KSR2_HUMAN
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 03-AUG-2022, entry version 151.
DE RecName: Full=Kinase suppressor of Ras 2;
DE Short=hKSR2;
DE EC=2.7.11.1 {ECO:0000269|PubMed:21441910};
GN Name=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 [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; CCDS61250.1; -. [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 PDBsum; 2Y4I; -.
DR PDBsum; 5KKR; -.
DR PDBsum; 7JUQ; -.
DR PDBsum; 7JUR; -.
DR PDBsum; 7JUS; -.
DR PDBsum; 7JUT; -.
DR PDBsum; 7JUU; -.
DR PDBsum; 7JUV; -.
DR AlphaFoldDB; Q6VAB6; -.
DR SMR; Q6VAB6; -.
DR BioGRID; 129567; 18.
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; Q6VAB6; -.
DR PeptideAtlas; Q6VAB6; -.
DR PRIDE; Q6VAB6; -.
DR ProteomicsDB; 67721; -. [Q6VAB6-1]
DR ProteomicsDB; 67722; -. [Q6VAB6-2]
DR Antibodypedia; 31354; 363 antibodies from 27 providers.
DR DNASU; 283455; -.
DR Ensembl; ENST00000339824.7; ENSP00000339952.4; ENSG00000171435.14. [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 CTD; 283455; -.
DR DisGeNET; 283455; -.
DR GeneCards; KSR2; -.
DR HGNC; HGNC:18610; KSR2.
DR HPA; ENSG00000171435; Group enriched (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; QWHWDSW; -.
DR OrthoDB; 281487at2759; -.
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; 11 hits in 1086 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 82 other tissues.
DR ExpressionAtlas; Q6VAB6; baseline and differential.
DR Genevisible; Q6VAB6; HS.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; IEA:UniProtKB-KW.
DR GO; GO:0019722; P:calcium-mediated signaling; IBA:GO_Central.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00029; C1; 1.
DR Gene3D; 1.10.150.50; -; 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; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF13543; SAM_KSR1; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 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.
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
