ID MINK1_RAT Reviewed; 1336 AA. AC F1LP90; DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot. DT 19-OCT-2011, sequence version 2. DT 23-FEB-2022, entry version 69. DE RecName: Full=Misshapen-like kinase 1; DE EC=2.7.11.1; DE AltName: Full=GCK family kinase MiNK; DE AltName: Full=MAPK/ERK kinase kinase kinase 6; DE Short=MEK kinase kinase 6; DE Short=MEKKK 6; DE AltName: Full=Misshapen/NIK-related kinase; DE AltName: Full=Mitogen-activated protein kinase kinase kinase kinase 6; GN Name=Mink1; Synonyms=Map4k6, Mink; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RX PubMed=15057822; DOI=10.1038/nature02426; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [2] RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH TANC1, AND TISSUE RP SPECIFICITY. RX PubMed=18930710; DOI=10.1016/j.bbrc.2008.10.038; RA Nonaka H., Takei K., Umikawa M., Oshiro M., Kuninaka K., Bayarjargal M., RA Asato T., Yamashiro Y., Uechi Y., Endo S., Suzuki T., Kariya K.; RT "MINK is a Rap2 effector for phosphorylation of the postsynaptic scaffold RT protein TANC1."; RL Biochem. Biophys. Res. Commun. 377:573-578(2008). RN [3] RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE. RX PubMed=21048137; DOI=10.1523/jneurosci.4124-10.2010; RA Hussain N.K., Hsin H., Huganir R.L., Sheng M.; RT "MINK and TNIK differentially act on Rap2-mediated signal transduction to RT regulate neuronal structure and AMPA receptor function."; RL J. Neurosci. 30:14786-14794(2010). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-643; SER-765; SER-782 AND RP SER-786, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Serine/threonine kinase which acts as a negative regulator of CC Ras-related Rap2-mediated signal transduction to control neuronal CC structure and AMPA receptor trafficking. Required for normal synaptic CC density, dendrite complexity, as well as surface AMPA receptor CC expression in hippocampal neurons. Can activate the JNK and MAPK14/p38 CC pathways and mediates stimulation of the stress-activated protein CC kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. CC Phosphorylates: TANC1 upon stimulation by RAP2A, MBP and SMAD1. Has an CC essential function in negative selection of thymocytes, perhaps by CC coupling NCK1 to activation of JNK1. {ECO:0000269|PubMed:21048137}. 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 -!- 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; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- SUBUNIT: Interacts with RAP2A and NCK1 (By similarity). Interacts with CC TANC1. {ECO:0000250, ECO:0000269|PubMed:18930710}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell junction, synapse, CC postsynaptic density {ECO:0000269|PubMed:21048137}. Cell projection, CC axon {ECO:0000269|PubMed:21048137}. Cell projection, dendrite CC {ECO:0000269|PubMed:21048137}. CC -!- DEVELOPMENTAL STAGE: Increased expression from E18 to adulthood seen in CC cortex and hippocampus (at protein level). CC {ECO:0000269|PubMed:21048137}. CC -!- PTM: Autophosphorylated. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr CC protein kinase family. STE20 subfamily. {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; AABR03073855; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR SMR; F1LP90; -. DR IntAct; F1LP90; 2. DR MINT; F1LP90; -. DR STRING; 10116.ENSRNOP00000050929; -. DR iPTMnet; F1LP90; -. DR PhosphoSitePlus; F1LP90; -. DR PaxDb; F1LP90; -. DR PRIDE; F1LP90; -. DR UCSC; RGD:1359135; rat. DR RGD; 1359135; Mink1. DR eggNOG; KOG0587; Eukaryota. DR InParanoid; F1LP90; -. DR Reactome; R-RNO-2559580; Oxidative Stress Induced Senescence. DR PRO; PR:F1LP90; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD. DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; ISO:RGD. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB. DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:RHEA. DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISO:RGD. DR GO; GO:0007268; P:chemical synaptic transmission; IMP:UniProtKB. DR GO; GO:0048813; P:dendrite morphogenesis; IMP:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central. DR GO; GO:0045060; P:negative thymic T cell selection; ISO:RGD. DR GO; GO:0070050; P:neuron cellular homeostasis; IMP:CACAO. DR GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central. DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:RGD. DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISO:RGD. DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD. DR GO; GO:2000311; P:regulation of AMPA receptor activity; IMP:UniProtKB. DR GO; GO:0030334; P:regulation of cell migration; ISO:RGD. DR GO; GO:0022407; P:regulation of cell-cell adhesion; ISO:RGD. DR GO; GO:0001952; P:regulation of cell-matrix adhesion; ISO:RGD. DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central. DR InterPro; IPR001180; CNH_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR Pfam; PF00780; CNH; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00036; CNH; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; SSF56112; 1. DR PROSITE; PS50219; CNH; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW ATP-binding; Cell junction; Cell projection; Cytoplasm; Kinase; KW Methylation; Nucleotide-binding; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Synapse; Transferase. FT CHAIN 1..1336 FT /note="Misshapen-like kinase 1" FT /id="PRO_0000413198" FT DOMAIN 25..289 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 1023..1310 FT /note="CNH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795" FT NP_BIND 31..39 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 299..347 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 363..383 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 395..890 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 870..1336 FT /note="Mediates interaction with RAP2A" FT /evidence="ECO:0000250" FT REGION 909..946 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 299..320 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 321..335 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 363..381 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 395..467 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 468..499 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 544..574 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 634..648 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 649..664 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 669..689 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 717..734 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 769..784 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 790..829 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 832..848 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 909..937 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 153 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 54 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 324 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JM52" FT MOD_RES 326 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JM52" FT MOD_RES 502 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q9JM52" FT MOD_RES 510 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q8N4C8" FT MOD_RES 643 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 703 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8N4C8" FT MOD_RES 756 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8N4C8" FT MOD_RES 765 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 781 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8N4C8" FT MOD_RES 782 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 786 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 895 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9JM52" SQ SEQUENCE 1336 AA; 150382 MW; A10289483BCD2F2D CRC64; MGDPAPARQS DFIFLVALRD PAGIFELVEV VGNGTYGQVY KGRHVKTGQL AAIKVMDVTE DEEEEIKQEI NMLKKYSHHR NIATYYGAFI KKSPPGNDDQ LWLVMEFCGA GSVTDLVKNT KGNALKEDCI AYICREILRG LAHLHAHKVI HRDIKGQNVL LTENAEVKLV DFGVSAQLDR TVGRRNTFIG TPYWMAPEVI ACDENPDATY DYRSDIWSLG ITAIEMAEGA PPLCDMHPMR ALFLIPRNPP PRLKSKKWSK KFTDFIDTCL IKTYLSRPPT EQLLKFPFIR DQPTERQVRI QLKDHIDRSR KKRGEKEETE YEYSGSEEED DSHGEEGEPS SIMNVPGEST LRREFLRLQQ ENKSNSEALK QQQQLQQQQQ RDPEAHIKHL LHQRQRRIEE QKEERRRVEE QQRREREQRK LQEKEQQRRL EDMQALRREE ERRQAEREQE YKRKQLEEQR QSERLQRQLQ QEHAYLNSQK QQQQQQQQQQ QQQQQQILPG DRKPLYHYGR GINPADKPAW AREVEERARM NKQQNSPLAK TKPSSAGPEP PIPQASPSPP GPLSQTPPMQ RPVEPQEGPH KSLVAHRVPL KPYAAPVPRS QSLQDQPTRN LAAFPASHDP DPAAVPTPTA TPSARGAVIR QNSDPTSEGP GPSPNPPSWV RPDNEAPPKV PQRTSSIATA LNTSGAGGSR PAQAVRARPR SNSAWQIYLQ RRAERGTPKP PGPPAQPPGP PNTSSNPDLR RSDPGWERSD SVLPASHGHL PQAGSLERNR NRVGASTKLD SSPVLSPGNK AKPEDHRSRP GRPADFVLLK ERTLDEAPKP PKKAMDYSSS SEEVESSEDE EEEGDGEPSE GSRDTPGGRS DGDTDSVSTM VVHDVEEVSG TQPSYGGGTM VVQRTPEEER SLLLADSNGY TNLPDVVQPS HSPTENSQGQ SPPTKDGGGD YQSRGLVKAP GKSSFTMFVD LGIYQPGGSG DTIPITALVG GEGGRLDQLQ FDVRKGSVVN VNPTNTRAHS ETPEIRKYKK RFNSEILCAA LWGVNLLVGT ENGLMLLDRS GQGKVYGLIG RRRFQQMDVL EGLNLLITIS GKRNKLRVYY LSWLRNKILH NDPEVEKKQG WTTVGDMEGC GHYRVVKYER IKFLVIALKN SVEVYAWAPK PYHKFMAFKS FADLPHRPLL VDLTVEEGQR LKVIYGSSAG FHAVDVDSGN SYDIYIPVHI QSQITPHAIV FLPNTDGMEM LLCYEDEGVY VNTYGRIIKD VVLQWGEMPT SVAYICSNQI MGWGEKAIEI RSVETGHLDG VFMHKRAQRL KFLCERNDKV FFASVRSGGS SQVYFMTLNR NCIMNW //