CDK5RAP2 CDK5 regulatory subunit associated protein 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CDK5RAP2provided by HGNC
Official Full Name: CDK5 regulatory subunit associated protein 2provided by HGNC
Primary source: HGNC:HGNC:18672
See related: Ensembl:ENSG00000136861 MIM:608201
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: C48; MCPH3; Cep215
Summary: This gene encodes a regulator of CDK5 (cyclin-dependent kinase 5) activity. The protein encoded by this gene is localized to the centrosome and Golgi complex, interacts with CDK5R1 and pericentrin (PCNT), plays a role in centriole engagement and microtubule nucleation, and has been linked to primary microcephaly and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]
Expression: Ubiquitous expression in testis (RPKM 15.8), bone marrow (RPKM 9.3) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 9q33.2

Exon count:: 39

Annotation release	Status	Assembly	Chr	Location
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	9	NC_000009.12 (120388869..120580170, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (123151147..123342448, complement)

Chromosome 9 - NC_000009.12 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?

The rs10984186 risk and rs4837766 protective polymorphic variants of theCDK5RAP2gene might act as potent genetic modifiers for AD risk and/or conversion by modulating the expres-sion of this gene.
Title: CDK5RAP2 gene and tau pathophysiology in late-onset sporadic Alzheimer's disease.
new clinical manifestation of CDK5RAP2 microcephaly and congenital cataracts in a consanguineous Saudi family
Title: A new association between CDK5RAP2 microcephaly and congenital cataracts.
ASPM protein is a spindle pole-focusing factor that functions redundantly with CDK5RAP2.
Title: Human microcephaly ASPM protein is a spindle pole-focusing factor that functions redundantly with CDK5RAP2.
A frameshift mutation in CDK5RAP2 gene is associated with primary microcephaly with speech impairment and sparse eyebrows in a consanguineous Pakistani family.
Title: A novel mutation in CDK5RAP2 gene causes primary microcephaly with speech impairment and sparse eyebrows in a consanguineous Pakistani family.
Using homozygosity mapping complemented with whole-exome, gene panel or Sanger sequencing, we identified 12 novel mutations in 3 known MCPH-associated genes - 9 in ASPM, 2 in MCPH1 and 1 in CDK5RAP2. The 2 MCPH1 mutations were homozygous microdeletions of 164,250 and 577,594 bp, respectively, for which we were able to map the exact breakpoints
Title: Genetic heterogeneity in Pakistani microcephaly families revisited.
Data suggest that CDK5RAP2 and CEP170 both interact with microtubule nucleation-promoting region of AKAP350A; CEP68 interacts with distal C-terminal region of AKAP350A; AKAP350A spans the bridge between centrioles. (CDK5RAP2 = CDK5 regulatory subunit associated protein 2; CEP170 = centrosomal protein 170kDa; AKAP350A = A kinase (PRKA) anchor protein (yotiao) 9; CEP68 = centrosomal protein 68kDa)
Title: The C-terminal region of A-kinase anchor protein 350 (AKAP350A) enables formation of microtubule-nucleation centers and interacts with pericentriolar proteins.
results suggest that EB1 cooperates with CDK5RAP2 and perhaps other SXIP-containing +TIPs in tracking growing microtubule tips.
Title: Microtubule plus-end tracking of end-binding protein 1 (EB1) is regulated by CDK5 regulatory subunit-associated protein 2.
CDK5RAP2 may play a role in primary microcephaly and interacts with components of the Hippo signaling pathway
Title: CDK5RAP2 interaction with components of the Hippo signaling pathway may play a role in primary microcephaly.
Three siblings with isolated agenesis of corpus callosum carry compound heterozygous variants, p.[Gly94Arg];[Asn1232Ser], in CDK5RAP2 gene.
Title: Exome sequencing identifies recessive CDK5RAP2 variants in patients with isolated agenesis of corpus callosum.
stabilization of the centrosome-spindle pole interface by the CEP215-HSET complex could promote survival of cancer cells containing supernumerary centrosomes.
Title: A CEP215-HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer.

Submit: New GeneRIF Correction See all GeneRIFs (32)

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

Associated conditions

Description	Tests
Primary autosomal recessive microcephaly 3 MedGen: C1858108 OMIM: 604804 GeneReviews: Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders	Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association of lipid-lowering response to statins in combined study populations. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Novel risk loci for rheumatoid arthritis in Han Chinese and congruence with risk variants in Europeans. NHGRI GWA Catalog NHGRI GWA 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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH104241 (e-PCR)
- UniSTS:98566

STS-T23995 (e-PCR)
- UniSTS:32793

D9S1099 (e-PCR)
- UniSTS:51069

D9S290 (e-PCR), detects polymorphism
- UniSTS:47999

WI-15097 (e-PCR)
- UniSTS:6025

AB056817 (e-PCR)
- UniSTS:480159

G20308 (e-PCR)
- UniSTS:22221

A005L20 (e-PCR)
- UniSTS:22222

Homology

Homologs of the CDK5RAP2 gene: The CDK5RAP2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and chicken.
Orthologs from Annotation Pipeline: 234 organisms have orthologs with human gene CDK5RAP2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
calmodulin binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
calmodulin binding	IDA Inferred from Direct Assay more info	PubMed
gamma-tubulin binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
gamma-tubulin binding	IDA Inferred from Direct Assay more info	PubMed
microtubule binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
microtubule binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
transcription regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
tubulin binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
G2/M transition of mitotic cell cycle	TAS Traceable Author Statement more info
brain development	ISS Inferred from Sequence or Structural Similarity more info
brain development	NAS Non-traceable Author Statement more info	PubMed
centriole replication	IBA Inferred from Biological aspect of Ancestor more info	PubMed
centriole replication	IMP Inferred from Mutant Phenotype more info	PubMed
centrosome cycle	IMP Inferred from Mutant Phenotype more info	PubMed
chromosome segregation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
chromosome segregation	IMP Inferred from Mutant Phenotype more info	PubMed
ciliary basal body-plasma membrane docking	TAS Traceable Author Statement more info
establishment of mitotic spindle orientation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
establishment of mitotic spindle orientation	ISS Inferred from Sequence or Structural Similarity more info
microtubule bundle formation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
microtubule bundle formation	IDA Inferred from Direct Assay more info	PubMed
microtubule cytoskeleton organization	IDA Inferred from Direct Assay more info	PubMed
microtubule organizing center organization	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of centriole replication	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of centriole replication	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of neuron differentiation	IEA Inferred from Electronic Annotation more info
neurogenesis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of microtubule polymerization	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of microtubule polymerization	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription, DNA-templated	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
regulation of G2/M transition of mitotic cell cycle	TAS Traceable Author Statement more info
regulation of mitotic cell cycle spindle assembly checkpoint	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of mitotic cell cycle spindle assembly checkpoint	IDA Inferred from Direct Assay more info	PubMed
regulation of neuron differentiation	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
cell junction	IDA Inferred from Direct Assay more info
centrosome	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytoskeleton	NAS Non-traceable Author Statement more info	PubMed
cytosol	TAS Traceable Author Statement more info
extracellular exosome	HDA more info	PubMed
colocalizes_with gamma-tubulin ring complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
colocalizes_with gamma-tubulin ring complex	IDA Inferred from Direct Assay more info	PubMed
microtubule	IDA Inferred from Direct Assay more info	PubMed
microtubule plus-end	IBA Inferred from Biological aspect of Ancestor more info	PubMed
microtubule plus-end	IDA Inferred from Direct Assay more info	PubMed
mitotic spindle pole	IBA Inferred from Biological aspect of Ancestor more info	PubMed
pericentriolar material	IBA Inferred from Biological aspect of Ancestor more info	PubMed
pericentriolar material	IDA Inferred from Direct Assay more info	PubMed
perinuclear region of cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
spindle pole	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: CDK5 regulatory subunit-associated protein 2

Names: CDK5 activator-binding protein C48; centrosomal protein 215 kDa; centrosomin

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_008999.1 RefSeqGene

Range

4993..196285

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001011649.3 → NP_001011649.1 CDK5 regulatory subunit-associated protein 2 isoform b

See identical proteins and their annotated locations for NP_001011649.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, compared to variant 1. The encoded isoform (b) is shorter compared to isoform a.

Source sequence(s)

AF448860, BC136275, BX495012, BX537759, BX953750

Consensus CDS

CCDS43871.1

UniProtKB/Swiss-Prot

Q96SN8

UniProtKB/TrEMBL

B9EG74

Related

ENSP00000353317.4, ENST00000360190.8

Conserved Domains (3) summary

cl14654
Location:289 → 497

V_Alix_like; Protein-interacting V-domain of mammalian Alix and related domains

COG0419
Location:105 → 667

SbcC; DNA repair exonuclease SbcCD ATPase subunit [Replication, recombination and repair]

pfam07989
Location:61 → 129

Cnn_1N; Centrosomin N-terminal motif 1
NM_001272039.1 → NP_001258968.1 CDK5 regulatory subunit-associated protein 2 isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site and lacks three in-frame exons in the coding region, compared to variant 1. The encoded isoform (c) is shorter compared to isoform a.

Source sequence(s)

AF448860, BC136275, BX495012, BX537708, BX953708

Consensus CDS

CCDS75888.1

UniProtKB/Swiss-Prot

Q96SN8

UniProtKB/TrEMBL

A0A0A0MRG9, B9EG74, Q7Z3M0

Related

ENSP00000354065.4, ENST00000360822.7

Conserved Domains (2) summary

cl14654
Location:289 → 497

V_Alix_like; Protein-interacting V-domain of mammalian Alix and related domains

pfam07989
Location:61 → 129

Cnn_1N; Centrosomin N-terminal motif 1
NM_018249.6 → NP_060719.4 CDK5 regulatory subunit-associated protein 2 isoform a

See identical proteins and their annotated locations for NP_060719.4

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

AF448860, AK122913, BX495012

Consensus CDS

CCDS6823.1

UniProtKB/Swiss-Prot

Q96SN8

UniProtKB/TrEMBL

B3KVI2

Related

ENSP00000343818.4, ENST00000349780.9

Conserved Domains (3) summary

cl14654
Location:289 → 497

V_Alix_like; Protein-interacting V-domain of mammalian Alix and related domains

COG0419
Location:105 → 667

SbcC; DNA repair exonuclease SbcCD ATPase subunit [Replication, recombination and repair]

pfam07989
Location:61 → 129

Cnn_1N; Centrosomin N-terminal motif 1

RNA

NR_073554.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses three alternate splice sites in internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AF448860, BC019577, BC143732, BX495012
NR_073555.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate splice site in an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AF448860, BC019577, BC143734, BQ428975, BX495012
NR_073556.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (6) uses two alternate splice sites in internal exons and contains an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AF448860, BC143755, BX471011, BX495012

Related

ENST00000473282.6
NR_073557.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (7) uses an alternate splice site in an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AF448860, BC019577, BC143764, BX495012
NR_073558.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (8) uses two alternate splice sites in internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AF448860, BC143760, BX471011, BX495012

Related

ENST00000480112.5

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p13 Primary Assembly

Range

120388869..120580170 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017014921.1 → XP_016870410.1 CDK5 regulatory subunit-associated protein 2 isoform X3
XM_011518860.1 → XP_011517162.1 CDK5 regulatory subunit-associated protein 2 isoform X1

Conserved Domains (2) summary

cl14654
Location:289 → 497

V_Alix_like; Protein-interacting V-domain of mammalian Alix and related domains

pfam07989
Location:61 → 129

Cnn_1N; Centrosomin N-terminal motif 1
XM_017014923.1 → XP_016870412.1 CDK5 regulatory subunit-associated protein 2 isoform X6
XM_006717185.1 → XP_006717248.1 CDK5 regulatory subunit-associated protein 2 isoform X4

Conserved Domains (2) summary

cl14654
Location:289 → 497

V_Alix_like; Protein-interacting V-domain of mammalian Alix and related domains

pfam07989
Location:61 → 129

Cnn_1N; Centrosomin N-terminal motif 1
XM_006717182.1 → XP_006717245.1 CDK5 regulatory subunit-associated protein 2 isoform X2

UniProtKB/Swiss-Prot

Q96SN8

Conserved Domains (3) summary

cl14654
Location:289 → 497

V_Alix_like; Protein-interacting V-domain of mammalian Alix and related domains

COG0419
Location:105 → 667

SbcC; DNA repair exonuclease SbcCD ATPase subunit [Replication, recombination and repair]

pfam07989
Location:61 → 129

Cnn_1N; Centrosomin N-terminal motif 1
XM_017014922.1 → XP_016870411.1 CDK5 regulatory subunit-associated protein 2 isoform X5
XM_017014924.1 → XP_016870413.1 CDK5 regulatory subunit-associated protein 2 isoform X7

Related

ENSP00000400395.1, ENST00000416449.5