DYRK1A dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A [Homo sapiens (human)] - Gene

Summary

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Official Symbol: DYRK1Aprovided by HGNC
Official Full Name: dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1Aprovided by HGNC
Primary source: HGNC:3091
See related: Ensembl:ENSG00000157540; HPRD:09018; MIM:600855; Vega:OTTHUMG00000086657
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: MNB; DYRK; HP86; MNBH; MRD7; DYRK1
Summary: This gene encodes a member of the Dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. This member contains a nuclear targeting signal sequence, a protein kinase domain, a leucine zipper motif, and a highly conservative 13-consecutive-histidine repeat. It catalyzes its autophosphorylation on serine/threonine and tyrosine residues. It may play a significant role in a signaling pathway regulating cell proliferation and may be involved in brain development. This gene is a homolog of Drosophila mnb (minibrain) gene and rat Dyrk gene. It is localized in the Down syndrome critical region of chromosome 21, and is considered to be a strong candidate gene for learning defects associated with Down syndrome. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region. These variants encode at least five different isoforms. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 21q22.13

Sequence :: Chromosome: 21; NC_000021.8 (38739859..38887679)

See DYRK1A in Epigenomics, MapViewer

Chromosome 21 - NC_000021.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

A negative correlation was detected between BDNF and DYRK1A levels in lymphoblastoid cell lines with complete aneuploidy of human chromosome 21.
Title: BDNF and DYRK1A are variable and inversely correlated in lymphoblastoid cell lines from Down syndrome patients.
our results highlight the role played by DYRK1A in brain development through the control of choline acetyltransferase expression
Title: Overexpression of DYRK1A inhibits choline acetyltransferase induction by oleic acid in cellular models of Down syndrome.
This study demonistrated that the Gene dosage-dependent association of DYRK1A with the cytoskeleton in the brain and lymphocytes in patient with down syndrome patients
Title: Gene dosage-dependent association of DYRK1A with the cytoskeleton in the brain and lymphocytes of down syndrome patients.
Mnb/Dyrk1a regulates food intake through the evolutionary conserved Sir2-FOXO-sNPF/NPY pathway in Drosophila melanogaster and mammals.
Title: Minibrain/Dyrk1a regulates food intake through the Sir2-FOXO-sNPF/NPY pathway in Drosophila and mammals.
Phosphorylation of SRp55 by Dyrk1A suppressed its ability to promote Tau exon 10 inclusion.
Title: Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) modulates serine/arginine-rich protein 55 (SRp55)-promoted Tau exon 10 inclusion.
This study showed Dyrk1A is shown to interact with and phosphorylate Munc18-1 at the Thr479 residue
Title: Phosphorylation of Munc18-1 by Dyrk1A regulates its interaction with Syntaxin 1 and X11α.
This study demonistrated that a significant association between a polymorphic marker for DYRK1A and alpha-synuclein dementias. PDD.
Title: A pilot study examining associations between DYRK1A and α-synuclein dementias.
analysis of phosphorylation regulated kinase 1A (DYRK1A) inhibitors
Title: Discovery of potent small molecule inhibitors of DYRK1A by structure-based virtual screening and bioassay.
Dyrk1a has a role in megakaryoblastic leukemia in Down syndrome and the murine model
Title: Increased dosage of the chromosome 21 ortholog Dyrk1a promotes megakaryoblastic leukemia in a murine model of Down syndrome.
Down syndrome subjects may exhibit not only upregulation of total DYRK1A, but also more subtle differences in phosphorylation levels of this kinase
Title: Form of dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A nonphosphorylated at tyrosine 145 and 147 is enriched in the nuclei of astroglial cells, adult hippocampal progenitors, and some cholinergic axon terminals.

Submit: New GeneRIF Correction See all (62)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Mental retardation, autosomal dominant 7

MIM: 614104

Genetic Testing Registry

NHGRI GWAS Catalog

A genome-wide association study of the metabolic syndrome in Indian Asian men.

Genome-wide association study identifies single nucleotide polymorphism in DYRK1A associated with replication of HIV-1 in monocyte-derived macrophages.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_001387.2	NP_004370.1	CREB1	BIND	PubMed	DYRK1A interacts with and phosphorylates CREB. This interaction was modeled on a demonstrated interaction between human DYRK1A and CREB from rat.
NP_001387.2	NP_055574.2	PHYHIP	BIND	PubMed	DYRK1A interacts with PAHX-AP1.
Q13627	Q96S94	CCNL2	HPRD	PubMed
Q13627	P16220	CREB1	HPRD	PubMed
Q13627	Q13627	DYRK1A	HPRD	PubMed
Q13627	Q12778	FOXO1	HPRD	PubMed
Q13627	P08151	GLI1	HPRD	PubMed
Q13627	Q92561	PHYHIP	HPRD	PubMed
Q13627	O75533	SF3B1	HPRD	PubMed
Q13627	P31946	YWHAB	HPRD	PubMed
Q13627	P62258	YWHAE	HPRD	PubMed
Q13627	P61981	YWHAG	HPRD	PubMed
BioGRID:108192	BioGRID:106770	AMPH	BioGRID	PubMed	Biochemical Activity
BioGRID:108192	BioGRID:106848	APP	BioGRID	PubMed	Reconstituted Complex
BioGRID:108192	BioGRID:107056	BARD1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108192	BioGRID:123566	CCNL2	BioGRID	PubMed	Biochemical Activity
BioGRID:108192	BioGRID:116302	CLASRP	BioGRID	PubMed	Biochemical Activity
BioGRID:108192	BioGRID:107623	CLTC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108192	BioGRID:115532	DCAF7	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Co-localization; Co-purification; Reconstituted Complex
BioGRID:108192	BioGRID:108099	DNM1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex
BioGRID:108192	BioGRID:108309	ELAVL1	BioGRID	PubMed	Affinity Capture-RNA
BioGRID:108192	BioGRID:118815	HIPK2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108192	BioGRID:109271	HIST1H2BB	BioGRID	PubMed	Biochemical Activity
BioGRID:108192	BioGRID:113946	HIST1H3A	BioGRID	PubMed	Biochemical Activity
BioGRID:108192	BioGRID:113955	HIST1H4A	BioGRID	PubMed	Biochemical Activity
BioGRID:108192	BioGRID:114995	ISG15	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108192	BioGRID:117727	LATS2	BioGRID	PubMed	Biochemical Activity
BioGRID:108192	BioGRID:124874	LIN52	BioGRID	PubMed	Biochemical Activity
BioGRID:108192	BioGRID:110378	MAP3K1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108192	BioGRID:110381	MAP3K5	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108192	BioGRID:111539	PRD	BioGRID	PubMed	Biochemical Activity
BioGRID:108192	BioGRID:109072	SFN	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108192	BioGRID:112353	SH3GL2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108192	BioGRID:110263	SMAD3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108192	BioGRID:112506	SNCA	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:108192	BioGRID:112324	SRSF1	BioGRID	PubMed	Biochemical Activity
BioGRID:108192	BioGRID:112327	SRSF4	BioGRID	PubMed	Biochemical Activity
BioGRID:108192	BioGRID:112328	SRSF5	BioGRID	PubMed	Biochemical Activity
BioGRID:108192	BioGRID:113039	TRAF3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108192	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108192	BioGRID:113364	YWHAG	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Cell Cycle, organism-specific biosystem (from REACTOME)
Cell Cycle, organism-specific biosystem
Cell Cycle
Cell Cycle, Mitotic, organism-specific biosystem (from REACTOME)
Cell Cycle, Mitotic, organism-specific biosystemThe replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried o...
G0 and Early G1, organism-specific biosystem (from REACTOME)
G0 and Early G1, organism-specific biosystemIn G0 and early G1 in quiescent cells, p130 (RBL2) bound to E2F4 or E2F5 and either DP1 or DP2, associates with the MuvB complex, forming an evolutionarily conserved DREAM complex, that represses tra...
Hedgehog Signaling Pathway, organism-specific biosystem (from WikiPathways)
Hedgehog Signaling Pathway, organism-specific biosystemThe Hedgehog proteins are a family of secreted ligands that include sonic hedgehog, Indian hedgehog and desert hedgehog in humans. Binding of Hedgehog ligands to their receptors, Patched 1 and 2, pre...
Mitotic G1-G1/S phases, organism-specific biosystem (from REACTOME)
Mitotic G1-G1/S phases, organism-specific biosystem
Mitotic G1-G1/S phases

General gene information

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Markers

SHGC-51948 (e-PCR)
- UniSTS:26628

Dyrk1a (e-PCR), detects polymorphism
- UniSTS:259077

D21S270 (e-PCR), detects polymorphism
- UniSTS:41735

STS-G06294 (e-PCR)
- UniSTS:10505

SHGC-105235 (e-PCR)
- UniSTS:169236

RH120501 (e-PCR)
- UniSTS:133666

DYRK1A__4795 (e-PCR)
- UniSTS:462887

SHGC-63617 (e-PCR)
- UniSTS:43866

DYRK1A (e-PCR)
- UniSTS:506204

SHGC-50010 (e-PCR)
- UniSTS:5746

D21S1972 (e-PCR)
- UniSTS:378

Dyrk1a (e-PCR), detects polymorphism
- UniSTS:536448

SHGC-87629 (e-PCR)
- UniSTS:9867

SHGC-87626 (e-PCR)
- UniSTS:67212

SHGC-51949 (e-PCR)
- UniSTS:16022

D21S394 (e-PCR)
- UniSTS:147863

SHGC-170065 (e-PCR)
- UniSTS:173721

D11Wox11 (e-PCR)
- UniSTS:518811

G34602 (e-PCR)
- UniSTS:70325

SHGC-87621 (e-PCR)
- UniSTS:40388

SHGC-52085 (e-PCR)
- UniSTS:25293

RH91183 (e-PCR)
- UniSTS:86487

Homology

Homologs of the DYRK1A gene: The DYRK1A gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
non-membrane spanning protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase activity	TAS Traceable Author Statement more info	PubMed
protein self-association	ISS Inferred from Sequence or Structural Similarity more info
protein serine/threonine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
protein serine/threonine/tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
protein tyrosine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
tau protein binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
mitotic cell cycle	TAS Traceable Author Statement more info
negative regulation of DNA damage response, signal transduction by p53 class mediator	ISS Inferred from Sequence or Structural Similarity more info
nervous system development	TAS Traceable Author Statement more info	PubMed
peptidyl-threonine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
peptidyl-tyrosine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein deacetylation	ISS Inferred from Sequence or Structural Similarity more info
protein autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info
protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
nuclear speck	ISS Inferred from Sequence or Structural Similarity more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	ISS Inferred from Sequence or Structural Similarity more info
ribonucleoprotein complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: dual specificity tyrosine-phosphorylation-regulated kinase 1A

Names: dual specificity tyrosine-phosphorylation-regulated kinase 1A; hMNB; MNB/DYRK protein kinase; serine/threonine kinase MNB; mnb protein kinase homolog hp86; protein kinase minibrain homolog; dual specificity YAK1-related kinase; serine/threonine-specific protein kinase

NP_001387.2

EC 2.7.12.1

NP_567824.1

EC 2.7.12.1

NP_569120.1

EC 2.7.12.1

NP_569122.1

EC 2.7.12.1

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_009366.1 RefSeqGene

Range

5001..152821

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001396.3 → NP_001387.2 dual specificity tyrosine-phosphorylation-regulated kinase 1A isoform 1

Status: REVIEWED

Description

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

Source sequence(s)

AP001421, U52373

Consensus CDS

CCDS42925.1

UniProtKB/Swiss-Prot

Q13627

Conserved Domains (2) summary

smart00220
Location:159 – 398
Blast Score: 583

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl09925
Location:159 – 479
Blast Score: 498

PKc_like; Protein Kinases, catalytic domain
NM_101395.2 → NP_567824.1 dual specificity tyrosine-phosphorylation-regulated kinase 1A isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) is alternatively spliced in the 5' UTR and in the 3' coding region, as compared to variant 1. It encodes a 179 aa shorter isoform which lacks the poly-His domain and has a different C-terminus, compared to isoform 1.

Source sequence(s)

AF108830, AP001421

Consensus CDS

CCDS42926.1

UniProtKB/Swiss-Prot

Q13627

Related

ENSP00000342690, OTTHUMP00000109090, ENST00000338785, OTTHUMT00000194799

Conserved Domains (2) summary

smart00220
Location:159 – 398
Blast Score: 563

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl09925
Location:159 – 479
Blast Score: 483

PKc_like; Protein Kinases, catalytic domain
NM_130436.2 → NP_569120.1 dual specificity tyrosine-phosphorylation-regulated kinase 1A isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) is alternatively spliced in the 5' UTR and in an internal region of the coding sequence, as compared to variant 1. It encodes a 9 aa shorter isoform which has identical N- and C-termini to those of isoform 1.

Source sequence(s)

AP001421, AP001428, D86550

Consensus CDS

CCDS13653.1

UniProtKB/Swiss-Prot

Q13627

Related

ENSP00000340373, OTTHUMP00000109091, ENST00000339659, OTTHUMT00000194801

Conserved Domains (2) summary

smart00220
Location:150 – 389
Blast Score: 584

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl09925
Location:150 – 470
Blast Score: 499

PKc_like; Protein Kinases, catalytic domain
NM_130438.2 → NP_569122.1 dual specificity tyrosine-phosphorylation-regulated kinase 1A isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks a 3' coding exon, as compared to variant 1. It encodes a 234 aa shorter isoform which lacks the poly-His domain and has a different C-terminus, compared to isoform 1.

Source sequence(s)

AF108830, AP001421

Consensus CDS

CCDS13654.1

UniProtKB/Swiss-Prot

Q13627

Conserved Domains (2) summary

smart00220
Location:159 – 398
Blast Score: 558

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl09925
Location:159 – 479
Blast Score: 478

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000021.8 Reference GRCh37.p10 Primary Assembly

Range

38739859..38887679

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000153.1 Alternate HuRef

Range

24215875..24363782

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018932.1 Alternate CHM1_1.0

Range

29287335..29435189

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_130437.2: Suppressed sequence

Description

NM_130437.2: This RefSeq was temporarily suppressed because currently there is not sufficient data to support this transcript.

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01057421.1	None
genomic	ABBA01057422.1	None
genomic	ABBA01057423.1 (74692..99436)	None
genomic	AMYH01012236.1 (1139..1186)	None
genomic	AMYH01012237.1	None
genomic	AP001413.1	None
genomic	AP001421.1	None
genomic	AP001428.1	None
genomic	AP001437.1 (46525..91528)	None
genomic	CH471079.2	EAX09702.1
		EAX09703.1
		EAX09704.1
		EAX09705.1
		EAX09706.1
		EAX09707.1
		EAX09708.1
mRNA	AB015282.1	BAA33975.1
mRNA	AB015283.1	BAA33976.1
mRNA	AB015284.1	BAA33977.1
mRNA	AF108830.1	AAD31169.1
mRNA	AJ001870.1	CAA05059.1
mRNA	AJ001871.1	CAA05060.1
mRNA	AK301752.1	BAG63214.1
mRNA	BC030515.1	None
mRNA	BC045802.1	None
mRNA	BC065184.1	None
mRNA	D85759.1	BAA12866.1
mRNA	D86550.1	BAA13110.1
mRNA	HF584751.1	CCQ44048.1
mRNA	HF584752.1	CCQ44049.1
mRNA	U52373.1	AAB18639.1
mRNA	U58496.1	AAC50939.1
mRNA	Z25423.1	CAA80910.1
other-genetic	BC156309.1	AAI56310.1
other-genetic	BC172505.1	AAI72505.1