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Q8IVT5 (KSR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Kinase suppressor of Ras 1
Gene names
Name:KSR1
Synonyms:KSR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length921 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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 By similarity. The binding of 14-3-3 proteins to phosphorylated KSR prevents the membrane localization. Interacts with isoform 1 of VRK2. Ref.11

Subcellular location

Cytoplasm. Membrane; Peripheral membrane protein By similarity. Endoplasmic reticulum membrane. 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 By similarity. Ref.11

Domain

The protein kinase domain is predicted to be catalytically inactive.

Post-translational modification

Phosphorylated on Ser-309 and, to a higher extent, on Ser-404 by MARK3. Dephosphorylated on Ser-404 by PPP2CA. In resting cells, phosphorylated KSR1 is cytoplasmic and in stimulated cells, dephosphorylated KSR1 is membrane-associated By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.

Contains 1 phorbol-ester/DAG-type zinc finger.

Contains 1 protein kinase domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

VRK2Q86Y074EBI-486984,EBI-1207615

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8IVT5-1)

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.
Isoform 2 (identifier: Q8IVT5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     502-524: VPSAGHCWKCLLIAESLKENAFN → D
     897-921: INSSKVVPRFERFGLGVLESSNPKM → L
Note: No experimental confirmation available.
Isoform 3 (identifier: Q8IVT5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-135: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 921921Kinase suppressor of Ras 1
PRO_0000086229

Regions

Domain611 – 881271Protein kinase
Zinc finger345 – 38945Phorbol-ester/DAG-type
Compositional bias17 – 215Poly-Gly
Compositional bias287 – 2904Poly-Pro

Sites

Metal binding3461Zinc 1 By similarity
Metal binding3581Zinc 2 By similarity
Metal binding3611Zinc 2 By similarity
Metal binding3711Zinc 1 By similarity
Metal binding3741Zinc 1 By similarity
Metal binding3791Zinc 2 By similarity
Metal binding3821Zinc 2 By similarity
Metal binding3891Zinc 1 By similarity

Amino acid modifications

Modified residue2681Phosphothreonine Ref.6 Ref.7 Ref.8
Modified residue2721Phosphothreonine Ref.8
Modified residue3091Phosphoserine Ref.5 Ref.13
Modified residue3321Phosphoserine Ref.6 Ref.8
Modified residue4041Phosphoserine Ref.8 Ref.10
Modified residue5671Phosphoserine Ref.8

Natural variations

Alternative sequence1 – 135135Missing in isoform 3.
VSP_012229
Alternative sequence502 – 52423VPSAG…ENAFN → D in isoform 2.
VSP_012230
Alternative sequence897 – 92125INSSK…SNPKM → L in isoform 2.
VSP_012231
Natural variant2251S → P. Ref.14
VAR_040658
Natural variant3571V → A. Ref.14
VAR_046048
Natural variant6611Q → H. Ref.14
VAR_046049

Experimental info

Sequence conflict241 – 26323FSEGL…TPRAL → EFRHTSALTQHTAHTQHTSA HTQ Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 21, 2004. Version 2.
Checksum: FBF2E4976215C313

FASTA921102,032
        10         20         30         40         50         60 
MDRAALRAAA MGEKKEGGGG GDAAEGGAGA AASRALQQCG QLQKLIDISI GSLRGLRTKC 

        70         80         90        100        110        120 
AVSNDLTQQE IRTLEAKLVR YICKQRQCKL SVAPGERTPE LNSYPRFSDW LYTFNVRPEV 

       130        140        150        160        170        180 
VQEIPRDLTL DALLEMNEAK VKETLRRCGA SGDECGRLQY ALTCLRKVTG LGGEHKEDSS 

       190        200        210        220        230        240 
WSSLDARRES GSGPSTDTLS AASLPWPPGS SQLGRAGNSA QGPRSISVSA LPASDSPTPS 

       250        260        270        280        290        300 
FSEGLSDTCI PLHASGRLTP RALHSFITPP TTPQLRRHTK LKPPRTPPPP SRKVFQLLPS 

       310        320        330        340        350        360 
FPTLTRSKSH ESQLGNRIDD VSSMRFDLSH GSPQMVRRDI GLSVTHRFST KSWLSQVCHV 

       370        380        390        400        410        420 
CQKSMIFGVK CKHCRLKCHN KCTKEAPACR ISFLPLTRLR RTESVPSDIN NPVDRAAEPH 

       430        440        450        460        470        480 
FGTLPKALTK KEHPPAMNHL DSSSNPSSTT SSTPSSPAPF PTSSNPSSAT TPPNPSPGQR 

       490        500        510        520        530        540 
DSRFNFPAAY FIHHRQQFIF PVPSAGHCWK CLLIAESLKE NAFNISAFAH AAPLPEAADG 

       550        560        570        580        590        600 
TRLDDQPKAD VLEAHEAEAE EPEAGKSEAE DDEDEVDDLP SSRRPWRGPI SRKASQTSVY 

       610        620        630        640        650        660 
LQEWDIPFEQ VELGEPIGQG RWGRVHRGRW HGEVAIRLLE MDGHNQDHLK LFKKEVMNYR 

       670        680        690        700        710        720 
QTRHENVVLF MGACMNPPHL AIITSFCKGR TLHSFVRDPK TSLDINKTRQ IAQEIIKGMG 

       730        740        750        760        770        780 
YLHAKGIVHK DLKSKNVFYD NGKVVITDFG LFGISGVVRE GRRENQLKLS HDWLCYLAPE 

       790        800        810        820        830        840 
IVREMTPGKD EDQLPFSKAA DVYAFGTVWY ELQARDWPLK NQAAEASIWQ IGSGEGMKRV 

       850        860        870        880        890        900 
LTSVSLGKEV SEILSACWAF DLQERPSFSL LMDMLEKLPK LNRRLSHPGH FWKSAEINSS 

       910        920 
KVVPRFERFG LGVLESSNPK M 

« Hide

Isoform 2 [UniParc].

Checksum: 192D0A1F797EEE87
Show »

FASTA87596,973
Isoform 3 [UniParc].

Checksum: 7BDC623DFE4B87BA
Show »

FASTA78687,358

References

« Hide 'large scale' references
[1]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Brain.
[3]"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] OF 241-897 (ISOFORM 2).
[4]"MAP kinase module: the Ksr connection."
Roy F., Therrien M.
Curr. Biol. 12:R325-R327(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[5]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-309, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[6]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-268 AND SER-332, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-268, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-268; THR-272; SER-332; SER-404 AND SER-567, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-404, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[11]"VRK2 inhibits mitogen-activated protein kinase signaling and inversely correlates with ErbB2 in human breast cancer."
Fernandez I.F., Blanco S., Lozano J., Lazo P.A.
Mol. Cell. Biol. 30:4687-4697(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH VRK2.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-309, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] PRO-225; ALA-357 AND HIS-661.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC069366 Genomic DNA. No translation available.
AC015688 Genomic DNA. No translation available.
BC042106 mRNA. Translation: AAH42106.1.
U43586 mRNA. Translation: AAC50354.1.
RefSeqNP_055053.1. NM_014238.1.
UniGeneHs.133534.

3D structure databases

ProteinModelPortalQ8IVT5.
SMRQ8IVT5. Positions 25-170, 343-390, 598-906.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114371. 11 interactions.
IntActQ8IVT5. 17 interactions.
MINTMINT-87143.
STRING9606.ENSP00000268763.

PTM databases

PhosphoSiteQ8IVT5.

Polymorphism databases

DMDM56749095.

Proteomic databases

MaxQBQ8IVT5.
PaxDbQ8IVT5.
PRIDEQ8IVT5.

Protocols and materials databases

DNASU8844.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000268763; ENSP00000268763; ENSG00000141068.
GeneID8844.
KEGGhsa:8844.

Organism-specific databases

CTD8844.
GeneCardsGC17P025783.
H-InvDBHIX0018394.
HIX0025516.
HIX0029273.
HGNCHGNC:6465. KSR1.
HPACAB009623.
HPA011215.
MIM601132. gene.
neXtProtNX_Q8IVT5.
PharmGKBPA30254.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000113263.
HOVERGENHBG052293.
InParanoidQ8IVT5.
KOK14958.
PhylomeDBQ8IVT5.

Enzyme and pathway databases

SignaLinkQ8IVT5.

Gene expression databases

ArrayExpressQ8IVT5.
BgeeQ8IVT5.
CleanExHS_KSR1.
GenevestigatorQ8IVT5.

Family and domain databases

InterProIPR011009. 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]
PfamPF13543. KSR1-SAM. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
SMARTSM00109. C1. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50011. 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]
ProtoNetSearch...

Other

ChiTaRSKSR1. human.
GeneWikiKSR1.
GenomeRNAi8844.
NextBio33204.
PROQ8IVT5.
SOURCESearch...

Entry information

Entry nameKSR1_HUMAN
AccessionPrimary (citable) accession number: Q8IVT5
Secondary accession number(s): Q13476
Entry history
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: December 21, 2004
Last modified: June 11, 2014
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM