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Protein

Kinase suppressor of Ras 2

Gene

Ksr2

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

  • ATP binding Source: UniProtKB-KW
  • MAP-kinase scaffold activity Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • mitogen-activated protein kinase kinase binding Source: MGI
  • protein serine/threonine kinase activity Source: UniProtKB-KW

GO - Biological processi

  • calcium-mediated signaling Source: MGI
  • positive regulation of MAPK cascade Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:3610315. Ksr2.

Subcellular locationi

  • Cytoplasm By similarity
  • Membrane By similarity; Peripheral membrane protein By similarity

GO - Cellular componenti

  • cytosol Source: MGI
  • plasma membrane Source: MGI
Complete GO annotation...

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

STRINGi10090.ENSMUSP00000137670.

Structurei

3D structure databases

ProteinModelPortaliQ3UVC0.
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

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 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.
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]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ3UVC0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000137670.

PTM databases

iPTMnetiQ3UVC0.
PhosphoSitePlusiQ3UVC0.

Proteomic databases

MaxQBiQ3UVC0.
PaxDbiQ3UVC0.
PRIDEiQ3UVC0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi333050.
KEGGimmu:333050.
UCSCiuc008zfw.2. mouse.

Organism-specific databases

CTDi283455.
MGIiMGI:3610315. Ksr2.

Phylogenomic databases

eggNOGiKOG0193. Eukaryota.
ENOG410Y4UP. LUCA.
HOGENOMiHOG000110293.
HOVERGENiHBG052293.
InParanoidiQ3UVC0.
KOiK18529.
PhylomeDBiQ3UVC0.

Miscellaneous databases

PROiQ3UVC0.
SOURCEiSearch...

Gene expression databases

CleanExiMM_KSR2.

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 nameiKSR2_MOUSE
AccessioniPrimary (citable) accession number: Q3UVC0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: May 15, 2007
Last modified: November 30, 2016
This is version 89 of the entry and version 2 of the sequence. [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

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.