12932319] [Abstract]
Cited for: INTERACTION WITH PPP2R1A AND PPP2CA, DEPHOSPHORYLATION BY PPP2CA.
[7]"MAP kinase module: the Ksr connection."
Roy F., Therrien M.
Curr. Biol. 12:R325-R327(2002) [PubMed: 12007434] [Abstract]
Cited for: REVIEW.
[8]"Solution structure and functional analysis of the cysteine-rich C1 domain of kinase suppressor of Ras (KSR)."
Zhou M., Horita D.A., Waugh D.S., Byrd R.A., Morrison D.K.
J. Mol. Biol. 315:435-446(2002) [PubMed: 11786023] [Abstract]
Cited for: STRUCTURE BY NMR OF 331-378 IN COMPLEX WITH ZINC.
+Additional computationally mapped references.

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Cross-references

Sequence databases

U43585 mRNA. Translation: AAC52382.1.
AL592551 Genomic DNA. Translation: CAI24047.1.
X81634 mRNA. Translation: CAA57288.1.
PIRI48379.
RefSeqNP_038599.1.
UniGeneMm.4745

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1KBENMR-A331-378[»]
1KBFNMR-A331-378[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ61097.

PTM databases

PhosphoSiteQ61097.

Genome annotation databases

EnsemblENSMUSG00000018334. Mus musculus. [Contig view]
GeneID16706.
KEGGmmu:16706.

Organism-specific databases

MGIMGI:105051. Ksr1.

Phylogenomic databases

HOGENOMQ61097.
HOVERGENQ61097.

Gene expression databases

ArrayExpressQ61097.
CleanExMM_KSR1.
GermOnlineENSMUSG00000018334. Mus musculus.

Family and domain databases

InterProIPR002219. DAG_PE_bd.
IPR000719. Prot_kinase_core.
IPR008271. Ser_thr_pkin_AS.
IPR001245. Tyr_pkinase.
[Graphical view]
PfamPF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00109. C1. 1 hit.
[Graphical view]
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]
BLOCKSSearch...
ProtoNetSearch...

Other Resources

NextBio290486.
SOURCESearch...

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Entry information

Entry nameKSR1_MOUSE
AccessionPrimary (citable) accession number: Q61097
Secondary accession number(s): Q61648, Q78DX8
Entry history
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: November 1, 1996
Last modified: November 4, 2008
This is version 68 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

UniProtKB secondary accession numbers

Index of UniProtKB secondary accession numbers

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents