Human Disease Model Report: kidney disease (postulated), SRC-kinase-related

General Information

Name

kidney disease (postulated), SRC-kinase-related

FlyBase ID

FBhh0000546

Disease Ontology Term

kidney disease

Parent Disease

OMIM

Overview

Drosophila nephrocytes are functionally homologous to vertebrate kidney podocytes; in both, slit diaphragms function as molecular filters during the process of blood and haemolymph filtration. In Drosophila larval nephrocytes, it has been shown that that diaphragm stability and the balance between slit diaphragm damage and repair are controlled by SRC-dependent phosphorylation of diaphragm components (FBrf0223688). This work was done using the fly Src family kinase, Src64B. Loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Src64B.

There are multiple members of the Src family of protein tyrosine kinases in both human and Drosophila: 9 human genes and 3 fly genes.

Animals homozygous for an amorphic mutation of Src64B survive to adult stage, but females are semi-sterile. In third-instar larvae, nephrocytes exhibit morphological changes. In a chemically-induced model of kidney disease using fly larvae (FBhh0000545), hyperactivation of Src64B is observed. Many genetic and physical interactions have been described for Dmel\Src64B; see below and in the Src64B gene report.

[updated Jun. 2017 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: kidney disease (postulated), SRC-kinase-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Loss of Src64B activity leads to a reduction in the number of filtration diaphragms in larval nephrocytes. Diaphragm injury caused by either attenuation or hyperactivation of Src64B can be repaired upon return to physiological levels of Src64B activity. When diaphragm damage is induced by administration of the drug puromycin aminonucleoside, hyperactivation of Src64B is observed.

(Tutor et al., 2014)

Genetics

Cellular phenotype and pathology

Molecular information

Src family kinase is a family of non-receptor tyrosine kinases that includes nine members in humans. Src family kinases contain six conserved domains: an N-terminal myristoylated segment, a SH2 domain, a SH3 domain, a linker region, a tyrosine kinase domain, and C-terminal tail. Src family kinases interact with many cellular cytosolic, nuclear and membrane proteins, modifying these proteins by phosphorylation of tyrosine residues. [from HGNC, Gene Family: Src family tyrosine kinases; http://www.genenames.org/cgi-bin/genefamilies/set/1388]

(FlyBase Curators, 2013-)

External links

Disease synonyms

nephropathy (postulated), SRC-kinase-related

nephrosis (postulated), SRC-kinase-related

Related Diseases

Related human health report(s)

kidney disease, PAN-induced

kidney disease (fly models overview)

Ortholog Information

Human gene(s) in FlyBase

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Src64B

Gene Snapshot

Src oncogene at 64B (Src64B) encodes a Src family nonreceptor tyrosine kinase. It has many biological roles, including ring canal morphogenesis in oogenesis and the male germline, microfilament ring constriction during cellularization, and modulation of growth and apoptosis. Some of its roles overlap with those of the product of Src42A. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Many to many: Dmel\Src64B is a member of the Src family of protein tyrosine kinases; there are 3 fly genes and 9 human genes in this family. Src64B is most closely related to human SRC and FYN, with which it shares 49-50% identity and 67% similarity. The other fly genes in this family are Src42A and Btk29A.

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 (11 groups)

Src64B

protein-protein

Interacting group

Assay

References

Src64B

enzymatic study, autoradiography

(Pedraza et al., 2004)

Src64B - 18w

anti tag coimmunoprecipitation, anti tag western blot

(Tamada et al., 2021)

Src64B - Cad96Ca

pull down, anti tag western blot, two hybrid

(Tsarouhas et al., 2014)

Src64B - CadN

pull down, anti tag western blot

(Pütz, 2019)

Src64B - Csk

enzymatic study, autoradiography

(Pedraza et al., 2004)

Src64B - drl

anti tag coimmunoprecipitation, anti tag western blot, two hybrid

(Petrova et al., 2013, Wouda et al., 2008)

Src64B - gcm2

two hybrid

(Hu et al., 2017.6.13)

Src64B - hzg

anti tag coimmunoprecipitation, western blot, multidimensional protein identification technology

(Nil et al., 2019)

Src64B - kirre

anti tag coimmunoprecipitation, western blot

(Tutor et al., 2014)

Src64B - stumps

anti bait coimmunoprecipitation, anti tag western blot

(Csiszar et al., 2010)

Src64B - Toll-6

anti tag coimmunoprecipitation, anti tag western blot

(Tamada et al., 2021)

Alleles Reported to Model Human Disease (Disease Ontology) (9 alleles)

Src64B

Models Based on Experimental Evidence ( 4 )

Allele

Disease

Evidence

References

Src64B^YF.UAS

model of kidney disease

CEA

(Tutor et al., 2014)

Src64B^UAS.cCa

model of cancer

CEA

(Enomoto et al., 2021)

CEA with Ras85D^V12.UAS

(Enomoto et al., 2021)

model of colorectal cancer

CEA

(Cordero et al., 2014)

model of intestinal cancer

CEA

(Nászai et al., 2021)

Src64B^UY1332

model of carcinoma

CEA

(Pagarigan et al., 2013)

Src64B^UAS.cUa

model of intestinal cancer

CEA

(Kohlmaier et al., 2015)

Modifiers Based on Experimental Evidence ( 8 )

Allele

Disease

Interaction

References

Src64B^GL00297

exacerbates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Feuillette et al., 2020)

Src64B^GD12263

ameliorates cancer

modeled by Ras85D^V12.UAS

(Ma et al., 2013)

Src64B^G7151

exacerbates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Feuillette et al., 2020)

Src64B^UAS.cCa

model of cancer

is ameliorated by Delta^DN.UAS

(Enomoto et al., 2021)

is ameliorated by Delta^RevF10

(Enomoto et al., 2021)

is ameliorated by N^ECN.UAS

(Enomoto et al., 2021)

is ameliorated by N^GD14477

(Enomoto et al., 2021)

is exacerbated by N^ICN.UAS

(Enomoto et al., 2021)

is ameliorated by shg^UAS.sgGFP

(Enomoto et al., 2021)

is exacerbated by zfh1^UAS.cPa

(Enomoto et al., 2021)

is ameliorated by Delta^DN.UAS

(Enomoto et al., 2021)

model of colorectal cancer

is ameliorated by Egfr^DN.UAS

(Cordero et al., 2014)

is ameliorated by Ras85D^KK108029

(Cordero et al., 2014)

is ameliorated by Ras85D^GD12553

(Cordero et al., 2014)

is ameliorated by Hsap\MATK^UAS.cVa

(Cordero et al., 2014)

model of intestinal cancer

is ameliorated by Rala^KK108989

(Nászai et al., 2021)

Src64B^JF03234

ameliorates cancer

modeled by Hsap\CDH3^UASp.cPa

(Faria et al., 2023)

exacerbates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Feuillette et al., 2020)

Src64B^UY1332

model of carcinoma

is ameliorated by PRL-1^UAS.cPa

(Pagarigan et al., 2013)

Src64B^HMC03327

ameliorates cancer

modeled by Hsap\CDH3^UASp.cPa

(Faria et al., 2023)

ameliorates lung adenocarcinoma

modeled by Hsap\KIF5B::Hsap\RET^UAS.cDa

(Das and Cagan, 2017)

Src64B^UAS.cUa

model of intestinal cancer

is ameliorated by Egfr^RNAi.UAS.cUa

(Kohlmaier et al., 2015)

is ameliorated by Stat92E^RNAi.UAS.cUa

(Kohlmaier et al., 2015)

is ameliorated by Egfr^RNAi.UAS.cUa

(Kohlmaier et al., 2015)

is ameliorated by Stat92E^RNAi.UAS.cUa

(Kohlmaier et al., 2015)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

w^*; P{UAS-Src64B.C}2

Src64B^YF.UAS

P{UAS-Src64B.YF}

y¹ w^*; P{UAS-Src64B.YF}121/CyO

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

Src64B^RNAi.UAS

P{UAS-Src64B.RNAi}

w^*; P{UAS-Src64B.RNAi}6.1

Src64B^GD12263

P{GD12263}

w¹¹¹⁸ P{GD12263}v35252

Src64B^JF03234

P{TRiP.JF03234}

y¹ v¹; P{TRiP.JF03234}attP2

Src64B^GL00297

P{TRiP.GL00297}

y¹ sc^* v¹ sev²¹; P{TRiP.GL00297}attP2

y¹ v¹; P{TRiP.HMC03327}attP40

Src64B^HMC05164

P{TRiP.HMC05164}

y¹ sc^* v¹ sev²¹; P{TRiP.HMC05164}attP40

Src64B^VSH330150

P{VSH330150}

P{VSH330150}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Src64B^UY1332

P-element activity

y¹ w^67c23; P{Mae-UAS.6.11}Src64B^UY1332

Src64B^ko

amorphic allele - genetic evidence

ends-out gene targeting

w^*; Src42A^E1/CyO; TI{TI}Src64B^ko/TM6B, Tb⁺

Src64B^G7151

P-element activity

y¹ w^*; P{EP}Src64B^G7151 CG32246^G7151

References (5)

Report Sections

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