CD5R1_SPECI
ID CD5R1_SPECI Reviewed; 307 AA.
AC Q4KYY2;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 25-MAY-2022, entry version 69.
DE RecName: Full=Cyclin-dependent kinase 5 activator 1;
DE Short=CDK5 activator 1;
DE AltName: Full=Cyclin-dependent kinase 5 regulatory subunit 1;
DE Contains:
DE RecName: Full=Cyclin-dependent kinase 5 activator 1, p35;
DE Contains:
DE RecName: Full=Cyclin-dependent kinase 5 activator 1, p25;
DE Flags: Precursor;
GN Name=CDK5R1;
OS Spermophilus citellus (European suslik) (Citellus citellus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Sciuromorpha; Sciuridae;
OC Xerinae; Marmotini; Spermophilus.
OX NCBI_TaxID=9997;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Stieler J.T., Siegemund T., Strijkstra A.M.;
RT "Molecular cloning of cyclin-dependent kinase 5, regulatory subunit (p35)
RT of Spermophilus citellus.";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: p35 is a neuron specific activator of CDK5. The complex
CC p35/CDK5 is required for neurite outgrowth and cortical lamination.
CC Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4
CC signaling. Activator of TPKII. The complex p35/CDK5 participates in the
CC regulation of the circadian clock by modulating the function of CLOCK
CC protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates
CC the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in
CC association with altered stability and subcellular distribution.
CC {ECO:0000250|UniProtKB:Q15078}.
CC -!- SUBUNIT: Heterodimer composed of a catalytic subunit CDK5 and a
CC regulatory subunit CDK5R1 (p25) and macromolecular complex composed of
CC at least CDK5, CDK5R1 (p35) and CDK5RAP1 or CDK5RAP2 or CDK5RAP3. Only
CC the heterodimer shows kinase activity (By similarity). Interacts with
CC EPHA4 and NGEF; may mediate the activation of NGEF by EPHA4 (By
CC similarity). Interacts with RASGRF2. The complex p35/CDK5 interacts
CC with CLOCK (By similarity). {ECO:0000250|UniProtKB:P61809,
CC ECO:0000250|UniProtKB:Q15078}.
CC -!- SUBCELLULAR LOCATION: [Cyclin-dependent kinase 5 activator 1, p35]:
CC Cell membrane {ECO:0000250|UniProtKB:Q15078}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q15078}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q15078}. Cell projection, neuron projection
CC {ECO:0000250|UniProtKB:Q15078}. Note=In the primary cortical neurons,
CC p35 is present in the peripheries and nerve terminals.
CC {ECO:0000250|UniProtKB:Q15078}.
CC -!- SUBCELLULAR LOCATION: [Cyclin-dependent kinase 5 activator 1, p25]:
CC Nucleus {ECO:0000250|UniProtKB:Q15078}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q15078}. Perikaryon
CC {ECO:0000250|UniProtKB:Q15078}. Note=The conversion of p35 to p25
CC relocalizes the protein from the cell periphery to the cytoplasm, in
CC nuclear and perinuclear regions. In the primary cortical neurons, p25
CC is primarily concentrated in the cell soma and is largely absent from
CC neurites. {ECO:0000250|UniProtKB:Q15078}.
CC -!- TISSUE SPECIFICITY: Brain and neuron specific.
CC -!- PTM: The p35 form is proteolytically cleaved by calpain, giving rise to
CC the p25 form. P35 has a 5 to 10 fold shorter half-life compared to p25.
CC The conversion results in deregulation of the CDK5 kinase: p25/CDK5
CC kinase displays an increased and altered tau phosphorylation in
CC comparison to the p35/CDK5 kinase in vivo (By similarity).
CC {ECO:0000250|UniProtKB:P61809}.
CC -!- PTM: Myristoylated. A proper myristoylation signal is essential for the
CC proper distribution of p35 (By similarity).
CC {ECO:0000250|UniProtKB:Q15078}.
CC -!- PTM: Phosphorylation at Ser-8 and Thr-138 by CDK5 prevents calpain-
CC mediated proteolysis. {ECO:0000250|UniProtKB:Q15078}.
CC -!- PTM: Ubiquitinated, leading to its degradation: degradation of p35 by
CC proteasome results in down-regulation of CDK5 activity. During this
CC process, CDK5 phosphorylates p35 and induces its ubiquitination and
CC subsequent degradation. Ubiquitinated by the CRL2(FEM1B) complex, which
CC recognizes the -Gly-Leu-Asp-Arg C-degron at the C-terminus, leading to
CC its degradation. {ECO:0000250|UniProtKB:Q15078}.
CC -!- SIMILARITY: Belongs to the cyclin-dependent kinase 5 activator family.
CC {ECO:0000305}.
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DR EMBL; AY654896; AAV64183.1; -; mRNA.
DR AlphaFoldDB; Q4KYY2; -.
DR SMR; Q4KYY2; -.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0016533; C:protein kinase 5 complex; IEA:InterPro.
DR GO; GO:0061575; F:cyclin-dependent protein serine/threonine kinase activator activity; IEA:InterPro.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; ISS:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR InterPro; IPR004944; CDK5_activator.
DR InterPro; IPR036915; Cyclin-like_sf.
DR PANTHER; PTHR23401; PTHR23401; 1.
DR Pfam; PF03261; CDK5_activator; 1.
DR PIRSF; PIRSF009324; Cdk5_activator; 1.
DR SUPFAM; SSF47954; SSF47954; 1.
PE 2: Evidence at transcript level;
KW Biological rhythms; Cell membrane; Cell projection; Cytoplasm; Lipoprotein;
KW Membrane; Nucleus; Phosphoprotein; Ubl conjugation.
FT CHAIN 1..307
FT /note="Cyclin-dependent kinase 5 activator 1, p35"
FT /id="PRO_0000250504"
FT CHAIN 99..307
FT /note="Cyclin-dependent kinase 5 activator 1, p25"
FT /id="PRO_0000250505"
FT REGION 96..136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 111..131
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 98..99
FT /note="Cleavage; by calpain"
FT /evidence="ECO:0000250|UniProtKB:P61809"
FT MOD_RES 8
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000250|UniProtKB:Q15078"
FT MOD_RES 138
FT /note="Phosphothreonine; by CDK5"
FT /evidence="ECO:0000250|UniProtKB:Q15078"
SQ SEQUENCE 307 AA; 34001 MW; FFD7A0AD14844330 CRC64;
MGTGLSLSPS YRKATLFEDG AATVGHYTAV QNSKNAKDKN LKRHSIISVL PWKRIVAVSA
KKKNSKKGQP NSSYQNNITH LNNENLKKSL SCANLSTFAQ PPPAQPPAPP ANQLSGSQTG
VSSSVKKAPH PSVTSAGTPK RVIVQASTSE LLRCLGEFLC RRCYRLKHLS PTDPVLWLRS
VDRSLLLQGW QDQGFITPAN VVFLYMLCRD VISSEVGSDH ELQAVLLTCL YLSYSYVGNE
ISYPLKPFLV ESCKEAFWDR CLSVINLMSS KMLQINADPH YFTQAFSDLK NESGQEDKKR
LLLGLDR
