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-SEP-2014, entry version 121.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RT   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.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   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.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   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.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: 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
RP   BY 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
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA   Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA   Blagoev B.;
RT   "System-wide temporal characterization of the proteome and
RT   phosphoproteome of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [9]
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
RT   KSR-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.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Membrane;
CC       Peripheral membrane protein (By similarity).
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         Note=No experimental confirmation available;
CC   -!- PTM: Phosphorylated on tyrosine.
CC   -!- SIMILARITY: Belongs to the CNKSR family.
CC   -!- SIMILARITY: Contains 1 CRIC domain.
CC   -!- SIMILARITY: Contains 1 PDZ (DHR) domain.
CC   -!- SIMILARITY: Contains 1 PH domain.
CC   -!- SIMILARITY: Contains 1 SAM (sterile alpha motif) domain.
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; CAH71543.1; -; Genomic_DNA.
DR   EMBL; AL391650; CAH71543.1; JOINED; Genomic_DNA.
DR   EMBL; AL391650; CAI17138.1; -; Genomic_DNA.
DR   EMBL; AL355877; CAI17138.1; JOINED; 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   RefSeq; NP_006305.2; NM_006314.2. [Q969H4-2]
DR   RefSeq; XP_006710344.1; XM_006710281.1. [Q969H4-1]
DR   UniGene; Hs.16232; -.
DR   PDB; 1WWV; NMR; -; A=1-78.
DR   PDBsum; 1WWV; -.
DR   ProteinModelPortal; Q969H4; -.
DR   SMR; Q969H4; 1-78, 217-252, 404-497.
DR   BioGrid; 115550; 9.
DR   IntAct; Q969H4; 3.
DR   MINT; MINT-1198255; -.
DR   STRING; 9606.ENSP00000354609; -.
DR   PhosphoSite; Q969H4; -.
DR   DMDM; 50400606; -.
DR   MaxQB; Q969H4; -.
DR   PaxDb; Q969H4; -.
DR   PRIDE; Q969H4; -.
DR   DNASU; 10256; -.
DR   Ensembl; ENST00000361530; ENSP00000354609; ENSG00000142675. [Q969H4-2]
DR   Ensembl; ENST00000374253; ENSP00000363371; ENSG00000142675. [Q969H4-1]
DR   GeneID; 10256; -.
DR   KEGG; hsa:10256; -.
DR   UCSC; uc001bln.4; human. [Q969H4-1]
DR   CTD; 10256; -.
DR   GeneCards; GC01P026503; -.
DR   H-InvDB; HIX0000288; -.
DR   HGNC; HGNC:19700; CNKSR1.
DR   HPA; HPA030847; -.
DR   HPA; HPA054309; -.
DR   MIM; 603272; gene.
DR   neXtProt; NX_Q969H4; -.
DR   PharmGKB; PA134901167; -.
DR   eggNOG; NOG251550; -.
DR   HOGENOM; HOG000231154; -.
DR   HOVERGEN; HBG051039; -.
DR   InParanoid; Q969H4; -.
DR   OMA; THDVYKP; -.
DR   OrthoDB; EOG71ZP0W; -.
DR   PhylomeDB; Q969H4; -.
DR   TreeFam; TF326495; -.
DR   SignaLink; Q969H4; -.
DR   EvolutionaryTrace; Q969H4; -.
DR   GeneWiki; CNKSR1; -.
DR   GenomeRNAi; 10256; -.
DR   NextBio; 38864; -.
DR   PRO; PR:Q969H4; -.
DR   ArrayExpress; Q969H4; -.
DR   Bgee; Q969H4; -.
DR   CleanEx; HS_CNKSR1; -.
DR   Genevestigator; Q969H4; -.
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 binding, bridging; 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; IPR019555; CRIC_domain_Chordata.
DR   InterPro; IPR001478; PDZ.
DR   InterPro; IPR001849; PH_domain.
DR   InterPro; IPR011993; PH_like_dom.
DR   InterPro; IPR001660; SAM.
DR   InterPro; IPR013761; SAM/pointed.
DR   InterPro; IPR021129; SAM_type1.
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; Complete proteome;
KW   Cytoplasm; Membrane; Phosphoprotein; Polymorphism; Reference proteome.
FT   CHAIN         1    720       Connector enhancer of kinase suppressor
FT                                of ras 1.
FT                                /FTId=PRO_0000089969.
FT   DOMAIN        7     70       SAM.
FT   DOMAIN       78    164       CRIC.
FT   DOMAIN      196    285       PDZ.
FT   DOMAIN      403    502       PH.
FT   COILED      615    646       Potential.
FT   COMPBIAS    285    378       Pro-rich.
FT   MOD_RES     314    314       Phosphoserine.
FT   VAR_SEQ     253    259       Missing (in isoform 2).
FT                                /FTId=VSP_010886.
FT   VARIANT     662    662       R -> W (in dbSNP:rs17163640).
FT                                /FTId=VAR_057790.
FT   MUTAGEN     493    493       W->A: No interaction with Rho.
FT   CONFLICT    694    694       H -> N (in Ref. 1; AAC80558).
FT   TURN          4      6
FT   TURN          9     11
FT   HELIX        12     19
FT   HELIX        21     24
FT   HELIX        28     31
FT   HELIX        35     38
FT   TURN         43     45
FT   HELIX        46     49
FT   HELIX        54     71
FT   TURN         76     78
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
//