Tsc2 TSC complex subunit 2 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Tsc2provided by RGD
Official Full Name: TSC complex subunit 2provided by RGD
Primary source: RGD:3908
See related: Ensembl:ENSRNOG00000011375 AllianceGenome:RGD:3908
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Rc
Summary: Enables GTPase activator activity and protein N-terminus binding activity. Involved in several processes, including negative regulation of cell population proliferation; negative regulation of signal transduction; and regulation of neuron projection development. Acts upstream of or within cell projection organization and negative regulation of cell size. Located in several cellular components, including caveola; growth cone; and neuronal cell body. Part of protein-containing complex. Is active in glutamatergic synapse. Used to study autism spectrum disorder; hepatic angiomyolipoma; and renal cell carcinoma. Biomarker of hepatocellular carcinoma. Human ortholog(s) of this gene implicated in hepatic angiomyolipoma; lymphangioleiomyomatosis; medulloblastoma; tuberous sclerosis; and tuberous sclerosis 2. Orthologous to human TSC2 (TSC complex subunit 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Brain (RPKM 105.2), Lung (RPKM 105.1) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 10q12

Exon count:: 43

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	10	NC_086028.1 (14125679..14160317, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	10	NC_051345.1 (13621135..13655773, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	10	NC_005109.4 (13962006..13996684, complement)

Chromosome 10 - NC_086028.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Ca2+/Calmodulin induces translocation of membrane-associated TSC2 to the nucleus where it suppresses CYP24A1 expression.
Title: Ca2+/Calmodulin induces translocation of membrane-associated TSC2 to the nucleus where it suppresses CYP24A1 expression.
Disruption of amygdala Tsc2 in adolescence leads to changed prelimbic cellular activity and generalized fear responses at adulthood in rats.
Title: Disruption of amygdala Tsc2 in adolescence leads to changed prelimbic cellular activity and generalized fear responses at adulthood in rats.
mTOR inhibitor improves autistic-like behaviors related to Tsc2 haploinsufficiency but not following developmental status epilepticus.
Title: mTOR inhibitor improves autistic-like behaviors related to Tsc2 haploinsufficiency but not following developmental status epilepticus.
Reduced expression of Tsc2 was also observed in the majority of the LOH-negative carcinomas.
Title: Interstitial chromosomal deletion of the tuberous sclerosis complex 2 locus is a signature for radiation-associated renal tumors in Eker rats.
TFE3 activation by mTORC1 signaling is involved in the development of abnormal ductal structures in Tsc2 knockout teratomas.
Title: Aberrant differentiation of Tsc2-deficient teratomas associated with activation of the mTORC1-TFE3 pathway.
Formation of ROS and activity of NADPH oxidases were significantly higher in mouse embryonic fibroblasts and in primary culture of rat renal proximal tubular epithelial tuberin-deficient cells compared to wild-type cells.
Title: Tuberin regulates reactive oxygen species in renal proximal cells, kidney from rodents, and kidney from patients with tuberous sclerosis complex.
Heterozygous TSC2 mutation not only affects the liver metabolism, but also skeletal muscle metabolism, via mitochondrial dysfunction.
Title: Metabolic abnormalities induced by mitochondrial dysfunction in skeletal muscle of the renal carcinoma Eker (TSC2+/-) rat model.
Therefore, we conclude that glycolysis is restrained in the livers of TSC2 heterozygous mutant rats, and these defects lead to abnormal production of acetoacetate.
Title: The tuberous sclerosis complex model Eker (TSC2+/-) rat exhibits hyperglycemia and hyperketonemia due to decreased glycolysis in the liver.
In vitro differentiation experiments using these ESCs combined with in vivo experiments may reveal the mechanism of the tissuespecific pathogenesis caused by the Tsc2 mutation and identify specific new therapeutic targets.
Title: Establishment of Tsc2‑deficient rat embryonic stem cells.
The N525S Tsc2 variant causes dominant embryonic lethality in Eker rats.
Title: Transgenic expression of the N525S-tuberin variant in Tsc2 mutant (Eker) rats causes dominant embryonic lethality.

Submit: New GeneRIF Correction See all GeneRIFs (42)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH142233 (e-PCR)
- UniSTS:231482

Tsc2 (e-PCR), detects polymorphism
- UniSTS:265681

Tsc2 (e-PCR), detects polymorphism
- UniSTS:265683

Tsc2 (e-PCR), detects polymorphism
- UniSTS:265685

RH94522 (e-PCR)
- UniSTS:119770

Tsc2 (e-PCR), detects polymorphism
- UniSTS:527589

RH138827 (e-PCR)
- UniSTS:220914

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables 14-3-3 protein binding	ISO Inferred from Sequence Orthology more info
enables GTPase activator activity	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables GTPase activator activity	IEA Inferred from Electronic Annotation more info
enables GTPase activator activity	ISO Inferred from Sequence Orthology more info
enables GTPase activator activity	TAS Traceable Author Statement more info	PubMed
enables Hsp90 protein binding	IEA Inferred from Electronic Annotation more info
enables Hsp90 protein binding	ISO Inferred from Sequence Orthology more info
enables phosphatase binding	IEA Inferred from Electronic Annotation more info
enables phosphatase binding	ISO Inferred from Sequence Orthology more info
enables phosphatase binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	IPI Inferred from Physical Interaction more info	PubMed
enables small GTPase binding	IEA Inferred from Electronic Annotation more info
enables small GTPase binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of B cell proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of T cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in anoikis	IEA Inferred from Electronic Annotation more info
involved_in anoikis	ISO Inferred from Sequence Orthology more info
acts_upstream_of cell population proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cell projection organization	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within cell projection organization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to insulin stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to starvation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to starvation	ISO Inferred from Sequence Orthology more info
involved_in cellular response to starvation	ISS Inferred from Sequence or Structural Similarity more info
involved_in establishment of cell polarity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in excitatory chemical synaptic transmission	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within glucose import	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within heart development	ISO Inferred from Sequence Orthology more info
involved_in inhibitory chemical synaptic transmission	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of B cell proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of T cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of TOR signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of TOR signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of TOR signaling	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of TOR signaling	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of TOR signaling	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of TORC1 signaling	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of TORC1 signaling	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of TORC1 signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of axonogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of cell size	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of epithelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of epithelial to mesenchymal transition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of fibroblast proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of insulin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of macroautophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of pinocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of vascular endothelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within neural tube closure	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive chemotaxis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of autophagy	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of dendritic spine development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of fibroblast migration	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of insulin receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of macroautophagy	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of macroautophagy	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of macroautophagy	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neuron projection development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein import into nucleus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein localization	ISO Inferred from Sequence Orthology more info
involved_in protein localization to cell surface	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein transport into plasma membrane raft	ISO Inferred from Sequence Orthology more info
involved_in regulation of cell cycle	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of endocytosis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of insulin receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in regulation of postsynapse organization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of postsynapse organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of small GTPase mediated signal transduction	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within response to hypoxia	ISO Inferred from Sequence Orthology more info
involved_in social behavior	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
NOT located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
part_of TSC1-TSC2 complex	IBA Inferred from Biological aspect of Ancestor more info
part_of TSC1-TSC2 complex	IEA Inferred from Electronic Annotation more info
part_of TSC1-TSC2 complex	ISO Inferred from Sequence Orthology more info
part_of TSC1-TSC2 complex	ISS Inferred from Sequence or Structural Similarity more info
located_in caveola	IDA Inferred from Direct Assay more info	PubMed
located_in cell projection	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
located_in growth cone	IDA Inferred from Direct Assay more info	PubMed
located_in lysosomal membrane	IEA Inferred from Electronic Annotation more info
is_active_in lysosomal membrane	ISO Inferred from Sequence Orthology more info
is_active_in lysosomal membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in lysosome	ISO Inferred from Sequence Orthology more info
located_in membrane	ISO Inferred from Sequence Orthology more info
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
NOT located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info
located_in postsynaptic density	IEA Inferred from Electronic Annotation more info
is_active_in postsynaptic density	ISO Inferred from Sequence Orthology more info
is_active_in synapse	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: tuberin

Names: renal carcinoma; tuberous sclerosis 2 homolog protein; tuberous sclerosis 2 protein homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_012680.3 → NP_036812.2 tuberin

See identical proteins and their annotated locations for NP_036812.2

Status: PROVISIONAL

Source sequence(s)

U24150

UniProtKB/Swiss-Prot

P49816

UniProtKB/TrEMBL

D3ZLW4

Related

ENSRNOP00000016221.1, ENSRNOT00000016221.4

Conserved Domains (3) summary

pfam02145
Location:1564 → 1750

Rap_GAP; Rap/ran-GAP

pfam03542
Location:555 → 903

Tuberin; Tuberin

pfam11864
Location:54 → 466

DUF3384; Domain of unknown function (DUF3384)

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCr8

Genomic

NC_086028.1 Reference GRCr8

Range

14125679..14160317 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063268444.1 → XP_063124514.1 tuberin isoform X16
XM_063268436.1 → XP_063124506.1 tuberin isoform X3
XM_063268441.1 → XP_063124511.1 tuberin isoform X10
XM_063268440.1 → XP_063124510.1 tuberin isoform X9
XM_063268438.1 → XP_063124508.1 tuberin isoform X5
XM_063268437.1 → XP_063124507.1 tuberin isoform X4
XM_063268443.1 → XP_063124513.1 tuberin isoform X14
XM_063268442.1 → XP_063124512.1 tuberin isoform X13
XM_063268435.1 → XP_063124505.1 tuberin isoform X16
XM_063268434.1 → XP_063124504.1 tuberin isoform X12
XM_039085236.2 → XP_038941164.1 tuberin isoform X15

UniProtKB/TrEMBL

D3ZLW4

Conserved Domains (3) summary

pfam02145
Location:1497 → 1683

Rap_GAP; Rap/ran-GAP

pfam03542
Location:554 → 902

Tuberin

pfam11864
Location:54 → 418

DUF3384; Domain of unknown function (DUF3384)
XM_063268433.1 → XP_063124503.1 tuberin isoform X11
XM_063268432.1 → XP_063124502.1 tuberin isoform X7
XM_039085229.2 → XP_038941157.1 tuberin isoform X6

UniProtKB/TrEMBL

D3ZLW4

Conserved Domains (3) summary

pfam02145
Location:1540 → 1726

Rap_GAP; Rap/ran-GAP

pfam03542
Location:554 → 902

Tuberin

pfam11864
Location:54 → 418

DUF3384; Domain of unknown function (DUF3384)
XM_039085227.2 → XP_038941155.1 tuberin isoform X3

UniProtKB/TrEMBL

D3ZLW4

Conserved Domains (3) summary

pfam02145
Location:1563 → 1749

Rap_GAP; Rap/ran-GAP

pfam03542
Location:554 → 902

Tuberin

pfam11864
Location:54 → 418

DUF3384; Domain of unknown function (DUF3384)
XM_063268439.1 → XP_063124509.1 tuberin isoform X17
XM_039085230.2 → XP_038941158.1 tuberin isoform X8

UniProtKB/TrEMBL

D3ZLW4

Conserved Domains (3) summary

pfam02145
Location:1525 → 1711

Rap_GAP; Rap/ran-GAP

pfam03542
Location:525 → 864

Tuberin

pfam11864
Location:54 → 419

DUF3384; Domain of unknown function (DUF3384)
XM_039085235.2 → XP_038941163.1 tuberin isoform X14

UniProtKB/TrEMBL

D3ZLW4

Related

ENSRNOP00000087212.1

Conserved Domains (3) summary

pfam02145
Location:1497 → 1683

Rap_GAP; Rap/ran-GAP

pfam03542
Location:555 → 903

Tuberin

pfam11864
Location:54 → 419

DUF3384; Domain of unknown function (DUF3384)
XM_039085233.2 → XP_038941161.1 tuberin isoform X10

UniProtKB/TrEMBL

D3ZLW4

Conserved Domains (3) summary

pfam02145
Location:1520 → 1706

Rap_GAP; Rap/ran-GAP

pfam03542
Location:555 → 903

Tuberin

pfam11864
Location:54 → 419

DUF3384; Domain of unknown function (DUF3384)
XM_039085234.2 → XP_038941162.1 tuberin isoform X13

UniProtKB/TrEMBL

D3ZLW4

Conserved Domains (3) summary

pfam02145
Location:1498 → 1684

Rap_GAP; Rap/ran-GAP

pfam03542
Location:555 → 903

Tuberin

pfam11864
Location:54 → 419

DUF3384; Domain of unknown function (DUF3384)
XM_039085232.2 → XP_038941160.1 tuberin isoform X9

UniProtKB/TrEMBL

D3ZLW4

Conserved Domains (3) summary

pfam02145
Location:1521 → 1707

Rap_GAP; Rap/ran-GAP

pfam03542
Location:555 → 903

Tuberin

pfam11864
Location:54 → 419

DUF3384; Domain of unknown function (DUF3384)
XM_063268431.1 → XP_063124501.1 tuberin isoform X5
XM_039085226.2 → XP_038941154.1 tuberin isoform X2

UniProtKB/TrEMBL

D3ZLW4

Conserved Domains (3) summary

pfam02145
Location:1563 → 1749

Rap_GAP; Rap/ran-GAP

pfam03542
Location:555 → 903

Tuberin

pfam11864
Location:54 → 419

DUF3384; Domain of unknown function (DUF3384)
XM_039085228.2 → XP_038941156.1 tuberin isoform X4

UniProtKB/TrEMBL

D3ZLW4

Related

ENSRNOP00000039381.6

Conserved Domains (3) summary

pfam02145
Location:1541 → 1727

Rap_GAP; Rap/ran-GAP

pfam03542
Location:555 → 903

Tuberin

pfam11864
Location:54 → 419

DUF3384; Domain of unknown function (DUF3384)
XM_006245909.5 → XP_006245971.2 tuberin isoform X1

UniProtKB/TrEMBL

A0A0G2JSL4, A6HCU1, D3ZLW4

Conserved Domains (3) summary

pfam02145
Location:1564 → 1750

Rap_GAP; Rap/ran-GAP

pfam03542
Location:555 → 903

Tuberin; Tuberin

pfam11864
Location:54 → 466

DUF3384; Domain of unknown function (DUF3384)
XM_008767544.4 → XP_008765766.1 tuberin isoform X18

UniProtKB/TrEMBL

D3ZLW4

Conserved Domains (3) summary

pfam02145
Location:1505 → 1691

Rap_GAP; Rap/ran-GAP

pfam03542
Location:496 → 844

Tuberin; Tuberin

pfam11864
Location:1 → 407

DUF3384; Domain of unknown function (DUF3384)
XM_063268445.1 → XP_063124515.1 tuberin isoform X19
XM_039085238.2 → XP_038941166.1 tuberin isoform X21

Conserved Domains (2) summary

pfam03542
Location:555 → 903

Tuberin

pfam11864
Location:54 → 419

DUF3384; Domain of unknown function (DUF3384)
XM_039085237.2 → XP_038941165.1 tuberin isoform X20

Conserved Domains (2) summary

pfam03542
Location:555 → 903

Tuberin

pfam11864
Location:54 → 419

DUF3384; Domain of unknown function (DUF3384)