FlyBase Gene Report: Dmel\Hsc70-3

General Information

Symbol

Dmel\Hsc70-3

Species

D. melanogaster

Name

Heat shock protein 70 cognate 3

Annotation Symbol

CG4147

Feature Type

protein_coding_gene

FlyBase ID

FBgn0001218

Gene Model Status

Current

Stock Availability

30 publicly available

Gene Summary

Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen. Involved in the correct folding of proteins and degradation of misfolded proteins (By similarity). Acts as a key repressor of the unfolded protein response (UPR) (By similarity). (UniProt, P29844)

Contribute a Gene Snapshot for this gene.

All Summaries

Alliance
Auto summary
Pathway
Gene Group
UniProtKB
Interactive Fly

Also Known As

BiP, Hsc3, Hsc70, Grp78, Hsc-70-3

Key Links

Genomic Location

Cytogenetic map

10E3-10E4

Sequence location

X:11,801,696..11,807,117 [-]

Recombination map

1-36

RefSeq locus

NC_004354 REGION:11801696..11807117

Sequence

Get Decorated FASTA

Genomic Maps

JBrowse

Other Genome Views

The following external sites may use different assemblies or annotations than FlyBase.

Function

Gene Ontology (GO) Annotations (23 terms)

Molecular Function (6 terms)

Terms Based on Experimental Evidence (2 terms)

CV Term

Evidence

References

enables ATP hydrolysis activity

inferred from direct assay

(Ham et al., 2014)

enables protein binding

inferred from physical interaction with UniProtKB:Q8SWV6

(Casey et al., 2017, Ham et al., 2014)

Terms Based on Predictions or Assertions (5 terms)

CV Term

Evidence

References

enables ATP binding

inferred from electronic annotation with InterPro:IPR013126

(InterPro Project Members, 2004-)

enables ATP hydrolysis activity

inferred from biological aspect of ancestor with PANTHER:PTN000452648

(GO Reference Genome Project, 2011-)

inferred from electronic annotation with InterPro:IPR013126

(InterPro Project Members, 2004-)

enables heat shock protein binding

inferred from biological aspect of ancestor with PANTHER:PTN000452648

(GO Reference Genome Project, 2011-)

enables protein folding chaperone

inferred from biological aspect of ancestor with PANTHER:PTN000452648

(GO Reference Genome Project, 2011-)

enables protein-transporting ATPase activity

inferred from sequence or structural similarity with UniProtKB:P16474

(Gene Ontology Curators, 2002-)

Biological Process (9 terms)

Terms Based on Experimental Evidence (5 terms)

CV Term

Evidence

References

involved_in intestinal stem cell homeostasis

inferred from mutant phenotype

(Wang et al., 2014)

involved_in negative regulation of organ growth

inferred from mutant phenotype

(Yang et al., 2022)

involved_in positive regulation of hippo signaling

inferred from mutant phenotype

(Yang et al., 2022)

involved_in regulatory ncRNA-mediated post-transcriptional gene silencing

inferred from mutant phenotype

(Dorner et al., 2006)

involved_in response to endoplasmic reticulum stress

inferred from mutant phenotype

(Wang et al., 2014)

Terms Based on Predictions or Assertions (4 terms)

CV Term

Evidence

References

involved_in endoplasmic reticulum unfolded protein response

inferred from biological aspect of ancestor with PANTHER:PTN001834223

(GO Reference Genome Project, 2011-)

involved_in ERAD pathway

inferred from biological aspect of ancestor with PANTHER:PTN001834223

(GO Reference Genome Project, 2011-)

involved_in protein refolding

inferred from biological aspect of ancestor with PANTHER:PTN000452648

(GO Reference Genome Project, 2011-)

involved_in sleep

traceable author statement

(Cirelli, 2003)

Cellular Component (8 terms)

Terms Based on Experimental Evidence (4 terms)

CV Term

Evidence

References

located_in endomembrane system

inferred from high throughput direct assay

(Tan et al., 2009)

part_of endoplasmic reticulum chaperone complex

inferred from physical interaction with FLYBASE:Xport-B; FB:FBgn0260234

(Chen et al., 2015)

located_in endoplasmic reticulum

inferred from direct assay

(Ryoo et al., 2007)

located_in extracellular space

inferred from direct assay

(Walker et al., 2006)

Terms Based on Predictions or Assertions (6 terms)

CV Term

Evidence

References

is_active_in cytoplasm

inferred from biological aspect of ancestor with PANTHER:PTN002321897

(GO Reference Genome Project, 2011-)

part_of endoplasmic reticulum chaperone complex

inferred from biological aspect of ancestor with PANTHER:PTN001834223

(GO Reference Genome Project, 2011-)

is_active_in endoplasmic reticulum lumen

inferred from biological aspect of ancestor with PANTHER:PTN001834223

(GO Reference Genome Project, 2011-)

located_in endoplasmic reticulum

non-traceable author statement

(Cirelli, 2003)

is_active_in membrane

inferred from biological aspect of ancestor with PANTHER:PTN001834223

(GO Reference Genome Project, 2011-)

is_active_in nucleus

inferred from biological aspect of ancestor with PANTHER:PTN001834223

(GO Reference Genome Project, 2011-)

Gene Group (FlyBase)

HEAT SHOCK PROTEIN 70 CHAPERONES

PROTEIN-TRANSPORTING ATPASES

Pathway (FlyBase)

POSITIVE REGULATORS OF HIPPO SIGNALING PATHWAY

Protein Family (UniProt)

Belongs to the heat shock protein 70 family. (P29844)

Protein Signatures (InterPro)

Catalytic Activity (EC/Rhea)

ATP hydrolysis activity
RHEA 13065:

Summaries

Gene Group (FlyBase)

HEAT SHOCK PROTEIN 70 CHAPERONES -: The Heat Shock Protein 70 (Hsp70) superfamily of chaperones assist in numerous folding processes and are upregulated by heat stress and toxic chemicals. Hsp70 chaperones share a highly conserved bipartite domain structure composed of an ATPase domain and a substrate-binding domain. (Adapted from PMID:17441502, FBrf0232269 and FBrf0174945).
PROTEIN-TRANSPORTING ATPASES -: Protein-transporting ATPases are the catalytic components of protein complexes that transport nuclear encoded (pre)proteins into organelles (eg. endoplasmic reticulum (ER), mitochondria) in an ATP-dependent manner. They include: the mitochondrial Hsp70 protein within the TIM complex that transports proteins across the inner mitochondrial membrane into the matrix; the Bsc1 protein that forms a homo-heptameric channel to translocate the iron-sulfur protein, a subunit of respiratory Complex III, across the inner mitochondrial membrane; and the BiP chaperone that provides the driving force for posttranslational translocation of proteins across the ER membrane via the Sec61 channel. (Adapted from PMID:12154367, PMID:32042153 and PMID:28564553.)

Pathway (FlyBase)

POSITIVE REGULATORS OF HIPPO SIGNALING PATHWAY -: The Hippo signaling pathway is an intracellular kinase cascade in which hpo kinase in complex with sav, phosphorylates wts kinase which, in turn, phosphorylates yki transcriptional co-activator leading to its cytosolic retention. Positive regulators of the pathway, enhance the cytosolic retention of yki, negatively regulating tissue growth (Adapted from FBrf0224870).

Protein Function (UniProtKB)

(UniProt, P29844)

Gene Model and Products

Number of Transcripts

Number of Unique Polypeptides

Please see the JBrowse view of Dmel\Hsc70-3 for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)

Isoform displayed:

Pfam protein domains

InterPro name

classification

start

end

Protein Domains (via SMART)

Isoform displayed:

SMART protein domains

InterPro name

classification

start

end

Structure

Protein 3D structure (Predicted by AlphaFold) (AlphaFold entry P29844)

If you don't see a structure in the viewer, refresh your browser.

Model Confidence:

Very high (pLDDT > 90)
Confident (90 > pLDDT > 70)
Low (70 > pLDDT > 50)
Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Experimentally Determined Structures

Crossreferences

Comments on Gene Model

Gene model reviewed during 5.51

Low-frequency RNA-Seq exon junction(s) not annotated.

Annotated transcripts do not represent all supported alternative splices within 5' UTR.

Gene model reviewed during 5.55

Transcript Data

Annotated Transcripts

Name

FlyBase ID

RefSeq ID

Length (nt)

Assoc. CDS (aa)

Hsc70-3-RA

FBtr0073609

NM_167306

3019

656

Hsc70-3-RB

FBtr0073608

NM_078577

3158

656

Hsc70-3-RC

FBtr0073611

NM_167307

2985

656

Hsc70-3-RD

FBtr0073610

NM_167308

3185

656

Hsc70-3-RE

FBtr0345166

NM_001298210

2988

656

Additional Transcript Data and Comments

Reported size (kB)

Comments

External Data

Crossreferences

Polypeptide Data

Annotated Polypeptides

Name

FlyBase ID

Predicted MW (kDa)

Length (aa)

Theoretical pI

UniProt

RefSeq ID

GenBank

Hsc70-3-PA

FBpp0073446

72.3

656

4.99

FBpp0073445

72.3

656

4.99

FBpp0073448

72.3

656

4.99

FBpp0073447

72.3

656

4.99

FBpp0311376

72.3

656

4.99

P29844

NP_001285139

AHN59609

Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

656 aa isoforms: Hsc70-3-PA, Hsc70-3-PB, Hsc70-3-PC, Hsc70-3-PD, Hsc70-3-PE

Additional Polypeptide Data and Comments

Reported size (kDa)

Comments

External Data

Post Translational Modification

AMPylation at Thr-518 by Fic inactivates the chaperome activity (PubMed:25395623, PubMed:29089387). In response to endoplasmic reticulum stress, de-AMPylation by the same protein, Fic, restores the chaperone activity (PubMed:29089387).

(UniProt, P29844)

Crossreferences

InterPro - A database of protein families, domains and functional sites

Linkouts

Sequences Consistent with the Gene Model

Nucleotide / Polypeptide Records

UniProt

Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Hsc70-3 using the Feature Mapper tool.

External Data

Crossreferences

Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.

Hsc70-3_1

Linkouts

Expression Data

Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

-0.73

Transcript Expression

Additional Descriptive Data

Marker for

Subcellular Localization

CV Term

Polypeptide Expression

immunolocalization

Stage

Tissue/Position (including subcellular localization)

Reference

third instar larval stage

wing disc

(Zhang et al., 2016)

cultured cell-line

• endoplasmic reticulum

(Han et al., 2004)

mass spectroscopy

Stage

Tissue/Position (including subcellular localization)

Reference

adult stage

adult head

• membrane

(Aradska et al., 2015)

day 5 of adulthood | male -- day 7 of adulthood | male

spermatozoon

(Wasbrough et al., 2010)

day 7 of adulthood -- day 49 of adulthood

adult heart

(Cammarato et al., 2011)

Additional Descriptive Data

Marker for

endoplasmic reticulum

(Han et al., 2004)

Subcellular Localization

CV Term

Evidence

References

located_in endomembrane system

inferred from high throughput direct assay

(Tan et al., 2009)

part_of endoplasmic reticulum chaperone complex

inferred from physical interaction with FLYBASE:Xport-B; FB:FBgn0260234

(Chen et al., 2015)

located_in endoplasmic reticulum

inferred from direct assay

(Ryoo et al., 2007)

located_in extracellular space

inferred from direct assay

(Walker et al., 2006)

Expression Deduced from Reporters

High-Throughput Expression Data

Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\Hsc70-3 in JBrowse

RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region

View exonic expression by developmental stage for Dmel\Hsc70-3

View exonic expression by tissue for Dmel\Hsc70-3

Bulk Downloads

RNA-Seq RPKM values for all genes

Reference

See Gelbart and Emmert, 2013 for analysis details and data files for all genes.

Developmental Proteome: Life Cycle

Developmental Proteome: Embryogenesis

External Data and Images

Linkouts

BDGP expression data - Patterns of gene expression in Drosophila embryogenesis

FBgn0001218

DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species

32133/tissue=All

EMBL-EBI Single Cell Expression Atlas - Single cell expression across species

FBgn0001218

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

FBgn0001218

FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data

FBgn0001218

Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns

CG4147

Flygut - An atlas of the Drosophila adult midgut

FBgn0001218

Images

FlyBase Wiki

Image Based Resources

Alleles, Insertions, Transgenic Constructs, and Aberrations

Classical and Insertion Alleles ( 39 )

For All Classical and Insertion Alleles Show

Other relevant insertions

Transgenic Constructs ( 14 )

For All Alleles Carried on Transgenic Constructs Show

Transgenic constructs containing/affecting coding region of Hsc70-3

Transgenic constructs containing regulatory region of Hsc70-3

Aberrations (Deficiencies and Duplications) ( 2 )

Inferred from experimentation ( 2 )

Gene duplicated in

Dp(1;Y)BSC1

(Cook et al., 2010, Gornek et al., 2000.2.4)

Dp(1;Y)BSC2

(Cook et al., 2010, Gornek et al., 2000.2.4)

Inferred from location ( 21 )

Variants

Variant Molecular Consequences

Alleles Representing Disease-Implicated Variants

Phenotypes

For more details about a specific phenotype click on the relevant allele symbol.

Lethality

Allele

lethal, with Scer\GAL4^how-24B

lethal, with Scer\GAL4^pnr-MD237

Hsc70-3^GD6484

lethal | dominant, with Scer\GAL4^unspecified

Hsc70-3^K97S.UAS

lethal | larval stage

Hsc70-3^G0407

lethal | paternal effect, with Scer\GAL4^VP16.bam

Hsc70-3^GD6484

lethal | pharate adult stage

Hsc70-3^G0407

lethal | prepupal stage

Hsc70-3^G0407

lethal | pupal stage

Hsc70-3^G0407

lethal | recessive

lethal - all die before end of larval stage

lethal - all die before end of larval stage, with Scer\GAL4^337Y

lethal - all die during embryonic stage

Hsc70-3^G0341

lethal - all die during P-stage, with Scer\GAL4^Mef2.PR

Hsc70-3^GD6484

partially lethal - majority die | recessive

Hsc70-3^G0407

viable

Hsc70-3^EY11233

viable, with Dcr-2^UAS.cDa, Scer\GAL4^elav.PLu

Hsc70-3^GD6484

viable, with Scer\GAL4^how-24B

Hsc70-3^UAS.cEa

viable, with Scer\GAL4^tin.CΔ4

Hsc70-3^GD6484

Sterility

Allele

fertile

Hsc70-3^EY11233

Other Phenotypes

Allele

abnormal behavior, with Scer\GAL4^156Y

Hsc70-3^D231S.UAS

abnormal neuroanatomy | adult stage, with Scer\GAL4^GH146

decreased cell number | larval stage | somatic clone, with Scer\GAL4^Act.PU

decreased size | spermatogenesis, with Scer\GAL4^VP16.bam

Hsc70-3^GD6484

some die during embryonic stage

Hsc70-3^G0341

some die during larval stage

some die during larval stage, with Scer\GAL4^337Y

Phenotype manifest in

Allele

adult antennal lobe projection neuron, with Scer\GAL4^GH146

eye, with Scer\GAL4^GMR.PU

Hsc70-3^K97S.UAS

eye-antennal disc | somatic clone, with Scer\GAL4^Act.PU

larva | third instar larval stage

Hsc70-3^G0466b

ommatidium, with Scer\GAL4^GMR.PU

Hsc70-3^K97S.UAS

pupa

Hsc70-3^G0407

rhabdomere R7, with Scer\GAL4^Rh3.PP

Hsc70-3^GS1150

spermatocyte cyst, with Scer\GAL4^VP16.bam

Hsc70-3^GD6484

spermatozoon | absent, with Scer\GAL4^VP16.bam

Hsc70-3^GD6484

testis, with Scer\GAL4^VP16.bam

Hsc70-3^GD6484

Orthologs

Downloads

Download All DIOPT Orthologs

Human Orthologs (via DIOPT v9.1)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Homo sapiens (Human) (21)

Hsap\HSPA5

14 of 14

Yes

6 of 14

6 of 14

6 of 14

6 of 14

6 of 14

6 of 14

4 of 14

3 of 14

Yes

2 of 14

2 of 14

2 of 14

2 of 14

2 of 14

1 of 14

Yes

Hsap\DENND6A

1 of 14

Hsap\DENND6B

1 of 14

Hsap\HSPA7

1 of 14

Yes

Hsap\HSPA12A

1 of 14

Hsap\HSPA12B

1 of 14

Hsap\SLC9C2

1 of 14

Model Organism Orthologs (via DIOPT v9.1)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Rattus norvegicus (Norway rat) (17)

Rnor\Hspa5

14 of 14

Yes

6 of 14

6 of 14

6 of 14

5 of 14

5 of 14

4 of 14

4 of 14

4 of 14

2 of 14

Yes

2 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

Yes

Mus musculus (laboratory mouse) (15)

Mmus\Hspa5

13 of 14

Yes

6 of 14

6 of 14

6 of 14

6 of 14

6 of 14

4 of 14

3 of 14

Yes

Mmus\Hspa14

2 of 14

Mmus\Ankrd45

1 of 14

Yes

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

Xenopus tropicalis (Western clawed frog) (17)

Xtro\hspa5

8 of 13

Yes

4 of 13

4 of 13

4 of 13

3 of 13

3 of 13

2 of 13

2 of 13

2 of 13

1 of 13

1 of 13

1 of 13

1 of 13

Yes

Xtro\hspa14

1 of 13

Xtro\hyou1

1 of 13

Xtro\prelid2

1 of 13

Yes

Xtro\XB5934250

1 of 13

Danio rerio (Zebrafish) (20)

Drer\hspa5

13 of 14

Yes

6 of 14

6 of 14

6 of 14

6 of 14

6 of 14

6 of 14

5 of 14

4 of 14

4 of 14

3 of 14

Yes

Drer\hspa14

2 of 14

Drer\ankrd45

1 of 14

Yes

Drer\hspa4a

1 of 14

Drer\hspa4b

1 of 14

Drer\hspa12a.2

1 of 14

Yes

1 of 14

1 of 14

1 of 14

1 of 14

Caenorhabditis elegans (Nematode, roundworm) (13)

Cele\hsp-3

14 of 14

Yes

Cele\hsp-4

14 of 14

Yes

Cele\F44E5.4

6 of 14

Yes

Cele\F44E5.5

6 of 14

Yes

Cele\hsp-1

6 of 14

Cele\hsp-70

6 of 14

Yes

Cele\hsp-6

4 of 14

Cele\stc-1

3 of 14

Yes

2 of 14

2 of 14

1 of 14

1 of 14

1 of 14

Anopheles gambiae (African malaria mosquito) (12)

Agam\AgaP_AGAP004192

12 of 12

Yes

5 of 12

5 of 12

5 of 12

4 of 12

4 of 12

3 of 12

2 of 12

2 of 12

2 of 12

2 of 12

Yes

Agam\AgaP_AGAP004946

1 of 12

Arabidopsis thaliana (thale-cress) (21)

Atha\BIP1

13 of 13

Yes

Atha\BIP2

13 of 13

Yes

Atha\BIP3

12 of 13

Yes

6 of 13

6 of 13

6 of 13

6 of 13

6 of 13

6 of 13

4 of 13

4 of 13

4 of 13

4 of 13

3 of 13

Yes

2 of 13

2 of 13

2 of 13

2 of 13

2 of 13

1 of 13

1 of 13

Saccharomyces cerevisiae (Brewer's yeast) (14)

Scer\KAR2

12 of 13

Yes

5 of 13

5 of 13

5 of 13

5 of 13

4 of 13

4 of 13

3 of 13

3 of 13

3 of 13

2 of 13

2 of 13

2 of 13

2 of 13

Yes

Schizosaccharomyces pombe (Fission yeast) (8)

Spom\bip1

12 of 12

Yes

Spom\ssa1

5 of 12

Spom\ssa2

5 of 12

Spom\sks2

4 of 12

Yes

3 of 12

1 of 12

1 of 12

1 of 12

Escherichia coli (enterobacterium) (4)

Ecol\dnaK

3 of 11

Yes

Ecol\hscA

2 of 11

Ecol\hscC

2 of 11

Ecol\yegD

2 of 11

Other Organism Orthologs (via OrthoDB)

Data provided directly from OrthoDB:Hsc70-3. Refer to their site for version information.

Paralogs

Downloads

Download All DIOPT Paralogs

Paralogs (via DIOPT v9.1)

Gene Symbol

Score

Source

Alignment

Drosophila melanogaster (Fruit fly) (15)

7 of 13

7 of 13

7 of 13

7 of 13

7 of 13

7 of 13

6 of 13

6 of 13

6 of 13

6 of 13

6 of 13

4 of 13

3 of 13

3 of 13

1 of 13

Human Disease Associations

FlyBase Human Disease Model Reports

Disease Ontology (DO) Annotations

Models Based on Experimental Evidence ( 0 )

Allele

Disease

Evidence

References

Potential Models Based on Orthology ( 0 )

Human Ortholog

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 4 )

Allele

Disease

Interaction

References

Hsc70-3^K97S.UAS

exacerbates Huntington's disease

modeled by Hsap\HTT^{128Q.1-336.UAS}

(Branco et al., 2008)

exacerbates olivopontocerebellar atrophy

modeled by Hsap\ATXN1^82Q.UAS

(Branco et al., 2008)

Hsc70-3^UAS.cEa

ameliorates autosomal dominant cerebellar ataxia

modeled by Hsap\ATXN7^{102Q.T.UAS.Tag:NLS(SV40-largeT)}

(Latouche et al., 2007)

ameliorates amyotrophic lateral sclerosis type 10

modeled by Hsap\TARDBP^UAS.cEa

(François-Moutal et al., 2022)

ameliorates erythrokeratodermia variabilis

modeled by Hsap\GJB3^{F137L.UAS.Tag:MYC}

(Tang et al., 2015)

Hsc70-3^{UAS.ORF.Tag:HA}

ameliorates cancer

modeled by Ras85D^V12.cUa.UAS, l(2)gl⁴

(Yang et al., 2022)

modeled by Ras85D^V12.cUa.UAS, scrib¹

(Yang et al., 2022)

modeled by wts^KK101055

(Yang et al., 2022)

modeled by yki^UAS.cHa

(Yang et al., 2022)

Hsc70-3^HMS00397

ameliorates Machado-Joseph disease

modeled by Hsap\ATXN3^{tr.Q78.UAS.Tag:HA}

(Tsou et al., 2015)

Disease Associations of Human Orthologs (via DIOPT v9.1 and OMIM)

Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.

Homo sapiens (Human)

Gene name

Score

OMIM

OMIM Phenotype

DO term

Complementation?

Transgene?

HSPA5; heat shock protein family A (Hsp70) member 5

14 of 14

138120

HSPA1A; heat shock protein family A (Hsp70) member 1A

6 of 14

140550

HSPA1B; heat shock protein family A (Hsp70) member 1B

6 of 14

603012

HSPA1L; heat shock protein family A (Hsp70) member 1 like

6 of 14

140559

HSPA2; heat shock protein family A (Hsp70) member 2

6 of 14

140560

HSPA6; heat shock protein family A (Hsp70) member 6

6 of 14

140555

HSPA8; heat shock protein family A (Hsp70) member 8

6 of 14

600816

HSPA9; heat shock protein family A (Hsp70) member 9

4 of 14

HEAT-SHOCK 70-KD PROTEIN 9; HSPA9

autosomal dominant sideroblastic anemia 4

HSPA13; heat shock protein family A (Hsp70) member 13

3 of 14

601100

Functional Complementation Data

Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.

Interactions

Summary of Physical Interactions

Interaction Browsers

View in FlyBase Interactions Browser View in MIST tool (external link)

Please see the Physical Interaction reports below for full details

protein-protein

Physical Interaction

Assay

References

Hsc70-3 - AdipoR

anti tag coimmunoprecipitation, anti tag western blot, Identification by mass spectrometry

(Arquier et al., 2021)

Hsc70-3 - Akt

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - B4

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - CG12691

experimental knowledge based

(Guruharsha et al., 2011)

Hsc70-3 - CG17343

experimental knowledge based

(Guruharsha et al., 2011)

Hsc70-3 - CG7737

experimental knowledge based

(Guruharsha et al., 2011)

Hsc70-3 - Dredd

anti tag coimmunoprecipitation, peptide massfingerprinting

(Fukuyama et al., 2012)

Hsc70-3 - Fic

enzymatic study, western blot, ampylation assay, autoradiography, Identification by mass spectrometry

(Casey et al., 2017, Ham et al., 2014)

Hsc70-3 - Gαo

pull down, peptide massfingerprinting

(Katanayeva et al., 2010)

Hsc70-3 - Hecw

pull down, Identification by mass spectrometry

(Fajner et al., 2021)

Hsc70-3 - Lkb1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - Myc

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - Nlg2

anti bait coimmunoprecipitation, western blot

(Tu et al., 2017)

Hsc70-3 - Pdk1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - Pi3K21B

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - Pi3K92E

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - Pten

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - Rheb

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - S6k

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - S6kII

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - Synd

experimental knowledge based

(Guruharsha et al., 2011)

Hsc70-3 - Tcs3

experimental knowledge based

(Guruharsha et al., 2011)

Hsc70-3 - Thor

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - Tsc1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - WRNexo

anti tag coimmunoprecipitation, anti tag western blot, pull down, western blot, Identification by mass spectrometry

(Wu et al., 2025)

Hsc70-3 - Xport-B

pull down, western blot, peptide massfingerprinting

(Chen et al., 2015)

Hsc70-3 - chico

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - cnk

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Hsc70-3 - foxo

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - gig

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - hbs

experimental knowledge based

(Guruharsha et al., 2011)

Hsc70-3 - melt

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - ninaE

pull down, western blot

(Chen et al., 2015)

Hsc70-3 - rictor

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - sima

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

Hsc70-3 - spag

pull down, autoradiography, anti tag coimmunoprecipitation, peptide massfingerprinting

(Benbahouche et al., 2014)

Hsc70-3 - yki

anti tag coimmunoprecipitation, anti tag western blot, proximity ligation assay, fluorescence microscopy, peptide massfingerprinting

(Yang et al., 2022, Kwon et al., 2013, Kwon et al., 2013)

RNA-protein

Physical Interaction

Assay

References

Hsc70-3 - PQBP1

anti bait coimmunoprecipitation, primer specific pcr

(Wan et al., 2015)

Summary of Genetic Interactions

Interaction Browsers

View in FlyBase Interactions Browser View in MIST tool (external link)

Please look at the allele data for full details of the genetic interactions

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

Delta

enhanceable

Hsc70-3

(Even et al., 2019)

suppressible

(Xu et al., 2025)

suppressible

(Mori et al., 2019)

meigo

enhanceable

Hsc70-3

(Sekine et al., 2013)

pcx

suppressible

Hsc70-3

(Yamakawa et al., 2012)

Ppt1

suppressible

Hsc70-3

(Buff et al., 2007)

rumi

enhanceable

Hsc70-3

(Haltom et al., 2014)

scrib

enhanceable

Hsc70-3

(Zheng et al., 2023)

Tcs3

suppressible

Hsc70-3

(Rojas-Benítez et al., 2017)

External Data

Linkouts

BioGRID - A database of protein and genetic interactions.

58539

DroID - A comprehensive database of gene and protein interactions.

FBgn0001218

MIST (genetic) - An integrated Molecular Interaction Database

32133

MIST (protein-protein) - An integrated Molecular Interaction Database

32133

Pathways

Signaling Pathways (FlyBase)

POSITIVE REGULATORS OF HIPPO SIGNALING PATHWAY

Metabolic Pathways

FlyBase

External Links

External Data

Linkouts

KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.

Class of Gene

gene_with_edited_transcript

(Graveley et al., 2011)

nuclear_gene

protein_coding_gene

Genomic Location and Detailed Mapping Data

Chromosome (arm)

Recombination map

1-36

Cytogenetic map

10E3-10E4

Sequence location

X:11,801,696..11,807,117 [-]

FlyBase Computed Cytological Location

Cytogenetic map

Evidence for location

10E3-10E4

Limits computationally determined from genome sequence between P{EP}EP345&P{EP}EP1409 and P{EP}ATP7^EP308

Experimentally Determined Cytological Location

Cytogenetic map

Notes

References

10E1-10E4

(determined by in situ hybridisation) 10E--F (determined by in situ hybridisation) 10E (determined by in situ hybridisation)

(Peter et al., 2002)

10E-10E

(determined by in situ hybridisation)

(Schäfer et al., 1999.12.2)

10E-10E

(determined by in situ hybridisation) 10E1--4 (determined by in situ hybridisation)

(Schäfer et al., 1999.8.12)

Experimentally Determined Recombination Data

Location

1-36

(FlyBase, 2016)

1-36.8

(Comeron et al., 2012)

Left of (cM)

Right of (cM)

Notes

Stocks and Reagents

Stocks (30)

Genomic Clones (13)

Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

cDNA Clones (322)

Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.

cDNA clones, fully sequenced

BDGP DGC clones

Other clones

Drosophila Genomics Resource Center cDNA clones

For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

FBgn0001218

cDNA Clones, End Sequenced (ESTs)

BDGP DGC clones

Other clones

RNAi and Array Information

Linkouts

DRSC - Results frm RNAi screens

FBgn0001218

Antibody Information

Laboratory Generated Antibodies

polyclonal

(Liu et al., 2022, Ryoo et al., 2007)

Commercially Available Antibodies

Cell Line Information

Publicly Available Cell Lines

Other Stable Cell Lines

Other Comments

Hsc70-3 can substitute for its mammalian counterpart and chaperone the secretion of active IgGs (human monoclonal antibody heavy and light chains expressed in Schneider cells). Hsc70-3 can also uniquely chaperone heavy chain dimers indicating mechanistic differences that may relate to the evolved need for retaining immature IgGs in vertebrates.

(Kirkpatrick et al., 1995)

Members of the hsc70 gene family (heat shock cognate genes) that reside within the same intracellular compartment in different organisms share greater amino acid identity than hsc70 proteins from the same organism but different organelles. This pattern of conservation indicates specialisation of hsc70 function.

(Rubin et al., 1993)

Hsc70-3 genomic and cDNA clones have been analyzed and sequenced.

(Rubin et al., 1990)

Relationship to Other Genes

Source for database merge of

Source for merge of: Hsc70-3 CG1579

(Whitfield, 2000.12.15)

Source for merge of: Hsc70-3 l(1)G0102 l(1)G0341 l(1)G0111 l(1)G0292 l(1)G0407

(Peter et al., 2002)

Source for merge of: Hsc70-3 anon-WO0138581.7

(FlyBase, 1996-)

Additional comments

Source for merge of Hsc70-3 anon-WO0138581.7 was sequence comparison ( date:051113 ).

(FlyBase, 1996-)

Nomenclature History

Source for database identify of

Nomenclature comments

Etymology

Synonyms and Secondary IDs (55)

Reported As

Symbol Synonym

A4V4C4_DROME

(Fukuyama et al., 2012)

BIP

(Delrio-Lorenzo et al., 2020)

BiP

(Nedachi et al., 2025, Xu et al., 2025, Li et al., 2024, Zheng et al., 2023, Boehm et al., 2022, Hill et al., 2020, Preissler et al., 2020, Hong et al., 2019, Mori et al., 2019, Guida et al., 2018, Moehlman et al., 2018, Casey et al., 2017, Marcora et al., 2017, Sekiya et al., 2017, Sepúlveda-Salinas and Ramos-Castañeda, 2017, Tu et al., 2017, Chow et al., 2015, Wan et al., 2015, Debattisti et al., 2014, Park et al., 2014, Coelho et al., 2013, Moore et al., 2013, Sekine et al., 2013, Bayat et al., 2012, Neumüller et al., 2012, Khanna et al., 2010, Maynard et al., 2010, Singh et al., 2010, Orso et al., 2009, Snee and Macdonald, 2009, Tsuda et al., 2008, Yogev et al., 2008, Challa et al., 2007, Naidoo et al., 2007, Plongthongkum et al., 2007, Tsruya et al., 2007, Gallet et al., 2006, Hollien and Weissman, 2006, Naidoo et al., 2006, Greene et al., 2005, Han et al., 2004, Cirelli, 2003, Lecuit and Wieschaus, 2000, Shaw et al., 2000, Kirkpatrick et al., 1995)

Bip

(Kongsung et al., 2024, Ito et al., 2023, Yang et al., 2022, Zarini-Gakiye et al., 2021, Napoli et al., 2019, Yan et al., 2019, Badinloo et al., 2018, Sekiya et al., 2017, Tang et al., 2015, Bi et al., 2014, Liu et al., 2009, Kramer and Hawley, 2003, The et al., 1999)

CG1579

(Hughes et al., 2008)

GRP78

(Sunderhaus et al., 2019, Sepúlveda-Salinas and Ramos-Castañeda, 2017, Coelho et al., 2013, Naidoo et al., 2007)

GRP87/Bip

(Zarini-Gakiye et al., 2021)

Grp78

(Arquier et al., 2021, Niccoli et al., 2016, Sanchez-Alvarez et al., 2015, Muhlig-Versen et al., 2005, Ahmed and Duncan, 2004)

HSC-70

(Richmond and Broadie, 2002)

HSC3

(Tsuda et al., 2017, Chen et al., 2015, Park et al., 2011, Saurin et al., 2001, Elefant and Palter, 1997, Elefant and Palter, 1995, Kirkpatrick et al., 1995, Rubin et al., 1993)

HSC70

(Latouche et al., 2007, Folk et al., 2006, Gunawardena et al., 2003, Singh and Lakhotia, 1995)

HSC70-3

(Kuo et al., 2013, Singh et al., 2010)

HSP70

(Liu et al., 2018)

HSP70er1

(Kaneko, 2022)

HSP7C_DROME

(Fukuyama et al., 2012)

HSPA5

(Sieber et al., 2020)

Hsc-3

(Nikolaidis and Nei, 2004)

Hsc-70-3

(Braunstein et al., 2020, Cabasso et al., 2019, Maor et al., 2013, Conant and Wagner, 2003)

Hsc3

(Mou et al., 2024, Vinatier et al., 2015, Griciuc et al., 2014, Sekine et al., 2013, van de Hoef et al., 2013, Bayat et al., 2012, Mendes et al., 2009, Tien et al., 2008, Tsuda et al., 2008, Rubin, 1992, Rubin, 1992, Wells and Palter, 1991, Rubin et al., 1990, Rubin et al., 1990)

Hsc3-BiP/GRP78

(Brown et al., 2017)

Hsc3p

(Elefant and Palter, 1999)

Hsc70

(Himalian et al., 2022, Rojas-Benítez et al., 2017, Groth et al., 2013, Fredriksson et al., 2012, Wellington and Zinsmaier, 2005, Tatar et al., 2003, Yue et al., 1999, Wilke et al., 1994)

Hsc70-3

(Zhu et al., 2025, Ozcelik et al., 2024, Vesala et al., 2024, Everman et al., 2023, Glashauser et al., 2023, Granat et al., 2023, Nieken et al., 2023, Yamada et al., 2023, Zheng et al., 2023, Huang et al., 2022, Kaneko, 2022, Känel et al., 2022, McCullough et al., 2022, Perlegos et al., 2022, Prakash et al., 2022, Rai and Tapadia, 2022, Azuma et al., 2021, Cabasso et al., 2021, Joy et al., 2021, Liguori et al., 2021, Lindsey et al., 2021, Silva et al., 2021, Yamazoe et al., 2021, Aromolaran et al., 2020, Gupta and Stocker, 2020, Martínez et al., 2020, Meyer-Nava et al., 2020, Vásquez-Procopio et al., 2020, Even et al., 2019, Guo et al., 2019, Katsube et al., 2019, Mori et al., 2019, Hall et al., 2018, Kucherenko and Shcherbata, 2018, Sakakibara et al., 2018, Galluzzi et al., 2017, Transgenic RNAi Project members, 2017-, Chen et al., 2015, Dent et al., 2015, Horan et al., 2015, Kwong et al., 2015, Štětina et al., 2015, Tang et al., 2015, Ugrankar et al., 2015, Benbahouche et al., 2014, Gonzalez et al., 2014, Haltom et al., 2014, Luck et al., 2014, Pathak et al., 2014, Radermacher et al., 2014, Colinet et al., 2013, Groth et al., 2013, Kockmann et al., 2013, Kwon et al., 2013, Kwon et al., 2013, Lundberg et al., 2013, O'Sullivan et al., 2013, Schertel et al., 2013, Taliaferro et al., 2013, Telonis-Scott et al., 2013, Yamamoto et al., 2013-, Yamakawa et al., 2012, Friedman et al., 2011, Cook et al., 2010, Gallach et al., 2010, Kallappagoudar et al., 2010, Katanayeva et al., 2010, Loewen and Feany, 2010, Müller et al., 2010, Müller et al., 2010, Wasbrough et al., 2010, Gruenewald et al., 2009, Tan et al., 2009, Worringer et al., 2009, Bettencourt et al., 2008, Branco et al., 2008, Brandt et al., 2008, Chen et al., 2008, Simonsen et al., 2008, Xun et al., 2008, Buff et al., 2007, Ravi Ram and Wolfner, 2007, Beller et al., 2006, Beller et al., 2006, Cermelli et al., 2006, Dorner et al., 2006, Walker et al., 2006, Walser et al., 2006, Kanuka et al., 2005, Rehwinkel et al., 2004)

Hsc70.3

(François-Moutal et al., 2022, Cheng and Chiang, 2018)

Hsc73

(Del Río and Montaner, 2021)

Hsp-c3

(Fisher et al., 2008)

anon-WO0138581.7

bip

(Chen et al., 2025, Gerstner et al., 2022, Cheng and Chiang, 2018, Hill et al., 2018, Zhang et al., 2016, Liang et al., 2014, Behr et al., 2007)

dBiP

(Suzuki et al., 2013)

dBip

(Tang et al., 2015)

dhsc70

(Rabindran et al., 1994)

dmBip

(Temviriyanukul et al., 2024)

dmHsc72

(Ahmed and Duncan, 2004)

grp78

(Tsakiri et al., 2019)

hsc3

(Marcora et al., 2017, Kim et al., 2015, Wang et al., 2014, Malzer et al., 2013, Farkas et al., 2008, Farkas et al., 2007, Ryoo et al., 2007, Ryoo et al., 2006)

hsc70

(Mehta et al., 1995, Ornelles and Penman, 1990)

hsc70-3

(Zhang et al., 2010, Kuronen et al., 2009, Norry et al., 2009, Behr et al., 2007, Ringrose et al., 2003, Shaw and Franken, 2003)

hsc72

(Kirkpatrick et al., 1995, Mehta et al., 1991)

l(1)G0102

(Cook et al., 2010, Schäfer et al., 1999.8.12)

l(1)G0111

(Schäfer et al., 1999.8.12)

l(1)G0292

(Schäfer et al., 1999.8.12)

l(1)G0341

(Schäfer et al., 1999.12.2)

l(1)G0407

(Schäfer et al., 1999.8.12)

l(1)G0466

Name Synonyms

70 kDa heat shock protein, endoplasmic reticulum 1

(Kaneko, 2022)

GRP78

(Katsube et al., 2019)

Heat shock 70-kDa protein cognate 3

(Pflieger et al., 2008)

Heat shock protein 70 cognate 3

(Shafer, 2025)

Heat shock protein cognate 3

(Cammarato et al., 2011)

Heat shock protein cognate 70-3

(Kim et al., 2015)

Hsc70-3

(Badinloo et al., 2018)

glucose-regulated protein 78kD/binding immunoglobulin protein

(Zarini-Gakiye et al., 2021)

heat shock cognate protein 3

(Ryoo et al., 2007, Cermelli et al., 2006)

heat shock protein cognate 72

(Breloy et al., 2016, Jaspers et al., 2012)

heat-shock cognate 70-3

(Maor et al., 2013)

immunoglobulin binding protein

(Naidoo et al., 2006)

Secondary FlyBase IDs

FBgn0027308
FBgn0027310
FBgn0028286
FBgn0028330
FBgn0029049
FBgn0030335
FBgn0040174
FBgn0044787

Datasets (0)

Study focus (0)

Experimental Role

Project

Project Type

Title

Study result (0)

Result

Result Type

Title

External Crossreferences and Linkouts ( 91 )

Sequence Crossreferences

NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.

32133

GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.

GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.

RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.

UniProt/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.

P29844

UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information

P29844

UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information

F3YDH0

Other crossreferences

AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.

P29844

BDGP expression data - Patterns of gene expression in Drosophila embryogenesis

FBgn0001218

DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species

32133/tissue=All

EMBL-EBI Single Cell Expression Atlas - Single cell expression across species

FBgn0001218

FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data

FBgn0001218

FlyMine - An integrated database for Drosophila genomics

FBgn0001218

InterPro - A database of protein families, domains and functional sites

KEGG Genes - Molecular building blocks of life in the genomic space.

dme:Dmel_CG4147

MARRVEL_MODEL - MARRVEL (model organism gene)

32133

Linkouts

BioGRID - A database of protein and genetic interactions.

58539

Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones

FBgn0001218

DroID - A comprehensive database of gene and protein interactions.

FBgn0001218

DRSC - Results frm RNAi screens

FBgn0001218

Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.

Hsc70-3_1

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

FBgn0001218

FlyCyc Genes - Genes from a BioCyc PGDB for Dmel

FBGN0001218

Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns

CG4147

Flygut - An atlas of the Drosophila adult midgut

FBgn0001218

FlyMet - A comprehensive tissue-specific metabolomics resource for Drosophila.

FBgn0001218

iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)

TC004425

KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.

MIST (genetic) - An integrated Molecular Interaction Database

32133

MIST (protein-protein) - An integrated Molecular Interaction Database

32133

References (326)

The following external sites may use different assemblies or annotations than FlyBase.

-0.73

Report Sections