CDK5R1

Last updated

CDK5R1
Protein CDK5R1 PDB 1h4l.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CDK5R1 , CDK5P35, CDK5R, NCK5A, p23, p25, p35, p35nck5a, cyclin-dependent kinase 5, regulatory subunit 1 (p35), cyclin dependent kinase 5 regulatory subunit 1
External IDs OMIM: 603460; MGI: 101764; HomoloGene: 31200; GeneCards: CDK5R1; OMA:CDK5R1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003885

NM_009871

RefSeq (protein)

NP_003876

NP_034001

Location (UCSC) Chr 17: 32.49 – 32.49 Mb Chr 11: 80.37 – 80.37 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Cyclin-dependent kinase 5 activator 1 is an enzyme that in humans is encoded by the CDK5R1 gene. [5] [6]

Contents

Function

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. [6]

In melanocytic cells CDK5R1 gene expression may be regulated by MITF. [7]

Interactions

CDK5R1 has been shown to interact with:

See also

Related Research Articles

<span class="mw-page-title-main">Cyclin-dependent kinase</span> Class of enzymes

Cyclin-dependent kinases (CDKs) are a predominant group of serine/threonine protein kinases involved in the regulation of the cell cycle and its progression, ensuring the integrity and functionality of cellular machinery. These regulatory enzymes play a crucial role in the regulation of eukaryotic cell cycle and transcription, as well as DNA repair, metabolism, and epigenetic regulation, in response to several extracellular and intracellular signals. They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. The catalytic activities of CDKs are regulated by interactions with CDK inhibitors (CKIs) and regulatory subunits known as cyclins. Cyclins have no enzymatic activity themselves, but they become active once they bind to CDKs. Without cyclin, CDK is less active than in the cyclin-CDK heterodimer complex. CDKs phosphorylate proteins on serine (S) or threonine (T) residues. The specificity of CDKs for their substrates is defined by the S/T-P-X-K/R sequence, where S/T is the phosphorylation site, P is proline, X is any amino acid, and the sequence ends with lysine (K) or arginine (R). This motif ensures CDKs accurately target and modify proteins, crucial for regulating cell cycle and other functions. Deregulation of the CDK activity is linked to various pathologies, including cancer, neurodegenerative diseases, and stroke.

<span class="mw-page-title-main">Cortactin</span> Protein found in humans

Cortactin is a monomeric protein located in the cytoplasm of cells that can be activated by external stimuli to promote polymerization and rearrangement of the actin cytoskeleton, especially the actin cortex around the cellular periphery. It is present in all cell types. When activated, it will recruit Arp2/3 complex proteins to existing actin microfilaments, facilitating and stabilizing nucleation sites for actin branching. Cortactin is important in promoting lamellipodia formation, invadopodia formation, cell migration, and endocytosis.

<span class="mw-page-title-main">FYN</span> Mammalian protein found in Homo sapiens

Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.

<span class="mw-page-title-main">MNAT1</span> Protein-coding gene in the species Homo sapiens

CDK-activating kinase assembly factor MAT1 is an enzyme that in humans is encoded by the MNAT1 gene.

<span class="mw-page-title-main">ATF1</span> Protein-coding gene in humans

Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene.

<span class="mw-page-title-main">CAMK4</span> Protein-coding gene in humans

Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene.

<span class="mw-page-title-main">Alpha-actinin-1</span> Protein-coding gene in the species Homo sapiens

Alpha-actinin-1 is a protein that in humans is encoded by the ACTN1 gene.

<span class="mw-page-title-main">Megakaryocyte-associated tyrosine kinase</span> Protein-coding gene in the species Homo sapiens

Megakaryocyte-associated tyrosine-protein kinase is an enzyme that in humans is encoded by the MATK gene.

<span class="mw-page-title-main">CDC2L1</span> Protein-coding gene in the species Homo sapiens

PITSLRE serine/threonine-protein kinase CDC2L1 is an enzyme that in humans is encoded by the CDK11B gene.

<span class="mw-page-title-main">CAMK1</span> Protein-coding gene in humans

Calcium/calmodulin-dependent protein kinase type 1 is an enzyme that in humans is encoded by the CAMK1 gene.

<span class="mw-page-title-main">PCTK1</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase PCTAIRE-1 is an enzyme that in humans is encoded by the CDK16 gene.

<span class="mw-page-title-main">MAP3K12</span>

Mitogen-activated protein kinase 12 is an enzyme that in humans is encoded by the MAP3K12 gene.

<span class="mw-page-title-main">Cyclin-dependent kinase 3</span> Protein-coding gene in the species Homo sapiens

Cell division protein kinase 3 is an enzyme that in humans is encoded by the CDK3 gene.

<span class="mw-page-title-main">CDK5RAP3</span> Protein-coding gene in humans

CDK5 regulatory subunit-associated protein 3 is a protein that in humans is encoded by the CDK5RAP3 gene.

<span class="mw-page-title-main">SORBS3</span> Protein-coding gene in the species Homo sapiens

Vinexin is a protein that in humans is encoded by the SORBS3 gene.

<span class="mw-page-title-main">CTDSPL</span> Protein-coding gene in the species Homo sapiens

CTD small phosphatase-like protein is an enzyme that in humans is encoded by the CTDSPL gene.

<span class="mw-page-title-main">CDK5R2</span> Protein-coding gene in humans

Cyclin-dependent kinase 5 activator 2 is an enzyme that in humans is encoded by the CDK5R2 gene.

<span class="mw-page-title-main">Cyclin-dependent kinase 5</span> Protein-coding gene in the species Homo sapiens

Cyclin-dependent kinase 5 is a protein, and more specifically an enzyme, that is encoded by the Cdk5 gene. It was discovered 15 years ago, and it is saliently expressed in post-mitotic central nervous system neurons (CNS).

<span class="mw-page-title-main">LMTK2</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase LMTK2 also known as Lemur tyrosine kinase 2 (LMTK2) is an enzyme that in humans is encoded by the LMTK2 gene.

Gentry Namón Patrick is an American biologist and Professor of Neurobiology at the University of California, San Diego. His research investigates the mechanisms that underpin synaptic activity in the central nervous system. He is interested in learning, the formation of memories and the processes that cause Alzheimer's disease and Parkinson's disease.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000176749 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000048895 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Tsai LH, Delalle I, Caviness VS Jr, Chae T, Harlow E (October 1994). "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5". Nature. 371 (6496): 419–23. Bibcode:1994Natur.371..419T. doi:10.1038/371419a0. PMID   8090221. S2CID   4267944.
  6. 1 2 "Entrez Gene: CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35)".
  7. Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi: 10.1111/j.1755-148X.2008.00505.x . PMID   19067971. S2CID   24698373.
  8. Cheng K, Li Z, Fu WY, Wang JH, Fu AK, Ip NY (August 2002). "Pctaire1 interacts with p35 and is a novel substrate for Cdk5/p35". J. Biol. Chem. 277 (35): 31988–93. doi: 10.1074/jbc.M201161200 . PMID   12084709.
  9. Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 2001). "Amphiphysin 1 binds the cyclin-dependent kinase (cdk) 5 regulatory subunit p35 and is phosphorylated by cdk5 and cdc2". J. Biol. Chem. 276 (11): 8104–10. doi: 10.1074/jbc.M008932200 . PMID   11113134.
  10. Kesavapany S, Lau KF, McLoughlin DM, Brownlees J, Ackerley S, Leigh PN, Shaw CE, Miller CC (January 2001). "p35/cdk5 binds and phosphorylates beta-catenin and regulates beta-catenin/presenilin-1 interaction". Eur. J. Neurosci. 13 (2): 241–7. doi:10.1046/j.1460-9568.2001.01376.x. PMID   11168528.
  11. Dhavan R, Greer PL, Morabito MA, Orlando LR, Tsai LH (September 2002). "The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent manner". J. Neurosci. 22 (18): 7879–91. doi:10.1523/JNEUROSCI.22-18-07879.2002. PMC   6758084 . PMID   12223541.
  12. 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". J. Biol. Chem. 275 (41): 31763–9. doi: 10.1074/jbc.M004358200 . PMID   10915792.
  13. Chen F, Studzinski GP (June 2001). "Expression of the neuronal cyclin-dependent kinase 5 activator p35Nck5a in human monocytic cells is associated with differentiation". Blood. 97 (12): 3763–7. doi: 10.1182/blood.V97.12.3763 . PMID   11389014.
  14. Tarricone C, Dhavan R, Peng J, Areces LB, Tsai LH, Musacchio A (September 2001). "Structure and regulation of the CDK5-p25(nck5a) complex". Mol. Cell. 8 (3): 657–69. doi: 10.1016/S1097-2765(01)00343-4 . PMID   11583627.
  15. Qu D, Li Q, Lim HY, Cheung NS, Li R, Wang JH, Qi RZ (March 2002). "The protein SET binds the neuronal Cdk5 activator p35nck5a and modulates Cdk5/p35nck5a activity". J. Biol. Chem. 277 (9): 7324–32. doi: 10.1074/jbc.M107270200 . hdl: 10536/DRO/DU:30101408 . PMID   11741927.

Further reading