CNKR2_HUMAN
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 03-AUG-2022, entry version 175.
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; 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; 11.
DR DIP; DIP-29736N; -.
DR IntAct; Q8WXI2; 9.
DR MINT; Q8WXI2; -.
DR STRING; 9606.ENSP00000368824; -.
DR ChEMBL; CHEMBL1938216; -.
DR iPTMnet; Q8WXI2; -.
DR PhosphoSitePlus; Q8WXI2; -.
DR BioMuta; CNKSR2; -.
DR DMDM; 50400586; -.
DR EPD; Q8WXI2; -.
DR jPOST; Q8WXI2; -.
DR MassIVE; Q8WXI2; -.
DR MaxQB; Q8WXI2; -.
DR PaxDb; Q8WXI2; -.
DR PeptideAtlas; Q8WXI2; -.
DR PRIDE; Q8WXI2; -.
DR ProteomicsDB; 75059; -. [Q8WXI2-1]
DR ProteomicsDB; 75060; -. [Q8WXI2-2]
DR ProteomicsDB; 75061; -. [Q8WXI2-4]
DR ProteomicsDB; 75062; -. [Q8WXI2-5]
DR Antibodypedia; 456; 116 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 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; EDMEMPP; -.
DR OrthoDB; 1121556at2759; -.
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; 11 hits in 695 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 148 other tissues.
DR ExpressionAtlas; Q8WXI2; baseline and differential.
DR Genevisible; Q8WXI2; HS.
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:0043005; C:neuron projection; 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 Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR010599; CNK2/3_dom.
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; PF06663; DUF1170; 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; SSF47769; SSF47769; 1.
DR SUPFAM; SSF50156; SSF50156; 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
