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FLASH GENE

Symbol

CDK5RAP2

contributors: mct - updated : 08-03-2015

HGNC name	CDK5 regulatory subunit associated protein 2
HGNC id	18672

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MCPH3 microcephaly primary 3
Location	9q33.2      Physical location : 123.151.147 - 123.342.437
Synonym name	CDK5 activator-binding protein C48
	centrosome-associated protein 215
Synonym symbol(s)	C48, FLJ10867, KIAA1633, CEP215, DKFZp686B1070, DKFZp686D1070

DNA

TYPE	functioning gene
STRUCTURE	191.29 kb     38 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_018249 37 - 6230 NP_060719 215 1893 - 2005 15793586 NM_001011649 37 splicing 5993 NP_001011649 - 1814 - 2005 15793586

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 Nervous brain basal nuclei corpus callosum       brain limbic system hippocampus       brain diencephalon thalamus     Reproductive male system testis       Respiratory lung         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective bone       Epithelial barrier lining neuroepithelium     Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	centrosome and Golgi-targeting domains in the C-terminal region with its core region highly homologous to the Motif 2 (CM2) of centrosomin (EIF3A)(CM2-like motif is essential for the association of the centrosome-targeting domain to pericentrin and AKAP9)
	multiple coiled-coil domains
	a gamma-tubulin complex (g-TuC)-binding domain conserved

conjugated

PhosphoP

HOMOLOGY

interspecies	homolog to Drosophila CG3571
	homolog to C.elegans T27E9.4a
	ortholog to murine Cdk5rap2

Homologene

FAMILY

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
	intracellular,nucleus
text	to the spindle poles of mitotic cells
	also localizes at the midbody ring
	localizes to microtubules and concentrates at the distal tips in addition to centrosomal localization
	in somatic cells, CDK5RAP2 localizes throughout the pericentriolar material in all stages of the cell cycle
	localizes to the Golgi complex in an ATP- and centrosome-dependent manner and associates with Golgi membranes independently of microtubules

basic FUNCTION	potential regulator of CDK5 activity via its interaction with CDK5R1
	functionally interacts with pericentrin, suggesting that both proteins influence centrosome cohesion through an indirect mechanism related to cytoskeletal dynamics
	pericentriolar structural component that functions in gamma-tubulin ring complex attachment and therefore in the microtubule organizing function of the centrosome
	targets growing microtubule tips in association with ANKS1B to regulate microtubule dynamics
	required for spindle checkpoint function and is a common target in paclitaxel and doxorubicin resistance
	may undertake a conserved mechanism for centrosomal localization
	involved in the centrosomal attachment of gamma-tubulin and centrosome cohesion
	may act in the attachment of gamma-tubulin complexes to, and microtubule nucleation at, the Golgi complex
	stimulates microtubule nucleation by the gamma-tubulin ring complex
	TUBG1 and its recruiting proteins (NEDD1 and CDK5RAP2) were localized at centrosomes of immature neurons, while they were lost at centrosomes in mature neurons

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	CDK5RAP2-ANKS1B complex regulates microtubule dynamics and stability
	in cancer cells with centrosome amplification, the CDK5RAP2-KIFC1 complex promotes the clustering of extra centrosomes into pseudo-bipolar spindles, thereby ensuring viable cell division

INTERACTION

DNA

RNA

small molecule

protein	binding to CDK5 (phosphorylated by Cdk5 kinase)
	associates with centrosomes throughout the cell cycle and does not appear to interact with CEP68, CEP250 or CROCC
	interacts directly with ANKS1B, a prototypic member of microtubule plus-end tracking proteins, and contains the basic and Ser-rich motif responsible for ANKS1B binding
	may associate with multiple proteins on the centrosomes
	interacts with SPAG5 and CEP72
	CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome, and they interact to promote centriole duplication
	MZT1 specifically binds fully assembled GTuRC to enable interaction with NEDD1 for targeting, and with the CM1 domain of CDK5RAP2 for stimulating nucleation activity

cell & other

REGULATION

Other

phosphorylated by NCLK

ASSOCIATED DISORDERS

corresponding disease(s)

MCPH3

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS