TTBK1 tau tubulin kinase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TTBK1provided by HGNC
Official Full Name: tau tubulin kinase 1provided by HGNC
Primary source: HGNC:HGNC:19140
See related: Ensembl:ENSG00000146216 MIM:619415; AllianceGenome:HGNC:19140
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: BDTK
Summary: Summary:This gene belongs to the casein kinase 1 superfamily. The encoded protein is a neuron-specific, serine/threonine and tyrosine kinase, which regulates phosphorylation of tau, a protein that associates with microtubule assemblies and stabilizes them. Genetic variants in this gene are associated with Alzheimer's disease. [provided by RefSeq, Jul 2016]
Expression: Biased expression in brain (RPKM 4.4), small intestine (RPKM 0.9) and 4 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p21.1

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (43243481..43288258)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (43072270..43117062)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (43211219..43255996)

Chromosome 6 - NC_000006.12 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?

Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis.
Title: Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis.
The structural, functional, and dynamic effect of Tau tubulin kinase1 upon a mutation: A neuro-degenerative hotspot.
Title: The structural, functional, and dynamic effect of Tau tubulin kinase1 upon a mutation: A neuro-degenerative hotspot.
Adult onset pan-neuronal human tau tubulin kinase 1 expression causes severe cerebellar neurodegeneration in mice.
Title: Adult onset pan-neuronal human tau tubulin kinase 1 expression causes severe cerebellar neurodegeneration in mice.
miR-219-5p inhibits tau phosphorylation by targeting TTBK1 and GSK-3beta in Alzheimer's disease.
Title: miR-219-5p inhibits tau phosphorylation by targeting TTBK1 and GSK-3β in Alzheimer's disease.
Our findings suggest a possible etiology for the two most common frontotemporal lobar degeneration subtypes through a TTBK1/2 activation driven mechanism of neurodegeneration
Title: Pathological phosphorylation of tau and TDP-43 by TTBK1 and TTBK2 drives neurodegeneration.
TTBK1/2 kinases may represent attractive targets for therapeutic intervention for TDP-43 proteinopathies such as Amyotrophic lateral sclerosis and Frontotemporal lobar degeneration-TDP.
Title: The tau tubulin kinases TTBK1/2 promote accumulation of pathological TDP-43.
X-ray diffraction data were collected and the structure of TTBK1 was determined by molecular replacement both as an apo structure and in complex with a kinase inhibitor
Title: The structure of human tau-tubulin kinase 1 both in the apo form and in complex with an inhibitor.
The study suggested that a role for TTBK1 in pre-tangle formation prior to the formation of fibrillar tau and strengthen the idea that tau is phosphorylated at Ser422 at an early/intermediate stage in NFT formation.
Title: Tau-tubulin kinase 1 expression, phosphorylation and co-localization with phospho-Ser422 tau in the Alzheimer's disease brain.
TTBK1 may play an important role in the pathogenesis of sporadic late-onset Alzheimer's disease in a Han Chinese population.
Title: Tau-tubulin kinase-1 gene variants are associated with Alzheimer's disease in Han Chinese.
This study demonistrated that TTBK1 is a promising new candidate tau phosphorylation-related gene for Alzheimer's disease risk.
Title: Genetic variations in tau-tubulin kinase-1 are linked to Alzheimer's disease in a Spanish case-control cohort.

Submit: New GeneRIF Correction See all GeneRIFs (12)

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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH140426 (e-PCR)
- UniSTS:222501

D6S1232E (e-PCR)
- UniSTS:151104

D6S282 (e-PCR), detects polymorphism
- UniSTS:19837

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables protein serine kinase activity	IGI Inferred from Genetic Interaction more info	PubMed
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables tau protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables tau-protein kinase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in learning or memory	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein binding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-serine phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-serine phosphorylation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in peptidyl-threonine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-tyrosine phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of positive regulation of astrocyte activation	IC Inferred by Curator more info	PubMed
involved_in positive regulation of cyclin-dependent protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cysteine-type endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of microglial cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein polymerization	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in substantia nigra development	HEP more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
part_of microtubule associated complex	IC Inferred by Curator more info
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in perinuclear region of cytoplasm	ISS Inferred from Sequence or Structural Similarity more info	PubMed

General protein information

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Preferred Names: tau-tubulin kinase 1

Names: brain-derived tau kinase

NP_115927.1

EC 2.7.11.1

XP_011513249.1

EC 2.7.11.1

XP_011513250.1

EC 2.7.11.1

XP_016866853.1

EC 2.7.11.1

XP_016866854.1

EC 2.7.11.1

XP_016866855.1

EC 2.7.11.1

XP_016866856.1

EC 2.7.11.1

XP_016866857.1

EC 2.7.11.1

XP_054212540.1

EC 2.7.11.1

XP_054212541.1

EC 2.7.11.1

XP_054212542.1

EC 2.7.11.1

XP_054212543.1

EC 2.7.11.1

XP_054212544.1

EC 2.7.11.1

XP_054212545.1

EC 2.7.11.1

XP_054212546.1

EC 2.7.11.1

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_051244.1 RefSeqGene

Range

4802..49579

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_032538.3 → NP_115927.1 tau-tubulin kinase 1

See identical proteins and their annotated locations for NP_115927.1

Status: REVIEWED

Source sequence(s)

AB218664, AK131217, AL133375, BC036764

Consensus CDS

CCDS34455.1

UniProtKB/Swiss-Prot

A2A2U5, Q2L6C6, Q5TCY1, Q6ZNH0, Q8N444, Q96JH2

Related

ENSP00000259750.4, ENST00000259750.9

Conserved Domains (2) summary

smart00220
Location:34 → 275

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14130
Location:33 → 294

STKc_TTBK1; Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase 1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

43243481..43288258

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017011364.2 → XP_016866853.1 tau-tubulin kinase 1 isoform X1
XM_017011365.2 → XP_016866854.1 tau-tubulin kinase 1 isoform X2
XM_011514947.3 → XP_011513249.1 tau-tubulin kinase 1 isoform X3

Conserved Domains (2) summary

smart00220
Location:34 → 275

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14130
Location:33 → 294

STKc_TTBK1; Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase 1
XM_017011366.2 → XP_016866855.1 tau-tubulin kinase 1 isoform X4
XM_017011367.2 → XP_016866856.1 tau-tubulin kinase 1 isoform X5

UniProtKB/TrEMBL

A0A994J709

Related

ENSP00000515493.1, ENST00000703836.1
XM_011514948.3 → XP_011513250.1 tau-tubulin kinase 1 isoform X6

Conserved Domains (1) summary

PHA03307
Location:420 → 713

PHA03307; transcriptional regulator ICP4; Provisional
XM_017011368.2 → XP_016866857.1 tau-tubulin kinase 1 isoform X7