CDK5R1
Cyclin-dependent kinase 5 activator 1
Also known as: CD5R1_HUMAN, Nck5a, p35, p35nck5a
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q15078
- Gene
- CDK5R1
- Ensembl
- ENSG00000176749
- Chromosome
- 17
- Canonical length
- 307 aa
- Protein class
- Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Vesicles
OverviewNCBI Gene
The protein encoded by this gene (p35) is a neuron-specific activator of cyclin-dependent kinase 5 (CDK5); the activation of CDK5 is required for proper development of the central nervous system. The p35 form of this protein is proteolytically cleaved by calpain, generating a p25 form. The cleavage of p35 into p25 results in relocalization of the protein from the cell periphery to nuclear and perinuclear regions. P25 deregulates CDK5 activity by prolonging its activation and changing its cellular location. The p25 form accumulates in the brain neurons of patients with Alzheimer's disease. This accumulation correlates with an increase in CDK5 kinase activity, and may lead to aberrantly phosphorylated forms of the microtubule-associated protein tau, which contributes to Alzheimer's disease. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
307 residues, UniProt reviewed canonical sequence.
>Q15078|CDK5R1
1 MGTVLSLSPS YRKATLFEDG AATVGHYTAV QNSKNAKDKN LKRHSIISVL PWKRIVAVSA
61 KKKNSKKVQP NSSYQNNITH LNNENLKKSL SCANLSTFAQ PPPAQPPAPP ASQLSGSQTG
121 GSSSVKKAPH PAVTSAGTPK RVIVQASTSE LLRCLGEFLC RRCYRLKHLS PTDPVLWLRS
181 VDRSLLLQGW QDQGFITPAN VVFLYMLCRD VISSEVGSDH ELQAVLLTCL YLSYSYMGNE
241 ISYPLKPFLV ESCKEAFWDR CLSVINLMSS KMLQINADPH YFTQVFSDLK NESGQEDKKR
301 LLLGLDRLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CDK5R1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.47
- Highest tissue expression
- 71 nTPM
Expression across tissuesHPA
Tissue
- cerebral cortex: 71 nTPM
- cerebellum: 57 nTPM
- hippocampal formation: 45 nTPM
- amygdala: 40 nTPM
- hypothalamus: 35 nTPM
- basal ganglia: 34 nTPM
Single-cell type
- brain inhibitory neurons: 43 nCPM
- brain excitatory neurons: 43 nCPM
- other brain neurons: 42 nCPM
- retinal amacrine cells: 34 nCPM
- esophageal apical cells: 27 nCPM
- late spermatids: 26 nCPM
Immune cell
- naive CD4 T-cell: 1.5 nTPM
- neutrophil: 1.2 nTPM
- memory CD4 T-cell: 1.1 nTPM
- naive CD8 T-cell: 0.9 nTPM
- gdT-cell: 0.8 nTPM
- MAIT T-cell: 0.6 nTPM
Brain region
- cerebral cortex: 168 nTPM
- hippocampal formation: 144 nTPM
- basal ganglia: 133 nTPM
- white matter: 111 nTPM
- amygdala: 108 nTPM
- thalamus: 89 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.38
- gnomAD pLI
- 0.91
- gnomAD missense Z
- 1.91
- DepMap mean gene effect
- -0.02
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- axon guidance
- axonal fasciculation
- brain development
- cerebellum development
- ephrin receptor signaling pathway
- G protein-coupled acetylcholine receptor signaling pathway
- G1 to G0 transition involved in cell differentiation
- hippocampus development
- ionotropic glutamate receptor signaling pathway
- layer formation in cerebral cortex
- microtubule cytoskeleton organization
- negative regulation of DNA-templated transcription
- neuron cell-cell adhesion
- neuron differentiation
- neuron migration
- neuron projection development
- peptidyl-serine phosphorylation
- peptidyl-threonine phosphorylation
- positive regulation of microtubule polymerization
- positive regulation of neuron apoptotic process
- positive regulation of protein targeting to membrane
- regulation of actin cytoskeleton organization
- regulation of cyclin-dependent protein serine/threonine kinase activity
- regulation of dendritic spine morphogenesis
- regulation of macroautophagy
- regulation of neuron differentiation
- rhythmic process
- superior olivary nucleus maturation
Molecular functions
- actin filament binding
- alpha-tubulin binding
- beta-tubulin binding
- cadherin binding
- calcium ion binding
- cyclin-dependent protein serine/threonine kinase activator activity
- ionotropic glutamate receptor binding
- kinase activity
- protease binding
- protein kinase activator activity
- protein kinase activity
- protein kinase binding
- protein serine/threonine kinase activator activity
Cellular components
- axon
- contractile muscle fiber
- cyclin-dependent protein kinase holoenzyme complex
- cytoplasm
- cytosol
- dendrite
- dendritic spine
- growth cone
- membrane
- neuromuscular junction
- neuron projection
- neuronal cell body
- nucleoplasm
- nucleus
- perikaryon
- perinuclear region of cytoplasm
- plasma membrane
- postsynaptic density
- protein kinase 5 complex
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CDK5R1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CDK5R1 as an antibody target. Whether an autoantibody or antibody against CDK5R1 could matter depends on whether native CDK5R1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CDK5R1 is annotated at the cell surface, where native CDK5R1 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label CDK5R1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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