FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: insulin pathway effects, RPS6KB-related
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General Information
Name
insulin pathway effects, RPS6KB-related
FlyBase ID
FBhh0000488
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes a potential fly model of type 2 diabetes or related disorders using loss-of-function mutations of Dmel\S6k, which is postulated to act in the Drosophila insulin pathway. Classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for the S6k gene.

In human, there are two genes orthologous to Dmel\S6k, RPS6KB2 and RPS6KB1, which encode members of the ribosomal S6 kinase family of serine/threonine kinases. The human gene Hsap\RPS6KB1 has been introduced into flies; heterologous rescue has not been tested.

Severe loss-of-function mutations of Dmel\S6k are homozygous lethal in the larval stages; larvae exhibit neuroanatomy and neurophysiology defects. Flies with partial loss-of-function alleles have reduced body weight, higher total lipid content, and reduced cholinesterase activity; no change in carbohydrate content is observed; some alleles exhibit impairment in retinal function. Evidence supports a model of S6k-mediated modulation of the hunger response via Drosophila insulin-like peptides (Ilp2, Ilp3, Ilp4) and the Drosophila neuropeptide Y ortholog (NPF). Extensive genetic interactions and a small number of physical interactions have been described for Dmel\S6k; see below and in the S6k gene report.

[updated Jan. 2020 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: insulin pathway effects, RPS6KB-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics

RPS6KB1 is associated with Obesity-related traits in a GWAS study (see GWAS Catalog, below in 'External links').

(FlyBase Curators, 2013-)
Cellular phenotype and pathology
Molecular information

The RPS6KB2 and RPS6KB1 genes encode members of the RSK (ribosomal S6 kinase) family of serine/threonine kinases, which phosphorylate the S6 ribosomal protein and eukaryotic translation initiation factor 4B (eIF4B). Phosphorylation of S6 leads to an increase in protein synthesis and cell proliferation. [from Gene Cards; RPS6KB2 and RPS6KB1; 2017.01.27]

(FlyBase Curators, 2013-)
External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
RPS6KB1; ribosomal protein S6 kinase B1
D. melanogaster ortholog (based on DIOPT)
Dmel\S6k
(DIOPT, 2013-)
Comments on ortholog(s)

Many to one (2 human to 1 Drosophila): the second orthologous gene in human is RPS6KB2; lower-scoring orthologs exist in both species.

Human gene (HGNC)
Symbol / Name
RPS6KB2; ribosomal protein S6 kinase B2
D. melanogaster ortholog (based on DIOPT)
Dmel\S6k
(DIOPT, 2013-)
Comments on ortholog(s)

Many to one (2 human to 1 Drosophila): the second orthologous gene in human is RPS6KB1; lower-scoring orthologs exist in both species.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Dmel\S6k
    Gene Snapshot
    Ribosomal protein S6 kinase (S6k) encodes an important component of the target of rapamycin pathway. It is involved in the control of synapse development, autophagy and cell size. [Date last reviewed: 2019-09-12]
    Molecular function (GO)
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human RPS6KB2 and RPS6KB1 (1 Drosophila to 2 human); lower-scoring orthologs exist in both species. Dmel\S6k shares 57-62% identity and 69-72% similarity with RPS6KB2 and RPS6KB1.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    H. sapiens (Human)
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (67 groups)
      S6k
      protein-protein
      Interacting group
      Assay
      References
      S6k - 14-3-3ζ
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Act5C
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Aldh
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - αCOP
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - ana2
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Arc42
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Arf1
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - AsnRS
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - β'COP
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - βTub56D
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - βTub60D
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - βTub97EF
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - bif
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - cathD
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - CCT1
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - CCT4
      pull down, western blot, anti bait coimmunoprecipitation
      (Kim and Choi, 2019)
      S6k - CCT5
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Cdc37
      anti tag coimmunoprecipitation, Identification by mass spectrometry, peptide massfingerprinting
      (Vinayagam et al., 2016, Glatter et al., 2011)
      S6k - CG1316
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - CG4972
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - CG5504
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Chc
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Chd64
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - cpa
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Dp1
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Dref
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Droj2
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - eEF1α1
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - eIF4A
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - fax
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Fib
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Gale
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - galla-2
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Gtpbp1
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Hel25E
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - His2B
      enzymatic study, autoradiography
      (Montagne et al., 2010)
      S6k - Hsc70-3
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Ipo9
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Kap-α3
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Kcmf1
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - kuk
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - l(1)G0320
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Ldh
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - levy
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - lic
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Mcad
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Mcm7
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Mec2
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - msn
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - mt:CoII
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Nfs1
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Pcb
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Pef
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Pp1-87B
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Pyk
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Rab27
      anti tag coimmunoprecipitation, western blot, proximity ligation assay, fluorescence microscopy
      (Lien et al., 2020)
      S6k - raptor
      anti tag coimmunoprecipitation, peptide massfingerprinting
      (Glatter et al., 2011)
      S6k - RPA1
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - RpS5a
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - Scsα1
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - ScsβA
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - sqd
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - sqh
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - SsRβ
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - tws
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - UQCR-C2
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      (Vinayagam et al., 2016)
      S6k - wrd
      anti tag coimmunoprecipitation, anti tag western blot
      (Hahn et al., 2010)
      Alleles Reported to Model Human Disease (Disease Ontology) (11 alleles)
      S6k
      Models Based on Experimental Evidence ( 3 )
      Modifiers Based on Experimental Evidence ( 10 )
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      References (8)