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Protein

Kinase suppressor of Ras 2

Gene

Ksr2

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

Functioni

Location-regulated scaffold connecting MEK to RAF. Has very low protein kinase activity and can phosphorylate MAP2K1 at several Ser and Thr residues with very low efficiency (in vitro). Interaction with BRAF enhances KSR2-mediated phosphorylation of MAP2K1 (in vitro). Blocks MAP3K8 kinase activity and MAP3K8-mediated signaling. Acts as a negative regulator of MAP3K3-mediated activation of ERK, JNK and NF-kappa-B pathways, inhibiting MAP3K3-mediated interleukin-8 production (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi414Zinc 1By similarity1
Metal bindingi426Zinc 2By similarity1
Metal bindingi429Zinc 2By similarity1
Metal bindingi439Zinc 1By similarity1
Metal bindingi442Zinc 1By similarity1
Metal bindingi447Zinc 2By similarity1
Metal bindingi450Zinc 2By similarity1
Metal bindingi457Zinc 1By similarity1
Active sitei796Proton donor/acceptorBy similarity1
Binding sitei798ATPPROSITE-ProRule annotation1
Binding sitei813ATPPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri413 – 457Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST45
Nucleotide bindingi682 – 690ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • calcium-mediated signaling Source: MGI
  • positive regulation of MAPK cascade Source: MGI

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Kinase suppressor of Ras 2 (EC:2.7.11.1)
Gene namesi
Name:Ksr2Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:3610315 Ksr2

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

Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002869651 – 959Kinase suppressor of Ras 2Add BLAST959

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei273PhosphothreonineCombined sources1
Modified residuei277PhosphothreonineCombined sources1
Modified residuei484Phosphoserine; by MARK3By similarity1
Modified residuei507PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated on Ser-484 by MARK3.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ3UVC0
PaxDbiQ3UVC0
PRIDEiQ3UVC0

PTM databases

iPTMnetiQ3UVC0
PhosphoSitePlusiQ3UVC0

Expressioni

Gene expression databases

CleanExiMM_KSR2

Interactioni

Subunit structurei

Interacts with MAP2K1, forming a heterodimer that can dimerize to form a heterotetramer. Interacts with MAP3K8, MAPK, RAS and RAF. Interacts with BRAF; this increases the low intrinsic protein kinase activity of KSR2 (By similarity).By similarity

GO - Molecular functioni

  • MAP-kinase scaffold activity Source: MGI
  • mitogen-activated protein kinase kinase binding Source: MGI

Protein-protein interaction databases

IntActiQ3UVC0, 1 interactor
STRINGi10090.ENSMUSP00000137670

Structurei

3D structure databases

ProteinModelPortaliQ3UVC0
SMRiQ3UVC0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini676 – 941Protein kinasePROSITE-ProRule annotationAdd BLAST266

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi171 – 294Pro-richSequence analysisAdd BLAST124
Compositional biasi520 – 563Pro-richSequence analysisAdd BLAST44

Domaini

The protein kinase domain is predicted to be catalytically inactive and seems to have very low intrinsic kinase activity. This low kinase activity can be increased by interaction with BRAF (By similarity).PROSITE-ProRule annotation

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri413 – 457Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST45

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0193 Eukaryota
ENOG410Y4UP LUCA
HOGENOMiHOG000110293
HOVERGENiHBG052293
InParanoidiQ3UVC0
KOiK18529
PhylomeDBiQ3UVC0

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

Sequencei

Sequence statusi: Complete.

Q3UVC0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDEENMTKSE EQQPLSLQKA LQQCELVQNM IDLSISNLEG LRTKCAASND
60 70 80 90 100
LTQKEIRTLE SKLVKYFSRQ LSCKKKVALQ ERNAELDGFP QLRHWFRIVD
110 120 130 140 150
VRKEVLEEIS PDQLSLEDLL EMTDEQVCET VEKYGANQEE CARLNASLSC
160 170 180 190 200
LRNVHKSGGN LSKQDWIIQW PTTEPGQESN PVCPPEPSPW IRTHLSQSPR
210 220 230 240 250
VQTKCPQHFC PTSPTPGTPV YTQVDRLTVD AYPNLCPPPP PLESGHRSLP
260 270 280 290 300
PSPRQRHVVR TPPRTPNIVT TVTPPGTPPM RRKNKLKPPG TPPPSSRKLI
310 320 330 340 350
HLIPGFTALH RSKSHEFQLG NRVDEANTPK AKKKSKPLNL KIHSGVGSCE
360 370 380 390 400
NIPAQQRSPL LSERSLRSFF VGHGPFLPST PPVHTEANFS ANTLSVPRWS
410 420 430 440 450
PQIPRRDLGN SIKHRFSTKY WMSQTCTVCG KGMLFGLKCK NCKLKCHNKC
460 470 480 490 500
TKEAPPCHLL IIHRGDSLCC FYPTDPARLV RTESVPCDIN NPVRKPARYS
510 520 530 540 550
DLHISQTLPK TNKINKDHIP VPYQPDSSSN PSSTTSSTPS SPAPPLPPSA
560 570 580 590 600
TPPSPLHPSP QCPRQKKNFN LPASHYYKYK QQFIFPDVVP VPETPTRAPQ
610 620 630 640 650
VILHPVTSNT ILEGNPLLQI EVEPTSENEE SHNEAEESED EFEEMNLSLL
660 670 680 690 700
SARSFPRKAS QTSIFLQEWD IPFEQLEIGE LIGKGRFGQV YHGRWHGEVA
710 720 730 740 750
IRLIDIERDN EDQLKAFKRE VMAYRQTRHE NVVLFMGACM SPPHLAIITS
760 770 780 790 800
LCKGRTLYSV VRDAKIVLDV NKTRQIAQEI VKGMGYLHAK GILHKDLKSK
810 820 830 840 850
NVFYDNGKVV ITDFGLFSIS GVLQAGRRDD KLRIQNGWLC HLAPEIIRQL
860 870 880 890 900
SPDTEEDKLP FSKHSDVFAL GTIWYELHAR EWPFKTQPAE AIIWQMGTGM
910 920 930 940 950
KPNLSQIGMG KEISDILLFC WAFEQEERPT FTKLMDMLEK LPKRNRRLSH

PGHFWKSAE
Length:959
Mass (Da):108,572
Last modified:May 15, 2007 - v2
Checksum:i5A56146F4C6E8AA2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC113299 Genomic DNA No translation available.
AC113303 Genomic DNA No translation available.
AC114617 Genomic DNA No translation available.
AK137433 mRNA Translation: BAE23350.1
RefSeqiNP_001299843.1, NM_001312914.1
UniGeneiMm.437947

Genome annotation databases

GeneIDi333050
KEGGimmu:333050
UCSCiuc008zfw.2 mouse

Similar proteinsi

Entry informationi

Entry nameiKSR2_MOUSE
AccessioniPrimary (citable) accession number: Q3UVC0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: May 15, 2007
Last modified: March 28, 2018
This is version 94 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

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