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Q61097

- KSR1_MOUSE

UniProt

Q61097 - KSR1_MOUSE

Protein

Kinase suppressor of Ras 1

Gene

Ksr1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    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.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi334 – 3341Zinc 11 Publication
    Metal bindingi346 – 3461Zinc 21 Publication
    Metal bindingi349 – 3491Zinc 21 Publication
    Metal bindingi359 – 3591Zinc 11 Publication
    Metal bindingi362 – 3621Zinc 11 Publication
    Metal bindingi367 – 3671Zinc 21 Publication
    Metal bindingi370 – 3701Zinc 21 Publication
    Metal bindingi377 – 3771Zinc 11 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri333 – 37745Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. ATP binding Source: InterPro
    2. MAP-kinase scaffold activity Source: MGI
    3. metal ion binding Source: UniProtKB-KW
    4. protein binding Source: IntAct
    5. protein serine/threonine kinase activity Source: InterPro

    GO - Biological processi

    1. intracellular signal transduction Source: InterPro
    2. positive regulation of MAPK cascade Source: MGI

    Keywords - Ligandi

    Metal-binding, Zinc

    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
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:105051. Ksr1.

    Subcellular locationi

    Cytoplasm. Membrane; Peripheral membrane protein. Endoplasmic reticulum membrane By similarity
    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.

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi297 – 2971S → A: Constitutive targeting to the plasma membrane; when associated with A-392. 1 Publication
    Mutagenesisi392 – 3921S → A: Constitutive targeting to the plasma membrane; when associated with A-297. 1 Publication
    Mutagenesisi397 – 3971I → A: Decrease in MARK3 binding; when associated with A-401. 1 Publication
    Mutagenesisi401 – 4011V → A: Decrease in MARK3 binding; when associated with A-397. 1 Publication
    Mutagenesisi572 – 5721G → E: Decrease in MEK binding. 1 Publication
    Mutagenesisi589 – 5891R → M: Almost no MEK binding. 1 Publication
    Mutagenesisi615 – 6151R → H: Decrease in MEK binding. 1 Publication
    Mutagenesisi700 – 7001D → V: Decrease in MEK binding. 1 Publication
    Mutagenesisi809 – 8091C → Y: No MEK binding. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 873873Kinase suppressor of Ras 1PRO_0000086230Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei256 – 2561PhosphothreonineBy similarity
    Modified residuei260 – 2601PhosphothreonineBy similarity
    Modified residuei297 – 2971Phosphoserine; by MARK31 Publication
    Modified residuei320 – 3201PhosphoserineBy similarity
    Modified residuei392 – 3921Phosphoserine; by MARK31 Publication
    Modified residuei518 – 5181PhosphoserineBy similarity

    Post-translational modificationi

    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.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ61097.
    PaxDbiQ61097.
    PRIDEiQ61097.

    PTM databases

    PhosphoSiteiQ61097.

    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

    ArrayExpressiQ61097.
    BgeeiQ61097.
    CleanExiMM_KSR1.
    GenevestigatoriQ61097.

    Interactioni

    Subunit structurei

    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. Interacts with VRK2 By similarity.By similarity

    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.

    Protein-protein interaction databases

    BioGridi201048. 18 interactions.
    IntActiQ61097. 8 interactions.
    MINTiMINT-99547.

    Structurei

    Secondary structure

    1
    873
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni30 – 323
    Helixi33 – 364
    Helixi37 – 393
    Helixi47 – 5812
    Helixi65 – 8218
    Helixi83 – 853
    Helixi88 – 903
    Turni94 – 963
    Helixi101 – 1033
    Turni108 – 1103
    Helixi111 – 1144
    Helixi118 – 1214
    Helixi130 – 1334
    Helixi138 – 1469
    Turni147 – 1493
    Helixi153 – 16210
    Helixi163 – 1675
    Beta strandi336 – 3394
    Beta strandi347 – 3493
    Beta strandi356 – 3594
    Turni360 – 3634
    Beta strandi364 – 3696
    Turni371 – 3733

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1KBENMR-A331-378[»]
    1KBFNMR-A331-378[»]
    2LPENMR-A25-170[»]
    ProteinModelPortaliQ61097.
    SMRiQ61097. Positions 25-170, 331-378, 501-865.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ61097.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini563 – 833271Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi17 – 215Poly-Gly
    Compositional biasi275 – 2784Poly-Pro
    Compositional biasi429 – 49163Ser-richAdd
    BLAST

    Domaini

    The protein kinase domain is predicted to be catalytically inactive.

    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)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri333 – 37745Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00750000117324.
    HOGENOMiHOG000113263.
    HOVERGENiHBG052293.
    InParanoidiQ61097.
    KOiK14958.
    OMAiEVSPMRF.
    OrthoDBiEOG7BP81Z.
    PhylomeDBiQ61097.
    TreeFamiTF317006.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR025561. KSR_SAM-like_dom.
    IPR002219. Prot_Kinase_C-like_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.
    [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. Align

    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

    MDRAALRAAA MGEKKEGGGG GAAADGGAGA AVSRALQQCG QLQKLIDISI    50
    GSLRGLRTKC SVSNDLTQQE IRTLEAKLVK YICKQQQSKL SVTPSDRTAE 100
    LNSYPRFSDW LYIFNVRPEV VQEIPQELTL DALLEMDEAK AKEMLRRWGA 150
    STEECSRLQQ ALTCLRKVTG LGGEHKMDSG WSSTDARDSS LGPPMDMLSS 200
    LGRAGASTQG PRSISVSALP ASDSPVPGLS EGLSDSCIPL HTSGRLTPRA 250
    LHSFITPPTT PQLRRHAKLK PPRTPPPPSR KVFQLLPSFP TLTRSKSHES 300
    QLGNRIDDVT PMKFELPHGS PQLVRRDIGL SVTHRFSTKS WLSQVCNVCQ 350
    KSMIFGVKCK HCRLKCHNKC TKEAPACRIT FLPLARLRRT ESVPSDINNP 400
    VDRAAEPHFG TLPKALTKKE HPPAMNLDSS SNPSSTTSST PSSPAPFLTS 450
    SNPSSATTPP NPSPGQRDSR FSFPDISACS QAAPLSSTAD STRLDDQPKT 500
    DVLGVHEAEA EEPEAGKSEA EDDEEDEVDD LPSSRRPWRG PISRKASQTS 550
    VYLQEWDIPF EQVELGEPIG QGRWGRVHRG RWHGEVAIRL LEMDGHNQDH 600
    LKLFKKEVMN YRQTRHENVV LFMGACMNPP HLAIITSFCK GRTLHSFVRD 650
    PKTSLDINKT RQIAQEIIKG MGYLHAKGIV HKDLKSKNVF YDNGKVVITD 700
    FGLFGISGVV REERRENQLK LSHDWLCYLA PEIVREMIPG RDEDQLPFSK 750
    AADVYAFGTV WYELQARDWP FKHQPAEALI WQIGSGEGVR RVLASVSLGK 800
    EVGEILSACW AFDLQERPSF SLLMDMLERL PKLNRRLSHP GHFWKSADIN 850
    SSKVMPRFER FGLGTLESGN PKM 873
    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)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei474 – 4741P → PAAYFIHHRQQFIFP in isoform 2. CuratedVSP_012232
    Alternative sequencei848 – 87326DINSS…GNPKM → EL in isoform 2. CuratedVSP_012233Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_006532335.1. [Q61097-2]
    UniGeneiMm.4745.

    Genome annotation databases

    EnsembliENSMUST00000018478; ENSMUSP00000018478; ENSMUSG00000018334. [Q61097-1]
    GeneIDi16706.
    KEGGimmu:16706.
    UCSCiuc007kkg.1. mouse. [Q61097-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U43585 mRNA. Translation: AAC52382.1 .
    AL592551 Genomic DNA. Translation: CAI24047.1 .
    X81634 mRNA. Translation: CAA57288.1 .
    CCDSi CCDS25117.1. [Q61097-1 ]
    PIRi I48379.
    RefSeqi NP_038599.1. NM_013571.2. [Q61097-1 ]
    XP_006532398.1. XM_006532335.1. [Q61097-2 ]
    UniGenei Mm.4745.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1KBE NMR - A 331-378 [» ]
    1KBF NMR - A 331-378 [» ]
    2LPE NMR - A 25-170 [» ]
    ProteinModelPortali Q61097.
    SMRi Q61097. Positions 25-170, 331-378, 501-865.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201048. 18 interactions.
    IntActi Q61097. 8 interactions.
    MINTi MINT-99547.

    PTM databases

    PhosphoSitei Q61097.

    Proteomic databases

    MaxQBi Q61097.
    PaxDbi Q61097.
    PRIDEi Q61097.

    Protocols and materials databases

    DNASUi 16706.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000018478 ; ENSMUSP00000018478 ; ENSMUSG00000018334 . [Q61097-1 ]
    GeneIDi 16706.
    KEGGi mmu:16706.
    UCSCi uc007kkg.1. mouse. [Q61097-1 ]

    Organism-specific databases

    CTDi 8844.
    MGIi MGI:105051. Ksr1.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00750000117324.
    HOGENOMi HOG000113263.
    HOVERGENi HBG052293.
    InParanoidi Q61097.
    KOi K14958.
    OMAi EVSPMRF.
    OrthoDBi EOG7BP81Z.
    PhylomeDBi Q61097.
    TreeFami TF317006.

    Miscellaneous databases

    EvolutionaryTracei Q61097.
    NextBioi 290486.
    PROi Q61097.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q61097.
    Bgeei Q61097.
    CleanExi MM_KSR1.
    Genevestigatori Q61097.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR025561. KSR_SAM-like_dom.
    IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
    IPR000719. Prot_kinase_dom.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF13543. KSR1-SAM. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view ]
    SMARTi SM00109. C1. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi 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.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 331-378 IN COMPLEX WITH ZINC.

    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: October 1, 2014
    This is version 127 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

    External Data

    Dasty 3