FlyBase Allele Report: Hsap\RAF1[gof.UAS]

General Information

Symbol

Hsap\RAF1^gof.UAS

Species

H. sapiens

Name

FlyBase ID

FBal0063224

Feature type

allele

Associated gene

Hsap\RAF1

Associated Insertion(s)

Carried in Construct

P{UAS-cRaf1.gof}

Also Known As

UAS-hRaf^Act

Key Links

Transgenic product class

gain_of_function_variant

(Brand and Perrimon, 1994)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

gain_of_function_variant

(Brand and Perrimon, 1994)

Mutagen

in vitro construct

(Brand and Perrimon, 1994)

Progenitor genotype

Carried in construct

P{UAS-cRaf1.gof}

Cytology

Description

Gain of function form of Hsap\RAF1 coding sequence is expressed under the influence of UASt regulatory sequences.

(Brand and Perrimon, 1994)

Allele components

Component

Use(s)

Regulatory region(s)

UASt

binary expression system - regulatory region

Encoded product / tool

Hsap\RAF1

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

Variant Molecular Consequences

Associated Sequence Data

DDBJ / EMBL / GenBank

DNA sequence

Protein sequence

UniProtKB/Swiss-Prot

UniProtKB/TrEMBL

Expression Data

Reporter Expression

Additional Information

Statement

Reference

Marker for

Reflects expression of

Reporter construct used in assay

Human Disease Associations

Disease Ontology (DO) Annotations

Models Based on Experimental Evidence ( 1 )

Disease

Evidence

References

model of cardiomyopathy

CEA

(Yu et al., 2013)

model of Noonan syndrome

CEA

(Yu et al., 2015)

model of cancer

CEA

(Wang et al., 2023, Markstein et al., 2014)

CEA with Pi3K92E^{UAS.Tag:MYC,Tag:PM(hKRAS)}

(Wang et al., 2023)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of cardiomyopathy

is ameliorated by Dsor1^RNAi.UAS.cUa

(Yu et al., 2013)

is ameliorated by rl^RNAi.UAS.cUa

(Yu et al., 2013)

model of Noonan syndrome

is ameliorated by yki^JF03119

(Yu et al., 2015)

is ameliorated by Tgi^UAS.B

(Yu et al., 2015)

Comments on Models/Modifiers Based on Experimental Evidence ( 0 )

Disease-implicated variant(s)

Phenotypic Data

Phenotypic Class

abnormal endomitotic cell cycle, with Scer\GAL4^tin.CΔ4

(Yu et al., 2013)

neoplasia | adult stage, with Scer\GAL4^NP5130

(Markstein et al., 2014)

Phenotype Manifest In

adult heart, with Scer\GAL4^tin.CΔ4

(Yu et al., 2015, Yu et al., 2013)

adult heart muscle cell, with Scer\GAL4^tin.CΔ4

(Yu et al., 2013)

adult hindgut, with Scer\GAL4^NP5130

(Markstein et al., 2014)

cardial cell, with Scer\GAL4^tin.CΔ4

(Yu et al., 2015, Yu et al., 2013)

dorsal appendage | maternal effect, with Scer\GAL4^55B

(Brand and Perrimon, 1994)

egg chorion | maternal effect, with Scer\GAL4^55B

(Brand and Perrimon, 1994)

embryo | maternal effect, with Scer\GAL4^55B

(Brand and Perrimon, 1994)

embryonic/larval hemocyte | increased number, with Scer\GAL4^Hml.Δ

(Sinenko and Mathey-Prevot, 2004)

embryonic/larval hemocyte | increased number, with Scer\GAL4^stop.Hml

(Sinenko and Mathey-Prevot, 2004)

enterocyte | increased number, with Scer\GAL4^NP5130

(Roti et al., 2013)

follicle cell | maternal effect, with Scer\GAL4^55B

(Brand and Perrimon, 1994)

intestinal stem cell | adult stage, with Scer\GAL4^NP5130

(Markstein et al., 2014)

intestinal stem cell | increased number, with Scer\GAL4^NP5130

(Roti et al., 2013)

myofilament, with Scer\GAL4^tin.CΔ4

(Yu et al., 2013)

nuclear chromosome, with Scer\GAL4^tin.CΔ4

(Yu et al., 2013)

visceral mesoderm & muscle founder cell | ectopic, with Scer\GAL4^twi.2PE

(Lee et al., 2003)

Detailed Description

Statement

Reference

Flies expressing Hsap\RAF1^gof.Scer\UAS under the control of Scer\GAL4^tin.CΔ4 show cardiac hypertrophy: the ventricular diameter at the end of systole and diastole is reduced compared with controls and the heart walls are thicker compared with controls. Cardiomyocytes lack well-defined circumferential fibers.

(Yu et al., 2015)

Expression of Hsap\RAF1^gof.Scer\UAS under the control of Scer\GAL4^esg-NP5130 leads to the formation of large heterogeneous intestinal stem cell-derived tumors in the adult intestine.

(Markstein et al., 2014)

Expression of Hsap\RAF1^gof.Scer\UAS in the intestinal stem cells under the control of Scer\GAL4^esg-NP5130 results in expansion of the esg-positive population, which is composed of diploid stem cells and polyploid enterocyte (EC) daughter cells. When flies are fed with the γ-secretase inhibitors DAPT or CpdE stem cell daughters fail to differentiate into EC cells and instead give rise mostly to additional stem cells, as well as some enteroendocrine daughter cells. Cyclopiazonic acid and thapsigargin also expand the stem cell population.

(Roti et al., 2013)

Hearts from flies expressing Scer\GAL4^tin.CΔ4>Hsap\RAF1^gof.Scer\UAS show reduced end-diastolic dimensions relative to controls. The transgenic hearts display myofiber disarray and increased heart wall thickness compared with controls. The number of cardiomyocytes is similar in the hearts from the transgenic flies to that of wild-type. Compared with controls, the transgenic hearts show an increase in cardiomyocyte ploidy, suggesting abnormal endoreplication.

(Yu et al., 2013)

Expression of Hsap\RAF1^gof.Scer\UAS under the control of either Scer\GAL4^Hml.Δ or Scer\GAL4^stop.Hml results in a 50- to 100-fold elevation in the number of circulating larval hemocytes compared to wild type.

(Sinenko and Mathey-Prevot, 2004)

Hsap\RAF1^gof.Scer\UAS; Scer\GAL4^twi.2PE embryos have increased numbers of visceral muscle founder cells.

(Lee et al., 2003)

Scer\GAL4 activation of Hsap\RAF1 in the follicle cells is sufficient to dorsalise the egg. In the severe cases embryos are twisted and lack nearly all ventral structures.

(Brand and Perrimon, 1994)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Suppressed by

Statement

Reference

Hsap\RAF1^gof.UAS, Scer\GAL4^tin.CΔ4 has abnormal endomitotic cell cycle phenotype, suppressible by fzr^GD9960, Scer\GAL4^tin.CΔ4

(Yu et al., 2013)

Phenotype Manifest In

Suppressed by

Statement

Reference

Hsap\RAF1^gof.UAS, Scer\GAL4^tin.CΔ4 has adult heart phenotype, suppressible | partially by yki^JF03119, Scer\GAL4^tin.CΔ4

(Yu et al., 2015)

Hsap\RAF1^gof.UAS, Scer\GAL4^tin.CΔ4 has cardial cell phenotype, suppressible | partially by yki^JF03119, Scer\GAL4^tin.CΔ4

(Yu et al., 2015)

Hsap\RAF1^gof.UAS, Scer\GAL4^tin.CΔ4 has adult heart phenotype, suppressible | partially by sd^GL00410, Scer\GAL4^tin.CΔ4

(Yu et al., 2015)

Hsap\RAF1^gof.UAS, Scer\GAL4^tin.CΔ4 has adult heart phenotype, suppressible | partially by sd^JF02514, Scer\GAL4^tin.CΔ4

(Yu et al., 2015)

Hsap\RAF1^gof.UAS, Scer\GAL4^tin.CΔ4 has adult heart phenotype, suppressible by Tgi^UAS.B, Scer\GAL4^tin.CΔ4

(Yu et al., 2015)

Hsap\RAF1^gof.UAS, Scer\GAL4^tin.CΔ4 has cardial cell phenotype, suppressible by fzr^GD9960, Scer\GAL4^tin.CΔ4

(Yu et al., 2013)

NOT Enhancer of

Statement

Reference

Hsap\RAF1^gof.UAS, Scer\GAL4^tin.CΔ4 is a non-enhancer of adult heart phenotype of Dsor1^RNAi.UAS.cUa, Scer\GAL4^tin.CΔ4

(Yu et al., 2013)

Hsap\RAF1^gof.UAS, Scer\GAL4^tin.CΔ4 is a non-enhancer of adult heart muscle cell phenotype of Dsor1^RNAi.UAS.cUa, Scer\GAL4^tin.CΔ4

(Yu et al., 2013)

Hsap\RAF1^gof.UAS, Scer\GAL4^tin.CΔ4 is a non-enhancer of adult heart muscle cell phenotype of Scer\GAL4^tin.CΔ4, rl^RNAi.UAS.cUa

(Yu et al., 2013)

NOT Suppressor of

Statement

Reference

Hsap\RAF1^gof.UAS, Scer\GAL4^tin.CΔ4 is a non-suppressor of adult heart phenotype of Dsor1^RNAi.UAS.cUa, Scer\GAL4^tin.CΔ4

(Yu et al., 2013)

Hsap\RAF1^gof.UAS, Scer\GAL4^tin.CΔ4 is a non-suppressor of adult heart muscle cell phenotype of Dsor1^RNAi.UAS.cUa, Scer\GAL4^tin.CΔ4

(Yu et al., 2013)

Hsap\RAF1^gof.UAS, Scer\GAL4^tin.CΔ4 is a non-suppressor of adult heart muscle cell phenotype of Scer\GAL4^tin.CΔ4, rl^RNAi.UAS.cUa

(Yu et al., 2013)

Other

Statement

Reference

Hsap\RAF1^gof.UAS, Pi3K92E^{UAS.Tag:MYC,Tag:PM(hKRAS)}, Scer\GAL4^dpp.blk1 has wing disc phenotype

(Wang et al., 2023)

Hsap\RAF1^gof.UAS, Scer\GAL4^NP5130 has enterocyte phenotype

(Roti et al., 2013)

Hsap\RAF1^gof.UAS, Scer\GAL4^NP5130 has enteroendocrine cell | increased number phenotype

(Roti et al., 2013)

Hsap\RAF1^gof.UAS, Scer\GAL4^NP5130 has intestinal stem cell | increased number phenotype

(Roti et al., 2013)

Additional Comments

Genetic Interactions

Statement

Reference

Xenogenetic Interactions

Statement

Reference

Expression of yki^JF03119 suppresses the cardiac hypertrophy seen in flies expressing Hsap\RAF1^gof.Scer\UAS under the control of Scer\GAL4^tin.CΔ4, returning the ventricular diameter at the end of diastole (EDD) and heart wall thickness to control levels. The cardiomyocytes abnormalities are partially suppressed.

Expression of sd^GL00410 does not suppress the cardiac hypertrophy seen in flies expressing Hsap\RAF1^gof.Scer\UAS under the control of Scer\GAL4^tin.CΔ4.

Expression of sd^JF02514 does not suppress the cardiac hypertrophy seen in flies expressing Hsap\RAF1^gof.Scer\UAS under the control of Scer\GAL4^tin.CΔ4.

Expression of Tgi^Scer\UAS.B suppresses the cardiac hypertrophy seen in flies expressing Hsap\RAF1^gof.Scer\UAS under the control of Scer\GAL4^tin.CΔ4.

(Yu et al., 2015)

When Ca-P60A^JF01948 is co-expressed with Hsap\RAF1^gof.Scer\UAS in the intestinal stem cells under the control of Scer\GAL4^esg-NP5130 the stem cell daughters fail to differentiate into EC cells and instead give rise mostly to additional stem cells, as well as some enteroendocrine daughter cells.

(Roti et al., 2013)

Cardiac-specific co-expression of Hsap\RAF1^gof.Scer\UAS does not change heart wall thickness and cardiomyocyte architecture in Scer\GAL4^tin.CΔ4>Dsor1^{dsRNA.Scer\UAS.cUa} expressing flies.

The cardiac specific expression of rap^GD9960 under the control of Scer\GAL4^tin.CΔ4 prevents the Hsap\RAF1^gof.Scer\UAS-induced increases in cardiomyocyte ploidy.

(Yu et al., 2013)

Complementation and Rescue Data

Comments

Images (0)

Mutant

Wild-type

Stocks (2)

Bloomington

2074

P{UAS-cRaf1.gof}ra2, y¹ w^*

Kyoto

106654