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Protein

Kinase suppressor of Ras 1

Gene

Ksr1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • ATP binding Source: InterPro
  • MAP-kinase scaffold activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • protein C-terminus binding Source: MGI
  • protein kinase activity Source: InterPro

GO - Biological processi

  • cAMP-mediated signaling Source: UniProtKB
  • positive regulation of MAPK cascade Source: UniProtKB
  • Ras protein signal transduction Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

Metal-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:105051. Ksr1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.
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

WithEntry#Exp.IntActNotes
Arhgef2Q608755EBI-1536336,EBI-772191
BRAFP150563EBI-1536336,EBI-365980From a different organism.
NME1P155317EBI-1536336,EBI-741141From a different organism.
VRK2Q86Y07-18EBI-1536336,EBI-1207633From a different organism.

GO - Molecular functioni

  • MAP-kinase scaffold activity Source: UniProtKB
  • protein C-terminus binding Source: MGI

Protein-protein interaction databases

BioGridi201048. 236 interactors.
IntActiQ61097. 8 interactors.
MINTiMINT-99547.
STRINGi10090.ENSMUSP00000018478.

Structurei

Secondary structure

1873
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni30 – 32Combined sources3
Helixi33 – 36Combined sources4
Helixi37 – 39Combined sources3
Helixi47 – 58Combined sources12
Helixi65 – 82Combined sources18
Helixi83 – 85Combined sources3
Helixi88 – 90Combined sources3
Turni94 – 96Combined sources3
Helixi101 – 103Combined sources3
Turni108 – 110Combined sources3
Helixi111 – 114Combined sources4
Helixi118 – 121Combined sources4
Helixi130 – 133Combined sources4
Helixi138 – 146Combined sources9
Turni147 – 149Combined sources3
Helixi153 – 162Combined sources10
Helixi163 – 167Combined sources5
Beta strandi336 – 339Combined sources4
Beta strandi347 – 349Combined sources3
Beta strandi356 – 359Combined sources4
Turni360 – 363Combined sources4
Beta strandi364 – 369Combined sources6
Turni371 – 373Combined sources3

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...

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

Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

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.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000113263.
HOVERGENiHBG052293.
InParanoidiQ61097.
KOiK14958.
OMAiEVSPMRF.
OrthoDBiEOG091G02ZN.
PhylomeDBiQ61097.
TreeFamiTF317006.

Family and domain databases

CDDicd00029. C1. 1 hit.
InterProiIPR011009. Kinase-like_dom.
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.
[Graphical view]
PfamiPF13543. KSR1-SAM. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
SMARTiSM00109. C1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. 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]

Sequences (2)i

Sequence statusi: Complete.

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

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

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. Translation: CAI24047.1.
X81634 mRNA. Translation: CAA57288.1.
CCDSiCCDS25117.1. [Q61097-1]
PIRiI48379.
RefSeqiNP_038599.1. NM_013571.2. [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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43585 mRNA. Translation: AAC52382.1.
AL592551 Genomic DNA. Translation: CAI24047.1.
X81634 mRNA. Translation: CAA57288.1.
CCDSiCCDS25117.1. [Q61097-1]
PIRiI48379.
RefSeqiNP_038599.1. NM_013571.2. [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. 236 interactors.
IntActiQ61097. 8 interactors.
MINTiMINT-99547.
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.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000113263.
HOVERGENiHBG052293.
InParanoidiQ61097.
KOiK14958.
OMAiEVSPMRF.
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.
PROiQ61097.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000018334.
CleanExiMM_KSR1.
ExpressionAtlasiQ61097. baseline and differential.
GenevisibleiQ61097. MM.

Family and domain databases

CDDicd00029. C1. 1 hit.
InterProiIPR011009. Kinase-like_dom.
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.
[Graphical view]
PfamiPF13543. KSR1-SAM. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
SMARTiSM00109. C1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiKSR1_MOUSE
AccessioniPrimary (citable) accession number: Q61097
Secondary accession number(s): Q61648, Q78DX8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 148 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.