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 13-NOV-2019, entry version 58. 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; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; 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., RA Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., RA Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., RA Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., RA Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., RA Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., RA Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., RA Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., RA Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., RA D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., RA Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., RA Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., RA Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., RA 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., RA Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., RA Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., RA Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., RA Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., RA Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., RA Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., RA 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., RA Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., RA Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., RA Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., RA Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., RA Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., RA Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., RA Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., RA Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., RA Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., RA Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., RA Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., RA Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., RA Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., RA Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into RT mammalian evolution."; RL Nature 428:493-521(2004). RN [2] RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH TANC1, AND RP TISSUE SPECIFICITY. RX PubMed=18930710; DOI=10.1016/j.bbrc.2008.10.038; RA Nonaka H., Takei K., Umikawa M., Oshiro M., Kuninaka K., RA Bayarjargal M., Asato T., Yamashiro Y., Uechi Y., Endo S., Suzuki T., RA Kariya K.; RT "MINK is a Rap2 effector for phosphorylation of the postsynaptic RT scaffold 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 RT to 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 RP AND SER-786, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., RA Lundby C., Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 RT different rat organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Serine/threonine kinase which acts as a negative CC regulator of Ras-related Rap2-mediated signal transduction to CC control neuronal structure and AMPA receptor trafficking. Required CC for normal synaptic density, dendrite complexity, as well as CC surface AMPA receptor expression in hippocampal neurons. Can CC activate the JNK and MAPK14/p38 pathways and mediates stimulation CC of the stress-activated protein kinase MAPK14/p38 MAPK downstream CC of the Raf/ERK pathway. Phosphorylates: TANC1 upon stimulation by CC RAP2A, MBP and SMAD1. Has an essential function in negative CC selection of thymocytes, perhaps by coupling NCK1 to activation of CC 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, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; CC 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 CC with TANC1. {ECO:0000250, ECO:0000269|PubMed:18930710}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell junction, CC synapse, postsynaptic density {ECO:0000269|PubMed:21048137}. Cell CC projection, axon {ECO:0000269|PubMed:21048137}. Cell projection, CC dendrite {ECO:0000269|PubMed:21048137}. CC -!- DEVELOPMENTAL STAGE: Increased expression from E18 to adulthood CC seen in 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; 1. DR STRING; 10116.ENSRNOP00000050929; -. DR iPTMnet; F1LP90; -. DR PhosphoSitePlus; F1LP90; -. DR jPOST; F1LP90; -. DR PaxDb; F1LP90; -. DR PRIDE; F1LP90; -. DR UCSC; RGD:1359135; rat. DR RGD; 1359135; Mink1. DR eggNOG; KOG0587; Eukaryota. DR eggNOG; ENOG410XPHR; LUCA. 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:0005623; C:cell; IEA:GOC. DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell. DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-KW. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB. DR GO; GO:0031532; P:actin cytoskeleton reorganization; IBA:GO_Central. DR GO; GO:0032147; P:activation of protein kinase activity; IBA:GO_Central. DR GO; GO:0007268; P:chemical synaptic transmission; IMP:UniProtKB. DR GO; GO:0048813; P:dendrite morphogenesis; IMP:UniProtKB. DR GO; GO:0070050; P:neuron cellular homeostasis; IMP:CACAO. DR GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central. DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB. DR GO; GO:2000311; P:regulation of AMPA receptor activity; IMP:UniProtKB. DR GO; GO:0023014; P:signal transduction by protein phosphorylation; 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; Complete proteome; KW Cytoplasm; Kinase; Methylation; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Serine/threonine-protein kinase; Synapse; KW Transferase. FT CHAIN 1 1336 Misshapen-like kinase 1. FT /FTId=PRO_0000413198. FT DOMAIN 25 289 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT DOMAIN 1023 1310 CNH. {ECO:0000255|PROSITE- FT ProRule:PRU00795}. FT NP_BIND 31 39 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 870 1336 Mediates interaction with RAP2A. FT {ECO:0000250}. FT COMPBIAS 359 496 Gln-rich. FT COMPBIAS 543 731 Pro-rich. FT COMPBIAS 828 831 Poly-Ser. FT COMPBIAS 838 843 Poly-Glu. FT ACT_SITE 153 153 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10027}. FT BINDING 54 54 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 324 324 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9JM52}. FT MOD_RES 326 326 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9JM52}. FT MOD_RES 502 502 Omega-N-methylarginine. FT {ECO:0000250|UniProtKB:Q9JM52}. FT MOD_RES 510 510 Omega-N-methylarginine. FT {ECO:0000250|UniProtKB:Q8N4C8}. FT MOD_RES 643 643 Phosphoserine. FT {ECO:0000244|PubMed:22673903}. FT MOD_RES 703 703 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8N4C8}. FT MOD_RES 756 756 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8N4C8}. FT MOD_RES 765 765 Phosphoserine. FT {ECO:0000244|PubMed:22673903}. FT MOD_RES 781 781 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8N4C8}. FT MOD_RES 782 782 Phosphoserine. FT {ECO:0000244|PubMed:22673903}. FT MOD_RES 786 786 Phosphoserine. FT {ECO:0000244|PubMed:22673903}. FT MOD_RES 895 895 Phosphothreonine. FT {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 //