Q16828 (DUS6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dual specificity protein phosphatase 6
EC=3.1.3.16
EC=3.1.3.48

Alternative name(s):
Dual specificity protein phosphatase PYST1
Mitogen-activated protein kinase phosphatase 3
Short name=MAP kinase phosphatase 3
Short name=MKP-3

Gene names

Name:	DUSP6
Synonyms:	MKP3, PYST1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	381 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Inactivates MAP kinases. Has a specificity for the ERK family.
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. A phosphoprotein + H2O = a protein + phosphate.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily. Contains 1 rhodanese domain. Contains 1 tyrosine-protein phosphatase domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome cell differentiation Inferred from electronic annotation. Source: Compara dorsal/ventral pattern formation Inferred from Biological aspect of Ancestor. Source: RefGenome innate immune response Traceable author statement. Source: Reactome negative regulation of ERK1 and ERK2 cascade Inferred from mutant phenotype PubMed 18771677. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome peptidyl-tyrosine dephosphorylation Inferred from direct assay Ref.1. Source: UniProtKB positive regulation of apoptotic process Inferred from direct assay PubMed 10846176. Source: UniProtKB regulation of endodermal cell fate specification Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of fibroblast growth factor receptor signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of heart growth Inferred from Biological aspect of Ancestor. Source: RefGenome response to drug Inferred from electronic annotation. Source: Compara response to growth factor stimulus Inferred from electronic annotation. Source: Compara response to nitrosative stress Inferred from expression pattern PubMed 10846176. Source: UniProtKB response to organic cyclic compound Inferred from electronic annotation. Source: Compara stress-activated MAPK cascade Traceable author statement. Source: Reactome toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Inferred from Biological aspect of Ancestor. Source: RefGenome nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	MAP kinase tyrosine/serine/threonine phosphatase activity Inferred from direct assay Ref.1. Source: UniProtKB protein tyrosine phosphatase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q16828-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q16828-2)

Also known as: DUSP6-ALT;

The sequence of this isoform differs from the canonical sequence as follows:
     134-279: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 381

381

Dual specificity protein phosphatase 6

PRO_0000094804

Regions

Domain

30 – 148

119

Rhodanese

Domain

206 – 381

176

Tyrosine-protein phosphatase

Sites

Active site

293

1

Phosphocysteine intermediate

Amino acid modifications

Modified residue

331

1

Phosphoserine By similarity

Natural variations

Alternative sequence

134 – 279

146

Missing in isoform 2.

VSP_005137

Natural variant

114

1

V → L. Ref.1 Ref.2 Ref.3
Corresponds to variant rs2279574 [ dbSNP | Ensembl ].

VAR_015113

Natural variant

144

1

S → A.
Corresponds to variant rs770087 [ dbSNP | Ensembl ].

VAR_051750

Natural variant

313

1

N → I.
Corresponds to variant rs12828557 [ dbSNP | Ensembl ].

VAR_051751

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

381

Helix Strand Turn

Details...

Beta strand

7 – 12

6

Beta strand

15 – 18

4

Helix

23 – 29

7

Beta strand

31 – 33

3

Beta strand

35 – 37

3

Helix

43 – 48

6

Beta strand

50 – 52

3

Helix

61 – 64

4

Turn

73 – 76

4

Helix

81 – 88

8

Beta strand

95 – 97

3

Beta strand

101 – 105

5

Helix

114 – 124

11

Helix

136 – 143

8

Beta strand

149 – 152

4

Beta strand

208 – 211

4

Beta strand

214 – 217

4

Helix

225 – 230

6

Beta strand

233 – 238

6

Beta strand

246 – 250

5

Beta strand

253 – 257

5

Helix

269 – 271

3

Helix

272 – 284

13

Beta strand

288 – 292

5

Helix

298 – 312

15

Helix

316 – 326

11

Helix

337 – 345

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 30, 2006. Version 2. Checksum: 386612227F5D3B2A	FASTA	381	42,320
	10 20 30 40 50 60 MIDTLRPVPF ASEMAISKTV AWLNEQLELG NERLLLMDCR PQELYESSHI ESAINVAIPG 70 80 90 100 110 120 IMLRRLQKGN LPVRALFTRG EDRDRFTRRC GTDTVVLYDE SSSDWNENTG GESVLGLLLK 130 140 150 160 170 180 KLKDEGCRAF YLEGGFSKFQ AEFSLHCETN LDGSCSSSSP PLPVLGLGGL RISSDSSSDI 190 200 210 220 230 240 ESDLDRDPNS ATDSDGSPLS NSQPSFPVEI LPFLYLGCAK DSTNLDVLEE FGIKYILNVT 250 260 270 280 290 300 PNLPNLFENA GEFKYKQIPI SDHWSQNLSQ FFPEAISFID EARGKNCGVL VHCLAGISRS 310 320 330 340 350 360 VTVTVAYLMQ KLNLSMNDAY DIVKMKKSNI SPNFNFMGQL LDFERTLGLS SPCDNRVPAQ 370 380 QLYFTTPSNQ NVYQVDSLQS T
	Isoform 2 (DUSP6-ALT) [UniParc]. Checksum: 24E84490A10D2D87	FASTA	235	26,468
	10 20 30 40 50 60 MIDTLRPVPF ASEMAISKTV AWLNEQLELG NERLLLMDCR PQELYESSHI ESAINVAIPG 70 80 90 100 110 120 IMLRRLQKGN LPVRALFTRG EDRDRFTRRC GTDTVVLYDE SSSDWNENTG GESVLGLLLK 130 140 150 160 170 180 KLKDEGCRAF YLEDEARGKN CGVLVHCLAG ISRSVTVTVA YLMQKLNLSM NDAYDIVKMK 190 200 210 220 230 KSNISPNFNF MGQLLDFERT LGLSSPCDNR VPAQQLYFTT PSNQNVYQVD SLQST

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase." Groom L.A., Sneddon A.A., Alessi D.R., Dowd S., Keyse S.M. EMBO J. 15:3621-3632(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-114. Tissue: Foreskin.
[2]	"Genomic analysis of DUSP6, a dual specificity MAP kinase phosphatase, in pancreatic cancer." Furukawa T., Yatsuoka T., Youssef E.M., Abe T., Yokoyama T., Fukushige S., Soeda E., Hoshi M., Hayashi Y., Sunamura M., Kobari M., Horii A. Cytogenet. Cell Genet. 82:156-159(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), VARIANT LEU-114. Tissue: Liver.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LEU-114.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon, Kidney, Skin and Stomach.
[5]	"Crystal structure of the MAPK phosphatase Pyst1 catalytic domain and implications for regulated activation." Stewart A.E., Dowd S., Keyse S.M., McDonald N.Q. Nat. Struct. Biol. 6:174-181(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 204-347.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X93920 mRNA. Translation: CAA63813.1.
AB013601 Genomic DNA. Translation: BAA31968.1.
AB013382 mRNA. Translation: BAA34369.1.
AB013602 mRNA. Translation: BAA31969.1.
BT006895 mRNA. Translation: AAP35541.1.
BC003143 mRNA. Translation: AAH03143.1.
BC003562 mRNA. Translation: AAH03562.1.
BC005047 mRNA. Translation: AAH05047.1.
BC037236 mRNA. Translation: AAH37236.1.

IPI

IPI00004390.
IPI00335706.

RefSeq

NP_001937.2. NM_001946.2.
NP_073143.2. NM_022652.2.

UniGene

Hs.298654.
Hs.718640.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HZM	NMR	-	A	1-154	[»]
1MKP	X-ray	2.35	A	205-347	[»]

ProteinModelPortal

Q16828.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16828. 3 interactions.

MINT

MINT-1442837.

STRING

9606.ENSP00000279488.

PTM databases

PhosphoSite

Q16828.

Polymorphism databases

DMDM

108860971.

Proteomic databases

PaxDb

Q16828.

PRIDE

Q16828.

Protocols and materials databases

DNASU

1848.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000279488; ENSP00000279488; ENSG00000139318.
ENST00000308385; ENSP00000307835; ENSG00000139318.

GeneID

1848.

KEGG

hsa:1848.

UCSC

uc001tay.3. human.
uc001taz.3. human.

Organism-specific databases

CTD

1848.

GeneCards

GC12M089741.

HGNC

HGNC:3072. DUSP6.

HPA

CAB017566.

MIM

602748. gene.

neXtProt

NX_Q16828.

PharmGKB

PA27529.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2453.

HOGENOM

HOG000294079.

HOVERGEN

HBG007347.

InParanoid

Q16828.

KO

K04459.

OMA

VFQLDPL.

OrthoDB

EOG4GB76F.

Enzyme and pathway databases

BRENDA

3.1.3.48. 2681.

Reactome

REACT_111102. Signal Transduction.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q16828.

Bgee

Q16828.

CleanEx

HS_DUSP6.

Genevestigator

Q16828.

GermOnline

ENSG00000139318. Homo sapiens.

Family and domain databases

Gene3D

3.40.250.10. 1 hit.

InterPro

IPR000340. Dual-sp_phosphatase_cat-dom.
IPR020422. Dual-sp_phosphatase_subgr_cat.
IPR024950. DUSP.
IPR008343. MKP.
IPR001763. Rhodanese-like_dom.
IPR000387. Tyr/Dual-sp_Pase.
[Graphical view]

PANTHER

PTHR10159. PTHR10159. 1 hit.

Pfam

PF00782. DSPc. 1 hit.
PF00581. Rhodanese. 1 hit.
[Graphical view]

PIRSF

PIRSF000939. MAPK_Ptase. 1 hit.

PRINTS

PR01764. MAPKPHPHTASE.

SMART

SM00195. DSPc. 1 hit.
SM00450. RHOD. 1 hit.
[Graphical view]

SUPFAM

SSF52821. Rhodanese-like. 1 hit.

PROSITE

PS50206. RHODANESE_3. 1 hit.
PS00383. TYR_PHOSPHATASE_1. False negative.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q16828.

ChEMBL

CHEMBL1250381.

ChiTaRS

DUSP6. human.

EvolutionaryTrace

Q16828.

GenomeRNAi

1848.

NextBio

7569.

SOURCE

Search...

Entry information

Entry name

DUS6_HUMAN

Accession

Primary (citable) accession number: Q16828
Secondary accession number(s): O75109, Q53Y75, Q9BSH6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 30, 2006
Last modified:	May 1, 2013
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.