Q8N4C8 (MINK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 113.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Misshapen-like kinase 1 EC=2.7.11.1 Alternative name(s): GCK family kinase MiNK MAPK/ERK kinase kinase kinase 6 Short name=MEK kinase kinase 6 Short name=MEKKK 6 Misshapen/NIK-related kinase Mitogen-activated protein kinase kinase kinase kinase 6 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 1332 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking. Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons. Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates: TANC1 upon stimulation by RAP2A, MBP and SMAD1. Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1. Ref.2 Ref.7 Ref.9 Ref.18 Isoform 4 can activate the JNK pathway. Involved in the regulation of actin cytoskeleton reorganization, cell-matrix adhesion, cell-cell adhesion and cell migration. Ref.2 Ref.7 Ref.9 Ref.18 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. UniProtKB Q9JM52 |
| Cofactor | Magnesium By similarity. UniProtKB Q9JM52 |
| Subunit structure | Interacts with TANC1 By similarity. Interacts with RAP2A. Isoform 4 interacts with NCK1. Ref.2 Ref.9 |
| Subcellular location | Cytoplasm. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density By similarity. Cell projection › axon By similarity. Cell projection › dendrite By similarity Ref.2 Ref.9. Isoform 4: Golgi apparatus Ref.2 Ref.9. |
| Tissue specificity | Expressed in the brain, isoform 2 is more abundant than isoform 1. Isoform 3 is ubiquitously expressed. Isoform 1 is most abundant in the skeletal muscle. Isoform 4 is ubiquitously expressed with relative high levels in brain, skeletal muscle, pancreas and testis. Ref.1 Ref.2 |
| Induction | Activated after Ras induction via a mechanism involving reactive oxygen species. Ref.7 |
| Post-translational modification | Autophosphorylated. Ref.2 |
| Sequence similarities | Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. Contains 1 CNH domain. Contains 1 protein kinase domain. |
Ontologies
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 3 Ref.1 (identifier: Q8N4C8-1) Also known as: MINK-alpha; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 1 Ref.1 (identifier: Q8N4C8-2) Also known as: MiNK-1; MINK-delta; The sequence of this isoform differs from the canonical sequence as follows: 696-732: Missing. | ||||||
| Isoform 2 Ref.1 (identifier: Q8N4C8-3) Also known as: MiNK-2; MINK-gamma; The sequence of this isoform differs from the canonical sequence as follows: 696-732: Missing. 800-800: A → ASYKRAIGE | ||||||
| Isoform 4 (identifier: Q8N4C8-4) Also known as: MINK-beta; The sequence of this isoform differs from the canonical sequence as follows: 581-600: Missing. | ||||||
| Isoform 5 (identifier: Q8N4C8-5) Also known as: MINK-eta; The sequence of this isoform differs from the canonical sequence as follows: 581-600: Missing. 696-732: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1332 | 1332 | Misshapen-like kinase 1 | PRO_0000086329 | |||||
Regions | |||||||||
| Domain | 25 – 289 | 265 | Protein kinase | ||||||
| Domain | 1019 – 1306 | 288 | CNH | ||||||
| Nucleotide binding | 31 – 39 | 9 | ATP By similarity UniProtKB O00506 | ||||||
| Region | 866 – 1332 | 467 | Mediates interaction with RAP2A | ||||||
| Compositional bias | 359 – 495 | 137 | Gln-rich | ||||||
| Compositional bias | 542 – 729 | 188 | Pro-rich | ||||||
Sites | |||||||||
| Active site | 153 | 1 | Proton acceptor By similarity UniProtKB O00506 | ||||||
| Binding site | 54 | 1 | ATP By similarity UniProtKB O00506 | ||||||
Amino acid modifications | |||||||||
| Modified residue | 641 | 1 | Phosphoserine Ref.12 | ||||||
| Modified residue | 763 | 1 | Phosphoserine Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.19 | ||||||
| Modified residue | 777 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 778 | 1 | Phosphoserine Ref.13 Ref.15 | ||||||
| Modified residue | 782 | 1 | Phosphoserine Ref.12 Ref.13 | ||||||
| Modified residue | 916 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 993 | 1 | Phosphoserine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 581 – 600 | 20 | Missing in isoform 4 and isoform 5. | VSP_041871 | |||||
| Alternative sequence | 696 – 732 | 37 | Missing in isoform 1, isoform 2 and isoform 5. Ref.1 | VSP_007059 | |||||
| Alternative sequence | 800 | 1 | A → ASYKRAIGE in isoform 2. Ref.1 | VSP_007060 | |||||
| Natural variant | 514 | 1 | A → T. Ref.20 Corresponds to variant rs56131206 [ dbSNP | Ensembl ]. | VAR_040799 | |||||
| Natural variant | 771 | 1 | V → A. Ref.2 Ref.6 Corresponds to variant rs11556634 [ dbSNP | Ensembl ]. | VAR_046058 | |||||
| Natural variant | 775 | 1 | P → L. Ref.2 Ref.6 Ref.12 Ref.13 Ref.14 Ref.15 Corresponds to variant rs11556635 [ dbSNP | Ensembl ]. | VAR_046059 | |||||
| Natural variant | 863 | 1 | V → I. Ref.20 Corresponds to variant rs2302319 [ dbSNP | Ensembl ]. | VAR_046060 | |||||
| Natural variant | 1010 | 1 | E → V in a gastric adenocarcinoma sample; somatic mutation. Ref.20 | VAR_046061 | |||||
| Natural variant | 1200 | 1 | I → V. Ref.20 | VAR_040800 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Molecular cloning of MINK, a novel member of mammalian GCK family kinases, which is up-regulated during postnatal mouse cerebral development." 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. FEBS Lett. 469:19-23(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Brain. |
| [2] | "Identification and functional characterization of a novel human misshapen/Nck interacting kinase-related kinase, hMINK beta." Hu Y., Leo C., Yu S., Huang B.C., Wang H., Shen M., Luo Y., Daniel-Issakani S., Payan D.G., Xu X. J. Biol. Chem. 279:54387-54397(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NCK1, TISSUE SPECIFICITY, ALTERNATIVE SPLICING, AUTOPHOSPHORYLATION, VARIANTS ALA-771 AND LEU-775. |
| [3] | Erratum Hu Y., Leo C., Yu S., Huang B.C., Wang H., Shen M., Luo Y., Daniel-Issakani S., Payan D.G., Xu X. J. Biol. Chem. 280:5128-5128(2005) |
| [4] | "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. Nusbaum C.Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANTS ALA-771 AND LEU-775. Tissue: Lymph. |
| [7] | "Involvement of MINK, a Ste20 family kinase, in Ras oncogene-induced growth arrest in human ovarian surface epithelial cells." Nicke B., Bastien J., Khanna S.J., Warne P.H., Cowling V., Cook S.J., Peters G., Delpuech O., Schulze A., Berns K., Mullenders J., Beijersbergen R.L., Bernards R., Ganesan T.S., Downward J., Hancock D.C. Mol. Cell 20:673-685(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION. |
| [8] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [9] | "MINK is a Rap2 effector for phosphorylation of the postsynaptic scaffold protein TANC1." Nonaka H., Takei K., Umikawa M., Oshiro M., Kuninaka K., Bayarjargal M., Asato T., Yamashiro Y., Uechi Y., Endo S., Suzuki T., Kariya K. Biochem. Biophys. Res. Commun. 377:573-578(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RAP2A, SUBCELLULAR LOCATION. |
| [10] | "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [11] | "Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, MASS SPECTROMETRY. Tissue: Platelet. |
| [12] | "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641; SER-763 AND SER-782, VARIANT [LARGE SCALE ANALYSIS] LEU-775, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [13] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763; SER-777; SER-778 AND SER-782, VARIANT [LARGE SCALE ANALYSIS] LEU-775, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [14] | "Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, VARIANT [LARGE SCALE ANALYSIS] LEU-775, MASS SPECTROMETRY. |
| [15] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-778, VARIANT [LARGE SCALE ANALYSIS] LEU-775, MASS SPECTROMETRY. Tissue: Leukemic T-cell. |
| [16] | "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [17] | "Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. |
| [18] | "Smad inhibition by the Ste20 kinase Misshapen." Kaneko S., Chen X., Lu P., Yao X., Wright T.G., Rajurkar M., Kariya K., Mao J., Ip Y.T., Xu L. Proc. Natl. Acad. Sci. U.S.A. 108:11127-11132(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [19] | "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-763, MASS SPECTROMETRY. |
| [20] | "Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. Stratton M.R.Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-514; ILE-863; VAL-1010 AND VAL-1200. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AB041926 mRNA. Translation: BAA94838.1. AB035698 mRNA. Translation: BAA90753.1. AY775058 mRNA. Translation: AAV41830.1. AC233723 Genomic DNA. No translation available. CH471108 Genomic DNA. Translation: EAW90401.1. CH471108 Genomic DNA. Translation: EAW90403.1. CH471108 Genomic DNA. Translation: EAW90399.1. CH471108 Genomic DNA. Translation: EAW90400.1. CH471108 Genomic DNA. Translation: EAW90402.1. BC034673 mRNA. Translation: AAH34673.1. |
| IPI | IPI00166680. IPI00218498. IPI00955938. |
| RefSeq | NP_001020108.1. NM_001024937.3. NP_056531.1. NM_015716.4. NP_722549.2. NM_153827.4. NP_733763.1. NM_170663.4. |
| UniGene | Hs.443417. |
3D structure databases | |
| ProteinModelPortal | Q8N4C8. |
| SMR | Q8N4C8. Positions 13-373. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q8N4C8. 2 interactions. |
| STRING | 9606.ENSP00000347427. |
PTM databases | |
| PhosphoSite | Q8N4C8. |
Polymorphism databases | |
| DMDM | 296437370. |
Proteomic databases | |
| PaxDb | Q8N4C8. |
| PRIDE | Q8N4C8. |
Protocols and materials databases | |
| DNASU | 50488. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000347992; ENSP00000269296; ENSG00000141503. ENST00000355280; ENSP00000347427; ENSG00000141503. ENST00000453408; ENSP00000406487; ENSG00000141503. |
| GeneID | 50488. |
| KEGG | hsa:50488. |
| UCSC | uc010vsk.2. human. uc010vsl.2. human. uc010vsn.2. human. |
Organism-specific databases | |
| CTD | 50488. |
| GeneCards | GC17P004736. |
| H-InvDB | HIX0013452. |
| HGNC | HGNC:17565. MINK1. |
| HPA | HPA056296. |
| MIM | 609426. gene. |
| neXtProt | NX_Q8N4C8. |
| PharmGKB | PA134910641. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | COG0515. |
| HOGENOM | HOG000290708. |
| HOVERGEN | HBG036506. |
| InParanoid | Q8N4C8. |
| KO | K04413. |
| OMA | GTQTPYG. |
Gene expression databases | |
| ArrayExpress | Q8N4C8. |
| Bgee | Q8N4C8. |
| CleanEx | HS_MINK1. |
| Genevestigator | Q8N4C8. |
| GermOnline | ENSG00000141503. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR001180. Citron. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view] |
| Pfam | PF00780. CNH. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view] |
| SMART | SM00036. CNH. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view] |
| SUPFAM | SSF56112. Kinase_like. 1 hit. |
| PROSITE | PS50219. CNH. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| ChEMBL | CHEMBL5518. |
| ChiTaRS | MINK1. human. |
| GenomeRNAi | 50488. |
| NextBio | 53052. |
| SOURCE | Search... |
Entry information
| Entry name | MINK1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q8N4C8 Secondary accession number(s): D3DTK3 Q9P2R8 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| Human chromosome 17 Human chromosome 17: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
