UniProtKB - Q16828 (DUS6_HUMAN)
Dual specificity protein phosphatase 6
DUSP6
Functioni
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).
By similarity2 PublicationsCatalytic activityi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 293 | Phosphocysteine intermediatePROSITE-ProRule annotation1 Publication | 1 |
GO - Molecular functioni
- MAP kinase tyrosine/serine/threonine phosphatase activity Source: UniProtKB
- phosphoprotein phosphatase activity Source: GO_Central
- protein serine/threonine phosphatase activity Source: UniProtKB-EC
- protein tyrosine/serine/threonine phosphatase activity Source: Reactome
- protein tyrosine/threonine phosphatase activity Source: GO_Central
- protein tyrosine phosphatase activity Source: Reactome
GO - Biological processi
- cell differentiation Source: Ensembl
- ERK1 and ERK2 cascade Source: Reactome
- MAPK cascade Source: Reactome
- negative regulation of ERK1 and ERK2 cascade Source: UniProtKB
- negative regulation of MAPK cascade Source: UniProtKB
- negative regulation of protein phosphorylation Source: Ensembl
- peptidyl-tyrosine dephosphorylation Source: UniProtKB
- positive regulation of apoptotic process Source: UniProtKB
- regulation of heart growth Source: GO_Central
- response to growth factor Source: Ensembl
- response to nitrosative stress Source: UniProtKB
- response to organic cyclic compound Source: Ensembl
- response to xenobiotic stimulus Source: Ensembl
Keywordsi
Molecular function | Hydrolase, Protein phosphatase |
Enzyme and pathway databases
BRENDAi | 3.1.3.16, 2681 3.1.3.48, 2681 |
PathwayCommonsi | Q16828 |
Reactomei | R-HSA-112409, RAF-independent MAPK1/3 activation R-HSA-202670, ERKs are inactivated R-HSA-5675221, Negative regulation of MAPK pathway R-HSA-9652817, Signaling by MAPK mutants |
SignaLinki | Q16828 |
SIGNORi | Q16828 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:DUSP6 Synonyms:MKP3, PYST1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3072, DUSP6 |
MIMi | 602748, gene |
neXtProti | NX_Q16828 |
VEuPathDBi | HostDB:ENSG00000139318 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Cytosol
- cytosol Source: HPA
Nucleus
- nucleoplasm Source: HPA
Other locations
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Involvement in diseasei
Hypogonadotropic hypogonadism 19 with or without anosmia (HH19)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_069943 | 77 | F → I in HH19. 1 PublicationCorresponds to variant dbSNP:rs587776978EnsemblClinVar. | 1 | |
Natural variantiVAR_069944 | 182 | S → F in HH19; rare variant associated with susceptibility to disease; the patient carries a second mutation in the HH-associated gene FGFR1. 1 PublicationCorresponds to variant dbSNP:rs139318648EnsemblClinVar. | 1 | |
Natural variantiVAR_069945 | 189 | N → S in HH19. 1 PublicationCorresponds to variant dbSNP:rs143946794EnsemblClinVar. | 1 | |
Natural variantiVAR_069946 | 346 | T → M in HH19; rare variant associated with susceptibility to disease; the patient carries a second variant in the HH-associated gene SPRY4. 1 PublicationCorresponds to variant dbSNP:rs146089505EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variant, Hypogonadotropic hypogonadism, Kallmann syndromeOrganism-specific databases
DisGeNETi | 1848 |
GeneReviewsi | DUSP6 |
MalaCardsi | DUSP6 |
MIMi | 615269, phenotype |
OpenTargetsi | ENSG00000139318 |
Orphaneti | 478, Kallmann syndrome 432, Normosmic congenital hypogonadotropic hypogonadism |
PharmGKBi | PA27529 |
Miscellaneous databases
Pharosi | Q16828, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1250381 |
Genetic variation databases
BioMutai | DUSP6 |
DMDMi | 108860971 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000094804 | 1 – 381 | Dual specificity protein phosphatase 6Add BLAST | 381 |
Proteomic databases
CPTACi | CPTAC-1564 |
EPDi | Q16828 |
jPOSTi | Q16828 |
MassIVEi | Q16828 |
MaxQBi | Q16828 |
PaxDbi | Q16828 |
PeptideAtlasi | Q16828 |
PRIDEi | Q16828 |
ProteomicsDBi | 61089 [Q16828-1] 61090 [Q16828-2] |
PTM databases
DEPODi | DUSP6 |
iPTMneti | Q16828 |
PhosphoSitePlusi | Q16828 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000139318, Expressed in pigmented layer of retina and 254 other tissues |
ExpressionAtlasi | Q16828, baseline and differential |
Genevisiblei | Q16828, HS |
Organism-specific databases
HPAi | ENSG00000139318, Tissue enhanced (salivary) |
Interactioni
Subunit structurei
Interacts with MAPK1/ERK2.
1 PublicationBinary interactionsi
Q16828
With | #Exp. | IntAct |
---|---|---|
APP [P05067] | 3 | EBI-746870,EBI-77613 |
MAPK1 [P28482] | 5 | EBI-746870,EBI-959949 |
MAPK3 [P27361] | 5 | EBI-746870,EBI-73995 |
PHB2 [Q99623] | 3 | EBI-746870,EBI-358348 |
TXK [P42681] | 3 | EBI-746870,EBI-7877438 |
Protein-protein interaction databases
BioGRIDi | 108181, 120 interactors |
ELMi | Q16828 |
IntActi | Q16828, 42 interactors |
MINTi | Q16828 |
STRINGi | 9606.ENSP00000279488 |
Chemistry databases
BindingDBi | Q16828 |
Miscellaneous databases
RNActi | Q16828, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q16828 |
BMRBi | Q16828 |
SMRi | Q16828 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q16828 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 30 – 148 | RhodanesePROSITE-ProRule annotationAdd BLAST | 119 | |
Domaini | 206 – 349 | Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST | 144 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 176 – 203 | DisorderedSequence analysisAdd BLAST | 28 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1717, Eukaryota |
GeneTreei | ENSGT00940000158342 |
InParanoidi | Q16828 |
OMAi | IEFDRWA |
PhylomeDBi | Q16828 |
TreeFami | TF105122 |
Family and domain databases
Gene3Di | 3.40.250.10, 1 hit 3.90.190.10, 1 hit |
InterProi | View protein in InterPro IPR000340, Dual-sp_phosphatase_cat-dom IPR008343, MKP IPR029021, Prot-tyrosine_phosphatase-like IPR001763, Rhodanese-like_dom IPR036873, Rhodanese-like_dom_sf IPR000387, Tyr_Pase_dom IPR020422, TYR_PHOSPHATASE_DUAL_dom |
Pfami | View protein in Pfam PF00782, DSPc, 1 hit PF00581, Rhodanese, 1 hit |
PIRSFi | PIRSF000939, MAPK_Ptase, 1 hit |
PRINTSi | PR01764, MAPKPHPHTASE |
SMARTi | View protein in SMART SM00195, DSPc, 1 hit SM00450, RHOD, 1 hit |
SUPFAMi | SSF52799, SSF52799, 1 hit SSF52821, SSF52821, 1 hit |
PROSITEi | View protein in PROSITE PS50206, RHODANESE_3, 1 hit PS50056, TYR_PHOSPHATASE_2, 1 hit PS50054, TYR_PHOSPHATASE_DUAL, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MIDTLRPVPF ASEMAISKTV AWLNEQLELG NERLLLMDCR PQELYESSHI
60 70 80 90 100
ESAINVAIPG IMLRRLQKGN LPVRALFTRG EDRDRFTRRC GTDTVVLYDE
110 120 130 140 150
SSSDWNENTG GESVLGLLLK KLKDEGCRAF YLEGGFSKFQ AEFSLHCETN
160 170 180 190 200
LDGSCSSSSP PLPVLGLGGL RISSDSSSDI ESDLDRDPNS ATDSDGSPLS
210 220 230 240 250
NSQPSFPVEI LPFLYLGCAK DSTNLDVLEE FGIKYILNVT PNLPNLFENA
260 270 280 290 300
GEFKYKQIPI SDHWSQNLSQ FFPEAISFID EARGKNCGVL VHCLAGISRS
310 320 330 340 350
VTVTVAYLMQ KLNLSMNDAY DIVKMKKSNI SPNFNFMGQL LDFERTLGLS
360 370 380
SPCDNRVPAQ QLYFTTPSNQ NVYQVDSLQS T
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF8VW29 | F8VW29_HUMAN | Protein-tyrosine-phosphatase | DUSP6 | 256 | Annotation score: | ||
F8VZA4 | F8VZA4_HUMAN | Dual-specificity protein phosphatas... | DUSP6 | 117 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_069943 | 77 | F → I in HH19. 1 PublicationCorresponds to variant dbSNP:rs587776978EnsemblClinVar. | 1 | |
Natural variantiVAR_015113 | 114 | V → L3 PublicationsCorresponds to variant dbSNP:rs2279574EnsemblClinVar. | 1 | |
Natural variantiVAR_051750 | 144 | S → A. Corresponds to variant dbSNP:rs770087Ensembl. | 1 | |
Natural variantiVAR_069944 | 182 | S → F in HH19; rare variant associated with susceptibility to disease; the patient carries a second mutation in the HH-associated gene FGFR1. 1 PublicationCorresponds to variant dbSNP:rs139318648EnsemblClinVar. | 1 | |
Natural variantiVAR_069945 | 189 | N → S in HH19. 1 PublicationCorresponds to variant dbSNP:rs143946794EnsemblClinVar. | 1 | |
Natural variantiVAR_051751 | 313 | N → I. Corresponds to variant dbSNP:rs12828557Ensembl. | 1 | |
Natural variantiVAR_069946 | 346 | T → M in HH19; rare variant associated with susceptibility to disease; the patient carries a second variant in the HH-associated gene SPRY4. 1 PublicationCorresponds to variant dbSNP:rs146089505EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_005137 | 134 – 279 | Missing in isoform 2. 1 PublicationAdd BLAST | 146 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS9033.1 [Q16828-1] CCDS9034.1 [Q16828-2] |
RefSeqi | NP_001937.2, NM_001946.3 [Q16828-1] NP_073143.2, NM_022652.3 [Q16828-2] |
Genome annotation databases
Ensembli | ENST00000279488.8; ENSP00000279488.6; ENSG00000139318.8 ENST00000308385.6; ENSP00000307835.6; ENSG00000139318.8 [Q16828-2] |
GeneIDi | 1848 |
KEGGi | hsa:1848 |
MANE-Selecti | ENST00000279488.8; ENSP00000279488.6; NM_001946.4; NP_001937.2 |
UCSCi | uc001tay.5, human [Q16828-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS9033.1 [Q16828-1] CCDS9034.1 [Q16828-2] |
RefSeqi | NP_001937.2, NM_001946.3 [Q16828-1] NP_073143.2, NM_022652.3 [Q16828-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1HZM | NMR | - | A | 1-154 | [»] | |
1MKP | X-ray | 2.35 | A | 205-347 | [»] | |
AlphaFoldDBi | Q16828 | |||||
BMRBi | Q16828 | |||||
SMRi | Q16828 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108181, 120 interactors |
ELMi | Q16828 |
IntActi | Q16828, 42 interactors |
MINTi | Q16828 |
STRINGi | 9606.ENSP00000279488 |
Chemistry databases
BindingDBi | Q16828 |
ChEMBLi | CHEMBL1250381 |
PTM databases
DEPODi | DUSP6 |
iPTMneti | Q16828 |
PhosphoSitePlusi | Q16828 |
Genetic variation databases
BioMutai | DUSP6 |
DMDMi | 108860971 |
Proteomic databases
CPTACi | CPTAC-1564 |
EPDi | Q16828 |
jPOSTi | Q16828 |
MassIVEi | Q16828 |
MaxQBi | Q16828 |
PaxDbi | Q16828 |
PeptideAtlasi | Q16828 |
PRIDEi | Q16828 |
ProteomicsDBi | 61089 [Q16828-1] 61090 [Q16828-2] |
Protocols and materials databases
Antibodypediai | 4315, 550 antibodies from 38 providers |
DNASUi | 1848 |
Genome annotation databases
Ensembli | ENST00000279488.8; ENSP00000279488.6; ENSG00000139318.8 ENST00000308385.6; ENSP00000307835.6; ENSG00000139318.8 [Q16828-2] |
GeneIDi | 1848 |
KEGGi | hsa:1848 |
MANE-Selecti | ENST00000279488.8; ENSP00000279488.6; NM_001946.4; NP_001937.2 |
UCSCi | uc001tay.5, human [Q16828-1] |
Organism-specific databases
CTDi | 1848 |
DisGeNETi | 1848 |
GeneCardsi | DUSP6 |
GeneReviewsi | DUSP6 |
HGNCi | HGNC:3072, DUSP6 |
HPAi | ENSG00000139318, Tissue enhanced (salivary) |
MalaCardsi | DUSP6 |
MIMi | 602748, gene 615269, phenotype |
neXtProti | NX_Q16828 |
OpenTargetsi | ENSG00000139318 |
Orphaneti | 478, Kallmann syndrome 432, Normosmic congenital hypogonadotropic hypogonadism |
PharmGKBi | PA27529 |
VEuPathDBi | HostDB:ENSG00000139318 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1717, Eukaryota |
GeneTreei | ENSGT00940000158342 |
InParanoidi | Q16828 |
OMAi | IEFDRWA |
PhylomeDBi | Q16828 |
TreeFami | TF105122 |
Enzyme and pathway databases
BRENDAi | 3.1.3.16, 2681 3.1.3.48, 2681 |
PathwayCommonsi | Q16828 |
Reactomei | R-HSA-112409, RAF-independent MAPK1/3 activation R-HSA-202670, ERKs are inactivated R-HSA-5675221, Negative regulation of MAPK pathway R-HSA-9652817, Signaling by MAPK mutants |
SignaLinki | Q16828 |
SIGNORi | Q16828 |
Miscellaneous databases
BioGRID-ORCSi | 1848, 19 hits in 1084 CRISPR screens |
ChiTaRSi | DUSP6, human |
EvolutionaryTracei | Q16828 |
GeneWikii | DUSP6 |
GenomeRNAii | 1848 |
Pharosi | Q16828, Tchem |
PROi | PR:Q16828 |
RNActi | Q16828, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000139318, Expressed in pigmented layer of retina and 254 other tissues |
ExpressionAtlasi | Q16828, baseline and differential |
Genevisiblei | Q16828, HS |
Family and domain databases
Gene3Di | 3.40.250.10, 1 hit 3.90.190.10, 1 hit |
InterProi | View protein in InterPro IPR000340, Dual-sp_phosphatase_cat-dom IPR008343, MKP IPR029021, Prot-tyrosine_phosphatase-like IPR001763, Rhodanese-like_dom IPR036873, Rhodanese-like_dom_sf IPR000387, Tyr_Pase_dom IPR020422, TYR_PHOSPHATASE_DUAL_dom |
Pfami | View protein in Pfam PF00782, DSPc, 1 hit PF00581, Rhodanese, 1 hit |
PIRSFi | PIRSF000939, MAPK_Ptase, 1 hit |
PRINTSi | PR01764, MAPKPHPHTASE |
SMARTi | View protein in SMART SM00195, DSPc, 1 hit SM00450, RHOD, 1 hit |
SUPFAMi | SSF52799, SSF52799, 1 hit SSF52821, SSF52821, 1 hit |
PROSITEi | View protein in PROSITE PS50206, RHODANESE_3, 1 hit PS50056, TYR_PHOSPHATASE_2, 1 hit PS50054, TYR_PHOSPHATASE_DUAL, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | DUS6_HUMAN | |
Accessioni | Q16828Primary (citable) accession number: Q16828 Secondary accession number(s): O75109, Q53Y75, Q9BSH6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | May 30, 2006 | |
Last modified: | May 25, 2022 | |
This is version 204 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families