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FLASH GENE

Symbol

TTBK2

contributors: mct - updated : 11-04-2019

HGNC name	tau tubulin kinase 2
HGNC id	19141

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	SCA11 spinocerebellar ataxia 11
Location	15q15.2      Physical location : 43.036.541 - 43.213.007
Synonym name	tau-tubulin kinase
Synonym symbol(s)	KIAA0847, TTBK, SCA11
EC.number	2.7.11.1

DNA

TYPE	functioning gene
STRUCTURE	176.47 kb     14 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_173500 14 - 5635 NP_775771 - 1244 - 2007 18037885

EXPRESSION

Type

widely

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive liver         Endocrine thyroid       highly Nervous brain hindbrain cerebellum   highly   brain limbic system hippocampus   highly   brain midbrain substantia nigra   highly Reproductive female system uterus cervix   highly   male system testis     highly Urinary kidney

cells

System Cell Pubmed Species Stage Rna symbol Nervous Purkinje cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminus encodeing a serine-threonine-tyrosine kinase domain
	C-terminal region showing homology to TTBK1, and the C-terminal tail was required to recruit TTBK2 to the centriole, and the kinase domain was required to promote ciliogenesis

HOMOLOGY

Homologene

FAMILY	protein kinase superfamily
	CK1 Ser/Thr protein kinase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,intermed filament
	intracellular,nucleus
text	TTBK2 is localized to the distal end of the mother centriole, where it promotes ciliogenesis through the displacement of the negative regulator CCP110 and the enrichment of IFT complex components at the base of the cilium

basic FUNCTION	playing an important role in the tau cascade and in spinocerebellar degeneration
	having a role in preventing tau toxicity
	Ser/Thr kinase that putatively phosphorylates residues Ser208 and Ser210 (numbered according to a 441-AA human tau isoform) in tau protein
	key biochemical functions of TTBK2 are required for ciliogenesis
	protein kinase important for transitioning centrioles from the cell cycle to postmitotic assembly of axonemes
	is a dedicated regulator of the initiation of ciliogenesis
	is not required for the formation of mature basal bodies, but is required to initiate assembly of the ciliary axoneme
	TTBK2 activity at the centrosome may lead to the removal of CCP110, either directly or indirectly, in order to prime the basal body for cilia formation
	TTBK2 also acts upstream of CEP164, contributing to the assembly of distal appendages
	is essential for regulating the growth of axonemal microtubules in ciliogenesis
	is a multifunctional kinase involved in important cellular processes and demands augmented efforts in investigating its function
	TTBK2 with MAPRE1/MAPRE3 phosphorylates KIF2A and antagonizes KIF2A-induced depolymerization at microtubules plus ends for cell migration
	is a key regulator of the assembly of primary cilia
	new functions for TTBK2 after cilia initiation in the control of cilia length, trafficking of a subset of SHH pathway components, including Smoothened (SMO), and cilia stability

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	is recruited to the centriole and transition zone near the ciliary base, and causes the loss of CCP110, an inhibitor of axonemal growth
	cell-cycle regulators target TTBK2 to the basal body, where it modifies specific targets to initiate ciliogenesis
	TTBK2 acts upstream of IFT and is required for the recruitment or retention of IFT complexes at the basal body prior to cilia assembly
	one of the major functions of CEP164 in ciliogenesis is to recruit active TTBK2 to centrioles
	TTBK2 has the potential to effectively phosphorylate CEP164 and CEP97 and inhibits the interaction between CEP164 and its binding partner DVL3 (an important regulator of ciliogenesis) in a kinase activity-dependent manner
	unlike NDE1, MCRS1 played a positive role for the initiation of ciliogenesis, possibly through its interaction with TTBK2
	TTBK2 down-regulates GRIK2 activity by decreasing the receptor protein abundance in the cell membrane via RAB5A-dependent endocytosis, an effect that may protect against neuroexcitotoxicity

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

SCA11

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS