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Protein

Kinase suppressor of Ras 1

Gene

Ksr1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Scaffolding protein that is part of a multiprotein signaling complex. Promotes phosphorylation of Raf family members and activation of downstream MAP kinases (PubMed:10409742, PubMed:12932319, PubMed:21102438). Promotes activation of MAPK1 and/or MAPK3, both in response to EGF and to cAMP (PubMed:21102438). Does not have kinase activity by itself (Probable).Curated3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi334Zinc 11 Publication1
Metal bindingi346Zinc 21 Publication1
Metal bindingi349Zinc 21 Publication1
Metal bindingi359Zinc 11 Publication1
Metal bindingi362Zinc 11 Publication1
Metal bindingi367Zinc 21 Publication1
Metal bindingi370Zinc 21 Publication1
Metal bindingi377Zinc 11 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri333 – 377Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST45

GO - Molecular functioni

GO - Biological processi

Keywordsi

LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-5673000 RAF activation
R-MMU-5674135 MAP2K and MAPK activation
R-MMU-5675221 Negative regulation of MAPK pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Kinase suppressor of Ras 1
Short name:
mKSR1
Alternative name(s):
Protein Hb
Gene namesi
Name:Ksr1
Synonyms:Ksr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:105051 Ksr1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi56 – 57LR → GS: No effect on the interaction with MAP2K1, MAP2K2 and YWHAE. Abolishes interaction with BRAF. Abolishes location at membrane ruffles. 2 Publications2
Mutagenesisi71I → A: Impairs interaction with BRAF and association with membrane ruffles; when associated with A-78. 1 Publication1
Mutagenesisi78L → A: Impairs interaction with BRAF and association with membrane ruffles; when associated with A-78. 1 Publication1
Mutagenesisi297S → A: Constitutive targeting to the plasma membrane; when associated with A-392. 1 Publication1
Mutagenesisi392S → A: Constitutive targeting to the plasma membrane; when associated with A-297. 1 Publication1
Mutagenesisi397I → A: Decrease in MARK3 binding; when associated with A-401. 1 Publication1
Mutagenesisi401V → A: Decrease in MARK3 binding; when associated with A-397. 1 Publication1
Mutagenesisi572G → E: Decrease in MEK binding. 1 Publication1
Mutagenesisi580G → E: Partial decrease in MAP2K1 and MAP2K2 binding. No effect on the interaction with YWHAE. 1 Publication1
Mutagenesisi589R → M: Severe decrease in MAP2K1 and MAP2K2 binding. No effect on the interaction with YWHAE. 2 Publications1
Mutagenesisi615R → H: Severe decrease in MAP2K1 and MAP2K2 binding. No effect on the interaction with YWHAE. 2 Publications1
Mutagenesisi700D → V: Decrease in MEK binding. 1 Publication1
Mutagenesisi809C → Y: Associates almost exclusively with the membrane. Loss of MAP2K2 and MAP2K2 binding and recruitment to the membrane. Loss of MAP kinase-mediated inhibition of ELK1 phosphorylation. No effect on the interaction with YWHAE. 2 Publications1
Mutagenesisi838S → A: Abolishes one phosphorylation site. Decreases phosphorylation by PKA. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862301 – 873Kinase suppressor of Ras 1Add BLAST873

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei256PhosphothreonineBy similarity1
Modified residuei260PhosphothreonineBy similarity1
Modified residuei297Phosphoserine; by MARK31 Publication1
Modified residuei320PhosphoserineCombined sources1
Modified residuei337PhosphoserineBy similarity1
Modified residuei392Phosphoserine; by MARK3Combined sources1 Publication1
Modified residuei411PhosphothreonineBy similarity1
Modified residuei518PhosphoserineCombined sources1
Modified residuei838Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylated on Ser-297 and, to a higher extent, on Ser-392 by MARK3 (PubMed:11741534). Dephosphorylated on Ser-392 by PPP2CA (PubMed:12932319). Phosphorylated KSR1 is cytoplasmic and dephosphorylated KSR1 is membrane-associated (Probable). Phosphorylated by PKA at Ser-838. Phosphorylation at Ser-838 is required for cAMP-dependent activation of MAPK1 and/or MAPK3 (PubMed:21102438).Curated5 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ61097
PaxDbiQ61097
PeptideAtlasiQ61097
PRIDEiQ61097

PTM databases

iPTMnetiQ61097
PhosphoSitePlusiQ61097

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiENSMUSG00000018334 Expressed in 198 organ(s), highest expression level in skeletal muscle tissue
CleanExiMM_KSR1
ExpressionAtlasiQ61097 baseline and differential
GenevisibleiQ61097 MM

Interactioni

Subunit structurei

Interacts with HSP90AA1/HSP90, YWHAB/14-3-3, CDC37, MAP2K1/MEK-1, MAP2K2/MEK-2, MARK3, PPP2R1A and PPP2CA (PubMed:10891492, PubMed:10409742, PubMed:11741534, PubMed:12932319). Interacts with YWHAE (PubMed:10409742). 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 (PubMed:8521512). Interacts with VRK2 (By similarity). Interacts with AKAP13 and BRAF. Identified in a complex with AKAP13, MAP2K1 and BRAF (PubMed:21102438, PubMed:23250398).By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201048, 238 interactors
CORUMiQ61097
IntActiQ61097, 8 interactors
MINTiQ61097
STRINGi10090.ENSMUSP00000018478

Structurei

Secondary structure

1873
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ61097
SMRiQ61097
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ61097

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini563 – 833Protein kinasePROSITE-ProRule annotationAdd BLAST271

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 170Mediates association with membranes1 PublicationAdd BLAST170

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi17 – 21Poly-Gly5
Compositional biasi275 – 278Poly-Pro4
Compositional biasi429 – 491Ser-richAdd BLAST63

Domaini

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).Sequence analysis1 Publication
The N-terminal region mediates interaction with BRAF and with membranes.1 Publication

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri333 – 377Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST45

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0193 Eukaryota
ENOG410Y4UP LUCA
GeneTreeiENSGT00930000150812
HOGENOMiHOG000113263
HOVERGENiHBG052293
InParanoidiQ61097
KOiK14958
OrthoDBiEOG091G02ZN
PhylomeDBiQ61097
TreeFamiTF317006

Family and domain databases

CDDicd00029 C1, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR025561 KSR_SAM-like_dom
IPR002219 PE/DAG-bd
IPR000719 Prot_kinase_dom
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF13543 KSR1-SAM, 1 hit
PF07714 Pkinase_Tyr, 1 hit
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 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

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q61097-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MDRAALRAAA MGEKKEGGGG GAAADGGAGA AVSRALQQCG QLQKLIDISI
60 70 80 90 100
GSLRGLRTKC SVSNDLTQQE IRTLEAKLVK YICKQQQSKL SVTPSDRTAE
110 120 130 140 150
LNSYPRFSDW LYIFNVRPEV VQEIPQELTL DALLEMDEAK AKEMLRRWGA
160 170 180 190 200
STEECSRLQQ ALTCLRKVTG LGGEHKMDSG WSSTDARDSS LGPPMDMLSS
210 220 230 240 250
LGRAGASTQG PRSISVSALP ASDSPVPGLS EGLSDSCIPL HTSGRLTPRA
260 270 280 290 300
LHSFITPPTT PQLRRHAKLK PPRTPPPPSR KVFQLLPSFP TLTRSKSHES
310 320 330 340 350
QLGNRIDDVT PMKFELPHGS PQLVRRDIGL SVTHRFSTKS WLSQVCNVCQ
360 370 380 390 400
KSMIFGVKCK HCRLKCHNKC TKEAPACRIT FLPLARLRRT ESVPSDINNP
410 420 430 440 450
VDRAAEPHFG TLPKALTKKE HPPAMNLDSS SNPSSTTSST PSSPAPFLTS
460 470 480 490 500
SNPSSATTPP NPSPGQRDSR FSFPDISACS QAAPLSSTAD STRLDDQPKT
510 520 530 540 550
DVLGVHEAEA EEPEAGKSEA EDDEEDEVDD LPSSRRPWRG PISRKASQTS
560 570 580 590 600
VYLQEWDIPF EQVELGEPIG QGRWGRVHRG RWHGEVAIRL LEMDGHNQDH
610 620 630 640 650
LKLFKKEVMN YRQTRHENVV LFMGACMNPP HLAIITSFCK GRTLHSFVRD
660 670 680 690 700
PKTSLDINKT RQIAQEIIKG MGYLHAKGIV HKDLKSKNVF YDNGKVVITD
710 720 730 740 750
FGLFGISGVV REERRENQLK LSHDWLCYLA PEIVREMIPG RDEDQLPFSK
760 770 780 790 800
AADVYAFGTV WYELQARDWP FKHQPAEALI WQIGSGEGVR RVLASVSLGK
810 820 830 840 850
EVGEILSACW AFDLQERPSF SLLMDMLERL PKLNRRLSHP GHFWKSADIN
860 870
SSKVMPRFER FGLGTLESGN PKM
Length:873
Mass (Da):96,755
Last modified:November 1, 1996 - v1
Checksum:iEAEEB23FAE715D94
GO
Isoform 2 (identifier: Q61097-2) [UniParc]FASTAAdd to basket
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

Show »
Length:863
Mass (Da):95,861
Checksum:iCAC9B367C41314FA
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5SXE4Q5SXE4_MOUSE
Kinase suppressor of Ras 1
Ksr1
637Annotation score:
Q5SXE2Q5SXE2_MOUSE
Kinase suppressor of Ras 1
Ksr1
205Annotation score:
A0A140LHS5A0A140LHS5_MOUSE
Kinase suppressor of Ras 1
Ksr1
432Annotation score:
Q5SXE1Q5SXE1_MOUSE
Kinase suppressor of Ras 1
Ksr1
80Annotation score:
A0A140LHP4A0A140LHP4_MOUSE
Kinase suppressor of Ras 1
Ksr1
65Annotation score:
A0A2I3BR95A0A2I3BR95_MOUSE
Kinase suppressor of Ras 1
Ksr1
818Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012232474P → PAAYFIHHRQQFIFP in isoform 2. Curated1
Alternative sequenceiVSP_012233848 – 873DINSS…GNPKM → EL in isoform 2. CuratedAdd BLAST26

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43585 mRNA Translation: AAC52382.1
AL592551 Genomic DNA No translation available.
X81634 mRNA Translation: CAA57288.1
CCDSiCCDS25117.1 [Q61097-1]
PIRiI48379
RefSeqiNP_001335136.1, NM_001348207.1
NP_038599.1, NM_013571.3 [Q61097-1]
XP_006532398.1, XM_006532335.3 [Q61097-2]
UniGeneiMm.4745

Genome annotation databases

EnsembliENSMUST00000018478; ENSMUSP00000018478; ENSMUSG00000018334 [Q61097-1]
GeneIDi16706
KEGGimmu:16706
UCSCiuc033fyo.1 mouse [Q61097-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43585 mRNA Translation: AAC52382.1
AL592551 Genomic DNA No translation available.
X81634 mRNA Translation: CAA57288.1
CCDSiCCDS25117.1 [Q61097-1]
PIRiI48379
RefSeqiNP_001335136.1, NM_001348207.1
NP_038599.1, NM_013571.3 [Q61097-1]
XP_006532398.1, XM_006532335.3 [Q61097-2]
UniGeneiMm.4745

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KBENMR-A331-378[»]
1KBFNMR-A331-378[»]
2LPENMR-A25-170[»]
ProteinModelPortaliQ61097
SMRiQ61097
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201048, 238 interactors
CORUMiQ61097
IntActiQ61097, 8 interactors
MINTiQ61097
STRINGi10090.ENSMUSP00000018478

PTM databases

iPTMnetiQ61097
PhosphoSitePlusiQ61097

Proteomic databases

EPDiQ61097
PaxDbiQ61097
PeptideAtlasiQ61097
PRIDEiQ61097

Protocols and materials databases

DNASUi16706
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000018478; ENSMUSP00000018478; ENSMUSG00000018334 [Q61097-1]
GeneIDi16706
KEGGimmu:16706
UCSCiuc033fyo.1 mouse [Q61097-1]

Organism-specific databases

CTDi8844
MGIiMGI:105051 Ksr1

Phylogenomic databases

eggNOGiKOG0193 Eukaryota
ENOG410Y4UP LUCA
GeneTreeiENSGT00930000150812
HOGENOMiHOG000113263
HOVERGENiHBG052293
InParanoidiQ61097
KOiK14958
OrthoDBiEOG091G02ZN
PhylomeDBiQ61097
TreeFamiTF317006

Enzyme and pathway databases

ReactomeiR-MMU-5673000 RAF activation
R-MMU-5674135 MAP2K and MAPK activation
R-MMU-5675221 Negative regulation of MAPK pathway

Miscellaneous databases

EvolutionaryTraceiQ61097
PROiPR:Q61097
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000018334 Expressed in 198 organ(s), highest expression level in skeletal muscle tissue
CleanExiMM_KSR1
ExpressionAtlasiQ61097 baseline and differential
GenevisibleiQ61097 MM

Family and domain databases

CDDicd00029 C1, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR025561 KSR_SAM-like_dom
IPR002219 PE/DAG-bd
IPR000719 Prot_kinase_dom
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF13543 KSR1-SAM, 1 hit
PF07714 Pkinase_Tyr, 1 hit
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 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
ProtoNetiSearch...

Entry informationi

Entry nameiKSR1_MOUSE
AccessioniPrimary (citable) accession number: Q61097
Secondary accession number(s): Q61648, Q78DX8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: November 1, 1996
Last modified: November 7, 2018
This is version 164 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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