ID MINK1_HUMAN Reviewed; 1332 AA. AC Q8N4C8; D3DTK3; D3DTK4; Q5U8Z0; Q9P1X1; Q9P2R8; DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 2. DT 27-MAR-2024, entry version 201. 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 {ECO:0000312|HGNC:HGNC:17565}; GN Synonyms=B55, MAP4K6 {ECO:0000250|UniProtKB:Q9JM52}, MINK GN {ECO:0000312|EMBL:BAA94838.1}, YSK2, ZC3; 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 {ECO:0000312|EMBL:AAH34673.1}; RN [1] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain; RX PubMed=10708748; DOI=10.1016/s0014-5793(00)01247-3; RA Dan I., Watanabe N.M., Kobayashi T., Yamashita-Suzuki K., Fukagaya Y., RA Kajikawa E., Kimura W.K., Nakashima T.M., Matsumoto K., Ninomiya-Tsuji J., RA Kusumi A.; RT "Molecular cloning of MINK, a novel member of mammalian GCK family kinases, RT which is up-regulated during postnatal mouse cerebral development."; RL FEBS Lett. 469:19-23(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, SUBCELLULAR LOCATION, RP INTERACTION WITH NCK1, TISSUE SPECIFICITY, ALTERNATIVE SPLICING, RP AUTOPHOSPHORYLATION, AND VARIANTS ALA-771 AND LEU-775. RX PubMed=15469942; DOI=10.1074/jbc.m404497200; RA Hu Y., Leo C., Yu S., Huang B.C., Wang H., Shen M., Luo Y., RA Daniel-Issakani S., Payan D.G., Xu X.; RT "Identification and functional characterization of a novel human RT misshapen/Nck interacting kinase-related kinase, hMINK beta."; RL J. Biol. Chem. 279:54387-54397(2004). RN [3] RP ERRATUM OF PUBMED:15469942. RA Hu Y., Leo C., Yu S., Huang B.C., Wang H., Shen M., Luo Y., RA Daniel-Issakani S., Payan D.G., Xu X.; RL J. Biol. Chem. 280:5128-5128(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [5] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANTS ALA-771 RP AND LEU-775. RC TISSUE=Lymph; 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 [7] RP FUNCTION, AND INDUCTION. RX PubMed=16337592; DOI=10.1016/j.molcel.2005.10.038; RA Nicke B., Bastien J., Khanna S.J., Warne P.H., Cowling V., Cook S.J., RA Peters G., Delpuech O., Schulze A., Berns K., Mullenders J., RA Beijersbergen R.L., Bernards R., Ganesan T.S., Downward J., Hancock D.C.; RT "Involvement of MINK, a Ste20 family kinase, in Ras oncogene-induced growth RT arrest in human ovarian surface epithelial cells."; RL Mol. Cell 20:673-685(2005). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [9] RP FUNCTION, INTERACTION WITH RAP2A, AND SUBCELLULAR LOCATION. 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641; SER-763 AND SER-782, RP VARIANT [LARGE SCALE ANALYSIS] LEU-775, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763; SER-777; SER-778 AND RP SER-782, VARIANT [LARGE SCALE ANALYSIS] LEU-775, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, VARIANT [LARGE SCALE RP ANALYSIS] LEU-775, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-778, VARIANT [LARGE SCALE RP ANALYSIS] LEU-775, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Leukemic 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [18] RP FUNCTION. RX PubMed=21690388; DOI=10.1073/pnas.1104128108; RA Kaneko S., Chen X., Lu P., Yao X., Wright T.G., Rajurkar M., Kariya K., RA Mao J., Ip Y.T., Xu L.; RT "Smad inhibition by the Ste20 kinase Misshapen."; RL Proc. Natl. Acad. Sci. U.S.A. 108:11127-11132(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641; SER-701; SER-754; RP SER-763 AND SER-778, VARIANT [LARGE SCALE ANALYSIS] LEU-775, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [22] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-509, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Colon carcinoma; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [23] RP VARIANTS [LARGE SCALE ANALYSIS] THR-514; ILE-863; VAL-1010 AND VAL-1200. 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). RN [24] RP VARIANT [LARGE SCALE ANALYSIS] LEU-775, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). 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. CC -!- FUNCTION: Isoform 4 can activate the JNK pathway. Involved in the CC regulation of actin cytoskeleton reorganization, cell-matrix adhesion, CC cell-cell adhesion and cell migration. 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:0000250|UniProtKB:Q9JM52}; 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:0000250|UniProtKB:Q9JM52}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:Q9JM52}; CC -!- SUBUNIT: Interacts with TANC1 (By similarity). Interacts with RAP2A. CC Isoform 4 interacts with NCK1. {ECO:0000250, CC ECO:0000269|PubMed:15469942, ECO:0000269|PubMed:18930710}. CC -!- INTERACTION: CC Q8N4C8; Q00613: HSF1; NbExp=2; IntAct=EBI-2133481, EBI-719620; CC Q8N4C8; O95819: MAP4K4; NbExp=2; IntAct=EBI-2133481, EBI-2511133; CC Q8N4C8; P31947: SFN; NbExp=3; IntAct=EBI-2133481, EBI-476295; CC Q8N4C8; P62258: YWHAE; NbExp=3; IntAct=EBI-2133481, EBI-356498; CC Q8N4C8-4; Q5VY09: IER5; NbExp=2; IntAct=EBI-11475194, EBI-1774000; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15469942, CC ECO:0000269|PubMed:18930710}. Postsynaptic density {ECO:0000250}. Cell CC projection, axon {ECO:0000250}. Cell projection, dendrite CC {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Golgi apparatus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=3 {ECO:0000269|PubMed:10708748}; Synonyms=MINK-alpha; CC IsoId=Q8N4C8-1; Sequence=Displayed; CC Name=1 {ECO:0000269|PubMed:10708748}; Synonyms=MiNK-1, MINK-delta; CC IsoId=Q8N4C8-2; Sequence=VSP_007059; CC Name=2 {ECO:0000269|PubMed:10708748}; Synonyms=MiNK-2, MINK-gamma; CC IsoId=Q8N4C8-3; Sequence=VSP_007059, VSP_007060; CC Name=4; Synonyms=MINK-beta; CC IsoId=Q8N4C8-4; Sequence=VSP_041871; CC Name=5; Synonyms=MINK-eta; CC IsoId=Q8N4C8-5; Sequence=VSP_041871, VSP_007059; CC -!- TISSUE SPECIFICITY: Expressed in the brain, isoform 2 is more abundant CC than isoform 1. Isoform 3 is ubiquitously expressed. Isoform 1 is most CC abundant in the skeletal muscle. Isoform 4 is ubiquitously expressed CC with relative high levels in brain, skeletal muscle, pancreas and CC testis. {ECO:0000269|PubMed:15469942}. CC -!- INDUCTION: Activated after Ras induction via a mechanism involving CC reactive oxygen species. {ECO:0000269|PubMed:16337592}. CC -!- PTM: Autophosphorylated. 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; AB041926; BAA94838.1; -; mRNA. DR EMBL; AB035698; BAA90753.1; -; mRNA. DR EMBL; AY775058; AAV41830.1; -; mRNA. DR EMBL; AC233723; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471108; EAW90401.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90403.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90399.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90400.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90402.1; -; Genomic_DNA. DR EMBL; BC034673; AAH34673.1; -; mRNA. DR CCDS; CCDS45588.1; -. [Q8N4C8-1] DR CCDS; CCDS45589.1; -. [Q8N4C8-3] DR CCDS; CCDS45590.1; -. [Q8N4C8-4] DR RefSeq; NP_001020108.1; NM_001024937.3. [Q8N4C8-4] DR RefSeq; NP_001308165.1; NM_001321236.1. DR RefSeq; NP_056531.1; NM_015716.4. [Q8N4C8-2] DR RefSeq; NP_722549.2; NM_153827.4. [Q8N4C8-1] DR RefSeq; NP_733763.1; NM_170663.4. [Q8N4C8-3] DR AlphaFoldDB; Q8N4C8; -. DR SMR; Q8N4C8; -. DR BioGRID; 119075; 176. DR IntAct; Q8N4C8; 70. DR MINT; Q8N4C8; -. DR STRING; 9606.ENSP00000347427; -. DR BindingDB; Q8N4C8; -. DR ChEMBL; CHEMBL5518; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; Q8N4C8; -. DR GuidetoPHARMACOLOGY; 2103; -. DR GlyCosmos; Q8N4C8; 1 site, 1 glycan. DR GlyGen; Q8N4C8; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8N4C8; -. DR PhosphoSitePlus; Q8N4C8; -. DR SwissPalm; Q8N4C8; -. DR BioMuta; MINK1; -. DR DMDM; 296437370; -. DR EPD; Q8N4C8; -. DR jPOST; Q8N4C8; -. DR MassIVE; Q8N4C8; -. DR MaxQB; Q8N4C8; -. DR PaxDb; 9606-ENSP00000347427; -. DR PeptideAtlas; Q8N4C8; -. DR ProteomicsDB; 71917; -. [Q8N4C8-1] DR ProteomicsDB; 71918; -. [Q8N4C8-2] DR ProteomicsDB; 71919; -. [Q8N4C8-3] DR ProteomicsDB; 71920; -. [Q8N4C8-4] DR ProteomicsDB; 71921; -. [Q8N4C8-5] DR Pumba; Q8N4C8; -. DR Antibodypedia; 5678; 261 antibodies from 32 providers. DR DNASU; 50488; -. DR Ensembl; ENST00000347992.11; ENSP00000269296.7; ENSG00000141503.17. [Q8N4C8-3] DR Ensembl; ENST00000355280.11; ENSP00000347427.6; ENSG00000141503.17. [Q8N4C8-1] DR Ensembl; ENST00000453408.7; ENSP00000406487.3; ENSG00000141503.17. [Q8N4C8-4] DR GeneID; 50488; -. DR KEGG; hsa:50488; -. DR MANE-Select; ENST00000355280.11; ENSP00000347427.6; NM_153827.5; NP_722549.2. DR UCSC; uc010vsl.3; human. [Q8N4C8-1] DR AGR; HGNC:17565; -. DR CTD; 50488; -. DR DisGeNET; 50488; -. DR GeneCards; MINK1; -. DR HGNC; HGNC:17565; MINK1. DR HPA; ENSG00000141503; Low tissue specificity. DR MIM; 609426; gene. DR neXtProt; NX_Q8N4C8; -. DR OpenTargets; ENSG00000141503; -. DR PharmGKB; PA134910641; -. DR VEuPathDB; HostDB:ENSG00000141503; -. DR eggNOG; KOG0587; Eukaryota. DR GeneTree; ENSGT00950000183196; -. DR InParanoid; Q8N4C8; -. DR OMA; QIPPGDR; -. DR OrthoDB; 2904475at2759; -. DR PhylomeDB; Q8N4C8; -. DR TreeFam; TF105138; -. DR PathwayCommons; Q8N4C8; -. DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence. DR SignaLink; Q8N4C8; -. DR SIGNOR; Q8N4C8; -. DR BioGRID-ORCS; 50488; 16 hits in 1191 CRISPR screens. DR ChiTaRS; MINK1; human. DR GeneWiki; MINK1; -. DR GenomeRNAi; 50488; -. DR Pharos; Q8N4C8; Tchem. DR PRO; PR:Q8N4C8; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q8N4C8; Protein. DR Bgee; ENSG00000141503; Expressed in CA1 field of hippocampus and 208 other cell types or tissues. DR ExpressionAtlas; Q8N4C8; baseline and differential. DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB. DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0007420; P:brain development; ISS:UniProtKB. DR GO; GO:0007268; P:chemical synaptic transmission; ISS:UniProtKB. DR GO; GO:0048813; P:dendrite morphogenesis; ISS:UniProtKB. DR GO; GO:0007254; P:JNK cascade; TAS:ProtInc. DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central. DR GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central. DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB. DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISS:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IMP:CACAO. DR GO; GO:2000311; P:regulation of AMPA receptor activity; ISS:UniProtKB. DR GO; GO:0030334; P:regulation of cell migration; IMP:UniProtKB. DR GO; GO:0022407; P:regulation of cell-cell adhesion; IMP:UniProtKB. DR GO; GO:0001952; P:regulation of cell-matrix adhesion; IMP:UniProtKB. DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central. DR CDD; cd06636; STKc_MAP4K4_6_N; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR47096:SF1; CNH DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR47096; MISSHAPEN LIKE KINASE 1; 1. DR Pfam; PF00780; CNH; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00036; CNH; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; Q8N4C8; HS. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Cell projection; Cytoplasm; KW Golgi apparatus; Kinase; Methylation; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Serine/threonine-protein kinase; Synapse; Transferase. FT CHAIN 1..1332 FT /note="Misshapen-like kinase 1" FT /id="PRO_0000086329" FT DOMAIN 25..289 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 1019..1306 FT /note="CNH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795" FT REGION 300..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..887 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 866..1332 FT /note="Mediates interaction with RAP2A" FT /evidence="ECO:0000269|PubMed:18930710" FT REGION 902..943 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 300..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..498 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 543..573 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 647..662 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 667..687 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 715..732 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 766..780 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 786..825 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 828..843 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 902..934 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 31..39 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 54 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" 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 501 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q9JM52" FT MOD_RES 509 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 641 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:23186163" FT MOD_RES 701 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 754 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 763 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 777 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 778 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 782 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976" FT MOD_RES 891 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9JM52" FT VAR_SEQ 581..600 FT /note="Missing (in isoform 4 and isoform 5)" FT /evidence="ECO:0000303|PubMed:15469942" FT /id="VSP_041871" FT VAR_SEQ 696..732 FT /note="Missing (in isoform 1, isoform 2 and isoform 5)" FT /evidence="ECO:0000303|PubMed:10708748" FT /id="VSP_007059" FT VAR_SEQ 800 FT /note="A -> ASYKRAIGE (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10708748" FT /id="VSP_007060" FT VARIANT 514 FT /note="A -> T (in dbSNP:rs56131206)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040799" FT VARIANT 771 FT /note="V -> A (in dbSNP:rs11556634)" FT /evidence="ECO:0000269|PubMed:15469942, FT ECO:0000269|PubMed:15489334" FT /id="VAR_046058" FT VARIANT 775 FT /note="P -> L (in dbSNP:rs11556635)" FT /evidence="ECO:0000269|PubMed:15469942, FT ECO:0000269|PubMed:15489334, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT /id="VAR_046059" FT VARIANT 863 FT /note="V -> I (in dbSNP:rs2302319)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_046060" FT VARIANT 1010 FT /note="E -> V (in a gastric adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_046061" FT VARIANT 1200 FT /note="I -> V" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040800" SQ SEQUENCE 1332 AA; 149822 MW; 3E3B182CDDB3659C CRC64; MGDPAPARSL DDIDLSALRD PAGIFELVEV VGNGTYGQVY KGRHVKTGQL AAIKVMDVTE DEEEEIKQEI NMLKKYSHHR NIATYYGAFI KKSPPGNDDQ LWLVMEFCGA GSVTDLVKNT KGNALKEDCI AYICREILRG LAHLHAHKVI HRDIKGQNVL LTENAEVKLV DFGVSAQLDR TVGRRNTFIG TPYWMAPEVI ACDENPDATY DYRSDIWSLG ITAIEMAEGA PPLCDMHPMR ALFLIPRNPP PRLKSKKWSK KFIDFIDTCL IKTYLSRPPT EQLLKFPFIR DQPTERQVRI QLKDHIDRSR KKRGEKEETE YEYSGSEEED DSHGEEGEPS SIMNVPGEST LRREFLRLQQ ENKSNSEALK QQQQLQQQQQ RDPEAHIKHL LHQRQRRIEE QKEERRRVEE QQRREREQRK LQEKEQQRRL EDMQALRREE ERRQAEREQE YKRKQLEEQR QSERLQRQLQ QEHAYLKSLQ QQQQQQQLQK QQQQQLLPGD RKPLYHYGRG MNPADKPAWA REVEERTRMN KQQNSPLAKS KPGSTGPEPP IPQASPGPPG PLSQTPPMQR PVEPQEGPHK SLVAHRVPLK PYAAPVPRSQ SLQDQPTRNL AAFPASHDPD PAIPAPTATP SARGAVIRQN SDPTSEGPGP SPNPPAWVRP DNEAPPKVPQ RTSSIATALN TSGAGGSRPA QAVRARPRSN SAWQIYLQRR AERGTPKPPG PPAQPPGPPN ASSNPDLRRS DPGWERSDSV LPASHGHLPQ AGSLERNRVG VSSKPDSSPV LSPGNKAKPD DHRSRPGRPA DFVLLKERTL DEAPRPPKKA MDYSSSSEEV ESSEDDEEEG EGGPAEGSRD TPGGRSDGDT DSVSTMVVHD VEEITGTQPP YGGGTMVVQR TPEEERNLLH ADSNGYTNLP DVVQPSHSPT ENSKGQSPPS KDGSGDYQSR GLVKAPGKSS FTMFVDLGIY QPGGSGDSIP ITALVGGEGT RLDQLQYDVR KGSVVNVNPT NTRAHSETPE IRKYKKRFNS EILCAALWGV NLLVGTENGL MLLDRSGQGK VYGLIGRRRF QQMDVLEGLN LLITISGKRN KLRVYYLSWL RNKILHNDPE VEKKQGWTTV GDMEGCGHYR VVKYERIKFL VIALKSSVEV YAWAPKPYHK FMAFKSFADL PHRPLLVDLT VEEGQRLKVI YGSSAGFHAV DVDSGNSYDI YIPVHIQSQI TPHAIIFLPN TDGMEMLLCY EDEGVYVNTY GRIIKDVVLQ WGEMPTSVAY ICSNQIMGWG EKAIEIRSVE TGHLDGVFMH KRAQRLKFLC ERNDKVFFAS VRSGGSSQVY FMTLNRNCIM NW //