ID KSR2_HUMAN Reviewed; 950 AA. AC Q6VAB6; A0PJT2; Q3B828; Q8N775; DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot. DT 29-MAY-2007, sequence version 2. DT 27-MAR-2024, entry version 160. DE RecName: Full=Kinase suppressor of Ras 2 {ECO:0000305}; DE Short=hKSR2; DE EC=2.7.11.1 {ECO:0000269|PubMed:21441910}; GN Name=KSR2 {ECO:0000312|HGNC:HGNC:18610}; 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 [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 122-950 (ISOFORM 1), FUNCTION, INTERACTION RP WITH MAP2K; RAS; RAF; MAPK AND MAP3K8, AND TISSUE SPECIFICITY. RC TISSUE=Testis; RX PubMed=12975377; DOI=10.1074/jbc.m306002200; RA Channavajhala P.L., Wu L., Cuozzo J.W., Hall J.P., Liu W., Lin L.-L., RA Zhang Y.; RT "Identification of a novel human kinase supporter of Ras (hKSR-2) that RT functions as a negative regulator of Cot (Tpl2) signaling."; RL J. Biol. Chem. 278:47089-47097(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 122-950 (ISOFORM 1). 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 [5] RP FUNCTION. RX PubMed=16039990; DOI=10.1016/j.bbrc.2005.07.009; RA Channavajhala P.L., Rao V.R., Spaulding V., Lin L.-L., Zhang Y.G.; RT "hKSR-2 inhibits MEKK3-activated MAP kinase and NF-kappaB pathways in RT inflammation."; RL Biochem. Biophys. Res. Commun. 334:1214-1218(2005). RN [6] RP FUNCTION, AND INTERACTION WITH BRAF; MAP2K1 AND MAP2K2. RX PubMed=29433126; DOI=10.1038/nature25478; RA Lavoie H., Sahmi M., Maisonneuve P., Marullo S.A., Thevakumaran N., Jin T., RA Kurinov I., Sicheri F., Therrien M.; RT "MEK drives BRAF activation through allosteric control of KSR proteins."; RL Nature 554:549-553(2018). RN [7] RP X-RAY CRYSTALLOGRAPHY (3.46 ANGSTROMS) OF 634-950 OF MUTANT ALA-786 IN RP COMPLEX WITH ATP AND MAP2K1, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY RP REGULATION, SUBUNIT, INTERACTION WITH BRAF AND MAP2K1, ACTIVE SITE, AND RP MUTAGENESIS OF ARG-718; ASP-786 AND ALA-879. RX PubMed=21441910; DOI=10.1038/nature09860; RA Brennan D.F., Dar A.C., Hertz N.T., Chao W.C., Burlingame A.L., RA Shokat K.M., Barford D.; RT "A Raf-induced allosteric transition of KSR stimulates phosphorylation of RT MEK."; RL Nature 472:366-369(2011). RN [8] RP VARIANT [LARGE SCALE ANALYSIS] SER-676. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Location-regulated scaffold connecting MEK to RAF. Has very CC low protein kinase activity and can phosphorylate MAP2K1 at several Ser CC and Thr residues with very low efficiency (in vitro). Acts as CC MAP2K1/MEK1-dependent allosteric activator of BRAF; upon binding to CC MAP2K1/MEK1, dimerizes with BRAF and promotes BRAF-mediated CC phosphorylation of MAP2K1/MEK1 (PubMed:29433126). Interaction with BRAF CC enhances KSR2-mediated phosphorylation of MAP2K1 (in vitro). Blocks CC MAP3K8 kinase activity and MAP3K8-mediated signaling. Acts as a CC negative regulator of MAP3K3-mediated activation of ERK, JNK and NF- CC kappa-B pathways, inhibiting MAP3K3-mediated interleukin-8 production. CC {ECO:0000269|PubMed:12975377, ECO:0000269|PubMed:16039990, CC ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:21441910}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:21441910}; CC -!- ACTIVITY REGULATION: Kinase activity is inhibited by ASC24. CC {ECO:0000269|PubMed:21441910}. CC -!- SUBUNIT: Heterodimerizes (via N-terminus) with BRAF (via N-terminus) in CC a MAP2K1/MEK1-dependent manner (PubMed:29433126). Interacts with BRAF; CC this increases the low intrinsic protein kinase activity of KSR2 CC (PubMed:21441910). Interacts with MAP2K1, forming a heterodimer that CC can dimerize to form a heterotetramer (PubMed:29433126, CC PubMed:21441910, PubMed:12975377). Interacts with MAP3K8, MAPK, RAS and CC RAF (PubMed:12975377). {ECO:0000269|PubMed:12975377, CC ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126}. CC -!- INTERACTION: CC Q6VAB6; Q16543: CDC37; NbExp=7; IntAct=EBI-6424389, EBI-295634; CC Q6VAB6; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-6424389, EBI-3867333; CC Q6VAB6; Q13451: FKBP5; NbExp=7; IntAct=EBI-6424389, EBI-306914; CC Q6VAB6; P07900: HSP90AA1; NbExp=6; IntAct=EBI-6424389, EBI-296047; CC Q6VAB6-1; P29678: MAP2K1; Xeno; NbExp=6; IntAct=EBI-15916808, EBI-1631983; 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=Q6VAB6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6VAB6-2; Sequence=VSP_012234, VSP_012235, VSP_012236, CC VSP_012237; CC -!- TISSUE SPECIFICITY: Mainly expressed in brain and kidney. CC {ECO:0000269|PubMed:12975377}. CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically CC inactive and seems to have very low intrinsic kinase activity. This low CC kinase activity can be increased by interaction with BRAF. CC -!- PTM: Phosphorylated on Ser-474 by MARK3. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr CC protein kinase family. {ECO:0000305}. CC -!- CAUTION: KSR2 binds ATP and has very low in vitro protein kinase CC activity; the physiological relevance of this activity is unknown. KSR2 CC is proposed to be in an inactive conformation by itself or in complex CC with MAP2K1. Interaction with BRAF is proposed to induce a conformation CC change that increases the low intrinsic kinase activity CC (PubMed:21441910). {ECO:0000305|PubMed:21441910}. 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; AK098831; BAC05426.1; -; mRNA. DR EMBL; AC073864; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC079127; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC084291; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC092936; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AY345972; AAQ24226.1; -; mRNA. DR EMBL; BC107106; AAI07107.1; -; mRNA. DR EMBL; BC107107; AAI07108.1; -; mRNA. DR EMBL; BC127603; AAI27604.1; -; mRNA. DR CCDS; CCDS61250.2; -. [Q6VAB6-1] DR RefSeq; NP_775869.3; NM_173598.4. [Q6VAB6-1] DR RefSeq; XP_011536527.1; XM_011538225.2. DR PDB; 2Y4I; X-ray; 3.46 A; B=634-950. DR PDB; 5KKR; X-ray; 3.51 A; B=634-950. DR PDB; 7JUQ; X-ray; 3.22 A; B=634-950. DR PDB; 7JUR; X-ray; 2.82 A; B=634-950. DR PDB; 7JUS; X-ray; 2.99 A; B=634-950. DR PDB; 7JUT; X-ray; 3.09 A; B=634-950. DR PDB; 7JUU; X-ray; 3.19 A; B=634-950. DR PDB; 7JUV; X-ray; 3.36 A; B=634-950. DR PDB; 7UMB; X-ray; 3.23 A; B=634-950. DR PDBsum; 2Y4I; -. DR PDBsum; 5KKR; -. DR PDBsum; 7JUQ; -. DR PDBsum; 7JUR; -. DR PDBsum; 7JUS; -. DR PDBsum; 7JUT; -. DR PDBsum; 7JUU; -. DR PDBsum; 7JUV; -. DR PDBsum; 7UMB; -. DR AlphaFoldDB; Q6VAB6; -. DR SMR; Q6VAB6; -. DR BioGRID; 129567; 44. DR DIP; DIP-59195N; -. DR IntAct; Q6VAB6; 141. DR MINT; Q6VAB6; -. DR STRING; 9606.ENSP00000389715; -. DR BindingDB; Q6VAB6; -. DR ChEMBL; CHEMBL3627583; -. DR iPTMnet; Q6VAB6; -. DR PhosphoSitePlus; Q6VAB6; -. DR BioMuta; KSR2; -. DR DMDM; 148886599; -. DR jPOST; Q6VAB6; -. DR MassIVE; Q6VAB6; -. DR MaxQB; Q6VAB6; -. DR PaxDb; 9606-ENSP00000389715; -. DR PeptideAtlas; Q6VAB6; -. DR ProteomicsDB; 67721; -. [Q6VAB6-1] DR ProteomicsDB; 67722; -. [Q6VAB6-2] DR Antibodypedia; 31354; 376 antibodies from 27 providers. DR DNASU; 283455; -. DR Ensembl; ENST00000339824.7; ENSP00000339952.4; ENSG00000171435.15. [Q6VAB6-1] DR GeneID; 283455; -. DR KEGG; hsa:283455; -. DR MANE-Select; ENST00000339824.7; ENSP00000339952.4; NM_173598.6; NP_775869.4. DR UCSC; uc058tua.1; human. [Q6VAB6-1] DR AGR; HGNC:18610; -. DR CTD; 283455; -. DR DisGeNET; 283455; -. DR GeneCards; KSR2; -. DR HGNC; HGNC:18610; KSR2. DR HPA; ENSG00000171435; Tissue enhanced (brain, pituitary gland). DR MIM; 610737; gene. DR neXtProt; NX_Q6VAB6; -. DR OpenTargets; ENSG00000171435; -. DR Orphanet; 521399; NON RARE IN EUROPE: Non rare obesity. DR PharmGKB; PA134914125; -. DR VEuPathDB; HostDB:ENSG00000171435; -. DR eggNOG; KOG0193; Eukaryota. DR GeneTree; ENSGT00940000158519; -. DR HOGENOM; CLU_006812_1_0_1; -. DR InParanoid; Q6VAB6; -. DR OMA; DSWDRPH; -. DR OrthoDB; 4560496at2759; -. DR PhylomeDB; Q6VAB6; -. DR TreeFam; TF317006; -. DR BRENDA; 2.7.11.25; 2681. DR PathwayCommons; Q6VAB6; -. 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; Q6VAB6; -. DR SIGNOR; Q6VAB6; -. DR BioGRID-ORCS; 283455; 13 hits in 1165 CRISPR screens. DR ChiTaRS; KSR2; human. DR GenomeRNAi; 283455; -. DR Pharos; Q6VAB6; Tbio. DR PRO; PR:Q6VAB6; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q6VAB6; Protein. DR Bgee; ENSG00000171435; Expressed in Brodmann (1909) area 23 and 84 other cell types or tissues. DR ExpressionAtlas; Q6VAB6; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005078; F:MAP-kinase scaffold activity; IEA:Ensembl. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IEA:Ensembl. DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:FlyBase. DR GO; GO:0019722; P:calcium-mediated signaling; IBA:GO_Central. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central. DR CDD; cd14153; PK_KSR2; 1. DR Gene3D; 3.30.60.20; -; 1. DR Gene3D; 6.10.140.1120; -; 1. DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR046349; C1-like_sf. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR025561; KSR_SAM-like_dom. DR InterPro; IPR002219; PE/DAG-bd. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR013761; SAM/pointed_sf. DR InterPro; IPR046861; SAM_KSR1_N. DR InterPro; IPR046933; SAM_KSR1_N_sf. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR23257:SF775; KINASE SUPPRESSOR OF RAS 2; 1. DR PANTHER; PTHR23257; SERINE-THREONINE PROTEIN KINASE; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF13543; SAM_KSR1; 1. DR Pfam; PF20406; SAM_KSR1_N; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF57889; Cysteine-rich domain; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. DR Genevisible; Q6VAB6; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Kinase; KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Serine/threonine-protein kinase; Transferase; Zinc; KW Zinc-finger. FT CHAIN 1..950 FT /note="Kinase suppressor of Ras 2" FT /id="PRO_0000086231" FT DOMAIN 666..931 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT ZN_FING 412..456 FT /note="Phorbol-ester/DAG-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226" FT REGION 239..296 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 498..556 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 280..294 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 512..527 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 528..549 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 786 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000305|PubMed:21441910" FT BINDING 413 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 425 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 428 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 438 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 441 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 446 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 449 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 456 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 672..680 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000269|PubMed:21441910" FT BINDING 788 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305|PubMed:21441910" FT BINDING 803 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305|PubMed:21441910" FT MOD_RES 272 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q3UVC0" FT MOD_RES 276 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q3UVC0" FT MOD_RES 474 FT /note="Phosphoserine; by MARK3" FT /evidence="ECO:0000250" FT MOD_RES 497 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q3UVC0" FT VAR_SEQ 1..303 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_012234" FT VAR_SEQ 304..329 FT /note="GFTALHRSKSHEFQLGHRVDEAHTPK -> MYNKKAKMEPNASESAIPARRQ FT RQPR (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_012235" FT VAR_SEQ 740..742 FT /note="SLC -> RPV (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_012236" FT VAR_SEQ 743..950 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_012237" FT VARIANT 676 FT /note="R -> S (in a lung adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040659" FT MUTAGEN 718 FT /note="R->H: Impairs formation of heterotetramers with FT MAP2K1, but not the formation of heterodimers." FT /evidence="ECO:0000269|PubMed:21441910" FT MUTAGEN 786 FT /note="D->A: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:21441910" FT MUTAGEN 879 FT /note="A->L: Impairs MAP2K1 binding." FT /evidence="ECO:0000269|PubMed:21441910" FT HELIX 656..658 FT /evidence="ECO:0007829|PDB:7JUR" FT STRAND 659..661 FT /evidence="ECO:0007829|PDB:7JUR" FT STRAND 667..673 FT /evidence="ECO:0007829|PDB:7JUR" FT STRAND 676..684 FT /evidence="ECO:0007829|PDB:7JUR" FT STRAND 688..695 FT /evidence="ECO:0007829|PDB:7JUR" FT STRAND 698..700 FT /evidence="ECO:0007829|PDB:7JUQ" FT HELIX 701..714 FT /evidence="ECO:0007829|PDB:7JUR" FT STRAND 725..727 FT /evidence="ECO:0007829|PDB:7JUR" FT STRAND 734..740 FT /evidence="ECO:0007829|PDB:7JUR" FT STRAND 744..746 FT /evidence="ECO:0007829|PDB:7JUR" FT HELIX 747..751 FT /evidence="ECO:0007829|PDB:7JUR" FT HELIX 760..779 FT /evidence="ECO:0007829|PDB:7JUR" FT HELIX 789..791 FT /evidence="ECO:0007829|PDB:7JUR" FT STRAND 792..795 FT /evidence="ECO:0007829|PDB:7JUR" FT STRAND 798..801 FT /evidence="ECO:0007829|PDB:7JUR" FT HELIX 806..809 FT /evidence="ECO:0007829|PDB:7JUR" FT STRAND 821..825 FT /evidence="ECO:0007829|PDB:7JUR" FT TURN 826..828 FT /evidence="ECO:0007829|PDB:7JUR" FT HELIX 829..831 FT /evidence="ECO:0007829|PDB:7JUR" FT HELIX 834..837 FT /evidence="ECO:0007829|PDB:7JUR" FT HELIX 846..848 FT /evidence="ECO:0007829|PDB:7JUR" FT HELIX 853..869 FT /evidence="ECO:0007829|PDB:7JUR" FT TURN 873..876 FT /evidence="ECO:0007829|PDB:7JUR" FT HELIX 879..887 FT /evidence="ECO:0007829|PDB:7JUR" FT HELIX 895..897 FT /evidence="ECO:0007829|PDB:7JUR" FT HELIX 901..910 FT /evidence="ECO:0007829|PDB:7JUR" FT HELIX 915..917 FT /evidence="ECO:0007829|PDB:7JUR" FT HELIX 921..929 FT /evidence="ECO:0007829|PDB:7JUR" SQ SEQUENCE 950 AA; 107632 MW; DFBC20F4E71077AD CRC64; MDEENMTKSE EQQPLSLQKA LQQCELVQNM IDLSISNLEG LRTKCATSND LTQKEIRTLE SKLVKYFSRQ LSCKKKVALQ ERNAELDGFP QLRHWFRIVD VRKEVLEEIS PGQLSLEDLL EMTDEQVCET VEKYGANREE CARLNASLSC LRNVHMSGGN LSKQDWTIQW PTTETGKENN PVCPPEPTPW IRTHLSQSPR VPSKCVQHYC HTSPTPGAPV YTHVDRLTVD AYPGLCPPPP LESGHRSLPP SPRQRHAVRT PPRTPNIVTT VTPPGTPPMR KKNKLKPPGT PPPSSRKLIH LIPGFTALHR SKSHEFQLGH RVDEAHTPKA KKKSKPLNLK IHSSVGSCEN IPSQQRSPLL SERSLRSFFV GHAPFLPSTP PVHTEANFSA NTLSVPRWSP QIPRRDLGNS IKHRFSTKYW MSQTCTVCGK GMLFGLKCKN CKLKCHNKCT KEAPPCHLLI IHRGDPARLV RTESVPCDIN NPLRKPPRYS DLHISQTLPK TNKINKDHIP VPYQPDSSSN PSSTTSSTPS SPAPPLPPSA TPPSPLHPSP QCTRQQKNFN LPASHYYKYK QQFIFPDVVP VPETPTRAPQ VILHPVTSNP ILEGNPLLQI EVEPTSENEE VHDEAEESED DFEEMNLSLL SARSFPRKAS QTSIFLQEWD IPFEQLEIGE LIGKGRFGQV YHGRWHGEVA IRLIDIERDN EDQLKAFKRE VMAYRQTRHE NVVLFMGACM SPPHLAIITS LCKGRTLYSV VRDAKIVLDV NKTRQIAQEI VKGMGYLHAK GILHKDLKSK NVFYDNGKVV ITDFGLFSIS GVLQAGRRED KLRIQNGWLC HLAPEIIRQL SPDTEEDKLP FSKHSDVFAL GTIWYELHAR EWPFKTQPAE AIIWQMGTGM KPNLSQIGMG KEISDILLFC WAFEQEERPT FTKLMDMLEK LPKRNRRLSH PGHFWKSAEL //