P67998 (KS6B1_RABIT) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 67.
History...
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Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Ribosomal protein S6 kinase beta-1 Short name=S6K-beta-1 Short name=S6K1 EC=2.7.11.1 Alternative name(s): 70 kDa ribosomal protein S6 kinase 1 Short name=P70S6K1 Short name=p70-S6K 1 Ribosomal protein S6 kinase I p70 ribosomal S6 kinase alpha Short name=p70 S6 kinase alpha Short name=p70 S6K-alpha Short name=p70 S6KA | ||
| Gene names |
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| Organism | Oryctolagus cuniculus (Rabbit) [Complete proteome] | ||
| Taxonomic identifier | 9986 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus |
Protein attributes
| Sequence length | 525 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at transcript level |
General annotation (Comments)
| Function | Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial RMP leading to dissociation of a RMP:PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at 'Thr-412', which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin By similarity. |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Enzyme regulation | Activation requires multiple phosphorylation events on serine/threonine residues. Activation appears to be first mediated by phosphorylation of multiple sites in the autoinhibitory domain, which facilitates phosphorylation at Thr-412, disrupting the autoinhibitory mechanism and allowing phosphorylation of Thr-252 by PDPK1. The active conformation of the kinase is believed to be stabilized by a mechanism involving three conserved phosphorylation sites located in the kinase domain activation loop (Thr-252) and in the AGC-kinase C-terminal domain (Ser-394 in the middle of the tail/linker region and Thr-412 within a hydrophobic motif at its end). Activated by mTORC1; isoform Alpha I and isoform Alpha II are sensitive to rapamycin, which inhibits activating phosphorylation at Thr-412. Activated by PDPK1 By similarity. |
| Subunit structure | Interacts with PPP1R9A/neurabin-1. Interacts with RPTOR. Interacts with IRS1. Interacts with EIF3B and EIF3C. Interacts with POLDIP3 and TRAF4 By similarity. |
| Subcellular location | Cytoplasm By similarity. Cell junction › synapse › synaptosome By similarity. Mitochondrion outer membrane By similarity. |
| Domain | The autoinhibitory domain is believed to block phosphorylation within the AGC-kinase C-terminal domain and the activation loop By similarity. The TOS (TOR signaling) motif is essential for activation by mTORC1 By similarity. |
| Post-translational modification | Phosphorylation at Thr-412 is regulated by mTORC1. The phosphorylation at this site is maintained by an agonist-dependent autophosphorylation mechanism. Activated by phosphorylation at Thr-252 by PDPK1 By similarity. |
| Sequence similarities | Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 protein kinase domain. |
Ontologies
Alternative products
| This entry describes 2 isoforms produced by alternative initiation. [Align] [Select] | ||||||
| Isoform Alpha I (identifier: P67998-1) 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 Alpha II (identifier: P67998-2) The sequence of this isoform differs from the canonical sequence as follows: 1-23: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 525 | 525 | Ribosomal protein S6 kinase beta-1 | PRO_0000024346 | |||||
Regions | |||||||||
| Domain | 91 – 352 | 262 | Protein kinase | ||||||
| Domain | 353 – 423 | 71 | AGC-kinase C-terminal | ||||||
| Nucleotide binding | 97 – 105 | 9 | ATP By similarity | ||||||
| Region | 424 – 525 | 102 | Autoinhibitory domain | ||||||
| Motif | 28 – 32 | 5 | TOS motif | ||||||
Sites | |||||||||
| Active site | 218 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 123 | 1 | ATP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 252 | 1 | Phosphothreonine; by PDPK1 By similarity | ||||||
| Modified residue | 304 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 394 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 412 | 1 | Phosphothreonine; by MTOR, NEK6 and NEK7 By similarity | ||||||
| Modified residue | 434 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 441 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 444 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 447 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 516 | 1 | N6-acetyllysine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 23 | 23 | Missing in isoform Alpha II. | VSP_018841 | |||||
Sequences
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References
| [1] | "cDNA encoding a 59 kDa homolog of ribosomal protein S6 kinase from rabbit liver." Harmann B., Kilimann M.W. FEBS Lett. 273:248-252(1990) [PubMed: 1699810] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | X54415 mRNA. Translation: CAA38279.1. |
| PIR | S12906. |
| RefSeq | NP_001095160.1. NM_001101690.1. |
| UniGene | Ocu.3260. |
3D structure databases | |
| ProteinModelPortal | P67998. |
| SMR | P67998. Positions 79-376. |
| ModBase | Search... |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| GeneID | 100009260. |
Organism-specific databases | |
| CTD | 6198. |
Phylogenomic databases | |
| eggNOG | maNOG05116. |
| GeneTree | ENSGT00600000084335. |
| HOVERGEN | HBG108317. |
| OrthoDB | EOG4Q2DFF. |
Family and domain databases | |
| InterPro | IPR000961. AGC-kinase_C. IPR011009. Kinase-like_dom. IPR017892. Pkinase_C. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR016238. Ribosomal_S6_kinase. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view] |
| Pfam | PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view] |
| PIRSF | PIRSF000605. Ribsml_S6_kin_1. 1 hit. |
| SMART | SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view] |
| SUPFAM | SSF56112. Kinase_like. 1 hit. |
| PROSITE | PS51285. AGC_KINASE_CTER. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Entry information
| Entry name | KS6B1_RABIT | ||||||||
| Accession | Primary (citable) accession number: P67998 Secondary accession number(s): P21425 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| SIMILARITY comments Index of protein domains and families |