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Protein

Connector enhancer of kinase suppressor of ras 2

Gene

CNKSR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May function as an adapter protein or regulator of Ras signaling pathways.1 Publication

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000149970-MONOMER.
ReactomeiR-HSA-5674135. MAP2K and MAPK activation.
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.
SignaLinkiQ8WXI2.
SIGNORiQ8WXI2.

Names & Taxonomyi

Protein namesi
Recommended name:
Connector enhancer of kinase suppressor of ras 2
Short name:
Connector enhancer of KSR 2
Alternative name(s):
CNK homolog protein 2
Short name:
CNK2
Gene namesi
Name:CNKSR2
Synonyms:CNK2, KIAA0902, KSR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:19701. CNKSR2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi22866.
OpenTargetsiENSG00000149970.
PharmGKBiPA134867759.

Polymorphism and mutation databases

BioMutaiCNKSR2.
DMDMi50400586.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000899701 – 1034Connector enhancer of kinase suppressor of ras 2Add BLAST1034

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei12PhosphoserineBy similarity1
Modified residuei338PhosphoserineBy similarity1
Modified residuei390PhosphoserineBy similarity1
Modified residuei683PhosphotyrosineBy similarity1
Modified residuei685PhosphoserineBy similarity1
Modified residuei687PhosphoserineBy similarity1
Modified residuei756PhosphoserineBy similarity1
Modified residuei767PhosphoserineBy similarity1
Modified residuei908PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on tyrosine.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8WXI2.
PaxDbiQ8WXI2.
PeptideAtlasiQ8WXI2.
PRIDEiQ8WXI2.

PTM databases

iPTMnetiQ8WXI2.
PhosphoSitePlusiQ8WXI2.

Expressioni

Gene expression databases

BgeeiENSG00000149970.
CleanExiHS_CNKSR2.
HS_KSR2.
GenevisibleiQ8WXI2. HS.

Organism-specific databases

HPAiHPA001502.

Interactioni

Subunit structurei

Interacts with RAF1, RAB2L and RAL GTPase proteins.1 Publication

Protein-protein interaction databases

BioGridi116534. 7 interactors.
DIPiDIP-29736N.
IntActiQ8WXI2. 3 interactors.
MINTiMINT-1784713.
STRINGi9606.ENSP00000368824.

Structurei

Secondary structure

11034
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi8 – 10Combined sources3
Helixi13 – 21Combined sources9
Helixi25 – 30Combined sources6
Helixi31 – 37Combined sources7
Helixi41 – 45Combined sources5
Helixi49 – 54Combined sources6
Helixi60 – 77Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EANNMR-A8-77[»]
3BS5X-ray2.00B5-84[»]
ProteinModelPortaliQ8WXI2.
SMRiQ8WXI2.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8WXI2.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 76SAMPROSITE-ProRule annotationAdd BLAST66
Domaini84 – 178CRICPROSITE-ProRule annotationAdd BLAST95
Domaini215 – 297PDZPROSITE-ProRule annotationAdd BLAST83
Domaini332 – 515DUF1170Add BLAST184
Domaini570 – 669PHPROSITE-ProRule annotationAdd BLAST100

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili875 – 904Sequence analysisAdd BLAST30

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi354 – 357Poly-Pro4
Compositional biasi703 – 706Poly-Pro4
Compositional biasi875 – 888Poly-GluAdd BLAST14

Sequence similaritiesi

Belongs to the CNKSR family.Curated
Contains 1 CRIC domain.PROSITE-ProRule annotation
Contains 1 DUF1170 domain.Curated
Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG1738. Eukaryota.
ENOG4110T89. LUCA.
GeneTreeiENSGT00390000017199.
HOGENOMiHOG000231501.
HOVERGENiHBG051040.
InParanoidiQ8WXI2.
KOiK17536.
OMAiSTKLEYK.
OrthoDBiEOG091G037J.
PhylomeDBiQ8WXI2.
TreeFamiTF326495.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.30.29.30. 1 hit.
2.30.42.10. 1 hit.
InterProiIPR010599. CNKSR2.
IPR017874. CRIC_domain.
IPR001478. PDZ.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR001660. SAM.
IPR013761. SAM/pointed.
[Graphical view]
PfamiPF10534. CRIC_ras_sig. 1 hit.
PF06663. DUF1170. 1 hit.
PF00595. PDZ. 1 hit.
PF00169. PH. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
SMARTiSM00228. PDZ. 1 hit.
SM00233. PH. 1 hit.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF50156. SSF50156. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS51290. CRIC. 1 hit.
PS50106. PDZ. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q8WXI2-1) [UniParc]FASTAAdd to basket
Also known as: CNK2A, KSR2A

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
MALIMEPVSK WSPSQVVDWM KGLDDCLQQY IKNFEREKIS GDQLLRITHQ
60 70 80 90 100
ELEDLGVSRI GHQELILEAV DLLCALNYGL ETENLKTLSH KLNASAKNLQ
110 120 130 140 150
NFITGRRRSG HYDGRTSRKL PNDFLTSVVD LIGAAKSLLA WLDRSPFAAV
160 170 180 190 200
TDYSVTRNNV IQLCLELTTI VQQDCTVYET ENKILHVCKT LSGVCDHIIS
210 220 230 240 250
LSSDPLVSQS AHLEVIQLAN IKPSEGLGMY IKSTYDGLHV ITGTTENSPA
260 270 280 290 300
DRCKKIHAGD EVIQVNHQTV VGWQLKNLVN ALREDPSGVI LTLKKRPQSM
310 320 330 340 350
LTSAPALLKN MRWKPLALQP LIPRSPTSSV ATPSSTISTP TKRDSSALQD
360 370 380 390 400
LYIPPPPAEP YIPRDEKGNL PCEDLRGHMV GKPVHKGSES PNSFLDQEYR
410 420 430 440 450
KRFNIVEEDT VLYCYEYEKG RSSSQGRRES TPTYGKLRPI SMPVEYNWVG
460 470 480 490 500
DYEDPNKMKR DSRRENSLLR YMSNEKIAQE EYMFQRNSKK DTGKKSKKKG
510 520 530 540 550
DKSNSPTHYS LLPSLQMDAL RQDIMGTPVP ETTLYHTFQQ SSLQHKSKKK
560 570 580 590 600
NKGPIAGKSK RRISCKDLGR GDCEGWLWKK KDAKSYFSQK WKKYWFVLKD
610 620 630 640 650
ASLYWYINEE DEKAEGFISL PEFKIDRASE CRKKYAFKAC HPKIKSFYFA
660 670 680 690 700
AEHLDDMNRW LNRINMLTAG YAERERIKQE QDYWSESDKE EADTPSTPKQ
710 720 730 740 750
DSPPPPYDTY PRPPSMSCAS PYVEAKHSRL SSTETSQSQS SHEEFRQEVT
760 770 780 790 800
GSSAVSPIRK TASQRRSWQD LIETPLTSSG LHYLQTLPLE DSVFSDSAAI
810 820 830 840 850
SPEHRRQSTL PTQKCHLQDH YGPYPLAESE RMQVLNGNGG KPRSFTLPRD
860 870 880 890 900
SGFNHCCLNA PVSACDPQDD VQPPEVEEEE EEEEEEGEAA GENIGEKSES
910 920 930 940 950
REEKLGDSLQ DLYRALEQAS LSPLGEHRIS TKMEYKLSFI KRCNDPVMNE
960 970 980 990 1000
KLHRLRILKS TLKAREGEVA IIDKVLDNPD LTSKEFQQWK QMYLDLFLDI
1010 1020 1030
CQNTTSNDPL SISSEVDVIT SSLAHTHSYI ETHV
Length:1,034
Mass (Da):117,535
Last modified:March 1, 2002 - v1
Checksum:iE43DB0D8D72D954C
GO
Isoform 2 (identifier: Q8WXI2-2) [UniParc]FASTAAdd to basket
Also known as: CNK2B, KSR2B

The sequence of this isoform differs from the canonical sequence as follows:
     899-1034: Missing.

Show »
Length:898
Mass (Da):101,874
Checksum:i4DFEFE26960DF70C
GO
Isoform 3 (identifier: Q8WXI2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     271-319: Missing.
     899-1034: Missing.

Note: No experimental confirmation available.
Show »
Length:849
Mass (Da):96,366
Checksum:iD95B2A7AC2639040
GO
Isoform 4 (identifier: Q8WXI2-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     435-464: Missing.

Note: No experimental confirmation available.
Show »
Length:1,004
Mass (Da):113,914
Checksum:iC635EA09FA4E6696
GO

Sequence cautioni

Isoform 2 : The sequence BAA74925 differs from that shown. Reason: Frameshift at positions 859, 929, 985 and 1019.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03568146R → H in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs771705122dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_043168271 – 319Missing in isoform 3. 1 PublicationAdd BLAST49
Alternative sequenceiVSP_043169435 – 464Missing in isoform 4. 1 PublicationAdd BLAST30
Alternative sequenceiVSP_010887899 – 1034Missing in isoform 2 and isoform 3. 3 PublicationsAdd BLAST136

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF418269 mRNA. Translation: AAL60502.1.
AF418270 mRNA. Translation: AAL60503.1.
AB020709 mRNA. Translation: BAA74925.2. Frameshift.
AK294728 mRNA. Translation: BAG57875.1.
AL928874, AL772392, AL807781 Genomic DNA. Translation: CAH70863.1.
AL928874, AL772392, AL807781 Genomic DNA. Translation: CAH70864.1.
AL807781, AL772392, AL928874 Genomic DNA. Translation: CAI39866.1.
AL807781, AL772392, AL928874 Genomic DNA. Translation: CAI39867.1.
AL772392, AL807781, AL928874 Genomic DNA. Translation: CAI40765.1.
AL772392, AL807781, AL928874 Genomic DNA. Translation: CAI40766.1.
CH471074 Genomic DNA. Translation: EAW98977.1.
BC126121 mRNA. Translation: AAI26122.1.
BC136289 mRNA. Translation: AAI36290.1.
BC143839 mRNA. Translation: AAI43840.1.
CCDSiCCDS14198.1. [Q8WXI2-1]
CCDS55387.1. [Q8WXI2-2]
CCDS55388.1. [Q8WXI2-5]
CCDS55389.1. [Q8WXI2-4]
RefSeqiNP_001162118.1. NM_001168647.2. [Q8WXI2-5]
NP_001162119.1. NM_001168648.2. [Q8WXI2-2]
NP_001162120.1. NM_001168649.2. [Q8WXI2-4]
NP_055742.2. NM_014927.4. [Q8WXI2-1]
UniGeneiHs.555917.

Genome annotation databases

EnsembliENST00000279451; ENSP00000279451; ENSG00000149970. [Q8WXI2-2]
ENST00000379510; ENSP00000368824; ENSG00000149970. [Q8WXI2-1]
ENST00000425654; ENSP00000397906; ENSG00000149970. [Q8WXI2-5]
ENST00000543067; ENSP00000444633; ENSG00000149970. [Q8WXI2-4]
GeneIDi22866.
KEGGihsa:22866.
UCSCiuc004czw.4. human. [Q8WXI2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF418269 mRNA. Translation: AAL60502.1.
AF418270 mRNA. Translation: AAL60503.1.
AB020709 mRNA. Translation: BAA74925.2. Frameshift.
AK294728 mRNA. Translation: BAG57875.1.
AL928874, AL772392, AL807781 Genomic DNA. Translation: CAH70863.1.
AL928874, AL772392, AL807781 Genomic DNA. Translation: CAH70864.1.
AL807781, AL772392, AL928874 Genomic DNA. Translation: CAI39866.1.
AL807781, AL772392, AL928874 Genomic DNA. Translation: CAI39867.1.
AL772392, AL807781, AL928874 Genomic DNA. Translation: CAI40765.1.
AL772392, AL807781, AL928874 Genomic DNA. Translation: CAI40766.1.
CH471074 Genomic DNA. Translation: EAW98977.1.
BC126121 mRNA. Translation: AAI26122.1.
BC136289 mRNA. Translation: AAI36290.1.
BC143839 mRNA. Translation: AAI43840.1.
CCDSiCCDS14198.1. [Q8WXI2-1]
CCDS55387.1. [Q8WXI2-2]
CCDS55388.1. [Q8WXI2-5]
CCDS55389.1. [Q8WXI2-4]
RefSeqiNP_001162118.1. NM_001168647.2. [Q8WXI2-5]
NP_001162119.1. NM_001168648.2. [Q8WXI2-2]
NP_001162120.1. NM_001168649.2. [Q8WXI2-4]
NP_055742.2. NM_014927.4. [Q8WXI2-1]
UniGeneiHs.555917.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EANNMR-A8-77[»]
3BS5X-ray2.00B5-84[»]
ProteinModelPortaliQ8WXI2.
SMRiQ8WXI2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116534. 7 interactors.
DIPiDIP-29736N.
IntActiQ8WXI2. 3 interactors.
MINTiMINT-1784713.
STRINGi9606.ENSP00000368824.

PTM databases

iPTMnetiQ8WXI2.
PhosphoSitePlusiQ8WXI2.

Polymorphism and mutation databases

BioMutaiCNKSR2.
DMDMi50400586.

Proteomic databases

MaxQBiQ8WXI2.
PaxDbiQ8WXI2.
PeptideAtlasiQ8WXI2.
PRIDEiQ8WXI2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000279451; ENSP00000279451; ENSG00000149970. [Q8WXI2-2]
ENST00000379510; ENSP00000368824; ENSG00000149970. [Q8WXI2-1]
ENST00000425654; ENSP00000397906; ENSG00000149970. [Q8WXI2-5]
ENST00000543067; ENSP00000444633; ENSG00000149970. [Q8WXI2-4]
GeneIDi22866.
KEGGihsa:22866.
UCSCiuc004czw.4. human. [Q8WXI2-1]

Organism-specific databases

CTDi22866.
DisGeNETi22866.
GeneCardsiCNKSR2.
HGNCiHGNC:19701. CNKSR2.
HPAiHPA001502.
MIMi300724. gene.
neXtProtiNX_Q8WXI2.
OpenTargetsiENSG00000149970.
PharmGKBiPA134867759.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1738. Eukaryota.
ENOG4110T89. LUCA.
GeneTreeiENSGT00390000017199.
HOGENOMiHOG000231501.
HOVERGENiHBG051040.
InParanoidiQ8WXI2.
KOiK17536.
OMAiSTKLEYK.
OrthoDBiEOG091G037J.
PhylomeDBiQ8WXI2.
TreeFamiTF326495.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000149970-MONOMER.
ReactomeiR-HSA-5674135. MAP2K and MAPK activation.
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.
SignaLinkiQ8WXI2.
SIGNORiQ8WXI2.

Miscellaneous databases

ChiTaRSiCNKSR2. human.
EvolutionaryTraceiQ8WXI2.
GeneWikiiCNKSR2.
GenomeRNAii22866.
PROiQ8WXI2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000149970.
CleanExiHS_CNKSR2.
HS_KSR2.
GenevisibleiQ8WXI2. HS.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.30.29.30. 1 hit.
2.30.42.10. 1 hit.
InterProiIPR010599. CNKSR2.
IPR017874. CRIC_domain.
IPR001478. PDZ.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR001660. SAM.
IPR013761. SAM/pointed.
[Graphical view]
PfamiPF10534. CRIC_ras_sig. 1 hit.
PF06663. DUF1170. 1 hit.
PF00595. PDZ. 1 hit.
PF00169. PH. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
SMARTiSM00228. PDZ. 1 hit.
SM00233. PH. 1 hit.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF50156. SSF50156. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS51290. CRIC. 1 hit.
PS50106. PDZ. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCNKR2_HUMAN
AccessioniPrimary (citable) accession number: Q8WXI2
Secondary accession number(s): B4DGR4
, B7ZLJ1, B9EG83, E7ESA4, O94976, Q5JPK4, Q5JPN0, Q8WXI1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: March 1, 2002
Last modified: November 30, 2016
This is version 136 of the entry and version 1 of the sequence. [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. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.