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dual-specificity tyrosine-phosphorylation regulated kinase 1A (protein kinase minibrain homolog, MNBH, HP86, dual specificity YAK1-related kinase, Dyrk1A)
Function:
1) role in signaling pathway regulating nuclear functions of cell proliferaration
2) phosphorylates Ser, Thr & Tyr
3) phosphorylates microtubule associated protein tau at Thr212
4) autophosphoryates on TYR
5) interacts with RANBP9
Compartment: nucleus
Alternative splicing: named isoforms=5
Expression:
- ubiquitous
- highest levels in skeletal muscle, testis, fetal lung, fetal kidney
- expressed in the developing central nervous system
Pathology:
1) overexpressed 1.5-fold in fetal Down syndrome brain
2) increased expression in cytoplasm & nuclei of scattered neurons of the neocortex, entorhinal cortex, hippocampus in Alzheimer's disease, Pick's disease & Down syndrome
a) found in fractions enriched in phosphorylated tau [2]
b) tau phosphorylation at Thr212 appears NOT to be the mechanism
General
nuclear protein
serine/threonine kinase
tyrosine kinase (protein tyrosine kinase, PTK)
Properties
SIZE: MW = 86 kD
entity length = 763 aa
COMPARTMENT: cell nucleus
MOTIF: nuclear translocation signal {117-134}
kinase domain
SITE: 159-479
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 165-173
ATP-binding site
NAME: ATP-binding site
SITE: 188-188
Tyr phosphorylation site {Y219}
aspartate residue {D287}
Tyr phosphorylation site {Y319}
Tyr phosphorylation site {Y321}
serine residue {509-515} (7)
calponin homology domain
NAME: calponin homology domain
SITE: 656-672
MOTIF: serine residue {664-671} (8)
STATE: active state
MISC-INFO: EC-2.7.1.-
Database Correlations
OMIM 600855
UniProt Q13627
Pfam PF00069
References
- UniProt :accession Q13627
- Ferrer I, Barrachina M, Puig B, Martinez de Lagran M, Marti E,
Avila J, Dierssen M.
Constitutive Dyrk1A is abnormally expressed in Alzheimer
disease, Down syndrome, Pick disease, and related transgenic
models.
Neurobiol Dis. 2005 Nov;20(2):392-400.
PMID: 16242644