ID CNKR2_HUMAN Reviewed; 1034 AA. AC Q8WXI2; B4DGR4; B7ZLJ1; B9EG83; E7ESA4; O94976; Q5JPK4; Q5JPN0; Q8WXI1; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2002, sequence version 1. DT 24-JUL-2024, entry version 186. DE RecName: Full=Connector enhancer of kinase suppressor of ras 2; DE Short=Connector enhancer of KSR 2; DE AltName: Full=CNK homolog protein 2; DE Short=CNK2; GN Name=CNKSR2; Synonyms=CNK2, KIAA0902, KSR2; 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] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH RP RAF1; RAB2L AND RAL GTPASE PROTEINS, AND PHOSPHORYLATION. RC TISSUE=Fetal brain; RX PubMed=14597674; DOI=10.1096/fj.02-1096com; RA Lanigan T.M., Liu A., Huang Y.Z., Mei L., Margolis B., Guan K.-L.; RT "Human homologue of Drosophila CNK interacts with Ras effector proteins Raf RT and Rlf."; RL FASEB J. 17:2048-2060(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=10048485; DOI=10.1093/dnares/5.6.355; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 5:355-364(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [5] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4). RC TISSUE=Brain, and Testis; 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-908, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-908, 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-908, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [10] RP STRUCTURE BY NMR OF 8-79. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the N-terminal SAM-domain of human KIAA0902 protein RT (connector enhancer of kinase suppressor of RAS 2)."; RL Submitted (JUL-2007) to the PDB data bank. RN [11] RP VARIANT [LARGE SCALE ANALYSIS] HIS-46. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [12] RP INVOLVEMENT IN MRXSHG. RX PubMed=25223753; DOI=10.1002/ana.24274; RA Vaags A.K., Bowdin S., Smith M.L., Gilbert-Dussardier B., RA Brocke-Holmefjord K.S., Sinopoli K., Gilles C., Haaland T.B., RA Vincent-Delorme C., Lagrue E., Harbuz R., Walker S., Marshall C.R., RA Houge G., Kalscheuer V.M., Scherer S.W., Minassian B.A.; RT "Absent CNKSR2 causes seizures and intellectual, attention, and language RT deficits."; RL Ann. Neurol. 76:758-764(2014). RN [13] RP INVOLVEMENT IN MRXSHG, AND VARIANT MRXSHG 712-ARG--VAL-1034 DEL. RX PubMed=28098945; DOI=10.1111/epi.13666; RA Damiano J.A., Burgess R., Kivity S., Lerman-Sagie T., Afawi Z., RA Scheffer I.E., Berkovic S.F., Hildebrand M.S.; RT "Frequency of CNKSR2 mutation in the X-linked epilepsy-aphasia spectrum."; RL Epilepsia 58:E40-E43(2017). CC -!- FUNCTION: May function as an adapter protein or regulator of Ras CC signaling pathways. {ECO:0000269|PubMed:14597674}. CC -!- SUBUNIT: Interacts with RAF1, RAB2L and RAL GTPase proteins. CC {ECO:0000269|PubMed:14597674}. CC -!- INTERACTION: CC Q8WXI2; P00533: EGFR; NbExp=2; IntAct=EBI-1045119, EBI-297353; CC Q8WXI2; Q8ML92: ave; Xeno; NbExp=5; IntAct=EBI-1045119, EBI-2563975; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=CNK2A, KSR2A; CC IsoId=Q8WXI2-1; Sequence=Displayed; CC Name=2; Synonyms=CNK2B, KSR2B; CC IsoId=Q8WXI2-2; Sequence=VSP_010887; CC Name=3; CC IsoId=Q8WXI2-4; Sequence=VSP_043168, VSP_010887; CC Name=4; CC IsoId=Q8WXI2-5; Sequence=VSP_043169; CC -!- PTM: Phosphorylated on tyrosine. {ECO:0000269|PubMed:14597674}. CC -!- DISEASE: Intellectual developmental disorder, X-linked, syndromic, CC Houge type (MRXSHG) [MIM:301008]: A disorder characterized by delayed CC development, intellectual disability, speech and language delay, and CC early-onset seizures. Carrier females may be mildly affected. CC {ECO:0000269|PubMed:25223753, ECO:0000269|PubMed:28098945}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the CNKSR family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: [Isoform 2]: CC Sequence=BAA74925.2; Type=Frameshift; Evidence={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; AF418269; AAL60502.1; -; mRNA. DR EMBL; AF418270; AAL60503.1; -; mRNA. DR EMBL; AB020709; BAA74925.2; ALT_FRAME; mRNA. DR EMBL; AK294728; BAG57875.1; -; mRNA. DR EMBL; AL928874; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL807781; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL772392; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471074; EAW98977.1; -; Genomic_DNA. DR EMBL; BC126121; AAI26122.1; -; mRNA. DR EMBL; BC136289; AAI36290.1; -; mRNA. DR EMBL; BC143839; AAI43840.1; -; mRNA. DR CCDS; CCDS14198.1; -. [Q8WXI2-1] DR CCDS; CCDS55387.1; -. [Q8WXI2-2] DR CCDS; CCDS55388.1; -. [Q8WXI2-5] DR CCDS; CCDS55389.1; -. [Q8WXI2-4] DR RefSeq; NP_001162118.1; NM_001168647.2. [Q8WXI2-5] DR RefSeq; NP_001162119.1; NM_001168648.2. [Q8WXI2-2] DR RefSeq; NP_001162120.1; NM_001168649.2. [Q8WXI2-4] DR RefSeq; NP_055742.2; NM_014927.4. [Q8WXI2-1] DR PDB; 2EAN; NMR; -; A=8-77. DR PDB; 3BS5; X-ray; 2.00 A; B=5-84. DR PDBsum; 2EAN; -. DR PDBsum; 3BS5; -. DR AlphaFoldDB; Q8WXI2; -. DR SMR; Q8WXI2; -. DR BioGRID; 116534; 17. DR DIP; DIP-29736N; -. DR IntAct; Q8WXI2; 10. DR MINT; Q8WXI2; -. DR STRING; 9606.ENSP00000368824; -. DR ChEMBL; CHEMBL1938216; -. DR GlyGen; Q8WXI2; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8WXI2; -. DR PhosphoSitePlus; Q8WXI2; -. DR BioMuta; CNKSR2; -. DR DMDM; 50400586; -. DR jPOST; Q8WXI2; -. DR MassIVE; Q8WXI2; -. DR PaxDb; 9606-ENSP00000368824; -. DR PeptideAtlas; Q8WXI2; -. DR ProteomicsDB; 75059; -. [Q8WXI2-1] DR ProteomicsDB; 75060; -. [Q8WXI2-2] DR ProteomicsDB; 75061; -. [Q8WXI2-4] DR ProteomicsDB; 75062; -. [Q8WXI2-5] DR Antibodypedia; 456; 117 antibodies from 18 providers. DR DNASU; 22866; -. DR Ensembl; ENST00000379510.5; ENSP00000368824.3; ENSG00000149970.16. [Q8WXI2-1] DR Ensembl; ENST00000425654.7; ENSP00000397906.2; ENSG00000149970.16. [Q8WXI2-5] DR Ensembl; ENST00000543067.6; ENSP00000444633.1; ENSG00000149970.16. [Q8WXI2-4] DR Ensembl; ENST00000642359.1; ENSP00000496709.1; ENSG00000149970.16. [Q8WXI2-2] DR GeneID; 22866; -. DR KEGG; hsa:22866; -. DR MANE-Select; ENST00000379510.5; ENSP00000368824.3; NM_014927.5; NP_055742.2. DR UCSC; uc004czw.4; human. [Q8WXI2-1] DR AGR; HGNC:19701; -. DR CTD; 22866; -. DR DisGeNET; 22866; -. DR GeneCards; CNKSR2; -. DR HGNC; HGNC:19701; CNKSR2. DR HPA; ENSG00000149970; Group enriched (brain, retina). DR MalaCards; CNKSR2; -. DR MIM; 300724; gene. DR MIM; 301008; phenotype. DR neXtProt; NX_Q8WXI2; -. DR OpenTargets; ENSG00000149970; -. DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy. DR Orphanet; 777; X-linked non-syndromic intellectual disability. DR PharmGKB; PA134867759; -. DR VEuPathDB; HostDB:ENSG00000149970; -. DR eggNOG; KOG1738; Eukaryota. DR GeneTree; ENSGT00940000156709; -. DR HOGENOM; CLU_013414_0_0_1; -. DR InParanoid; Q8WXI2; -. DR OMA; DQRETQN; -. DR OrthoDB; 5406576at2759; -. DR PhylomeDB; Q8WXI2; -. DR TreeFam; TF326495; -. DR PathwayCommons; Q8WXI2; -. 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; Q8WXI2; -. DR SIGNOR; Q8WXI2; -. DR BioGRID-ORCS; 22866; 18 hits in 767 CRISPR screens. DR ChiTaRS; CNKSR2; human. DR EvolutionaryTrace; Q8WXI2; -. DR GeneWiki; CNKSR2; -. DR GenomeRNAi; 22866; -. DR Pharos; Q8WXI2; Tbio. DR PRO; PR:Q8WXI2; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q8WXI2; Protein. DR Bgee; ENSG00000149970; Expressed in Brodmann (1909) area 23 and 149 other cell types or tissues. DR ExpressionAtlas; Q8WXI2; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0099147; C:extrinsic component of postsynaptic density membrane; IEA:Ensembl. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0019901; F:protein kinase binding; IDA:MGI. DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI. DR GO; GO:0099173; P:postsynapse organization; IEA:Ensembl. DR GO; GO:0009966; P:regulation of signal transduction; IEA:InterPro. DR CDD; cd00992; PDZ_signaling; 1. 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; IPR010599; CNK2/3_dom. DR InterPro; IPR051566; CNKSR. 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:SF21; CONNECTOR ENHANCER OF KINASE SUPPRESSOR OF RAS 2; 1. DR Pfam; PF06663; CNK2_3_dom; 1. DR Pfam; PF10534; CRIC_ras_sig; 1. DR Pfam; PF00595; PDZ; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF00536; SAM_1; 1. DR SMART; SM00228; PDZ; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00454; SAM; 1. DR SUPFAM; SSF50156; PDZ domain-like; 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. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; KW Disease variant; Intellectual disability; Membrane; Phosphoprotein; KW Reference proteome. FT CHAIN 1..1034 FT /note="Connector enhancer of kinase suppressor of ras 2" FT /id="PRO_0000089970" FT DOMAIN 11..76 FT /note="SAM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184" FT DOMAIN 84..178 FT /note="CRIC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00621" FT DOMAIN 215..297 FT /note="PDZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 332..515 FT /note="DUF1170" FT DOMAIN 570..669 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT REGION 324..349 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 480..510 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 539..559 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 682..766 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 864..905 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 875..904 FT /evidence="ECO:0000255" FT COMPBIAS 324..346 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 543..559 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 682..696 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 698..712 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 726..766 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 871..890 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 891..905 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 12 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q80YA9" FT MOD_RES 338 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q80YA9" FT MOD_RES 390 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q80YA9" FT MOD_RES 683 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q80YA9" FT MOD_RES 685 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q80YA9" FT MOD_RES 687 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q80YA9" FT MOD_RES 756 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1T4" FT MOD_RES 767 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1T4" FT MOD_RES 908 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569" FT VAR_SEQ 271..319 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043168" FT VAR_SEQ 435..464 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_043169" FT VAR_SEQ 899..1034 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:10048485, FT ECO:0000303|PubMed:14597674, ECO:0000303|PubMed:14702039" FT /id="VSP_010887" FT VARIANT 46 FT /note="R -> H (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs771705122)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035681" FT VARIANT 712..1034 FT /note="Missing (in MRXSHG)" FT /evidence="ECO:0000269|PubMed:28098945" FT /id="VAR_080600" FT HELIX 8..10 FT /evidence="ECO:0007829|PDB:3BS5" FT HELIX 13..21 FT /evidence="ECO:0007829|PDB:3BS5" FT HELIX 25..30 FT /evidence="ECO:0007829|PDB:3BS5" FT HELIX 31..37 FT /evidence="ECO:0007829|PDB:3BS5" FT HELIX 41..45 FT /evidence="ECO:0007829|PDB:3BS5" FT HELIX 49..54 FT /evidence="ECO:0007829|PDB:3BS5" FT HELIX 60..77 FT /evidence="ECO:0007829|PDB:3BS5" SQ SEQUENCE 1034 AA; 117535 MW; E43DB0D8D72D954C CRC64; MALIMEPVSK WSPSQVVDWM KGLDDCLQQY IKNFEREKIS GDQLLRITHQ ELEDLGVSRI GHQELILEAV DLLCALNYGL ETENLKTLSH KLNASAKNLQ NFITGRRRSG HYDGRTSRKL PNDFLTSVVD LIGAAKSLLA WLDRSPFAAV TDYSVTRNNV IQLCLELTTI VQQDCTVYET ENKILHVCKT LSGVCDHIIS LSSDPLVSQS AHLEVIQLAN IKPSEGLGMY IKSTYDGLHV ITGTTENSPA DRCKKIHAGD EVIQVNHQTV VGWQLKNLVN ALREDPSGVI LTLKKRPQSM LTSAPALLKN MRWKPLALQP LIPRSPTSSV ATPSSTISTP TKRDSSALQD LYIPPPPAEP YIPRDEKGNL PCEDLRGHMV GKPVHKGSES PNSFLDQEYR KRFNIVEEDT VLYCYEYEKG RSSSQGRRES TPTYGKLRPI SMPVEYNWVG DYEDPNKMKR DSRRENSLLR YMSNEKIAQE EYMFQRNSKK DTGKKSKKKG DKSNSPTHYS LLPSLQMDAL RQDIMGTPVP ETTLYHTFQQ SSLQHKSKKK NKGPIAGKSK RRISCKDLGR GDCEGWLWKK KDAKSYFSQK WKKYWFVLKD ASLYWYINEE DEKAEGFISL PEFKIDRASE CRKKYAFKAC HPKIKSFYFA AEHLDDMNRW LNRINMLTAG YAERERIKQE QDYWSESDKE EADTPSTPKQ DSPPPPYDTY PRPPSMSCAS PYVEAKHSRL SSTETSQSQS SHEEFRQEVT GSSAVSPIRK TASQRRSWQD LIETPLTSSG LHYLQTLPLE DSVFSDSAAI SPEHRRQSTL PTQKCHLQDH YGPYPLAESE RMQVLNGNGG KPRSFTLPRD SGFNHCCLNA PVSACDPQDD VQPPEVEEEE EEEEEEGEAA GENIGEKSES REEKLGDSLQ DLYRALEQAS LSPLGEHRIS TKMEYKLSFI KRCNDPVMNE KLHRLRILKS TLKAREGEVA IIDKVLDNPD LTSKEFQQWK QMYLDLFLDI CQNTTSNDPL SISSEVDVIT SSLAHTHSYI ETHV //