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 27-MAR-2024, entry version 192. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 17. 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; 9606-ENSP00000363371; -. DR PeptideAtlas; Q969H4; -. DR ProteomicsDB; 75763; -. [Q969H4-1] DR ProteomicsDB; 75764; -. [Q969H4-2] DR Antibodypedia; 30569; 179 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 AGR; HGNC:19700; -. 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; RDVVGWP; -. DR OrthoDB; 5406576at2759; -. 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 1145 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 175 other cell types or tissues. DR ExpressionAtlas; Q969H4; baseline and differential. 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:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; TAS:ProtInc. DR CDD; cd01260; PH_CNK_mammalian-like; 1. DR CDD; cd09511; SAM_CNK1_2_3-suppressor; 1. DR Gene3D; 2.30.42.10; -; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1. DR InterPro; IPR049628; CNK1-3_SAM. 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 PANTHER; PTHR12844; CONNECTOR ENCHANCER OF KINASE SUPPRESSOR OF RAS; 1. DR PANTHER; PTHR12844:SF10; CONNECTOR ENHANCER OF KINASE SUPPRESSOR OF RAS 1; 1. DR Pfam; PF10534; CRIC_ras_sig; 1. DR Pfam; PF00169; PH; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00454; SAM; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF47769; SAM/Pointed domain; 1. DR PROSITE; PS51290; CRIC; 1. DR PROSITE; PS50106; PDZ; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50105; SAM_DOMAIN; 1. DR Genevisible; Q969H4; HS. 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 //