Q8IWQ3 (BRSK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 95.
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: Serine/threonine-protein kinase BRSK2 EC=2.7.11.1 Alternative name(s): Brain-selective kinase 2 EC=2.7.11.26 Brain-specific serine/threonine-protein kinase 2 Short name=BR serine/threonine-protein kinase 2 Serine/threonine-protein kinase 29 Serine/threonine-protein kinase SAD-A | ||||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||||
| Taxonomic identifier | 9606 [NCBI] | ||||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 736 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Serine/threonine-protein kinase that plays a key role in polarization of neurons. Phosphorylates MAPT/TAU and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Ser-579'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in post-mitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. Ref.8 Ref.16 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. ATP + [tau protein] = ADP + [tau protein] phosphate. |
| Cofactor | Magnesium By similarity. |
| Enzyme regulation | Activated by phosphorylation on Thr-174 by STK11/LKB1. Ref.8 |
| Post-translational modification | Phosphorylated at Thr-174 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not phosphorylated at Thr-174 by CaMKK2. In contrast, it is phosphorylated and activated by CaMKK1. May be inactivated via dephosphorylation of Thr-174 by PP2C. May be phosphorylated at Thr-260 by PKA. However phosphorylation at Thr-260 by PKA was not comfirmed later (Ref.10). Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 |
| Sequence similarities | Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. Contains 1 protein kinase domain. Contains 1 UBA domain. |
| Sequence caution | The sequence AAD09654.1 differs from that shown. Reason: Erroneous termination at position 663. Translated as Gly. The sequence AAD09654.1 differs from that shown. Reason: Frameshift at position 640. The sequence AAH24291.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Neurogenesis |
| Coding sequence diversity | Alternative splicing |
| Ligand | ATP-binding Magnesium Metal-binding Nucleotide-binding |
| Molecular function | Kinase Serine/threonine-protein kinase Transferase |
| PTM | Phosphoprotein |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Biological process | axonogenesis Inferred from sequence or structural similarity. Source: UniProtKB establishment of cell polarityInferred from sequence or structural similarity. Source: UniProtKB |
| Molecular function | ATP binding Inferred from direct assay Ref.8. Source: UniProtKB magnesium ion bindingInferred from direct assay Ref.8. Source: UniProtKB protein serine/threonine kinase activityInferred from direct assay Ref.8. Source: UniProtKB tau-protein kinase activityInferred from sequence or structural similarity. Source: UniProtKB |
| Complete GO annotation... | |
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q8IWQ3-1) 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 2 (identifier: Q8IWQ3-2) The sequence of this isoform differs from the canonical sequence as follows: 647-674: DTTNCMEMMTGRLSKCGSPLSNFFDVIK → EPPPPAPGLSWGAGLKGQKVATSYESSL 675-736: Missing. | ||||||
| Isoform 3 (identifier: Q8IWQ3-3) The sequence of this isoform differs from the canonical sequence as follows: 664-668: SPLSN → IIPKS 669-736: Missing. | ||||||
| Isoform 4 (identifier: Q8IWQ3-4) The sequence of this isoform differs from the canonical sequence as follows: 408-408: Q → QSKAMFSKSLDIAEAHPQFSKED 647-674: DTTNCMEMMTGRLSKCGSPLSNFFDVIK → EPPPPAPGLSWGAGLKGQKVATSYESSL 675-736: Missing. | ||||||
| Note: Phosphorylated on Ser-416. | ||||||
| Isoform 5 (identifier: Q8IWQ3-5) The sequence of this isoform differs from the canonical sequence as follows: 1-30: MTSTGKDGGAQHAQYVGPYRLEKTLGKGQT → MSPEGHPSRW...TWLCLQPSPA 663-678: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 736 | 736 | Serine/threonine-protein kinase BRSK2 | PRO_0000085670 | |||||
Regions | |||||||||
| Domain | 19 – 270 | 252 | Protein kinase | ||||||
| Domain | 297 – 339 | 43 | UBA | ||||||
| Nucleotide binding | 25 – 33 | 9 | ATP By similarity | ||||||
| Compositional bias | 424 – 468 | 45 | Pro-rich | ||||||
Sites | |||||||||
| Active site | 141 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 48 | 1 | ATP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 174 | 1 | Phosphothreonine; by LKB1 Ref.8 Ref.10 | ||||||
| Modified residue | 178 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 260 | 1 | Phosphothreonine; by PKA Potential | ||||||
| Modified residue | 294 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 367 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 382 | 1 | Phosphoserine Ref.12 Ref.13 Ref.14 | ||||||
| Modified residue | 389 | 1 | Phosphothreonine Ref.13 | ||||||
| Modified residue | 393 | 1 | Phosphoserine Ref.12 Ref.13 Ref.14 | ||||||
| Modified residue | 412 | 1 | Phosphoserine Ref.14 | ||||||
| Modified residue | 422 | 1 | Phosphothreonine Ref.13 | ||||||
| Modified residue | 423 | 1 | Phosphoserine Ref.12 Ref.13 | ||||||
| Modified residue | 427 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 435 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 466 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 489 | 1 | Phosphoserine Ref.11 | ||||||
| Modified residue | 509 | 1 | Phosphothreonine Ref.14 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 30 | 30 | MTSTG…GKGQT → MSPEGHPSRWARPRRPCICP SSLCSPREPRSGPAVGRGGA AHHRVPAGHTPGPQLLQPHL HLPQGQTWLCLQPSPA in isoform 5. | VSP_022603 | |||||
| Alternative sequence | 408 | 1 | Q → QSKAMFSKSLDIAEAHPQFS KED in isoform 4. | VSP_013945 | |||||
| Alternative sequence | 647 – 674 | 28 | DTTNC…FDVIK → EPPPPAPGLSWGAGLKGQKV ATSYESSL in isoform 2 and isoform 4. | VSP_008154 | |||||
| Alternative sequence | 663 – 678 | 16 | Missing in isoform 5. | VSP_022604 | |||||
| Alternative sequence | 664 – 668 | 5 | SPLSN → IIPKS in isoform 3. | VSP_008156 | |||||
| Alternative sequence | 669 – 736 | 68 | Missing in isoform 3. | VSP_008157 | |||||
| Alternative sequence | 675 – 736 | 62 | Missing in isoform 2 and isoform 4. | VSP_008155 | |||||
Experimental info | |||||||||
| Mutagenesis | 174 | 1 | T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. Ref.8 Ref.10 | ||||||
| Mutagenesis | 260 | 1 | T → A: Decreased phosphorylation. Ref.9 | ||||||
| Mutagenesis | 310 | 1 | G → A: Decreased activation of kinase activity. Ref.10 | ||||||
| Sequence conflict | 251 | 1 | I → S in AAP97723. Ref.2 | ||||||
| Sequence conflict | 251 | 1 | I → S in AAP97724. Ref.2 | ||||||
| Sequence conflict | 251 | 1 | I → S in AAP97725. Ref.2 | ||||||
| Sequence conflict | 251 | 1 | I → S in AAP97726. Ref.2 | ||||||
| Sequence conflict | 251 | 1 | I → S in AAP97727. Ref.2 | ||||||
| Sequence conflict | 251 | 1 | I → S in AAN87839. Ref.2 | ||||||
| Sequence conflict | 251 | 1 | I → S in CAA07196. Ref.5 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "SAD: a presynaptic kinase associated with synaptic vesicles and the active zone cytomatrix that regulates neurotransmitter release." Inoue E., Mochida S., Takagi H., Higa S., Deguchi-Tawarada M., Takao-Rikitsu E., Inoue M., Yao I., Takeuchi K., Kitajima I., Setou M., Ohtsuka T., Takai Y. Neuron 50:261-275(2006) [PubMed: 16630837] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). |
| [2] | Guo J.H., Yu L. Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). Tissue: Brain. |
| [3] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). Tissue: Amygdala. |
| [4] | "Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. Sakaki Y.Nature 440:497-500(2006) [PubMed: 16554811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "Characterization of 16 novel human genes showing high similarity to yeast sequences." Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B., Cannata N., Zimbello R., Lanfranchi G., Valle G. Yeast 18:69-80(2001) [PubMed: 11124703] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 72-736 (ISOFORM 2). Tissue: Brain. |
| [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 454-736 (ISOFORM 2). Tissue: Eye. |
| [7] | "Repeat-directed isolation of a novel gene preferentially expressed from the maternal allele in human placenta." Miura K., Miyoshi O., Yun K., Inazawa J., Miyamoto T., Hayashi H., Masuzaki H., Yoshimura S., Niikawa N., Jinno Y., Ishimaru T. J. Hum. Genet. 44:1-9(1999) [PubMed: 9929968] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 463-736 (ISOFORM 3). |
| [8] | "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1." Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R. EMBO J. 23:833-843(2004) [PubMed: 14976552] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-174, MUTAGENESIS OF THR-174. |
| [9] | "BRSK2 is activated by cyclic AMP-dependent protein kinase A through phosphorylation at Thr260." Guo Z., Tang W., Yuan J., Chen X., Wan B., Gu X., Luo K., Wang Y., Yu L. Biochem. Biophys. Res. Commun. 347:867-871(2006) [PubMed: 16870137] [Abstract] Cited for: PHOSPHORYLATION AT THR-260, MUTAGENESIS OF THR-260. |
| [10] | "Investigating the regulation of brain-specific kinases 1 and 2 by phosphorylation." Bright N.J., Carling D., Thornton C. J. Biol. Chem. 283:14946-14954(2008) [PubMed: 18339622] [Abstract] Cited for: PHOSPHORYLATION AT THR-174, MUTAGENESIS OF THR-174 AND GLY-310. |
| [11] | "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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-489, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [12] | "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382; SER-393 AND SER-423, MASS SPECTROMETRY. Tissue: Embryonic kidney. |
| [13] | "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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-294; SER-367; SER-382; THR-389; SER-393; THR-422; SER-423; SER-427; SER-435 AND SER-466, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416 (ISOFORM 4), MASS SPECTROMETRY. |
| [14] | "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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382; SER-393; SER-412 AND THR-509, MASS SPECTROMETRY. Tissue: Leukemic T-cell. |
| [15] | "Calmodulin-dependent protein kinase kinase-beta activates AMPK without forming a stable complex: synergistic effects of Ca2+ and AMP." Fogarty S., Hawley S.A., Green K.A., Saner N., Mustard K.J., Hardie D.G. Biochem. J. 426:109-118(2010) [PubMed: 19958286] [Abstract] Cited for: PHOSPHORYLATION. |
| [16] | "Persistence of the cell-cycle checkpoint kinase Wee1 in SadA- and SadB-deficient neurons disrupts neuronal polarity." Muller M., Lutter D., Puschel A.W. J. Cell Sci. 123:286-294(2010) [PubMed: 20026642] [Abstract] Cited for: FUNCTION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AY505125 mRNA. Translation: AAS86443.1. AF533876 mRNA. Translation: AAP97723.1. AF533877 mRNA. Translation: AAP97724.1. AF533878 mRNA. Translation: AAP97725.1. AF533879 mRNA. Translation: AAP97726.1. AF533880 mRNA. Translation: AAP97727.1. AY166857 mRNA. Translation: AAN87839.1. AK131534 mRNA. Translation: BAD18671.1. AC091196 Genomic DNA. No translation available. AC136297 Genomic DNA. No translation available. AJ006701 mRNA. Translation: CAA07196.1. BC024291 mRNA. Translation: AAH24291.1. Different initiation. AF020089 mRNA. Translation: AAD09654.1. Sequence problems. |
| IPI | IPI00028344. IPI00339265. IPI00339266. IPI00604667. IPI00744296. |
| RefSeq | NP_003948.2. NM_003957.2. |
| UniGene | Hs.170819. |
3D structure databases | |
| ProteinModelPortal | Q8IWQ3. |
| SMR | Q8IWQ3. Positions 14-336. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q8IWQ3. 1 interaction. |
| STRING | Q8IWQ3. |
PTM databases | |
| PhosphoSite | Q8IWQ3. |
Polymorphism databases | |
| DMDM | 116241272. |
Proteomic databases | |
| PRIDE | Q8IWQ3. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000382179; ENSP00000371614; ENSG00000174672. |
| GeneID | 9024. |
| KEGG | hsa:9024. |
| UCSC | uc001lth.1. human. uc001lti.2. human. uc001ltj.1. human. uc001ltm.2. human. uc009ycv.1. human. |
Organism-specific databases | |
| CTD | 9024. |
| GeneCards | GC11P001368. |
| HGNC | HGNC:11405. BRSK2. |
| MIM | 609236. gene. |
| neXtProt | NX_Q8IWQ3. |
| PharmGKB | PA36212. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG06728. |
| GeneTree | ENSGT00570000078909. |
| HOGENOM | HBG715635. |
| HOVERGEN | HBG007240. |
| InParanoid | Q8IWQ3. |
| OMA | RINGTNA. |
| PhylomeDB | Q8IWQ3. |
Gene expression databases | |
| ArrayExpress | Q8IWQ3. |
| Bgee | Q8IWQ3. |
| CleanEx | HS_BRSK2. |
| Genevestigator | Q8IWQ3. |
| GermOnline | ENSG00000174672. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view] |
| KO | K08796. |
| Pfam | PF00069. Pkinase. 1 hit. [Graphical view] |
| SMART | SM00220. S_TKc. 1 hit. [Graphical view] |
| SUPFAM | SSF56112. Kinase_like. 1 hit. |
| PROSITE | PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS50030. UBA. False negative. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 33809. |
| SOURCE | Search... |
Entry information
| Entry name | BRSK2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q8IWQ3 Secondary accession number(s): O60843 Q8TB60 | ||||||||
| 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 11 Human chromosome 11: entries, gene names and cross-references to MIM |
| 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