CNKR1_HUMAN
ID CNKR1_HUMAN Reviewed; 720 AA.
AC Q969H4; B1AMW9; O95381;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Connector enhancer of kinase suppressor of ras 1;
DE Short=Connector enhancer of KSR 1;
DE AltName: Full=CNK homolog protein 1;
DE Short=CNK1;
DE Short=hCNK1;
DE AltName: Full=Connector enhancer of KSR-like;
GN Name=CNKSR1; Synonyms=CNK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Neuroepithelium;
RX PubMed=9814705; DOI=10.1016/s0092-8674(00)81766-3;
RA Therrien M., Wong A.M., Rubin G.M.;
RT "CNK, a RAF-binding multidomain protein required for RAS signaling.";
RL Cell 95:343-353(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH RHO AND RALGDS, AND MUTAGENESIS OF TRP-493.
RX PubMed=14749388; DOI=10.1128/mcb.24.4.1736-1746.2004;
RA Jaffe A.B., Aspenstroem P., Hall A.;
RT "Human CNK1 acts as a scaffold protein, linking Rho and Ras signal
RT transduction pathways.";
RL Mol. Cell. Biol. 24:1736-1746(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307 AND SER-314, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP STRUCTURE BY NMR OF 1-78.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the SAM domain of human connector enhancer of KSR-
RT like protein CNK1.";
RL Submitted (JUL-2005) to the PDB data bank.
CC -!- FUNCTION: May function as an adapter protein or regulator of Ras
CC signaling pathways.
CC -!- SUBUNIT: Interacts with RHO and RALGDS. {ECO:0000269|PubMed:14749388}.
CC -!- INTERACTION:
CC Q969H4; Q15438: CYTH1; NbExp=4; IntAct=EBI-741671, EBI-997830;
CC Q969H4; Q99418: CYTH2; NbExp=3; IntAct=EBI-741671, EBI-448974;
CC Q969H4; O43739: CYTH3; NbExp=4; IntAct=EBI-741671, EBI-741648;
CC Q969H4; O43739-2: CYTH3; NbExp=4; IntAct=EBI-741671, EBI-11974015;
CC Q969H4; Q8WWE8: CYTH4; NbExp=3; IntAct=EBI-741671, EBI-10277443;
CC Q969H4; Q9UIA0: CYTH4; NbExp=4; IntAct=EBI-741671, EBI-11521003;
CC Q969H4; Q13526: PIN1; NbExp=6; IntAct=EBI-741671, EBI-714158;
CC Q969H4; Q9Y4C2-2: TCAF1; NbExp=3; IntAct=EBI-741671, EBI-11974855;
CC Q969H4; Q8N5A5-2: ZGPAT; NbExp=3; IntAct=EBI-741671, EBI-10183064;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q969H4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q969H4-2; Sequence=VSP_010886;
CC -!- PTM: Phosphorylated on tyrosine.
CC -!- SIMILARITY: Belongs to the CNKSR family. {ECO:0000305}.
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DR EMBL; AF100153; AAC80558.1; -; mRNA.
DR EMBL; BT006900; AAP35546.1; -; mRNA.
DR EMBL; AL355877; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL391650; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07842.1; -; Genomic_DNA.
DR EMBL; BC011604; AAH11604.1; -; mRNA.
DR EMBL; BC012797; AAH12797.1; -; mRNA.
DR CCDS; CCDS276.1; -. [Q969H4-2]
DR CCDS; CCDS72732.1; -. [Q969H4-1]
DR RefSeq; NP_001284576.1; NM_001297647.1. [Q969H4-1]
DR RefSeq; NP_001284577.1; NM_001297648.1.
DR RefSeq; NP_006305.2; NM_006314.2. [Q969H4-2]
DR PDB; 1WWV; NMR; -; A=1-78.
DR PDBsum; 1WWV; -.
DR AlphaFoldDB; Q969H4; -.
DR SMR; Q969H4; -.
DR BioGRID; 115550; 44.
DR CORUM; Q969H4; -.
DR IntAct; Q969H4; 16.
DR MINT; Q969H4; -.
DR STRING; 9606.ENSP00000363371; -.
DR ChEMBL; CHEMBL4296242; -.
DR iPTMnet; Q969H4; -.
DR PhosphoSitePlus; Q969H4; -.
DR BioMuta; CNKSR1; -.
DR DMDM; 50400606; -.
DR EPD; Q969H4; -.
DR jPOST; Q969H4; -.
DR MassIVE; Q969H4; -.
DR MaxQB; Q969H4; -.
DR PaxDb; Q969H4; -.
DR PeptideAtlas; Q969H4; -.
DR PRIDE; Q969H4; -.
DR ProteomicsDB; 75763; -. [Q969H4-1]
DR ProteomicsDB; 75764; -. [Q969H4-2]
DR Antibodypedia; 30569; 156 antibodies from 26 providers.
DR DNASU; 10256; -.
DR Ensembl; ENST00000361530.11; ENSP00000354609.6; ENSG00000142675.18. [Q969H4-2]
DR Ensembl; ENST00000374253.9; ENSP00000363371.5; ENSG00000142675.18. [Q969H4-1]
DR GeneID; 10256; -.
DR KEGG; hsa:10256; -.
DR MANE-Select; ENST00000361530.11; ENSP00000354609.6; NM_006314.3; NP_006305.2. [Q969H4-2]
DR UCSC; uc001blm.5; human. [Q969H4-1]
DR CTD; 10256; -.
DR DisGeNET; 10256; -.
DR GeneCards; CNKSR1; -.
DR HGNC; HGNC:19700; CNKSR1.
DR HPA; ENSG00000142675; Tissue enhanced (skeletal).
DR MIM; 603272; gene.
DR neXtProt; NX_Q969H4; -.
DR OpenTargets; ENSG00000142675; -.
DR PharmGKB; PA134901167; -.
DR VEuPathDB; HostDB:ENSG00000142675; -.
DR eggNOG; KOG1738; Eukaryota.
DR GeneTree; ENSGT00940000159599; -.
DR HOGENOM; CLU_013414_1_0_1; -.
DR InParanoid; Q969H4; -.
DR OMA; ANALLFW; -.
DR PhylomeDB; Q969H4; -.
DR TreeFam; TF326495; -.
DR PathwayCommons; Q969H4; -.
DR Reactome; R-HSA-5674135; MAP2K and MAPK activation.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR SignaLink; Q969H4; -.
DR SIGNOR; Q969H4; -.
DR BioGRID-ORCS; 10256; 12 hits in 1067 CRISPR screens.
DR ChiTaRS; CNKSR1; human.
DR EvolutionaryTrace; Q969H4; -.
DR GeneWiki; CNKSR1; -.
DR GenomeRNAi; 10256; -.
DR Pharos; Q969H4; Tchem.
DR PRO; PR:Q969H4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q969H4; protein.
DR Bgee; ENSG00000142675; Expressed in hindlimb stylopod muscle and 173 other tissues.
DR ExpressionAtlas; Q969H4; baseline and differential.
DR Genevisible; Q969H4; HS.
DR GO; GO:0005938; C:cell cortex; IDA:MGI.
DR GO; GO:0005911; C:cell-cell junction; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; IPI:MGI.
DR GO; GO:0007266; P:Rho protein signal transduction; IPI:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; TAS:ProtInc.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR017874; CRIC_domain.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR Pfam; PF10534; CRIC_ras_sig; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00536; SAM_1; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR PROSITE; PS51290; CRIC; 1.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; Membrane;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..720
FT /note="Connector enhancer of kinase suppressor of ras 1"
FT /id="PRO_0000089969"
FT DOMAIN 7..70
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT DOMAIN 78..164
FT /note="CRIC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00621"
FT DOMAIN 196..285
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 403..502
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 285..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 504..573
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 676..720
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 615..646
FT /evidence="ECO:0000255"
FT COMPBIAS 298..312
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 325..339
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 347..361
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 535..572
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 679..695
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 253..259
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9814705"
FT /id="VSP_010886"
FT VARIANT 662
FT /note="R -> W (in dbSNP:rs17163640)"
FT /id="VAR_057790"
FT MUTAGEN 493
FT /note="W->A: No interaction with Rho."
FT /evidence="ECO:0000269|PubMed:14749388"
FT CONFLICT 694
FT /note="H -> N (in Ref. 1; AAC80558)"
FT /evidence="ECO:0000305"
FT TURN 4..6
FT /evidence="ECO:0007829|PDB:1WWV"
FT TURN 9..11
FT /evidence="ECO:0007829|PDB:1WWV"
FT HELIX 12..19
FT /evidence="ECO:0007829|PDB:1WWV"
FT HELIX 21..24
FT /evidence="ECO:0007829|PDB:1WWV"
FT HELIX 28..31
FT /evidence="ECO:0007829|PDB:1WWV"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:1WWV"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:1WWV"
FT HELIX 46..49
FT /evidence="ECO:0007829|PDB:1WWV"
FT HELIX 54..71
FT /evidence="ECO:0007829|PDB:1WWV"
FT TURN 76..78
FT /evidence="ECO:0007829|PDB:1WWV"
SQ SEQUENCE 720 AA; 79706 MW; E090785D1486D84B CRC64;
MEPVETWTPG KVATWLRGLD DSLQDYPFED WQLPGKNLLQ LCPQSLEALA VRSLGHQELI
LGGVEQLQAL SSRLQTENLQ SLTEGLLGAT HDFQSIVQGC LGDCAKTPID VLCAAVELLH
EADALLFWLS RYLFSHLNDF SACQEIRDLL EELSQVLHED GPAAEKEGTV LRICSHVAGI
CHNILVCCPK ELLEQKAVLE QVQLDSPLGL EIHTTSNCQH FVSQVDTQVP TDSRLQIQPG
DEVVQINEQV VVREERDMVG WPRKNMVREL LREPAGLSLV LKKIPIPETP PQTPPQVLDS
PHQRSPSLSL APLSPRAPSE DVFAFDLSSN PSPGPSPAWT DSASLGPEPL PIPPEPPAIL
PAGVAGTPGL PESPDKSPVG RKKSKGLATR LSRRRVSCRE LGRPDCDGWL LLRKAPGGFM
GPRWRRRWFV LKGHTLYWYR QPQDEKAEGL INVSNYSLES GHDQKKKYVF QLTHDVYKPF
IFAADTLTDL SMWVRHLITC ISKYQSPGRA PPPREEDCYS ETEAEDPDDE AGSHSASPSP
AQAGSPLHGD TSPAATPTQR SPRTSFGSLT DSSEEALEGM VRGLRQGGVS LLGQPQPLTQ
EQWRSSFMRR NRDPQLNERV HRVRALQSTL KAKLQELQVL EEVLGDPELT GEKFRQWKEQ
NRELYSEGLG AWGVAQAEGS SHILTSDSTE QSPHSLPSDP EEHSHLCPLT SESSLRPPDL
