DUSP6 (dual specificity phosphatase 6)

Gene

• Entrez ID: 1848
• Gene name: Dual specificity phosphatase 6
• Gene symbol: DUSP6
• Synonyms: HH19, MKP3, PYST1
• Chromosome: 12
• Chromosome location: 12q21.33
• Summary: The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK2, is expressed in a variety of tissues with the highest levels in heart and pancreas, and unlike most other members of this family, is localized in the cytoplasm. Mutations in this gene have been associated with congenital hypogonadotropic hypogonadism. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs139318648	G>A,C	Risk-factor	Missense variant, intron variant, coding sequence variant
rs143946794	T>C	Pathogenic	Missense variant, intron variant, coding sequence variant
rs146089505	G>A	Risk-factor	Missense variant, coding sequence variant
rs587776978	A>T	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006481	hsa-miR-181a-5p	Luciferase reporter assay, Western blot	17382377
MIRT006481	hsa-miR-181a-5p	Flow, Microarray, qRT-PCR	25477247
MIRT018633	hsa-miR-335-5p	Microarray	18185580
MIRT020032	hsa-miR-375	Microarray	20215506
MIRT438607	hsa-miR-125b-5p	Luciferase reporter assay, Western blot, qRT-PCR	25001178
MIRT613131	hsa-miR-4328	HITS-CLIP	23824327
MIRT613132	hsa-miR-216b-3p	HITS-CLIP	23824327
MIRT613133	hsa-miR-603	HITS-CLIP	23824327
MIRT613134	hsa-miR-8485	HITS-CLIP	23824327
MIRT613135	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT613136	hsa-miR-145-5p	HITS-CLIP	23824327
MIRT613137	hsa-miR-5195-3p	HITS-CLIP	23824327
MIRT615020	hsa-miR-1185-2-3p	HITS-CLIP	23824327
MIRT615021	hsa-miR-1185-1-3p	HITS-CLIP	23824327
MIRT615022	hsa-let-7f-2-3p	HITS-CLIP	23824327
MIRT615023	hsa-miR-4789-5p	HITS-CLIP	23824327
MIRT615024	hsa-miR-98-3p	HITS-CLIP	23824327
MIRT615025	hsa-let-7f-1-3p	HITS-CLIP	23824327
MIRT615026	hsa-let-7b-3p	HITS-CLIP	23824327
MIRT615027	hsa-let-7a-3p	HITS-CLIP	23824327
MIRT624077	hsa-miR-1178-3p	HITS-CLIP	23824327
MIRT624078	hsa-miR-342-3p	HITS-CLIP	23824327
MIRT658836	hsa-miR-4666a-3p	HITS-CLIP	23824327
MIRT658837	hsa-miR-381-3p	HITS-CLIP	23824327
MIRT658838	hsa-miR-300	HITS-CLIP	23824327

Transcription factors

Transcription factor	Regulation	Reference
ETS1	Unknown	20097731

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	TAS
GO:0000187	Process	Activation of MAPK activity	TAS
GO:0000188	Process	Inactivation of MAPK activity	IBA	21873635
GO:0000188	Process	Inactivation of MAPK activity	IDA	8670865
GO:0004721	Function	Phosphoprotein phosphatase activity	IBA	21873635
GO:0004725	Function	Protein tyrosine phosphatase activity	IEA
GO:0005515	Function	Protein binding	IPI	12840032, 31980649, 32296183, 32814053
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005737	Component	Cytoplasm	IDA	8670865, 9788880
GO:0005829	Component	Cytosol	IBA	21873635
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006470	Process	Protein dephosphorylation	IBA	21873635
GO:0008330	Function	Protein tyrosine/threonine phosphatase activity	IBA	21873635
GO:0014070	Process	Response to organic cyclic compound	IEA
GO:0017017	Function	MAP kinase tyrosine/serine/threonine phosphatase activity	IBA	21873635
GO:0017017	Function	MAP kinase tyrosine/serine/threonine phosphatase activity	IDA	8670865
GO:0030154	Process	Cell differentiation	IEA
GO:0035335	Process	Peptidyl-tyrosine dephosphorylation	IBA	21873635
GO:0035335	Process	Peptidyl-tyrosine dephosphorylation	IDA	8670865
GO:0035970	Process	Peptidyl-threonine dephosphorylation	IBA	21873635
GO:0042493	Process	Response to drug	IEA
GO:0043065	Process	Positive regulation of apoptotic process	IBA	21873635
GO:0043065	Process	Positive regulation of apoptotic process	IDA	10846176
GO:0051019	Function	Mitogen-activated protein kinase binding	IBA	21873635
GO:0051409	Process	Response to nitrosative stress	IEP	10846176
GO:0060420	Process	Regulation of heart growth	IBA	21873635
GO:0070373	Process	Negative regulation of ERK1 and ERK2 cascade	IBA	21873635
GO:0070373	Process	Negative regulation of ERK1 and ERK2 cascade	IMP	18771677
GO:0070848	Process	Response to growth factor	IEA
GO:0106306	Function	Protein serine phosphatase activity	IEA
GO:0106307	Function	Protein threonine phosphatase activity	IEA

Other IDs

• MIM: 602748
• HGNC: 3072
• e!Ensembl: ENSG00000139318

Protein

• UniProt ID: Q16828
• Protein name: Dual specificity protein phosphatase 6 (EC 3.1.3.16) (EC 3.1.3.48) (Dual specificity protein phosphatase PYST1) (Mitogen-activated protein kinase phosphatase 3) (MAP kinase phosphatase 3) (MKP-3)
• Protein function: Inactivates MAP kinases. Has a specificity for the ERK family (PubMed:9858808). Plays an important role in alleviating chronic postoperative pain. Necessary for the normal dephosphorylation of the long-lasting phosphorylated forms of spinal MAPK1/3 and MAP kinase p38 induced by peripheral surgery, which drives the resolution of acute postoperative allodynia (By similarity). Also important for dephosphorylation of MAPK1/3 in local wound tissue, which further contributes to resolution of acute pain (By similarity). Promotes cell differentiation by regulating MAPK1/MAPK3 activity and regulating the expression of AP1 transcription factors (PubMed:29043977).
• PDB: 1HZM, 1MKP
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00581	Rhodanese	19 → 142	Rhodanese-like domain	Domain
  PF00782	DSPc	214 → 346	Dual specificity phosphatase, catalytic domain	Domain

• Sequence:

  MIDTLRPVPFASEMAISKTVAWLNEQLELGNERLLLMDCRPQELYESSHIESAINVAIPG
  IMLRRLQKGNLPVRALFTRGEDRDRFTRRCGTDTVVLYDESSSDWNENTGGESVLGLLLK
  KLKDEGCRAFYLEGGFSKFQAEFSLHCETNLDGSCSSSSPPLPVLGLGGLRISSDSSSDI
  ESDLDRDPNSATDSDGSPLSNSQPSFPVEILPFLYLGCAKDSTNLDVLEEFGIKYILNVT
  PNLPNLFENAGEFKYKQIPISDHWSQNLSQFFPEAISFIDEARGKNCGVLVHCLAGISRS
  VTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTLGLSSPCDNRVPAQ
  QLYFTTPSNQNVYQVDSLQST

• Sequence length: 381