BTRC beta-transducin repeat containing E3 ubiquitin protein ligase [Homo sapiens (human)] - Gene

Summary

Official Symbol: BTRCprovided by HGNC
Official Full Name: beta-transducin repeat containing E3 ubiquitin protein ligaseprovided by HGNC
Primary source: HGNC:HGNC:1144
See related: Ensembl:ENSG00000166167 MIM:603482; AllianceGenome:HGNC:1144
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FWD1; FBW1A; FBXW1; bTrCP; FBXW1A; bTrCP1; betaTrCP; BETA-TRCP
Summary: This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbws class; in addition to an F-box, this protein contains multiple WD-40 repeats. The encoded protein mediates degradation of CD4 via its interaction with HIV-1 Vpu. It has also been shown to ubiquitinate phosphorylated NFKBIA (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), targeting it for degradation and thus activating nuclear factor kappa-B. Alternatively spliced transcript variants have been described. A related pseudogene exists in chromosome 6. [provided by RefSeq, Mar 2012]
Expression: Ubiquitous expression in brain (RPKM 11.6), testis (RPKM 7.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 10q24.32

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (101354048..101557313)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (102238054..102441353)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (103113922..103317070)

Chromosome 10 - NC_000010.11 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: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

beta-TrCP-Mediated Proteolysis of Mis18beta Prevents Mislocalization of CENP-A and Chromosomal Instability.
Title: β-TrCP-Mediated Proteolysis of Mis18β Prevents Mislocalization of CENP-A and Chromosomal Instability.
SelK promotes glioblastoma cell proliferation by inhibiting beta-TrCP1 mediated ubiquitin-dependent degradation of CDK4.
Title: SelK promotes glioblastoma cell proliferation by inhibiting β-TrCP1 mediated ubiquitin-dependent degradation of CDK4.
Decidual stromal cells-derived exosomes incurred insufficient migration and invasion of trophoblast by disturbing of beta-TrCP-mediated snail ubiquitination and degradation in unexplained recurrent spontaneous abortion.
Title: Decidual stromal cells-derived exosomes incurred insufficient migration and invasion of trophoblast by disturbing of β-TrCP-mediated snail ubiquitination and degradation in unexplained recurrent spontaneous abortion.
Sequence variants in DLX5, HOXD13 and 445 kb-microduplication surrounding BTRC cause split-hand/foot malformation in three different families.
Title: Sequence variants in DLX5, HOXD13 and 445 kb-microduplication surrounding BTRC cause split-hand/foot malformation in three different families.
Exosomal GPT2 derived from triple-negative breast cancer cells promotes metastasis by activating BTRC.
Title: Exosomal GPT2 derived from triple-negative breast cancer cells promotes metastasis by activating BTRC.
Ubiquitin E3 ligase beta-TrCP negatively regulates surface protein of hepatitis B virus.
Title: Ubiquitin E3 ligase β-TrCP negatively regulates surface protein of hepatitis B virus.
Pan-cancer analysis of FBXW family with potential implications in prognosis and immune infiltration.
Title: Pan-cancer analysis of FBXW family with potential implications in prognosis and immune infiltration.
circHIPK3 prevents cardiac senescence by acting as a scaffold to recruit ubiquitin ligase to degrade HuR.
Title: circHIPK3 prevents cardiac senescence by acting as a scaffold to recruit ubiquitin ligase to degrade HuR.
The current status and future prospects for therapeutic targeting of KEAP1-NRF2 and beta-TrCP-NRF2 interactions in cancer chemoresistance.
Title: The current status and future prospects for therapeutic targeting of KEAP1-NRF2 and β-TrCP-NRF2 interactions in cancer chemoresistance.
WBP2 promotes BTRC mRNA stability to drive migration and invasion in triple-negative breast cancer via NF-kappaB activation.
Title: WBP2 promotes BTRC mRNA stability to drive migration and invasion in triple-negative breast cancer via NF-κB activation.

Submit: New GeneRIF Correction See all GeneRIFs (152)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vpu	vpu	Vpu requires BTRC to degrade BST2 (tetherin) but does not require BTRC for Vpu-mediated BST2 (tetherin) antagonism	PubMed
	vpu	HIV-1 Vpu-induced cleavage of IRF3 is largely dependent on the ability of Vpu to interact with beta-TrCP, and mutation of the Vpu phosphorylation sites Ser52 and Ser56 greatly decreases the function of Vpu-induced IRF3 cleavage	PubMed
	vpu	Interaction of HIV-1 Vpu with betaTrCP is required for Vpu ubiquitination and degradation by the proteasome. Amino acid substitutions at serine's 52 and 56 of Vpu abolish the interaction with betaTrCP	PubMed
	vpu	Binding of HIV-1 Vpu to beta-TrCP requires two phosphoserine residues on Vpu (amino acids 52 and 56) and results in recruitment of beta-TrCP to cellular membranes	PubMed
	vpu	Through binding to beta-TrCP, HIV-1 Vpu targets CD4 for degradation in the endoplasmic reticulum and also inhibits IkappaB-alpha degradation as well as NF-kappaB activation	PubMed
	vpu	Chimeras between the TMD of HIV-1 M Vpu and the cytoplasmic domains of SIVcpzPtt, SIVcpzPts, and SIVgor Vpu proteins are capable of binding to human beta-TrCP	PubMed
	vpu	Most HIV-1 Vpu proteins from Cameroonian group N viruses are unable to bind beta-TrCP because of lack of a functional beta-TrCP binding site DSGxxS in Vpu	PubMed
	vpu	HIV-1 Vpu S61A mutant efficiently interacts with endogenous betaTrCP and strongly stabilizes beta-catenin	PubMed
	vpu	HIV-1 Vpu stabilizes cellular Cdc25A and differentially affects betaTrCP-mediated degradation events at different phases of the cell cycle	PubMed
	vpu	Poly-ubiquitination of the CD4 cytosolic tail by SCFbeta-TrCP is required for HIV-1 Vpu-induced CD4 degradation	PubMed
	vpu	HIV-1 Vpu interferes with beta-TrCP to inhibit TNF-alpha-induced activation of NFkappaB	PubMed
	vpu	The invariant leucine 63 and the valine 68 within the predicted second alpha-helical domain of the HIV-1 Vpu cytoplasmic tail are required for CD4 down-modulation. L63A and V68A mutants still bind CD4 and retain the ability to interact with beta-TrCP1	PubMed
	vpu	HIV-1 Vpu and beta-TrCP co-immunoprecipitate with tetherin	PubMed
	vpu	HIV-1 Vpu expression leads to stabilization and upregulation of p53 via inhibiting association of p53 with beta-TrCP and its subsequent ubiquitination	PubMed
	vpu	HIV-1 Vpu interacts with BST-2 in the trans-Golgi network or in early endosomes, leading to lysosomal degradation of BST-2. Vpu-mediated downregulation of BST-2 depends on cellular ubiquitination machinery via betaTrCP	PubMed
	vpu	Co-depletion of beta-TrCP1 and beta-TrCP2 support Vpu's activity to enhance virus release and to downregulate endogenous tetherin in TZM-bl cells	PubMed
	vpu	HIV-1 Vpu is a strong competitive inhibitor of beta-TrCP and impairs the degradation of SCF-beta-TrCP substrates such as IKBalpha, ATF4 and beta-catenin	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-16946 (e-PCR)
- UniSTS:23594

D10S1167 (e-PCR)
- UniSTS:149305

D10S1240 (e-PCR)
- UniSTS:64609

WIAF-1661 (e-PCR)
- UniSTS:47728

D10S1239 (e-PCR), detects polymorphism
- UniSTS:31944

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables beta-catenin binding	IDA Inferred from Direct Assay more info	PubMed
enables ligase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	IEA Inferred from Electronic Annotation more info
enables protein phosphorylated amino acid binding	IEA Inferred from Electronic Annotation more info
enables ubiquitin ligase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin-like ligase-substrate adaptor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in branching involved in mammary gland duct morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in cellular response to organic cyclic compound	IEA Inferred from Electronic Annotation more info
involved_in mammary gland epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of DNA-binding transcription factor activity	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of smoothened signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in non-canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ubiquitin protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in protein K48-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein dephosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein destabilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein polyubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein polyubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of canonical NF-kappaB signal transduction	IEA Inferred from Electronic Annotation more info
involved_in regulation of canonical Wnt signaling pathway	IC Inferred by Curator more info	PubMed
involved_in regulation of cell cycle	IEA Inferred from Electronic Annotation more info
involved_in regulation of circadian rhythm	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of proteasomal protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in rhythmic process	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of SCF ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IC Inferred by Curator more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleoplasm	TAS Traceable Author Statement more info

General protein information

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Preferred Names: F-box/WD repeat-containing protein 1A

Names: E3RSIkappaB; F-box and WD repeats protein beta-TrCP; F-box and WD-repeat protein 1B; beta-TrCP1; epididymis tissue protein Li 2a; pIkappaBalpha-E3 receptor subunit

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.

Genomic

NG_009234.1 RefSeqGene

Range

5098..208246

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001256856.2 → NP_001243785.1 F-box/WD repeat-containing protein 1A isoform 3

See identical proteins and their annotated locations for NP_001243785.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1.

Source sequence(s)

AK313417, BC006204, CR749295

Consensus CDS

CCDS73183.1

UniProtKB/TrEMBL

B7Z3H4, Q68DS0

Related

ENSP00000377088.5, ENST00000393441.8

Conserved Domains (4) summary

cd00200
Location:277 → 555

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:280 → 315

7WD40; WD40 repeat [structural motif]

pfam12125
Location:113 → 151

Beta-TrCP_D; D domain of beta-TrCP

pfam12937
Location:155 → 202

F-box-like
NM_003939.5 → NP_003930.1 F-box/WD repeat-containing protein 1A isoform 2

See identical proteins and their annotated locations for NP_003930.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AF129530, AK313417, BC006204, CR749295

Consensus CDS

CCDS7511.1

UniProtKB/TrEMBL

B2R8L3

Related

ENSP00000385339.2, ENST00000408038.6

Conserved Domains (4) summary

cd00200
Location:267 → 545

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:270 → 305

7WD40; WD40 repeat [structural motif]

pfam12125
Location:103 → 141

Beta-TrCP_D; D domain of beta-TrCP

pfam12937
Location:145 → 192

F-box-like
NM_033637.4 → NP_378663.1 F-box/WD repeat-containing protein 1A isoform 1

See identical proteins and their annotated locations for NP_378663.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

BC006204, BC027994, CR749295

Consensus CDS

CCDS7512.1

UniProtKB/Swiss-Prot

B5MD49, Q5W141, Q5W142, Q9Y213, Q9Y297

UniProtKB/TrEMBL

A0A0S2Z4P6, A0A0S2Z507

Related

ENSP00000359206.3, ENST00000370187.8

Conserved Domains (4) summary

cd00200
Location:303 → 581

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:306 → 341

7WD40; WD40 repeat [structural motif]

pfam12125
Location:139 → 177

Beta-TrCP_D; D domain of beta-TrCP

pfam12937
Location:181 → 228

F-box-like

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000010.11 Reference GRCh38.p14 Primary Assembly

Range

101354048..101557313

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047425986.1 → XP_047281942.1 F-box/WD repeat-containing protein 1A isoform X7
XM_006718054.3 → XP_006718117.1 F-box/WD repeat-containing protein 1A isoform X1

UniProtKB/TrEMBL

A0A0S2Z507

Conserved Domains (5) summary

COG2319
Location:417 → 713

WD40; WD40 repeat [General function prediction only]

cd00200
Location:430 → 708

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

pfam12125
Location:266 → 304

Beta-TrCP_D; D domain of beta-TrCP

pfam12937
Location:308 → 355

F-box-like; F-box-like

sd00039
Location:433 → 468

7WD40; WD40 repeat [structural motif]
XM_017016870.2 → XP_016872359.1 F-box/WD repeat-containing protein 1A isoform X2

UniProtKB/TrEMBL

A0A0S2Z507
XM_017016874.2 → XP_016872363.1 F-box/WD repeat-containing protein 1A isoform X5

UniProtKB/TrEMBL

B2R8L3

Conserved Domains (4) summary

cd00200
Location:241 → 519

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:244 → 279

7WD40; WD40 repeat [structural motif]

pfam12125
Location:77 → 115

Beta-TrCP_D; D domain of beta-TrCP

pfam12937
Location:119 → 166

F-box-like
XM_047425987.1 → XP_047281943.1 F-box/WD repeat-containing protein 1A isoform X8
XM_017016871.2 → XP_016872360.1 F-box/WD repeat-containing protein 1A isoform X3

UniProtKB/TrEMBL

Q68DS0

Conserved Domains (4) summary

cd00200
Location:285 → 563

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:288 → 323

7WD40; WD40 repeat [structural motif]

pfam12125
Location:121 → 159

Beta-TrCP_D; D domain of beta-TrCP

pfam12937
Location:163 → 210

F-box-like
XM_047425983.1 → XP_047281939.1 F-box/WD repeat-containing protein 1A isoform X4
XM_017016873.3 → XP_016872362.1 F-box/WD repeat-containing protein 1A isoform X3

UniProtKB/TrEMBL

Q68DS0

Conserved Domains (4) summary

cd00200
Location:285 → 563

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:288 → 323

7WD40; WD40 repeat [structural motif]

pfam12125
Location:121 → 159

Beta-TrCP_D; D domain of beta-TrCP

pfam12937
Location:163 → 210

F-box-like
XM_047425984.1 → XP_047281940.1 F-box/WD repeat-containing protein 1A isoform X4
XM_047425985.1 → XP_047281941.1 F-box/WD repeat-containing protein 1A isoform X7
XM_024448247.2 → XP_024304015.1 F-box/WD repeat-containing protein 1A isoform X7

UniProtKB/TrEMBL

Q68DS0

Conserved Domains (4) summary

cd00200
Location:204 → 482

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:207 → 242

7WD40; WD40 repeat [structural motif]

pfam12125
Location:40 → 78

Beta-TrCP_D; D domain of beta-TrCP

pfam12937
Location:82 → 129

F-box-like
XM_011540320.3 → XP_011538622.1 F-box/WD repeat-containing protein 1A isoform X6

UniProtKB/TrEMBL

Q68DS0

Conserved Domains (5) summary

COG2319
Location:222 → 518

WD40; WD40 repeat [General function prediction only]

cd00200
Location:235 → 513

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

pfam12125
Location:71 → 109

Beta-TrCP_D; D domain of beta-TrCP

pfam12937
Location:113 → 160

F-box-like; F-box-like

sd00039
Location:238 → 273

7WD40; WD40 repeat [structural motif]

Alternate T2T-CHM13v2.0

Genomic

NC_060934.1 Alternate T2T-CHM13v2.0

Range

102238054..102441353

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054367115.1 → XP_054223090.1 F-box/WD repeat-containing protein 1A isoform X8
XM_054367108.1 → XP_054223083.1 F-box/WD repeat-containing protein 1A isoform X2
XM_054367107.1 → XP_054223082.1 F-box/WD repeat-containing protein 1A isoform X1
XM_054367113.1 → XP_054223088.1 F-box/WD repeat-containing protein 1A isoform X5
XM_054367109.1 → XP_054223084.1 F-box/WD repeat-containing protein 1A isoform X3
XM_054367111.1 → XP_054223086.1 F-box/WD repeat-containing protein 1A isoform X4
XM_054367110.1 → XP_054223085.1 F-box/WD repeat-containing protein 1A isoform X3
XM_054367112.1 → XP_054223087.1 F-box/WD repeat-containing protein 1A isoform X4
XM_054367114.1 → XP_054223089.1 F-box/WD repeat-containing protein 1A isoform X7