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Protein

Connector enhancer of kinase suppressor of ras 1

Gene

CNKSR1

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.

GO - Molecular functioni

  1. protein binding, bridging Source: MGI

GO - Biological processi

  1. Ras protein signal transduction Source: MGI
  2. Rho protein signal transduction Source: MGI
  3. transmembrane receptor protein tyrosine kinase signaling pathway Source: ProtInc
Complete GO annotation...

Enzyme and pathway databases

SignaLinkiQ969H4.

Names & Taxonomyi

Protein namesi
Recommended name:
Connector enhancer of kinase suppressor of ras 1
Short name:
Connector enhancer of KSR 1
Alternative name(s):
CNK homolog protein 1
Short name:
CNK1
Short name:
hCNK1
Connector enhancer of KSR-like
Gene namesi
Name:CNKSR1
Synonyms:CNK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:19700. CNKSR1.

Subcellular locationi

  1. Cytoplasm By similarity
  2. Membrane By similarity; Peripheral membrane protein By similarity

GO - Cellular componenti

  1. cell-cell junction Source: ProtInc
  2. cell cortex Source: MGI
  3. plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi493 – 4931W → A: No interaction with Rho. 1 Publication

Organism-specific databases

PharmGKBiPA134901167.

Polymorphism and mutation databases

BioMutaiCNKSR1.
DMDMi50400606.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 720720Connector enhancer of kinase suppressor of ras 1PRO_0000089969Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei314 – 3141Phosphoserine2 Publications

Post-translational modificationi

Phosphorylated on tyrosine.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ969H4.
PaxDbiQ969H4.
PRIDEiQ969H4.

PTM databases

PhosphoSiteiQ969H4.

Expressioni

Gene expression databases

BgeeiQ969H4.
CleanExiHS_CNKSR1.
ExpressionAtlasiQ969H4. baseline and differential.
GenevestigatoriQ969H4.

Organism-specific databases

HPAiHPA030847.
HPA054309.

Interactioni

Subunit structurei

Interacts with RHO and RALGDS.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CYTH3O437394EBI-741671,EBI-741648
CYTH4Q8WWE83EBI-741671,EBI-10277443
PIN1Q135263EBI-741671,EBI-714158

Protein-protein interaction databases

BioGridi115550. 12 interactions.
IntActiQ969H4. 5 interactions.
MINTiMINT-1198255.
STRINGi9606.ENSP00000354609.

Structurei

Secondary structure

1
720
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni4 – 63Combined sources
Turni9 – 113Combined sources
Helixi12 – 198Combined sources
Helixi21 – 244Combined sources
Helixi28 – 314Combined sources
Helixi35 – 384Combined sources
Turni43 – 453Combined sources
Helixi46 – 494Combined sources
Helixi54 – 7118Combined sources
Turni76 – 783Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WWVNMR-A1-78[»]
ProteinModelPortaliQ969H4.
SMRiQ969H4. Positions 1-78, 404-497.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ969H4.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini7 – 7064SAMPROSITE-ProRule annotationAdd
BLAST
Domaini78 – 16487CRICPROSITE-ProRule annotationAdd
BLAST
Domaini196 – 28590PDZPROSITE-ProRule annotationAdd
BLAST
Domaini403 – 502100PHPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili615 – 64632Sequence AnalysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi285 – 37894Pro-richAdd
BLAST

Sequence similaritiesi

Belongs to the CNKSR family.Curated
Contains 1 CRIC domain.PROSITE-ProRule annotation
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

eggNOGiNOG251550.
GeneTreeiENSGT00390000017199.
HOGENOMiHOG000231154.
HOVERGENiHBG051039.
InParanoidiQ969H4.
OMAiTHDVYKP.
OrthoDBiEOG71ZP0W.
PhylomeDBiQ969H4.
TreeFamiTF326495.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.30.29.30. 1 hit.
2.30.42.10. 1 hit.
InterProiIPR017874. CRIC_domain.
IPR019555. CRIC_domain_Chordata.
IPR001478. PDZ.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR021129. SAM_type1.
[Graphical view]
PfamiPF10534. CRIC_ras_sig. 1 hit.
PF00169. PH. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
PROSITEiPS51290. CRIC. 1 hit.
PS50106. PDZ. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q969H4-1) [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
MEPVETWTPG KVATWLRGLD DSLQDYPFED WQLPGKNLLQ LCPQSLEALA
60 70 80 90 100
VRSLGHQELI LGGVEQLQAL SSRLQTENLQ SLTEGLLGAT HDFQSIVQGC
110 120 130 140 150
LGDCAKTPID VLCAAVELLH EADALLFWLS RYLFSHLNDF SACQEIRDLL
160 170 180 190 200
EELSQVLHED GPAAEKEGTV LRICSHVAGI CHNILVCCPK ELLEQKAVLE
210 220 230 240 250
QVQLDSPLGL EIHTTSNCQH FVSQVDTQVP TDSRLQIQPG DEVVQINEQV
260 270 280 290 300
VVREERDMVG WPRKNMVREL LREPAGLSLV LKKIPIPETP PQTPPQVLDS
310 320 330 340 350
PHQRSPSLSL APLSPRAPSE DVFAFDLSSN PSPGPSPAWT DSASLGPEPL
360 370 380 390 400
PIPPEPPAIL PAGVAGTPGL PESPDKSPVG RKKSKGLATR LSRRRVSCRE
410 420 430 440 450
LGRPDCDGWL LLRKAPGGFM GPRWRRRWFV LKGHTLYWYR QPQDEKAEGL
460 470 480 490 500
INVSNYSLES GHDQKKKYVF QLTHDVYKPF IFAADTLTDL SMWVRHLITC
510 520 530 540 550
ISKYQSPGRA PPPREEDCYS ETEAEDPDDE AGSHSASPSP AQAGSPLHGD
560 570 580 590 600
TSPAATPTQR SPRTSFGSLT DSSEEALEGM VRGLRQGGVS LLGQPQPLTQ
610 620 630 640 650
EQWRSSFMRR NRDPQLNERV HRVRALQSTL KAKLQELQVL EEVLGDPELT
660 670 680 690 700
GEKFRQWKEQ NRELYSEGLG AWGVAQAEGS SHILTSDSTE QSPHSLPSDP
710 720
EEHSHLCPLT SESSLRPPDL
Length:720
Mass (Da):79,706
Last modified:December 1, 2001 - v1
Checksum:iE090785D1486D84B
GO
Isoform 2 (identifier: Q969H4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     253-259: Missing.

Note: No experimental confirmation available.

Show »
Length:713
Mass (Da):78,790
Checksum:iBF7383CCDA911E7E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti694 – 6941H → N in AAC80558 (PubMed:9814705).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti662 – 6621R → W.
Corresponds to variant rs17163640 [ dbSNP | Ensembl ].
VAR_057790

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei253 – 2597Missing in isoform 2. 1 PublicationVSP_010886

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF100153 mRNA. Translation: AAC80558.1.
BT006900 mRNA. Translation: AAP35546.1.
AL355877, AL391650 Genomic DNA. Translation: CAH71543.1.
AL391650, AL355877 Genomic DNA. Translation: CAI17138.1.
CH471059 Genomic DNA. Translation: EAX07842.1.
BC011604 mRNA. Translation: AAH11604.1.
BC012797 mRNA. Translation: AAH12797.1.
CCDSiCCDS276.1. [Q969H4-2]
CCDS72732.1. [Q969H4-1]
RefSeqiNP_001284576.1. NM_001297647.1. [Q969H4-1]
NP_001284577.1. NM_001297648.1.
NP_006305.2. NM_006314.2. [Q969H4-2]
UniGeneiHs.16232.

Genome annotation databases

EnsembliENST00000361530; ENSP00000354609; ENSG00000142675. [Q969H4-2]
ENST00000374253; ENSP00000363371; ENSG00000142675. [Q969H4-1]
GeneIDi10256.
KEGGihsa:10256.
UCSCiuc001bln.4. human. [Q969H4-1]

Polymorphism and mutation databases

BioMutaiCNKSR1.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF100153 mRNA. Translation: AAC80558.1.
BT006900 mRNA. Translation: AAP35546.1.
AL355877, AL391650 Genomic DNA. Translation: CAH71543.1.
AL391650, AL355877 Genomic DNA. Translation: CAI17138.1.
CH471059 Genomic DNA. Translation: EAX07842.1.
BC011604 mRNA. Translation: AAH11604.1.
BC012797 mRNA. Translation: AAH12797.1.
CCDSiCCDS276.1. [Q969H4-2]
CCDS72732.1. [Q969H4-1]
RefSeqiNP_001284576.1. NM_001297647.1. [Q969H4-1]
NP_001284577.1. NM_001297648.1.
NP_006305.2. NM_006314.2. [Q969H4-2]
UniGeneiHs.16232.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WWVNMR-A1-78[»]
ProteinModelPortaliQ969H4.
SMRiQ969H4. Positions 1-78, 404-497.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115550. 12 interactions.
IntActiQ969H4. 5 interactions.
MINTiMINT-1198255.
STRINGi9606.ENSP00000354609.

PTM databases

PhosphoSiteiQ969H4.

Polymorphism and mutation databases

BioMutaiCNKSR1.
DMDMi50400606.

Proteomic databases

MaxQBiQ969H4.
PaxDbiQ969H4.
PRIDEiQ969H4.

Protocols and materials databases

DNASUi10256.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361530; ENSP00000354609; ENSG00000142675. [Q969H4-2]
ENST00000374253; ENSP00000363371; ENSG00000142675. [Q969H4-1]
GeneIDi10256.
KEGGihsa:10256.
UCSCiuc001bln.4. human. [Q969H4-1]

Organism-specific databases

CTDi10256.
GeneCardsiGC01P026503.
H-InvDBHIX0000288.
HGNCiHGNC:19700. CNKSR1.
HPAiHPA030847.
HPA054309.
MIMi603272. gene.
neXtProtiNX_Q969H4.
PharmGKBiPA134901167.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG251550.
GeneTreeiENSGT00390000017199.
HOGENOMiHOG000231154.
HOVERGENiHBG051039.
InParanoidiQ969H4.
OMAiTHDVYKP.
OrthoDBiEOG71ZP0W.
PhylomeDBiQ969H4.
TreeFamiTF326495.

Enzyme and pathway databases

SignaLinkiQ969H4.

Miscellaneous databases

ChiTaRSiCNKSR1. human.
EvolutionaryTraceiQ969H4.
GeneWikiiCNKSR1.
GenomeRNAii10256.
NextBioi38864.
PROiQ969H4.
SOURCEiSearch...

Gene expression databases

BgeeiQ969H4.
CleanExiHS_CNKSR1.
ExpressionAtlasiQ969H4. baseline and differential.
GenevestigatoriQ969H4.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.30.29.30. 1 hit.
2.30.42.10. 1 hit.
InterProiIPR017874. CRIC_domain.
IPR019555. CRIC_domain_Chordata.
IPR001478. PDZ.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR021129. SAM_type1.
[Graphical view]
PfamiPF10534. CRIC_ras_sig. 1 hit.
PF00169. PH. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
PROSITEiPS51290. CRIC. 1 hit.
PS50106. PDZ. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "CNK, a RAF-binding multidomain protein required for RAS signaling."
    Therrien M., Wong A.M., Rubin G.M.
    Cell 95:343-353(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Neuroepithelium.
  2. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  3. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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 1).
    Tissue: Placenta.
  6. "Human CNK1 acts as a scaffold protein, linking Rho and Ras signal transduction pathways."
    Jaffe A.B., Aspenstroem P., Hall A.
    Mol. Cell. Biol. 24:1736-1746(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RHO AND RALGDS, MUTAGENESIS OF TRP-493.
  7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  8. "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-314, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "Solution structure of the SAM domain of human connector enhancer of KSR-like protein CNK1."
    RIKEN structural genomics initiative (RSGI)
    Submitted (JUL-2005) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 1-78.

Entry informationi

Entry nameiCNKR1_HUMAN
AccessioniPrimary (citable) accession number: Q969H4
Secondary accession number(s): B1AMW9, O95381
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: December 1, 2001
Last modified: April 29, 2015
This is version 128 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 1
    Human chromosome 1: 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

External Data

Dasty 3

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 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.