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Protein

Kinase suppressor of Ras 1

Gene

KSR1

Organism
Homo sapiens (Human)
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. Promotes activation of MAPK1 and/or MAPK3, both in response to EGF and to cAMP. Does not have kinase activity by itself.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi348Zinc 1By similarity1
Metal bindingi360Zinc 2By similarity1
Metal bindingi363Zinc 2By similarity1
Metal bindingi373Zinc 1By similarity1
Metal bindingi376Zinc 1By similarity1
Metal bindingi381Zinc 2By similarity1
Metal bindingi384Zinc 2By similarity1
Metal bindingi391Zinc 1By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri347 – 391Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST45

GO - Molecular functioni

GO - Biological processi

Keywordsi

LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5673000 RAF activation
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants
R-HSA-6802949 Signaling by RAS mutants
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF
SignaLinkiQ8IVT5
SIGNORiQ8IVT5

Names & Taxonomyi

Protein namesi
Recommended name:
Kinase suppressor of Ras 1
Gene namesi
Name:KSR1
Synonyms:KSR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000141068.13
HGNCiHGNC:6465 KSR1
MIMi601132 gene
neXtProtiNX_Q8IVT5

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

Organism-specific databases

DisGeNETi8844
OpenTargetsiENSG00000141068
PharmGKBiPA30254

Polymorphism and mutation databases

BioMutaiKSR1
DMDMi56749095

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862291 – 923Kinase suppressor of Ras 1Add BLAST923

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei270PhosphothreonineCombined sources1
Modified residuei274PhosphothreonineCombined sources1
Modified residuei311PhosphoserineCombined sources1
Modified residuei334PhosphoserineCombined sources1
Modified residuei351PhosphoserineCombined sources1
Modified residuei406PhosphoserineCombined sources1
Modified residuei425PhosphothreonineCombined sources1
Modified residuei569PhosphoserineCombined sources1
Modified residuei888PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on Ser-311 and, to a higher extent, on Ser-406 by MARK3. Dephosphorylated on Ser-406 by PPP2CA. In resting cells, phosphorylated KSR1 is cytoplasmic and in stimulated cells, dephosphorylated KSR1 is membrane-associated. Phosphorylated by PKA at Ser-888. Phosphorylation at Ser-888 is required for cAMP-dependent activation of MAPK1 and/or MAPK3 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8IVT5
MaxQBiQ8IVT5
PaxDbiQ8IVT5
PeptideAtlasiQ8IVT5
PRIDEiQ8IVT5
ProteomicsDBi70766
70767 [Q8IVT5-2]
70768 [Q8IVT5-3]

PTM databases

iPTMnetiQ8IVT5
PhosphoSitePlusiQ8IVT5

Expressioni

Gene expression databases

BgeeiENSG00000141068 Expressed in 196 organ(s), highest expression level in body of pancreas
CleanExiHS_KSR1
ExpressionAtlasiQ8IVT5 baseline and differential
GenevisibleiQ8IVT5 HS

Organism-specific databases

HPAiCAB009623
HPA011215

Interactioni

Subunit structurei

Interacts with HSP90AA1/HSP90, YWHAE/14-3-3, CDC37, MAP2K1/MEK-1 and MAP2K2/MEK-2 (PubMed:10409742). Interacts with 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 (By similarity). Interacts with isoform 1 of VRK2 (PubMed:20679487). Interacts with AKAP13 and BRAF (PubMed:21102438). Identified in a complex with AKAP13, MAP2K1 and BRAF (By similarity).By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114371, 99 interactors
CORUMiQ8IVT5
DIPiDIP-32619N
IntActiQ8IVT5, 351 interactors
MINTiQ8IVT5
STRINGi9606.ENSP00000323178

Structurei

Secondary structure

1923
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8IVT5
SMRiQ8IVT5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini613 – 883Protein kinasePROSITE-ProRule annotationAdd BLAST271

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 172Mediates association with membranesBy similarityAdd BLAST172

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi17 – 21Poly-Gly5
Compositional biasi289 – 292Poly-Pro4

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 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.Sequence analysisBy similarity
The N-terminal region mediates interaction with BRAF and with membranes.By similarity

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri347 – 391Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST45

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0193 Eukaryota
ENOG410Y4UP LUCA
GeneTreeiENSGT00930000150812
HOGENOMiHOG000113263
HOVERGENiHBG052293
InParanoidiQ8IVT5
KOiK14958
PhylomeDBiQ8IVT5
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 (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8IVT5-1) [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 GDAAAAEGGA GAAASRALQQ CGQLQKLIDI
60 70 80 90 100
SIGSLRGLRT KCAVSNDLTQ QEIRTLEAKL VRYICKQRQC KLSVAPGERT
110 120 130 140 150
PELNSYPRFS DWLYTFNVRP EVVQEIPRDL TLDALLEMNE AKVKETLRRC
160 170 180 190 200
GASGDECGRL QYALTCLRKV TGLGGEHKED SSWSSLDARR ESGSGPSTDT
210 220 230 240 250
LSAASLPWPP GSSQLGRAGN SAQGPRSISV SALPASDSPT PSFSEGLSDT
260 270 280 290 300
CIPLHASGRL TPRALHSFIT PPTTPQLRRH TKLKPPRTPP PPSRKVFQLL
310 320 330 340 350
PSFPTLTRSK SHESQLGNRI DDVSSMRFDL SHGSPQMVRR DIGLSVTHRF
360 370 380 390 400
STKSWLSQVC HVCQKSMIFG VKCKHCRLKC HNKCTKEAPA CRISFLPLTR
410 420 430 440 450
LRRTESVPSD INNPVDRAAE PHFGTLPKAL TKKEHPPAMN HLDSSSNPSS
460 470 480 490 500
TTSSTPSSPA PFPTSSNPSS ATTPPNPSPG QRDSRFNFPA AYFIHHRQQF
510 520 530 540 550
IFPVPSAGHC WKCLLIAESL KENAFNISAF AHAAPLPEAA DGTRLDDQPK
560 570 580 590 600
ADVLEAHEAE AEEPEAGKSE AEDDEDEVDD LPSSRRPWRG PISRKASQTS
610 620 630 640 650
VYLQEWDIPF EQVELGEPIG QGRWGRVHRG RWHGEVAIRL LEMDGHNQDH
660 670 680 690 700
LKLFKKEVMN YRQTRHENVV LFMGACMNPP HLAIITSFCK GRTLHSFVRD
710 720 730 740 750
PKTSLDINKT RQIAQEIIKG MGYLHAKGIV HKDLKSKNVF YDNGKVVITD
760 770 780 790 800
FGLFGISGVV REGRRENQLK LSHDWLCYLA PEIVREMTPG KDEDQLPFSK
810 820 830 840 850
AADVYAFGTV WYELQARDWP LKNQAAEASI WQIGSGEGMK RVLTSVSLGK
860 870 880 890 900
EVSEILSACW AFDLQERPSF SLLMDMLEKL PKLNRRLSHP GHFWKSADIN
910 920
SSKVVPRFER FGLGVLESSN PKM
Length:923
Mass (Da):102,160
Last modified:September 3, 2014 - v3
Checksum:i61BF0F1598349540
GO
Isoform 2 (identifier: Q8IVT5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     504-526: VPSAGHCWKCLLIAESLKENAFN → D
     898-923: DINSSKVVPRFERFGLGVLESSNPKM → EL

Note: No experimental confirmation available.
Show »
Length:877
Mass (Da):97,115
Checksum:iB316183895D9A4BD
GO
Isoform 3 (identifier: Q8IVT5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-137: Missing.

Note: No experimental confirmation available.
Show »
Length:786
Mass (Da):87,344
Checksum:i7BDD722CFE4B87BA
GO
Isoform 4 (identifier: Q8IVT5-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-137: Missing.
     898-923: DINSSKVVPRFERFGLGVLESSNPKM → EL

Note: No experimental confirmation available.
Show »
Length:762
Mass (Da):84,697
Checksum:i3034D20D01F33E66
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MQW1A0A0A0MQW1_HUMAN
Kinase suppressor of Ras 1
KSR1
846Annotation score:
A0A2R8Y5H9A0A2R8Y5H9_HUMAN
Kinase suppressor of Ras 1
KSR1
928Annotation score:
A0A2R8Y4X0A0A2R8Y4X0_HUMAN
Kinase suppressor of Ras 1
KSR1
829Annotation score:
A8MY87A8MY87_HUMAN
Kinase suppressor of Ras 1
KSR1
612Annotation score:
J3QQL4J3QQL4_HUMAN
Kinase suppressor of Ras 1
KSR1
139Annotation score:
J3QSG8J3QSG8_HUMAN
Kinase suppressor of Ras 1
KSR1
113Annotation score:
J3QLI1J3QLI1_HUMAN
Kinase suppressor of Ras 1
KSR1
98Annotation score:
J3QR75J3QR75_HUMAN
Kinase suppressor of Ras 1
KSR1
155Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti243 – 265FSEGL…TPRAL → EFRHTSALTQHTAHTQHTSA HTQ in AAH42106 (PubMed:8521512).CuratedAdd BLAST23

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040658227S → P1 Publication1
Natural variantiVAR_046048359V → A1 Publication1
Natural variantiVAR_046049663Q → H1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0556551 – 137Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST137
Alternative sequenceiVSP_055656504 – 526VPSAG…ENAFN → D in isoform 2. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_055657898 – 923DINSS…SNPKM → EL in isoform 2 and isoform 4. 1 PublicationAdd BLAST26

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC069366 Genomic DNA No translation available.
AC015688 Genomic DNA No translation available.
BC042106 mRNA Translation: AAH42106.1
U43586 mRNA Translation: AAC50354.1
CCDSiCCDS58532.1 [Q8IVT5-4]
RefSeqiNP_055053.1, NM_014238.1 [Q8IVT5-4]
XP_011523731.1, XM_011525429.2 [Q8IVT5-1]
XP_016880760.1, XM_017025271.1 [Q8IVT5-3]
XP_016880761.1, XM_017025272.1 [Q8IVT5-3]
XP_016880762.1, XM_017025273.1 [Q8IVT5-3]
XP_016880763.1, XM_017025274.1 [Q8IVT5-3]
XP_016880764.1, XM_017025275.1 [Q8IVT5-3]
XP_016880765.1, XM_017025276.1 [Q8IVT5-3]
UniGeneiHs.133534

Genome annotation databases

EnsembliENST00000398988; ENSP00000381958; ENSG00000141068 [Q8IVT5-4]
ENST00000509603; ENSP00000438795; ENSG00000141068 [Q8IVT5-4]
GeneIDi8844
KEGGihsa:8844
UCSCiuc002gzo.2 human [Q8IVT5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC069366 Genomic DNA No translation available.
AC015688 Genomic DNA No translation available.
BC042106 mRNA Translation: AAH42106.1
U43586 mRNA Translation: AAC50354.1
CCDSiCCDS58532.1 [Q8IVT5-4]
RefSeqiNP_055053.1, NM_014238.1 [Q8IVT5-4]
XP_011523731.1, XM_011525429.2 [Q8IVT5-1]
XP_016880760.1, XM_017025271.1 [Q8IVT5-3]
XP_016880761.1, XM_017025272.1 [Q8IVT5-3]
XP_016880762.1, XM_017025273.1 [Q8IVT5-3]
XP_016880763.1, XM_017025274.1 [Q8IVT5-3]
XP_016880764.1, XM_017025275.1 [Q8IVT5-3]
XP_016880765.1, XM_017025276.1 [Q8IVT5-3]
UniGeneiHs.133534

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5VYKX-ray1.75A/C27-172[»]
ProteinModelPortaliQ8IVT5
SMRiQ8IVT5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114371, 99 interactors
CORUMiQ8IVT5
DIPiDIP-32619N
IntActiQ8IVT5, 351 interactors
MINTiQ8IVT5
STRINGi9606.ENSP00000323178

PTM databases

iPTMnetiQ8IVT5
PhosphoSitePlusiQ8IVT5

Polymorphism and mutation databases

BioMutaiKSR1
DMDMi56749095

Proteomic databases

EPDiQ8IVT5
MaxQBiQ8IVT5
PaxDbiQ8IVT5
PeptideAtlasiQ8IVT5
PRIDEiQ8IVT5
ProteomicsDBi70766
70767 [Q8IVT5-2]
70768 [Q8IVT5-3]

Protocols and materials databases

DNASUi8844
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000398988; ENSP00000381958; ENSG00000141068 [Q8IVT5-4]
ENST00000509603; ENSP00000438795; ENSG00000141068 [Q8IVT5-4]
GeneIDi8844
KEGGihsa:8844
UCSCiuc002gzo.2 human [Q8IVT5-1]

Organism-specific databases

CTDi8844
DisGeNETi8844
EuPathDBiHostDB:ENSG00000141068.13
GeneCardsiKSR1
H-InvDBiHIX0018394
HIX0025516
HIX0029273
HGNCiHGNC:6465 KSR1
HPAiCAB009623
HPA011215
MIMi601132 gene
neXtProtiNX_Q8IVT5
OpenTargetsiENSG00000141068
PharmGKBiPA30254
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0193 Eukaryota
ENOG410Y4UP LUCA
GeneTreeiENSGT00930000150812
HOGENOMiHOG000113263
HOVERGENiHBG052293
InParanoidiQ8IVT5
KOiK14958
PhylomeDBiQ8IVT5
TreeFamiTF317006

Enzyme and pathway databases

ReactomeiR-HSA-5673000 RAF activation
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants
R-HSA-6802949 Signaling by RAS mutants
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF
SignaLinkiQ8IVT5
SIGNORiQ8IVT5

Miscellaneous databases

ChiTaRSiKSR1 human
GeneWikiiKSR1
GenomeRNAii8844
PROiPR:Q8IVT5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141068 Expressed in 196 organ(s), highest expression level in body of pancreas
CleanExiHS_KSR1
ExpressionAtlasiQ8IVT5 baseline and differential
GenevisibleiQ8IVT5 HS

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_HUMAN
AccessioniPrimary (citable) accession number: Q8IVT5
Secondary accession number(s): F8WEA9, H7BYU0, Q13476
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: September 3, 2014
Last modified: November 7, 2018
This is version 154 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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