ID CNKR2_HUMAN Reviewed; 1034 AA. AC Q8WXI2; B9EG83; O94976; Q5JPK4; Q5JPN0; Q8WXI1; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2002, sequence version 1. DT 18-MAY-2010, entry version 75. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION RP WITH 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 RT proteins Raf and Rlf."; RL FASEB J. 17:2048-2060(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX MEDLINE=99156230; PubMed=10048485; DOI=10.1093/dnares/5.6.355; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XII. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 5:355-364(1998). RN [3] 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., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA 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., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA 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., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA 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., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA 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., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-908, AND MASS RP SPECTROMETRY. RC TISSUE=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 [7] 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 RT protein (connector enhancer of kinase suppressor of RAS 2)."; RL Submitted (JUL-2007) to the PDB data bank. RN [8] 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., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: May function as an adapter protein or regulator of Ras CC signaling pathways. CC -!- SUBUNIT: Interacts with RAF1, RAB2L and RAL GTPase proteins. CC -!- INTERACTION: CC Q86TA1:MOBKL2B; NbExp=1; IntAct=EBI-1045119, EBI-751703; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane CC protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; 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 Note=Ref.2 (BAA74925) sequence differs from that shown due to CC frameshifts in positions 859, 929, 985 and 1019; CC -!- PTM: Phosphorylated on tyrosine. CC -!- SIMILARITY: Belongs to the CNKSR family. CC -!- SIMILARITY: Contains 1 CRIC domain. CC -!- SIMILARITY: Contains 1 DUF1170 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; AF418269; AAL60502.1; -; mRNA. DR EMBL; AF418270; AAL60503.1; -; mRNA. DR EMBL; AB020709; BAA74925.2; ALT_FRAME; mRNA. DR EMBL; AL928874; CAH70863.1; -; Genomic_DNA. DR EMBL; AL772392; CAH70863.1; JOINED; Genomic_DNA. DR EMBL; AL807781; CAH70863.1; JOINED; Genomic_DNA. DR EMBL; AL928874; CAH70864.1; -; Genomic_DNA. DR EMBL; AL772392; CAH70864.1; JOINED; Genomic_DNA. DR EMBL; AL807781; CAH70864.1; JOINED; Genomic_DNA. DR EMBL; AL807781; CAI39866.1; -; Genomic_DNA. DR EMBL; AL772392; CAI39866.1; JOINED; Genomic_DNA. DR EMBL; AL928874; CAI39866.1; JOINED; Genomic_DNA. DR EMBL; AL807781; CAI39867.1; -; Genomic_DNA. DR EMBL; AL772392; CAI39867.1; JOINED; Genomic_DNA. DR EMBL; AL928874; CAI39867.1; JOINED; Genomic_DNA. DR EMBL; AL772392; CAI40765.1; -; Genomic_DNA. DR EMBL; AL807781; CAI40765.1; JOINED; Genomic_DNA. DR EMBL; AL928874; CAI40765.1; JOINED; Genomic_DNA. DR EMBL; AL772392; CAI40766.1; -; Genomic_DNA. DR EMBL; AL807781; CAI40766.1; JOINED; Genomic_DNA. DR EMBL; AL928874; CAI40766.1; JOINED; Genomic_DNA. DR EMBL; CH471074; EAW98977.1; -; Genomic_DNA. DR EMBL; BC126121; AAI26122.1; -; mRNA. DR EMBL; BC136289; AAI36290.1; -; mRNA. DR IPI; IPI00435208; -. DR IPI; IPI00435209; -. DR RefSeq; NP_001162119.1; -. DR RefSeq; NP_055742.2; -. DR UniGene; Hs.555917; -. 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 SMR; Q8WXI2; 200-304, 562-669. DR DIP; DIP-29736N; -. DR IntAct; Q8WXI2; 5. DR STRING; Q8WXI2; -. DR PhosphoSite; Q8WXI2; -. DR PRIDE; Q8WXI2; -. DR Ensembl; ENST00000379510; ENSP00000368824; ENSG00000149970; Homo sapiens. DR GeneID; 22866; -. DR UCSC; uc004czw.1; human. DR UCSC; uc004czx.1; human. DR CTD; 22866; -. DR GeneCards; GC0XP021302; -. DR H-InvDB; HIX0020793; -. DR HGNC; HGNC:19701; CNKSR2. DR HPA; HPA001502; -. DR PharmGKB; PA134867759; -. DR eggNOG; prNOG17949; -. DR HOGENOM; HBG403049; -. DR HOVERGEN; HBG051040; -. DR InParanoid; Q8WXI2; -. DR OMA; GHYDGRT; -. DR PhylomeDB; Q8WXI2; -. DR NextBio; 43387; -. DR ArrayExpress; Q8WXI2; -. DR Bgee; Q8WXI2; -. DR CleanEx; HS_CNKSR2; -. DR CleanEx; HS_KSR2; -. DR Genevestigator; Q8WXI2; -. DR GermOnline; ENSG00000149970; Homo sapiens. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0009966; P:regulation of signal transduction; IEA:InterPro. DR InterPro; IPR010599; CNKSR2. DR InterPro; IPR017874; CRIC_domain. DR InterPro; IPR019555; CRIC_domain_Chordata. DR InterPro; IPR001478; PDZ/DHR/GLGF. DR InterPro; IPR011993; PH_type. DR InterPro; IPR001849; Pleckstrin_homology. DR InterPro; IPR001660; SAM. DR InterPro; IPR010993; SAM_homology. DR InterPro; IPR013761; SAM_type. DR InterPro; IPR021129; SAM_type1. DR Gene3D; G3DSA:2.30.29.30; PH_type; 1. DR Gene3D; G3DSA:1.10.150.50; SAM_type; 1. 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; SSF50156; PDZ; 1. DR SUPFAM; SSF47769; SAM_homology; 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. FT CHAIN 1 1034 Connector enhancer of kinase suppressor FT of ras 2. FT /FTId=PRO_0000089970. FT DOMAIN 11 76 SAM. FT DOMAIN 84 178 CRIC. FT DOMAIN 215 297 PDZ. FT DOMAIN 332 515 DUF1170. FT DOMAIN 570 669 PH. FT COILED 875 904 Potential. FT COMPBIAS 354 357 Poly-Pro. FT COMPBIAS 703 706 Poly-Pro. FT COMPBIAS 875 888 Poly-Glu. FT MOD_RES 248 248 Phosphoserine (By similarity). FT MOD_RES 325 325 Phosphoserine (By similarity). FT MOD_RES 390 390 Phosphoserine (By similarity). FT MOD_RES 467 467 Phosphoserine (By similarity). FT MOD_RES 846 846 Phosphothreonine (By similarity). FT MOD_RES 908 908 Phosphoserine. FT VAR_SEQ 899 1034 Missing (in isoform 2). FT /FTId=VSP_010887. FT VARIANT 46 46 R -> H (in a colorectal cancer sample; FT somatic mutation). FT /FTId=VAR_035681. FT HELIX 8 10 FT HELIX 13 21 FT HELIX 25 30 FT HELIX 31 37 FT HELIX 41 45 FT HELIX 49 54 FT HELIX 60 77 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 //