Full text data of MINK1
MINK1
(B55, MAP4K6, MINK, YSK2, ZC3)
[Confidence: low (only semi-automatic identification from reviews)]
Misshapen-like kinase 1; 2.7.11.1 (GCK family kinase MiNK; MAPK/ERK kinase kinase kinase 6; MEK kinase kinase 6; MEKKK 6; Misshapen/NIK-related kinase; Mitogen-activated protein kinase kinase kinase kinase 6)
Misshapen-like kinase 1; 2.7.11.1 (GCK family kinase MiNK; MAPK/ERK kinase kinase kinase 6; MEK kinase kinase 6; MEKKK 6; Misshapen/NIK-related kinase; Mitogen-activated protein kinase kinase kinase kinase 6)
UniProt
Q8N4C8
ID MINK1_HUMAN Reviewed; 1332 AA.
AC Q8N4C8; D3DTK3; D3DTK4; Q5U8Z0; Q9P1X1; Q9P2R8;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 18-MAY-2010, sequence version 2.
DT 22-JAN-2014, entry version 120.
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=B55, MAP4K6, MINK, YSK2, ZC3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
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.,
RA Ninomiya-Tsuji J., Kusumi A.;
RT "Molecular cloning of MINK, a novel member of mammalian GCK family
RT kinases, which is up-regulated during postnatal mouse cerebral
RT development.";
RL FEBS Lett. 469:19-23(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, SUBCELLULAR
RP LOCATION, INTERACTION WITH NCK1, TISSUE SPECIFICITY, ALTERNATIVE
RP SPLICING, 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.
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.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA 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
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RP ALA-771 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
RT project: 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.,
RA Hancock D.C.;
RT "Involvement of MINK, a Ste20 family kinase, in Ras oncogene-induced
RT growth 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 MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling 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.,
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, AND MASS
RP SPECTROMETRY.
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.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, AND MASS
RP SPECTROMETRY.
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
RP SER-782, VARIANT [LARGE SCALE ANALYSIS] LEU-775, AND MASS
RP SPECTROMETRY.
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
RT the 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
RP AND SER-782, VARIANT [LARGE SCALE ANALYSIS] LEU-775, AND MASS
RP SPECTROMETRY.
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
RP SCALE ANALYSIS] LEU-775, AND MASS SPECTROMETRY.
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
RP SCALE ANALYSIS] LEU-775, AND MASS SPECTROMETRY.
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 MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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.,
RA Kariya K., 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 MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-514; ILE-863; VAL-1010 AND
RP VAL-1200.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [21]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-775, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
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.
CC -!- FUNCTION: Isoform 4 can activate the JNK pathway. Involved in the
CC regulation of actin cytoskeleton reorganization, cell-matrix
CC adhesion, cell-cell adhesion and cell migration.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Magnesium (By similarity).
CC -!- SUBUNIT: Interacts with TANC1 (By similarity). Interacts with
CC RAP2A. Isoform 4 interacts with NCK1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell junction, synapse,
CC postsynaptic cell membrane, postsynaptic density (By similarity).
CC Cell projection, axon (By similarity). Cell projection, dendrite
CC (By similarity).
CC -!- SUBCELLULAR LOCATION: Isoform 4: Golgi apparatus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=3; Synonyms=MINK-alpha;
CC IsoId=Q8N4C8-1; Sequence=Displayed;
CC Name=1; Synonyms=MiNK-1, MINK-delta;
CC IsoId=Q8N4C8-2; Sequence=VSP_007059;
CC Name=2; 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
CC abundant than isoform 1. Isoform 3 is ubiquitously expressed.
CC Isoform 1 is most abundant in the skeletal muscle. Isoform 4 is
CC ubiquitously expressed with relative high levels in brain,
CC skeletal muscle, pancreas and testis.
CC -!- INDUCTION: Activated after Ras induction via a mechanism involving
CC reactive oxygen species.
CC -!- PTM: Autophosphorylated.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily.
CC -!- SIMILARITY: Contains 1 CNH domain.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
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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 RefSeq; NP_001020108.1; NM_001024937.3.
DR RefSeq; NP_056531.1; NM_015716.4.
DR RefSeq; NP_722549.2; NM_153827.4.
DR RefSeq; NP_733763.1; NM_170663.4.
DR UniGene; Hs.443417; -.
DR ProteinModelPortal; Q8N4C8; -.
DR SMR; Q8N4C8; 13-313.
DR IntAct; Q8N4C8; 2.
DR STRING; 9606.ENSP00000347427; -.
DR ChEMBL; CHEMBL5518; -.
DR GuidetoPHARMACOLOGY; 2103; -.
DR PhosphoSite; Q8N4C8; -.
DR DMDM; 296437370; -.
DR PaxDb; Q8N4C8; -.
DR PRIDE; Q8N4C8; -.
DR DNASU; 50488; -.
DR Ensembl; ENST00000347992; ENSP00000269296; ENSG00000141503.
DR Ensembl; ENST00000355280; ENSP00000347427; ENSG00000141503.
DR Ensembl; ENST00000453408; ENSP00000406487; ENSG00000141503.
DR GeneID; 50488; -.
DR KEGG; hsa:50488; -.
DR UCSC; uc010vsl.2; human.
DR CTD; 50488; -.
DR GeneCards; GC17P004736; -.
DR H-InvDB; HIX0013452; -.
DR HGNC; HGNC:17565; MINK1.
DR HPA; HPA056296; -.
DR MIM; 609426; gene.
DR neXtProt; NX_Q8N4C8; -.
DR PharmGKB; PA134910641; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000290708; -.
DR HOVERGEN; HBG036506; -.
DR InParanoid; Q8N4C8; -.
DR KO; K04413; -.
DR OMA; GTQTPYG; -.
DR OrthoDB; EOG73803V; -.
DR Reactome; REACT_120956; Cellular responses to stress.
DR SignaLink; Q8N4C8; -.
DR ChiTaRS; MINK1; human.
DR GeneWiki; MINK1; -.
DR GenomeRNAi; 50488; -.
DR NextBio; 53052; -.
DR PRO; PR:Q8N4C8; -.
DR ArrayExpress; Q8N4C8; -.
DR Bgee; Q8N4C8; -.
DR CleanEx; HS_MINK1; -.
DR Genevestigator; Q8N4C8; -.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0005083; F:small GTPase regulator activity; IEA:InterPro.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0048813; P:dendrite morphogenesis; ISS:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; TAS:ProtInc.
DR GO; GO:0045060; P:negative thymic T cell selection; IEA:Ensembl.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:2000311; P:regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate 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:0007268; P:synaptic transmission; ISS:UniProtKB.
DR InterPro; IPR001180; Citron.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR028556; MINK1.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24361:SF196; PTHR24361:SF196; 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; 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 Alternative splicing; ATP-binding; Cell junction; Cell membrane;
KW Cell projection; Complete proteome; Cytoplasm; Golgi apparatus;
KW Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Postsynaptic cell membrane; Reference proteome;
KW Serine/threonine-protein kinase; Synapse; Transferase.
FT CHAIN 1 1332 Misshapen-like kinase 1.
FT /FTId=PRO_0000086329.
FT DOMAIN 25 289 Protein kinase.
FT DOMAIN 1019 1306 CNH.
FT NP_BIND 31 39 ATP (By similarity).
FT REGION 866 1332 Mediates interaction with RAP2A.
FT COMPBIAS 359 495 Gln-rich.
FT COMPBIAS 542 729 Pro-rich.
FT ACT_SITE 153 153 Proton acceptor (By similarity).
FT BINDING 54 54 ATP (By similarity).
FT MOD_RES 641 641 Phosphoserine.
FT MOD_RES 763 763 Phosphoserine.
FT MOD_RES 777 777 Phosphoserine.
FT MOD_RES 778 778 Phosphoserine.
FT MOD_RES 782 782 Phosphoserine.
FT VAR_SEQ 581 600 Missing (in isoform 4 and isoform 5).
FT /FTId=VSP_041871.
FT VAR_SEQ 696 732 Missing (in isoform 1, isoform 2 and
FT isoform 5).
FT /FTId=VSP_007059.
FT VAR_SEQ 800 800 A -> ASYKRAIGE (in isoform 2).
FT /FTId=VSP_007060.
FT VARIANT 514 514 A -> T (in dbSNP:rs56131206).
FT /FTId=VAR_040799.
FT VARIANT 771 771 V -> A (in dbSNP:rs11556634).
FT /FTId=VAR_046058.
FT VARIANT 775 775 P -> L (in dbSNP:rs11556635).
FT /FTId=VAR_046059.
FT VARIANT 863 863 V -> I (in dbSNP:rs2302319).
FT /FTId=VAR_046060.
FT VARIANT 1010 1010 E -> V (in a gastric adenocarcinoma
FT sample; somatic mutation).
FT /FTId=VAR_046061.
FT VARIANT 1200 1200 I -> V.
FT /FTId=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
//
ID MINK1_HUMAN Reviewed; 1332 AA.
AC Q8N4C8; D3DTK3; D3DTK4; Q5U8Z0; Q9P1X1; Q9P2R8;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 18-MAY-2010, sequence version 2.
DT 22-JAN-2014, entry version 120.
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=B55, MAP4K6, MINK, YSK2, ZC3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
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.,
RA Ninomiya-Tsuji J., Kusumi A.;
RT "Molecular cloning of MINK, a novel member of mammalian GCK family
RT kinases, which is up-regulated during postnatal mouse cerebral
RT development.";
RL FEBS Lett. 469:19-23(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, SUBCELLULAR
RP LOCATION, INTERACTION WITH NCK1, TISSUE SPECIFICITY, ALTERNATIVE
RP SPLICING, 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.
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.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA 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
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RP ALA-771 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
RT project: 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.,
RA Hancock D.C.;
RT "Involvement of MINK, a Ste20 family kinase, in Ras oncogene-induced
RT growth 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 MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling 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.,
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, AND MASS
RP SPECTROMETRY.
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.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, AND MASS
RP SPECTROMETRY.
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
RP SER-782, VARIANT [LARGE SCALE ANALYSIS] LEU-775, AND MASS
RP SPECTROMETRY.
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
RT the 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
RP AND SER-782, VARIANT [LARGE SCALE ANALYSIS] LEU-775, AND MASS
RP SPECTROMETRY.
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
RP SCALE ANALYSIS] LEU-775, AND MASS SPECTROMETRY.
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
RP SCALE ANALYSIS] LEU-775, AND MASS SPECTROMETRY.
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 MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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.,
RA Kariya K., 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 MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-514; ILE-863; VAL-1010 AND
RP VAL-1200.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [21]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-775, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
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.
CC -!- FUNCTION: Isoform 4 can activate the JNK pathway. Involved in the
CC regulation of actin cytoskeleton reorganization, cell-matrix
CC adhesion, cell-cell adhesion and cell migration.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Magnesium (By similarity).
CC -!- SUBUNIT: Interacts with TANC1 (By similarity). Interacts with
CC RAP2A. Isoform 4 interacts with NCK1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell junction, synapse,
CC postsynaptic cell membrane, postsynaptic density (By similarity).
CC Cell projection, axon (By similarity). Cell projection, dendrite
CC (By similarity).
CC -!- SUBCELLULAR LOCATION: Isoform 4: Golgi apparatus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=3; Synonyms=MINK-alpha;
CC IsoId=Q8N4C8-1; Sequence=Displayed;
CC Name=1; Synonyms=MiNK-1, MINK-delta;
CC IsoId=Q8N4C8-2; Sequence=VSP_007059;
CC Name=2; 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
CC abundant than isoform 1. Isoform 3 is ubiquitously expressed.
CC Isoform 1 is most abundant in the skeletal muscle. Isoform 4 is
CC ubiquitously expressed with relative high levels in brain,
CC skeletal muscle, pancreas and testis.
CC -!- INDUCTION: Activated after Ras induction via a mechanism involving
CC reactive oxygen species.
CC -!- PTM: Autophosphorylated.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily.
CC -!- SIMILARITY: Contains 1 CNH domain.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
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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 RefSeq; NP_001020108.1; NM_001024937.3.
DR RefSeq; NP_056531.1; NM_015716.4.
DR RefSeq; NP_722549.2; NM_153827.4.
DR RefSeq; NP_733763.1; NM_170663.4.
DR UniGene; Hs.443417; -.
DR ProteinModelPortal; Q8N4C8; -.
DR SMR; Q8N4C8; 13-313.
DR IntAct; Q8N4C8; 2.
DR STRING; 9606.ENSP00000347427; -.
DR ChEMBL; CHEMBL5518; -.
DR GuidetoPHARMACOLOGY; 2103; -.
DR PhosphoSite; Q8N4C8; -.
DR DMDM; 296437370; -.
DR PaxDb; Q8N4C8; -.
DR PRIDE; Q8N4C8; -.
DR DNASU; 50488; -.
DR Ensembl; ENST00000347992; ENSP00000269296; ENSG00000141503.
DR Ensembl; ENST00000355280; ENSP00000347427; ENSG00000141503.
DR Ensembl; ENST00000453408; ENSP00000406487; ENSG00000141503.
DR GeneID; 50488; -.
DR KEGG; hsa:50488; -.
DR UCSC; uc010vsl.2; human.
DR CTD; 50488; -.
DR GeneCards; GC17P004736; -.
DR H-InvDB; HIX0013452; -.
DR HGNC; HGNC:17565; MINK1.
DR HPA; HPA056296; -.
DR MIM; 609426; gene.
DR neXtProt; NX_Q8N4C8; -.
DR PharmGKB; PA134910641; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000290708; -.
DR HOVERGEN; HBG036506; -.
DR InParanoid; Q8N4C8; -.
DR KO; K04413; -.
DR OMA; GTQTPYG; -.
DR OrthoDB; EOG73803V; -.
DR Reactome; REACT_120956; Cellular responses to stress.
DR SignaLink; Q8N4C8; -.
DR ChiTaRS; MINK1; human.
DR GeneWiki; MINK1; -.
DR GenomeRNAi; 50488; -.
DR NextBio; 53052; -.
DR PRO; PR:Q8N4C8; -.
DR ArrayExpress; Q8N4C8; -.
DR Bgee; Q8N4C8; -.
DR CleanEx; HS_MINK1; -.
DR Genevestigator; Q8N4C8; -.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0005083; F:small GTPase regulator activity; IEA:InterPro.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0048813; P:dendrite morphogenesis; ISS:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; TAS:ProtInc.
DR GO; GO:0045060; P:negative thymic T cell selection; IEA:Ensembl.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:2000311; P:regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate 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:0007268; P:synaptic transmission; ISS:UniProtKB.
DR InterPro; IPR001180; Citron.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR028556; MINK1.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24361:SF196; PTHR24361:SF196; 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; 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 Alternative splicing; ATP-binding; Cell junction; Cell membrane;
KW Cell projection; Complete proteome; Cytoplasm; Golgi apparatus;
KW Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Postsynaptic cell membrane; Reference proteome;
KW Serine/threonine-protein kinase; Synapse; Transferase.
FT CHAIN 1 1332 Misshapen-like kinase 1.
FT /FTId=PRO_0000086329.
FT DOMAIN 25 289 Protein kinase.
FT DOMAIN 1019 1306 CNH.
FT NP_BIND 31 39 ATP (By similarity).
FT REGION 866 1332 Mediates interaction with RAP2A.
FT COMPBIAS 359 495 Gln-rich.
FT COMPBIAS 542 729 Pro-rich.
FT ACT_SITE 153 153 Proton acceptor (By similarity).
FT BINDING 54 54 ATP (By similarity).
FT MOD_RES 641 641 Phosphoserine.
FT MOD_RES 763 763 Phosphoserine.
FT MOD_RES 777 777 Phosphoserine.
FT MOD_RES 778 778 Phosphoserine.
FT MOD_RES 782 782 Phosphoserine.
FT VAR_SEQ 581 600 Missing (in isoform 4 and isoform 5).
FT /FTId=VSP_041871.
FT VAR_SEQ 696 732 Missing (in isoform 1, isoform 2 and
FT isoform 5).
FT /FTId=VSP_007059.
FT VAR_SEQ 800 800 A -> ASYKRAIGE (in isoform 2).
FT /FTId=VSP_007060.
FT VARIANT 514 514 A -> T (in dbSNP:rs56131206).
FT /FTId=VAR_040799.
FT VARIANT 771 771 V -> A (in dbSNP:rs11556634).
FT /FTId=VAR_046058.
FT VARIANT 775 775 P -> L (in dbSNP:rs11556635).
FT /FTId=VAR_046059.
FT VARIANT 863 863 V -> I (in dbSNP:rs2302319).
FT /FTId=VAR_046060.
FT VARIANT 1010 1010 E -> V (in a gastric adenocarcinoma
FT sample; somatic mutation).
FT /FTId=VAR_046061.
FT VARIANT 1200 1200 I -> V.
FT /FTId=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
//
MIM
609426
*RECORD*
*FIELD* NO
609426
*FIELD* TI
*609426 MISSHAPEN/NIK-RELATED KINASE 1; MINK1
;;MINK
*FIELD* TX
DESCRIPTION
MINK1 belongs to the germinal center kinase (GCK) family. GCKs regulate
read morea wide variety of cellular processes by coupling cell surface receptors
to mitogen-activated protein kinase (MAPK) pathways, such as the JNK
pathway (see 601158) (Hu et al., 2004).
CLONING
Dan et al. (2000) cloned mouse Mink based on its upregulated expression
during postnatal cerebral development. The deduced protein contains
1,300 amino acids and has a calculated molecular mass of 146 kD. Mink
has an N-terminal kinase domain, an intermediate region, and a
C-terminal GCK homology domain. The intermediate region of Mink contains
2 glutamine-rich motifs and 8 proline-rich motifs, which are putative
SH3 domain-binding regions. Mink is highly homologous to several group I
GCKs, including NIK (MAP3K14; 604655) and its Drosophila homolog,
Misshapen. By searching sequence databases, Dan et al. (2000) identified
human MINK, which encodes a predicted 1,296-amino acid protein that
shares 97% identity and a similar structure with the mouse protein.
Northern blot analysis of mouse tissues detected abundant expression in
brain, with lower levels in kidney, spleen, and heart. Longer exposure
showed expression in all tissues tested.
By screening a Jurkat cDNA library for genes conferring resistance to
Taxol-induced cell death, Hu et al. (2004) identified an antisense
fragment of human MINK1. They screened a HeLa cell cDNA library using
the fragment as probe and obtained a full-length MINK1 splice variant
that they termed MINK1-beta. The predicted 1,312-amino acid human
MINK1-beta protein and its mouse homolog share 98% identity in the
N-terminal kinase and C-terminal citron (605629) homology domains. Their
intermediate domains share at least 80% sequence similarity. RT-PCR
analysis identified 5 alternatively spliced variants of MINK1, including
MINK1-beta. The longest isoform, MINK1-alpha, contains 1,332 amino
acids. The other variants encode proteins that vary in their
intermediate domains. Northern blot analysis, which did not distinguish
between the variants, revealed ubiquitous expression of MINK1, with
highest levels in brain, skeletal muscle, pancreas, and testis. RT-PCR
analysis showed that the MINK1 variants have distinct expression
patterns. MINK1-alpha was expressed ubiquitously, with higher levels in
most tissues than the other variants. MINK1-gamma was predominantly
expressed in brain, and MINK1-delta was most abundant in skeletal
muscle. MINK1-beta and MINK1-epsilon were expressed as minor forms in
almost every tissue tested.
GENE FUNCTION
Dan et al. (2000) found that mouse Mink activated the JNK and p38 (see
600289) pathways.
Using kinase assays, Hu et al. (2004) found that MINK1-beta
phosphorylated myelin basic protein (MBP; 159430), as well as itself,
and activated the JNK pathway independently of its kinase activity.
MINK1-beta did not activate the ERK (e.g., MAPK1; 176948) and p38
pathways. Yeast 2-hybrid and GST pull-down assays showed that MINK1-beta
associated with the SH3 domain of NCK (NCK1; 600508). Fluorescence
microscopy demonstrated that MINK1-beta was involved in modulating cell
morphology, possibly through its effects on actin organization and cell
adhesion to the extracellular matrix. MINK1-beta appeared to be
associated with the Golgi apparatus.
McCarty et al. (2005) noted that thymocytes that engage MHC-self peptide
complexes with intermediate affinity are expanded in the thymus through
a process of positive selection, whereas those that bind to these
complexes with high affinity are eliminated through a process of
negative selection. They demonstrated that MINK1 is an essential
signaling element that couples the T-cell receptor to negative, but not
positive, selection.
GENE STRUCTURE
Dan et al. (2000) determined that the MINK1 gene covers more than 63 kb
of genomic DNA and contains 31 exons.
Dan et al. (2002) found that the terminal exons of the MINK1 and CHRNE
(100725) genes overlap in a tail-to-tail manner on opposite DNA strands
in hominoid genomes, but not in the mouse. They suggested that the
potentially hazardous mutations responsible for the exon overlap managed
to escape evolutionary pressures by differential temporospatial
expression of the 2 genes.
MAPPING
By genomic sequence analysis, Dan et al. (2002) mapped the MINK1 gene to
chromosome 17p13.1.
*FIELD* RF
1. Dan, I.; Watanabe, N. M.; Kajikawa, E.; Ishida, T.; Pandey, A.;
Kusumi, A.: Overlapping of MINK and CHRNE gene loci in the course
of mammalian evolution. Nucleic Acids Res. 30: 2906-2910, 2002.
2. Dan, I.; Watanabe, N. M.; Kobayashi, T.; Yamashita-Suzuki, K.;
Fukagaya, Y.; Kajikawa, E.; Kimura, W. K.; Nakashima, T. M.; Matsumoto,
K.; Ninomiya-Tsuji, J.; Kusumi, A.: Molecular cloning of MINK, a
novel member of mammalian GCK family kinases, which is up-regulated
during postnatal mouse cerebral development. FEBS Lett. 469: 19-23,
2000.
3. Hu, Y.; Leo, C.; Yu, S.; Huang, B. C. B.; Wang, H.; Shen, M.; Luo,
Y.; Daniel-Issakani, S.; Payan, D. G.; Xu, X.: Identification and
functional characterization of a novel human Misshapen/Nck interacting
kinase-related kinase, hMINK-beta. J. Biol. Chem. 279: 54387-54397,
2004. Note: Erratum: J. Biol. Chem. 280: 5128 only, 2005.
4. McCarty, N.; Paust, S.; Ikizawa, K.; Dan, I.; Li, X.; Cantor, H.
: Signaling by the kinase MINK is essential in the negative selection
of autoreactive thymocytes. Nature Immun. 6: 65-72, 2005. Note:
Erratum: Nature Immun. 6: 219 only, 2005.
*FIELD* CD
Paul J. Converse: 6/17/2005
*FIELD* ED
carol: 04/11/2013
mgross: 6/17/2005
*RECORD*
*FIELD* NO
609426
*FIELD* TI
*609426 MISSHAPEN/NIK-RELATED KINASE 1; MINK1
;;MINK
*FIELD* TX
DESCRIPTION
MINK1 belongs to the germinal center kinase (GCK) family. GCKs regulate
read morea wide variety of cellular processes by coupling cell surface receptors
to mitogen-activated protein kinase (MAPK) pathways, such as the JNK
pathway (see 601158) (Hu et al., 2004).
CLONING
Dan et al. (2000) cloned mouse Mink based on its upregulated expression
during postnatal cerebral development. The deduced protein contains
1,300 amino acids and has a calculated molecular mass of 146 kD. Mink
has an N-terminal kinase domain, an intermediate region, and a
C-terminal GCK homology domain. The intermediate region of Mink contains
2 glutamine-rich motifs and 8 proline-rich motifs, which are putative
SH3 domain-binding regions. Mink is highly homologous to several group I
GCKs, including NIK (MAP3K14; 604655) and its Drosophila homolog,
Misshapen. By searching sequence databases, Dan et al. (2000) identified
human MINK, which encodes a predicted 1,296-amino acid protein that
shares 97% identity and a similar structure with the mouse protein.
Northern blot analysis of mouse tissues detected abundant expression in
brain, with lower levels in kidney, spleen, and heart. Longer exposure
showed expression in all tissues tested.
By screening a Jurkat cDNA library for genes conferring resistance to
Taxol-induced cell death, Hu et al. (2004) identified an antisense
fragment of human MINK1. They screened a HeLa cell cDNA library using
the fragment as probe and obtained a full-length MINK1 splice variant
that they termed MINK1-beta. The predicted 1,312-amino acid human
MINK1-beta protein and its mouse homolog share 98% identity in the
N-terminal kinase and C-terminal citron (605629) homology domains. Their
intermediate domains share at least 80% sequence similarity. RT-PCR
analysis identified 5 alternatively spliced variants of MINK1, including
MINK1-beta. The longest isoform, MINK1-alpha, contains 1,332 amino
acids. The other variants encode proteins that vary in their
intermediate domains. Northern blot analysis, which did not distinguish
between the variants, revealed ubiquitous expression of MINK1, with
highest levels in brain, skeletal muscle, pancreas, and testis. RT-PCR
analysis showed that the MINK1 variants have distinct expression
patterns. MINK1-alpha was expressed ubiquitously, with higher levels in
most tissues than the other variants. MINK1-gamma was predominantly
expressed in brain, and MINK1-delta was most abundant in skeletal
muscle. MINK1-beta and MINK1-epsilon were expressed as minor forms in
almost every tissue tested.
GENE FUNCTION
Dan et al. (2000) found that mouse Mink activated the JNK and p38 (see
600289) pathways.
Using kinase assays, Hu et al. (2004) found that MINK1-beta
phosphorylated myelin basic protein (MBP; 159430), as well as itself,
and activated the JNK pathway independently of its kinase activity.
MINK1-beta did not activate the ERK (e.g., MAPK1; 176948) and p38
pathways. Yeast 2-hybrid and GST pull-down assays showed that MINK1-beta
associated with the SH3 domain of NCK (NCK1; 600508). Fluorescence
microscopy demonstrated that MINK1-beta was involved in modulating cell
morphology, possibly through its effects on actin organization and cell
adhesion to the extracellular matrix. MINK1-beta appeared to be
associated with the Golgi apparatus.
McCarty et al. (2005) noted that thymocytes that engage MHC-self peptide
complexes with intermediate affinity are expanded in the thymus through
a process of positive selection, whereas those that bind to these
complexes with high affinity are eliminated through a process of
negative selection. They demonstrated that MINK1 is an essential
signaling element that couples the T-cell receptor to negative, but not
positive, selection.
GENE STRUCTURE
Dan et al. (2000) determined that the MINK1 gene covers more than 63 kb
of genomic DNA and contains 31 exons.
Dan et al. (2002) found that the terminal exons of the MINK1 and CHRNE
(100725) genes overlap in a tail-to-tail manner on opposite DNA strands
in hominoid genomes, but not in the mouse. They suggested that the
potentially hazardous mutations responsible for the exon overlap managed
to escape evolutionary pressures by differential temporospatial
expression of the 2 genes.
MAPPING
By genomic sequence analysis, Dan et al. (2002) mapped the MINK1 gene to
chromosome 17p13.1.
*FIELD* RF
1. Dan, I.; Watanabe, N. M.; Kajikawa, E.; Ishida, T.; Pandey, A.;
Kusumi, A.: Overlapping of MINK and CHRNE gene loci in the course
of mammalian evolution. Nucleic Acids Res. 30: 2906-2910, 2002.
2. Dan, I.; Watanabe, N. M.; Kobayashi, T.; Yamashita-Suzuki, K.;
Fukagaya, Y.; Kajikawa, E.; Kimura, W. K.; Nakashima, T. M.; Matsumoto,
K.; Ninomiya-Tsuji, J.; Kusumi, A.: Molecular cloning of MINK, a
novel member of mammalian GCK family kinases, which is up-regulated
during postnatal mouse cerebral development. FEBS Lett. 469: 19-23,
2000.
3. Hu, Y.; Leo, C.; Yu, S.; Huang, B. C. B.; Wang, H.; Shen, M.; Luo,
Y.; Daniel-Issakani, S.; Payan, D. G.; Xu, X.: Identification and
functional characterization of a novel human Misshapen/Nck interacting
kinase-related kinase, hMINK-beta. J. Biol. Chem. 279: 54387-54397,
2004. Note: Erratum: J. Biol. Chem. 280: 5128 only, 2005.
4. McCarty, N.; Paust, S.; Ikizawa, K.; Dan, I.; Li, X.; Cantor, H.
: Signaling by the kinase MINK is essential in the negative selection
of autoreactive thymocytes. Nature Immun. 6: 65-72, 2005. Note:
Erratum: Nature Immun. 6: 219 only, 2005.
*FIELD* CD
Paul J. Converse: 6/17/2005
*FIELD* ED
carol: 04/11/2013
mgross: 6/17/2005