IBTK inhibitor of Bruton tyrosine kinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: IBTKprovided by HGNC
Official Full Name: inhibitor of Bruton tyrosine kinaseprovided by HGNC
Primary source: HGNC:HGNC:17853
See related: Ensembl:ENSG00000005700 MIM:606457; AllianceGenome:HGNC:17853
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: BTKI; BTBD26
Summary: Bruton tyrosine kinase (BTK) is a protein tyrosine kinase that is expressed in B cells, macrophages, and neutrophils. The protein encoded by this gene binds to BTK and downregulates BTK's kinase activity. In addition, the encoded protein disrupts BTK-mediated calcium mobilization and negatively regulates the activation of nuclear factor-kappa-B-driven transcription. This gene has a pseudogene on chromosome 18. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]
Expression: Ubiquitous expression in adrenal (RPKM 16.4), thyroid (RPKM 13.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6q14.1

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (82169987..82247744, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (83379383..83457139, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (82879704..82957461, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

IBtkalpha Activates the beta-Catenin-Dependent Transcription of MYC through Ubiquitylation and Proteasomal Degradation of GSK3beta in Cancerous B Cells.
Title: IBtkα Activates the β-Catenin-Dependent Transcription of MYC through Ubiquitylation and Proteasomal Degradation of GSK3β in Cancerous B Cells.
RNA interference of Inhibitor of brutons tyrosine kinase-isoform alpha up regulated the expression of pro-apoptotic genes, including TNF, CRADD, CASP7, BNIP3 and BIRC3 and is a novel marker of CLL progression promoting cell growth and resistance to apoptosis.
Title: The expression of inhibitor of bruton's tyrosine kinase gene is progressively up regulated in the clinical course of chronic lymphocytic leukaemia conferring resistance to apoptosis.
Data suggest that IBTKalpha is (a) localized in hepatocytes in endoplasmic reticulum (ER), (b) associates with specific proteins (LC3b, SEC16A, SEC31A), and (c) plays role in autophagy. Progression of nonalcoholic fatty liver disease is associated with changes in liver: (a) up-regulation of expression of IBTKalpha, (b) unfolded protein response, (c) ER stress, and (d) inhibition of autophagy.
Title: Function of inhibitor of Bruton's tyrosine kinase isoform α (IBTKα) in nonalcoholic steatohepatitis links autophagy and the unfolded protein response.
The results indicate that IBTKa differently modulates gene expression and RNA splicing in HeLa and K562 cells, demonstrating a novel biological role of this protein.
Title: IBTK Differently Modulates Gene Expression and RNA Splicing in HeLa and K562 Cells.
CRL3(IBTK) is a novel ubiquitin ligase with regulatory roles in cellular pathways, such as the Pdcd4-dependent translation of mRNAs
Title: CRL3IBTK Regulates the Tumor Suppressor Pdcd4 through Ubiquitylation Coupled to Proteasomal Degradation.
Depletion of IBTKalpha by short hairpin RNA reduced viability of cultured cells coincident with increased caspase 3/7 cleavage, suggesting that IBTKalpha is a key regulator in determining cell fate during the UPR.
Title: Selective mRNA translation during eIF2 phosphorylation induces expression of IBTKα.
A novel pathway of Btk regulation via protein kinase C phosphorylation of IBtkgamma.
Title: Btk regulation in human and mouse B cells via protein kinase C phosphorylation of IBtkγ.
three novel (Ala347fsX55, I355T, and Thr324fsX24) mutations in Bruton's tyrosine kinase in patients with X-linked agammaglobulinemia
Title: Mutations of Bruton's tyrosine kinase gene in Brazilian patients with X-linked agammaglobulinemia.
The IBTK gene encodes the proteins IBtk-alpha, beta and gamma that regulate the B cell receptor signalling through Bruton's tyrosine kinase, which promotes B cell survival and differentiation.
Title: Computational analysis and in vivo validation of a microRNA encoded by the IBTK gene, a regulator of B-lymphocytes differentiation and survival.
Identification of three IBTKalpha, IBTKbeta and IBTKgamma mRNAs, whose transcription is driven by two distinct promoter regions.
Title: Physical and functional characterization of the genetic locus of IBtk, an inhibitor of Bruton's tyrosine kinase: evidence for three protein isoforms of IBtk.

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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

EBI GWAS Catalog

Description
Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. EBI GWAS Catalog EBI GWAS CatalogPubMed

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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Replication interactions

Interaction	Pubs
Knockdown of inhibitor of Bruton agammaglobulinemia tyrosine kinase (IBTK) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D6S1882 (e-PCR)
- UniSTS:39699

D6S1188E (e-PCR)
- UniSTS:68394

D6S1780 (e-PCR)
- UniSTS:1904

D1S1423 (e-PCR)
- UniSTS:149619

RH69271 (e-PCR)
- UniSTS:76660

IBTK__6437 (e-PCR)
- UniSTS:463993

D6S1109E (e-PCR)
- UniSTS:8371

A002S42 (e-PCR)
- UniSTS:58853

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein kinase binding	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine kinase inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein tyrosine kinase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within negative regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in release of sequestered calcium ion into cytosol	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within release of sequestered calcium ion into cytosol	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in nucleoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: inhibitor of Bruton tyrosine kinase

Names: BTK-binding protein; Bruton agammaglobulinemia tyrosine kinase inhibitor; inhibitor of Bruton's tyrosine kinase-alpha; inhibitor of Bruton's tyrosine kinase-beta; inhibitor of Bruton's tyrosine kinase-gamma

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_047139.1 RefSeqGene

Range

5011..82768

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001300906.2 → NP_001287835.1 inhibitor of Bruton tyrosine kinase isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice acceptor site in the 3' coding region, compared to variant 1. It encodes a shorter isoform (2), compared to isoform 1.

Source sequence(s)

AK123460, BC143745, BM670666, DQ005633

Consensus CDS

CCDS75486.1

UniProtKB/TrEMBL

B7ZLE0, E7EPI0

Related

ENSP00000426405.1, ENST00000510291.5

Conserved Domains (8) summary

smart00225
Location:769 → 867

BTB; Broad-Complex, Tramtrack and Bric a brac

COG5184
Location:227 → 458

ATS1; Alpha-tubulin suppressor and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton]

cd00204
Location:25 → 135

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

cd14821
Location:871 → 931

SPOP_C_like; BACK-like Domain C-terminal to BTB in speckle-type POZ protein (SPOP) and similar proteins

pfam00415
Location:195 → 244

RCC1; Regulator of chromosome condensation (RCC1) repeat

pfam00651
Location:761 → 867

BTB; BTB/POZ domain

pfam12796
Location:25 → 116

Ank_2; Ankyrin repeats (3 copies)

sd00045
Location:51 → 82

ANK; ANK repeat [structural motif]
NM_015525.4 → NP_056340.2 inhibitor of Bruton tyrosine kinase isoform 1

Status: REVIEWED

Description

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

Source sequence(s)

BM670666, DQ005633

Consensus CDS

CCDS34490.1

UniProtKB/Swiss-Prot

Q2QKU2, Q2QKU3, Q2QKU4, Q5TFD7, Q5TFD9, Q8IUQ9, Q8IUY7, Q8TAI4, Q9HBI8, Q9P2D0, Q9Y3T8

UniProtKB/TrEMBL

B7ZLE0

Related

ENSP00000305721.7, ENST00000306270.12

Conserved Domains (8) summary

smart00225
Location:769 → 867

BTB; Broad-Complex, Tramtrack and Bric a brac

COG5184
Location:227 → 458

ATS1; Alpha-tubulin suppressor and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton]

cd00204
Location:25 → 135

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

cd14821
Location:871 → 931

SPOP_C_like; BACK-like Domain C-terminal to BTB in speckle-type POZ protein (SPOP) and similar proteins

pfam00415
Location:195 → 244

RCC1; Regulator of chromosome condensation (RCC1) repeat

pfam00651
Location:761 → 867

BTB; BTB/POZ domain

pfam12796
Location:25 → 116

Ank_2; Ankyrin repeats (3 copies)

sd00045
Location:51 → 82

ANK; ANK repeat [structural motif]

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_000006.12 Reference GRCh38.p14 Primary Assembly

Range

82169987..82247744 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 PATCHES

Genomic

NW_013171802.1 Reference GRCh38.p14 PATCHES

Range

29599..107356 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054331876.1 → XP_054187851.1 inhibitor of Bruton tyrosine kinase isoform X2

UniProtKB/TrEMBL

B7ZLE0
XM_054331875.1 → XP_054187850.1 inhibitor of Bruton tyrosine kinase isoform X1

UniProtKB/TrEMBL

B7ZLE0