CDK5RAP2

Protein with roles in formation and stability of microtubules

CDK5RAP2

Identifiers

Aliases

CDK5RAP2, C48, Cep215, MCPH3, CDK5 regulatory subunit associated protein 2

External IDs

OMIM: 608201; MGI: 2384875; HomoloGene: 49533; GeneCards: CDK5RAP2; OMA:CDK5RAP2 - orthologs

Gene location (Human)

Chr.	Chromosome 9 (human)^[1]

Band	9q33.2	Start	120,388,875 bp^[1]
Band	9q33.2	End	120,580,170 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 4 (mouse)^[2]

Band	4\|4 C2	Start	70,135,093 bp^[2]
Band	4\|4 C2	End	70,328,680 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

sural nerve

ventricular zone

right coronary artery

ganglionic eminence

muscle of thigh

gastrocnemius muscle

tendon of biceps brachii

minor salivary glands

ascending aorta

epithelium of colon

Top expressed in

tail of embryo

seminiferous tubule

spermatid

vestibular membrane of cochlear duct

genital tubercle

zygote

spermatocyte

ventricular zone

secondary oocyte

vestibular sensory epithelium

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	microtubule binding tubulin binding protein binding protein kinase binding calmodulin binding gamma-tubulin binding
Cellular component	cytoplasm cytosol mitotic spindle pole centrosome Golgi apparatus spindle pole pericentriolar material microtubule organizing center microtubule plus-end cell junction perinuclear region of cytoplasm cytoskeleton microtubule extracellular exosome
Biological process	regulation of neuron differentiation negative regulation of centriole replication neurogenesis negative regulation of neuron differentiation chromosome segregation positive regulation of transcription, DNA-templated brain development G2/M transition of mitotic cell cycle microtubule bundle formation regulation of spindle checkpoint establishment of mitotic spindle orientation centriole replication microtubule organizing center organization microtubule cytoskeleton organization ciliary basal body-plasma membrane docking centrosome cycle regulation of G2/M transition of mitotic cell cycle positive regulation of microtubule polymerization regulation of mitotic cell cycle spindle assembly checkpoint
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


55755


214444

Ensembl


ENSG00000136861


ENSMUSG00000039298

UniProt


Q96SN8


P68254 Q8K389

RefSeq (mRNA)


NM_001011649 NM_001272039 NM_018249


NM_145990 NM_001313762

RefSeq (protein)


NP_001011649 NP_001258968 NP_060719


NP_035869 NP_001300691 NP_666102

Location (UCSC)

Chr 9: 120.39 – 120.58 Mb

Chr 4: 70.14 – 70.33 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

CDK5 regulatory subunit-associated protein 2 is a protein that in humans is encoded by the CDK5RAP2 gene. It has necessary roles in the formation and stability of microtubules from the centrosome^[5] and has been found to be linked to human brain size variation in males.^[6] Multiple transcript variants exist for this gene, but the full-length nature of only two has been determined.^[7]^[8]

CDK5RAP2 is homologous to the Drosophila protein centrosomin (cnn)^[9] and paralogous to myomegalin, which in mammals contains an Olduvai domain, a domain implicated in human brain size evolution.^[10]^[11]

Function

CDK5RAP2 is necessary for the proper formation, anchoring and orientation of microtubules from the centrosome. It binds with the γ-tubulin ring complex (γTuRC), and this is required for the γTuRC to attach to the centrosome.^[5] CDK5RAP2 also binds to p25, a form of CDK5R1 that serves as the activating subunit of CDK5, which is involved in the regulation of neuronal differentiation. CDK5RAP2 therefore has a role in neuronal differentiation.^[8] CDK5RAP2 is also necessary as a scaffolding protein in the centrosomal corona of Dictyostelium.^[12]

Clinical significance

Human brain size variation

An MRI study has demonstrated a link between common human variation in the CDK5RAP2 gene and brain structure. More specifically, associations were found between several single nucleotide polymorphisms (SNPs) and brain cortical surface area and total brain volume. These associations were found exclusively in male subjects, and all SNPs were located either in the last 7 introns or downstream of the gene. The functional significance of these loci is not yet known. However, given their location close to regulatory elements, it is possible that they are involved in gene regulation, which suggests that common variance in brain structure could be associated with differences in gene regulation rather than protein structure, consistent with findings in other complex human traits.^[6] CDK5RAP2 is a paralogue of myomegalin, which in mammals contains an Olduvai domain, a domain with human-specific duplications that have been implicated in human brain size evolution.^[10]^[11]

Autosomal recessive primary microcephaly

Mutations in CDK5RAP2 cause autosomal recessive primary microcephaly type 3.^[13]^[5]

Interactions

CDK5RAP2 has been shown to interact with CDK5R1^[14] and pericentrin (PCTN).^[8]

History

The gene was discovered in 2000^[15] and was first characterised in 2007.^[5]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000136861 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000039298 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c ^d Fong KW, Choi YK, Rattner JB, Qi RZ (January 2008). "CDK5RAP2 is a pericentriolar protein that functions in centrosomal attachment of the gamma-tubulin ring complex". Molecular Biology of the Cell. 19 (1): 115–25. doi:10.1091/mbc.E07-04-0371. PMC 2174194. PMID 17959831.
^ ^a ^b Rimol LM, Agartz I, Djurovic S, Brown AA, Roddey JC, Kähler AK, et al. (January 2010). "Sex-dependent association of common variants of microcephaly genes with brain structure". Proceedings of the National Academy of Sciences of the United States of America. 107 (1): 384–8. Bibcode:2010PNAS..107..384R. doi:10.1073/pnas.0908454107. PMC 2806758. PMID 20080800.
^ Ching YP, Qi Z, Wang JH (January 2000). "Cloning of three novel neuronal Cdk5 activator binding proteins". Gene. 242 (1–2): 285–94. doi:10.1016/S0378-1119(99)00499-0. PMID 10721722.
^ ^a ^b ^c "Entrez Gene: CDK5RAP2 CDK5 regulatory subunit associated protein 2".
^ Barr AR, Kilmartin JV, Gergely F (April 2010). "CDK5RAP2 functions in centrosome to spindle pole attachment and DNA damage response". The Journal of Cell Biology. 189 (1): 23–39. doi:10.1083/jcb.200912163. PMC 2854379. PMID 20368616.
^ ^a ^b Dumas L, Kim YH, Karimpour-Fard A, Cox M, Hopkins J, Pollack JR, Sikela JM (September 2007). "Gene copy number variation spanning 60 million years of human and primate evolution". Genome Research. 17 (9): 1266–77. doi:10.1101/gr.6557307. PMC 1950895. PMID 17666543.
^ ^a ^b O'Bleness MS, Dickens CM, Dumas LJ, Kehrer-Sawatzki H, Wyckoff GJ, Sikela JM (September 2012). "Evolutionary history and genome organization of DUF1220 protein domains". G3. 2 (9): 977–86. doi:10.1534/g3.112.003061. PMC 3429928. PMID 22973535.
^ Pitzen V, Askarzada S, Gräf R, Meyer I (April 2018). "CDK5RAP2 Is an Essential Scaffolding Protein of the Corona of the Dictyostelium Centrosome". Cells. 7 (4): 32. doi:10.3390/cells7040032. PMC 5946109. PMID 29690637.
^ "OMIM Entry - # 604804 - MICROCEPHALY 3, PRIMARY, AUTOSOMAL RECESSIVE; MCPH3". www.omim.org. Retrieved 2020-01-06.
^ Wang X, Ching YP, Lam WH, Qi Z, Zhang M, Wang JH (October 2000). "Identification of a common protein association region in the neuronal Cdk5 activator". The Journal of Biological Chemistry. 275 (41): 31763–9. doi:10.1074/jbc.M004358200. PMID 10915792.
^ Ching YP, Qi Z, Wang JH (January 2000). "Cloning of three novel neuronal Cdk5 activator binding proteins". Gene. 242 (1–2): 285–94. doi:10.1016/S0378-1119(99)00499-0. PMID 10721722.