FlyBase Gene Report: Dmel\mthl3

METHUSELAH-TYPE RECEPTORS -: Methuselah GPCRs are Class B GPCRs, forming the B3 subgroup. The gene family's founding member methuselah (mth) was identified as a Drosophila GPCR involved in the modulation of life span and stress response. No counterpart for the methuselah gene family have been identified in vertebrates. (Adapted from FBrf0129744 and FBrf0218628).

Gene Model and Products

Number of Transcripts

Number of Unique Polypeptides

Please see the GBrowse view of Dmel\mthl3 or the JBrowse view of Dmel\mthl3 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

Comments on Gene Model

Apparent introns not annotated: probable artifacts due to repetitive sequence.

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

Gene model reviewed during 5.50

Sequence Ontology: Class of Gene

nuclear_gene

protein_coding_gene

Transcript Data

Annotated Transcripts

Name

FlyBase ID

RefSeq ID

Length (nt)

Assoc. CDS (aa)

mthl3-RA

FBtr0086955

NM_145335

1985

511

mthl3-RB

FBtr0340211

NM_001299597

2296

511

mthl3-RC

FBtr0340212

NM_001299598

2047

511

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

RefSeq ID

GenBank

mthl3-PA

FBpp0086111

58.8

511

8.81

NP_663308

AAF57863

mthl3-PB

FBpp0309186

58.8

511

8.81

NP_001286526

AHN56322

mthl3-PC

FBpp0309187

58.8

511

8.81

NP_001286527

AHN56323

Polypeptides with Identical Sequences

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

511 aa isoforms: mthl3-PA, mthl3-PB, mthl3-PC

Additional Polypeptide Data and Comments

Reported size (kDa)

Comments

External Data

Crossreferences

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

Linkouts

Sequences Consistent with the Gene Model

Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\mthl3 using the Feature Mapper tool.

External Data

Crossreferences

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

Linkouts

Gene Ontology (6 terms)

Molecular Function (1 term)

Terms Based on Experimental Evidence (0 terms)

Terms Based on Predictions or Assertions (1 term)

CV Term

Evidence

References

G protein-coupled receptor activity

inferred from sequence or structural similarity

(Brody and Cravchik, 2000)

inferred from sequence or structural similarity with FLYBASE:mth; FB:FBgn0023000

(FlyBase Curators, 2008--)

Biological Process (4 terms)

Terms Based on Experimental Evidence (0 terms)

Terms Based on Predictions or Assertions (4 terms)

CV Term

Evidence

References

cell surface receptor signaling pathway

inferred from electronic annotation with InterPro:IPR017981

(assigned by InterPro )

(FlyBase Curators et al., 2004-)

determination of adult lifespan

inferred from sequence or structural similarity with UniProtKB:O97148

(assigned by UniProt )

(UniProt Curators, 2002-)

G protein-coupled receptor signaling pathway

inferred from sequence or structural similarity with FLYBASE:mth; FB:FBgn0023000

(FlyBase Curators, 2008--)

inferred from sequence or structural similarity

(Brody and Cravchik, 2000)

response to starvation

inferred from sequence or structural similarity with UniProtKB:O97148

(assigned by UniProt )

(UniProt Curators, 2002-)

Cellular Component (1 term)

Terms Based on Experimental Evidence (0 terms)

Terms Based on Predictions or Assertions (1 term)

CV Term

Evidence

References

integral component of membrane

inferred from sequence or structural similarity with FLYBASE:mth; FB:FBgn0023000

(FlyBase Curators, 2008--)

inferred from sequence or structural similarity

(Brody and Cravchik, 2000)

Expression Data

Expression Summary Ribbons

Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.

For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.

Transcript Expression

in situ

Stage

Tissue/Position (including subcellular localization)

Reference

third instar larval stage

morphogenetic furrow

(Patel et al., 2012)

wing disc

(Patel et al., 2012)

embryonic abdominal neuromere

(Patel et al., 2012)

Additional Descriptive Data

mthl3 expression is observed in third instar larvae at the morphogenetic furrow and surrounding vertex, in the wing disc, and in the abdominal neuromeres.

(Patel et al., 2012)

Marker for

Subcellular Localization

CV Term

Polypeptide Expression

Additional Descriptive Data

Marker for

Subcellular Localization

CV Term

Evidence

References

Expression Deduced from Reporters

High-Throughput Expression Data

Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\mthl3 in GBrowse 2

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

View exonic expression by developmental stage for Dmel\mthl3

View exonic expression by tissue for Dmel\mthl3

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

FBgn0028956

FLIGHT - Cell culture data for RNAi and other high-throughput technologies

FBgn0028956

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

CG6530-RA

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

CG6530

Flygut - An atlas of the Drosophila adult midgut

FBgn0028956

Images

FlyBase Wiki

Image Based Resources

Alleles, Insertions, and Transgenic Constructs

Classical and Insertion Alleles ( 11 )

For All Classical and Insertion Alleles Show

Other relevant insertions

Transgenic Constructs ( 5 )

For All Alleles Carried on Transgenic Constructs Show

Transgenic constructs containing/affecting coding region of mthl3

Transgenic constructs containing regulatory region of mthl3

Deletions and Duplications ( 0 )

Phenotypes

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

Lethality

Allele

viable

mthl3^EY08706

Sterility

Allele

fertile

mthl3^EY08706

Phenotype manifest in

Allele

Orthologs

Downloads

Download All DIOPT Orthologs

Download All OrthoDB Orthologs

Human Orthologs (via DIOPT v7.1)

Homo sapiens (Human) (23)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Hsap\ADGRG7

2 of 15

Yes

Hsap\ADGRD1

1 of 15

Hsap\ADGRD2

1 of 15

Yes

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

Yes

Hsap\ADGRF3

1 of 15

Yes

Hsap\ADGRF4

1 of 15

Yes

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

Model Organism Orthologs (via DIOPT v7.1)

Mus musculus (laboratory mouse) (20)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Mmus\Adgre1

2 of 15

Yes

Mmus\Adgrg7

2 of 15

Yes

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

Yes

Mmus\Adgrf3

1 of 15

Yes

Mmus\Adgrf4

1 of 15

Yes

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

Rattus norvegicus (Norway rat) (13)

Rnor\Adgrd1

1 of 13

Yes

Rnor\Adgre1

1 of 13

Yes

Rnor\Adgre5

1 of 13

Yes

Rnor\Adgrf2

1 of 13

Yes

Rnor\Adgrf3

1 of 13

Yes

Rnor\Adgrf4

1 of 13

Yes

Rnor\Adgrf5

1 of 13

Yes

Rnor\Adgrg2

1 of 13

Yes

Rnor\Adgrg3

1 of 13

Yes

Rnor\Adgrg5

1 of 13

Yes

Rnor\Adgrg6

1 of 13

Yes

Rnor\Adgrg7

1 of 13

Yes

Rnor\Adgrl2

1 of 13

Yes

Xenopus tropicalis (Western clawed frog) (8)

Xtro\adgrd1

1 of 12

Yes

Xtro\adgre5

1 of 12

Yes

Xtro\adgrf1

1 of 12

Yes

Xtro\adgrf3

1 of 12

Yes

Xtro\adgrg1

1 of 12

Yes

Xtro\adgrl1

1 of 12

Yes

Xtro\adgrv1

1 of 12

Yes

Xtro\gpr157

1 of 12

Yes

Danio rerio (Zebrafish) (23)

Drer\adgrg6

2 of 15

Yes

Drer\adgrd2

1 of 15

Yes

1 of 15

1 of 15

1 of 15

1 of 15

Yes

Drer\adgrf6

1 of 15

Yes

Drer\adgrf11

1 of 15

Yes

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

Yes

Drer\fbn2b

1 of 15

Yes

1 of 15

1 of 15

1 of 15

1 of 15

Caenorhabditis elegans (Nematode, roundworm) (2)

Cele\lat-2

2 of 15

Yes

Cele\lat-1

1 of 15

Arabidopsis thaliana (thale-cress) (1)

Atha\GCR1

1 of 9

Yes

Saccharomyces cerevisiae (Brewer's yeast) (0)

No records found.

Schizosaccharomyces pombe (Fission yeast) (0)

No records found.

Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG0919063V )

Organism

Common Name

Gene

AAA Syntenic Ortholog

Multiple Dmel Genes in this Orthologous Group

Drosophila melanogaster

fruit fly

Dmel\mthl3

Drosophila melanogaster

fruit fly

Dmel\mth

Drosophila melanogaster

fruit fly

Dmel\mthl4

Drosophila melanogaster

fruit fly

Dmel\mthl2

Drosophila suzukii

Spotted wing Drosophila

Dsuz\DS10_00003566

Drosophila suzukii

Spotted wing Drosophila

Dsuz\DS10_00013361

Drosophila suzukii

Spotted wing Drosophila

Drosophila simulans

Drosophila simulans

Drosophila simulans

Drosophila sechellia

Drosophila sechellia

Drosophila sechellia

Drosophila sechellia

Drosophila sechellia

Drosophila sechellia

Drosophila sechellia

Drosophila erecta

Drosophila erecta

Drosophila erecta

Drosophila erecta

Drosophila erecta

Drosophila erecta

Drosophila yakuba

Drosophila yakuba

Drosophila yakuba

Drosophila yakuba

Drosophila ananassae

Drosophila pseudoobscura pseudoobscura

Dpse\GA19967

Drosophila persimilis

Dper\GL16143

Drosophila willistoni

Dwil\GK20993

Drosophila willistoni

Dwil\GK25390

Drosophila willistoni

Dwil\GK20982

Drosophila willistoni

Dwil\GK12065

Drosophila virilis

Dvir\GJ12490

Drosophila mojavensis

Drosophila grimshawi

Drosophila grimshawi

Drosophila grimshawi

Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( None identified )

No non-Drosophilid orthologies identified

Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( None identified )

No non-Dipteran orthologies identified

Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X035J )

Organism

Common Name

Gene

Multiple Dmel Genes in this Orthologous Group

Ixodes scapularis

Black-legged tick

Isca\ISCW023673

Ixodes scapularis

Black-legged tick

Isca\ISCW023674

Ixodes scapularis

Black-legged tick

Isca\ISCW023671

Ixodes scapularis

Black-legged tick

Isca\ISCW023670

Stegodyphus mimosarum

African social velvet spider

Smim\KFM81725.1

Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( None identified )

No non-Arthropod Metazoa orthologies identified

Paralogs

Downloads

Download All DIOPT Paralogs

Paralogs (via DIOPT v7.1)

Drosophila melanogaster (Fruit fly) (17)

Gene Symbol

Score

Source

Alignment

5 of 10

4 of 10

mth

4 of 10

3 of 10

3 of 10

3 of 10

3 of 10

3 of 10

3 of 10

2 of 10

2 of 10

2 of 10

2 of 10

1 of 10

1 of 10

1 of 10

1 of 10

Human Disease Associations

FlyBase Human Disease Model Reports

Disease Model Summary Ribbon

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 ( 0 )

Allele

Disease

Interaction

References

Disease Associations of Human Orthologs (via DIOPT v7.1 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?

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

esyN Network Diagram

Interactions Browser

Summary of Genetic Interactions

esyN Network Diagram

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

External Data

Linkouts

BioGRID - A database of protein and genetic interactions.

62655

DroID - A comprehensive database of gene and protein interactions.

FBgn0028956

InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.

36961

Pathways

Signaling Pathways (FlyBase)

Metabolic Pathways

External Data

Linkouts

Genomic Location and Detailed Mapping Data

Chromosome (arm)

Recombination map

2-82

Cytogenetic map

54B16-54B16

Sequence location

2R:17,448,533..17,452,598 [-]

FlyBase Computed Cytological Location

Cytogenetic map

Evidence for location

54B16-54B16

Limits computationally determined from genome sequence between P{EP}l(2)k01209^EP2177&P{lacW}k11012a and P{lacW}l(2)k07433^k07433

Experimentally Determined Cytological Location

Cytogenetic map

Notes

References

54C1-54C4

(determined by in situ hybridisation)

(Spradling et al., 1999)

54A-54A

(determined by in situ hybridisation)

(Roch et al., 1998)

54C1-54C4

(BDGP Project Members, 1994-1999)

Experimentally Determined Recombination Data

Location

2-82

(FlyBase, 2016)

2-86.2

(Comeron et al., 2012)

Left of (cM)

Right of (cM)

Notes

Stocks and Reagents

Stocks (12)

Bloomington

84533

w^*; TI{TI}mthl3^attP/CyO

41887

y¹ v¹; P{TRiP.HMS02309}attP40

62625

w¹¹¹⁸; PBac{IT.GAL4}mthl3^0079-G4

65627

w¹¹¹⁸; PBac{IT.GAL4}mthl3^1236-G4

62496

y¹ v¹; P{TRiP.HMJ24020}attP40/CyO

66181

w¹¹¹⁸; PBac{IT.GAL4}mthl3^1420-G4/CyO

16906

y¹ w^67c23; P{EPgy2}mthl3^EY08706

36822

y¹ sc^* v¹ sev²¹; P{TRiP.GL01054}attP2/TM3, Sb¹

5574

y¹ w^67c23; Df(2R)k10408, P{lacW}mthl3^k10408 veil^k10408/CyO

Kyoto

108308

y¹ w^67c23; Df(2R)k10408, P{lacW}mthl3^k10408/CyO

103912

y^* w^*; P{GawB}mthl3^NP1167 / CyO, P{UAS-lacZ.UW14}UW14

VDRC

v104033

P{KK112523}VIE-260B

Genomic Clones (9)

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

cDNA Clones (29)

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 GBrowse for alignment of the cDNAs and ESTs to the gene model.

cDNA clones, fully sequences

BDGP DGC clones

GM02553

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.

FBgn0028956

cDNA Clones, End Sequenced (ESTs)

BDGP DGC clones

RNAi and Array Information

Linkouts

DRSC - Results frm RNAi screens

FBgn0028956

GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents

36961

Antibody Information

Laboratory Generated Antibodies

Commercially Available Antibodies

Other Information

Relationship to Other Genes

Source for database identify of

Source for database merge of

Source for merge of: BEST:GM02553 CG6530

(Bayraktaroglu, 2000.11.2)

Source for merge of: mthl3 anon-WO0170980.52 anon-WO0170980.53

(FlyBase, 1996-)

Additional comments

Source for merge of mthl3 anon-WO0170980.52 anon-WO0170980.53 was sequence comparison ( date:051113 ).

(FlyBase, 1996-)

Other Comments

Identification: transcription unit identified during molecular analysis of the robl genomic region.

(Bowman et al., 1999)

Origin and Etymology

Discoverer

Etymology

Identification

External Crossreferences and Linkouts ( 43 )

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.

36961

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

Q9V818

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

A0A0B4LFS2

Other crossreferences

BDGP expression data - Patterns of gene expression in Drosophila embryogenesis

FBgn0028956

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

FBgn0028956

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

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

CG6530

Flygut - An atlas of the Drosophila adult midgut

FBgn0028956

GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents

36961

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

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

Dmel_CG6530

modMine - A data warehouse for the modENCODE project

FBgn0028956

Linkouts

ApoDroso - Functional genomic database for photoreceptor development, survival and function

11010-mthl3[k11012a]

BioGRID - A database of protein and genetic interactions.

62655

DPiM - Drosophila Protein interaction map

FBgn0028956

DroID - A comprehensive database of gene and protein interactions.

FBgn0028956

DRSC - Results frm RNAi screens

FBgn0028956

FLIGHT - Cell culture data for RNAi and other high-throughput technologies

FBgn0028956

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

CG6530-RA

FlyCyc Genes - Genes from a BioCyc PGDB for Dmel

FBGN0028956

FlyMine - An integrated database for Drosophila genomics

FBgn0028956

InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.

36961

Synonyms and Secondary IDs (15)

Reported As

Symbol Synonym

104/8

(Roch et al., 1998)

BEST:GM02553

(Giot et al., 2003)

CG6530

(Friedrich and Jones, 2016, Li et al., 2013, Chen et al., 2012, Ni et al., 2011.7.19, Ni et al., 2010.12.1, Zhang et al., 2010, Keleman et al., 2009.8.5, Perkins et al., 2009, Schiess et al., 2009, Burnette, 2001.5.23, Harmar, 2001, Mount, 2001.8.14, Whitfield, 2001.9.10)

GENE 1

(Bowman et al., 1999)

Mth-3

(Cvejic et al., 2004)

Mthl3

(Sung et al., 2017)

anon-WO0170980.52

anon-WO0170980.53

gene 1

(Bowman, 1999.11.11)

l(2)k10408

(BDGP Project Members, 1994-1999)

mthl-3

(Paré et al., 2012)

mthl3

(Rao and Deng, 2019.10.23, Clandinin and Owens, 2016-, Friedrich and Jones, 2016, Sujkowski et al., 2015, Jalvingh et al., 2014, Lai et al., 2014, Araújo et al., 2013, Chintapalli et al., 2013, Durdevic et al., 2013, Nawaz et al., 2012, Patel et al., 2012, Bina et al., 2010, Ja et al., 2009, Lai et al., 2007)

Name Synonyms

Mth-like 3

(West et al., 2001)

methuselah-like 3

(Lai et al., 2014, Lai et al., 2007)

mth-like 3

(Brody and Cravchik, 2000)

Secondary FlyBase IDs

FBgn0034220
FBgn0046526
FBgn0046527

Datasets (0)

Study focus (0)

Experimental Role

Project

Project Type

Title

References (62)

Report Sections

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