Q9Y6W6 (DUS10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dual specificity protein phosphatase 10
EC=3.1.3.16
EC=3.1.3.48

Alternative name(s):
Mitogen-activated protein kinase phosphatase 5
Short name=MAP kinase phosphatase 5
Short name=MKP-5

Gene names

Name:	DUSP10
Synonyms:	MKP5

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	482 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Protein phosphatase involved in the inactivation of MAP kinases. Has a specificity for the MAPK11/MAPK12/MAPK13/MAPK14 subfamily. Ref.9
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.7 Ref.9 A phosphoprotein + H2O = a protein + phosphate. Ref.7 Ref.9
Subunit structure	Monomer. Interacts with MAPK14. Ref.7 Ref.8 Ref.9
Subcellular location	Cytoplasm. Nucleus.
Tissue specificity	Detected in brain. Ref.7
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 Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protein phosphatase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	JNK cascade Traceable author statement Ref.1. Source: ProtInc negative regulation of JNK cascade Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of JUN kinase activity Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of respiratory burst involved in inflammatory response Inferred from electronic annotation. Source: Compara peptidyl-tyrosine dephosphorylation Inferred from electronic annotation. Source: GOC regulation of adaptive immune response Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	MAP kinase tyrosine/serine/threonine phosphatase activity Inferred from Biological aspect of Ancestor. Source: RefGenome 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: Q9Y6W6-1)

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: Q9Y6W6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-342: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 482

482

Dual specificity protein phosphatase 10

PRO_0000094813

Regions

Domain

168 – 285

118

Rhodanese

Domain

384 – 453

70

Tyrosine-protein phosphatase

Region

199 – 215

17

Interaction with MAP kinases

Sites

Active site

408

1

Phosphocysteine intermediate Probable

Natural variations

Alternative sequence

1 – 342

342

Missing in isoform 2.

VSP_036549

Experimental info

Mutagenesis

180 – 181

2

FM → DD: Reduced enzyme activity with MAPK14. Ref.9

Mutagenesis

203 – 204

2

RR → AA: Strongly reduced affinity for MAPK14. Almost abolishes enzyme activity with MAPK14. Ref.9

Secondary structure

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482

Helix Strand Turn

Details...

Helix

152 – 160

9

Beta strand

173 – 176

4

Helix

180 – 185

6

Beta strand

186 – 188

3

Helix

199 – 206

8

Helix

212 – 217

6

Helix

224 – 230

7

Beta strand

233 – 236

4

Helix

243 – 245

3

Beta strand

248 – 250

3

Helix

251 – 261

11

Beta strand

267 – 269

3

Helix

272 – 276

5

Turn

277 – 279

3

Helix

281 – 283

3

Beta strand

284 – 286

3

Beta strand

323 – 326

4

Beta strand

329 – 332

4

Helix

336 – 338

3

Helix

340 – 345

6

Beta strand

348 – 353

6

Beta strand

356 – 358

3

Helix

363 – 365

3

Beta strand

368 – 372

5

Beta strand

378 – 380

3

Helix

384 – 386

3

Helix

387 – 399

13

Beta strand

403 – 407

5

Beta strand

409 – 413

5

Helix

414 – 426

13

Helix

431 – 441

11

Helix

449 – 463

15

Helix

478 – 482

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: A8CB74ABF9498CD4	FASTA	482	52,642
	10 20 30 40 50 60 MPPSPLDDRV VVALSRPVRP QDLNLCLDSS YLGSANPGSN SHPPVIATTV VSLKAANLTY 70 80 90 100 110 120 MPSSSGSARS LNCGCSSASC CTVATYDKDN QAQTQAIAAG TTTTAIGTST TCPANQMVNN 130 140 150 160 170 180 NENTGSLSPS SGVGSPVSGT PKQLASIKII YPNDLAKKMT KCSKSHLPSQ GPVIIDCRPF 190 200 210 220 230 240 MEYNKSHIQG AVHINCADKI SRRRLQQGKI TVLDLISCRE GKDSFKRIFS KEIIVYDENT 250 260 270 280 290 300 NEPSRVMPSQ PLHIVLESLK REGKEPLVLK GGLSSFKQNH ENLCDNSLQL QECREVGGGA 310 320 330 340 350 360 SAASSLLPQP IPTTPDIENA ELTPILPFLF LGNEQDAQDL DTMQRLNIGY VINVTTHLPL 370 380 390 400 410 420 YHYEKGLFNY KRLPATDSNK QNLRQYFEEA FEFIEEAHQC GKGLLIHCQA GVSRSATIVI 430 440 450 460 470 480 AYLMKHTRMT MTDAYKFVKG KRPIISPNLN FMGQLLEFEE DLNNGVTPRI LTPKLMGVET VV
	Isoform 2 [UniParc]. Checksum: CE151F365D042516	FASTA	140	16,110
	10 20 30 40 50 60 MQRLNIGYVI NVTTHLPLYH YEKGLFNYKR LPATDSNKQN LRQYFEEAFE FIEEAHQCGK 70 80 90 100 110 120 GLLIHCQAGV SRSATIVIAY LMKHTRMTMT DAYKFVKGKR PIISPNLNFM GQLLEFEEDL 130 140 NNGVTPRILT PKLMGVETVV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5." Tanoue T., Moriguchi T., Nishida E. J. Biol. Chem. 274:19949-19956(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"MKP5, a new member of the MAP kinase phosphatase family, which selectively dephosphorylates stress-activated kinases." Theodosiou A., Smith A., Gillieron C., Arkinstall S., Ashworth A. Oncogene 18:6981-6988(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORMS 1 AND 2). Tissue: Brain, Lung, PNS and Testis.
[7]	"Crystal structure of the catalytic domain of human MAP kinase phosphatase 5: structural insight into constitutively active phosphatase." Jeong D.G., Yoon T.S., Kim J.H., Shim M.Y., Jung S.K., Son J.H., Ryu S.E., Kim S.J. J. Mol. Biol. 360:946-955(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 320-467, CATALYTIC ACTIVITY, SUBUNIT, TISSUE SPECIFICITY, ACTIVE SITE.
[8]	"Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5." Tao X., Tong L. Protein Sci. 16:880-886(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 148-287, SUBUNIT, ACTIVE SITE.
[9]	"A distinct interaction mode revealed by the crystal structure of the kinase p38alpha with the MAPK binding domain of the phosphatase MKP5." Zhang Y.Y., Wu J.W., Wang Z.X. Sci. Signal. 4:RA88-RA88(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) OF 139-288 IN COMPLEX WITH MAPK14, FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH MAPK14, MUTAGENESIS OF 180-PHE-MET-181 AND 203-ARG-ARG-204.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB026436 mRNA. Translation: BAA81668.1.
AF179212 mRNA. Translation: AAD51857.1.
AK022513 mRNA. Translation: BAB14070.1.
AL590966 Genomic DNA. Translation: CAH71120.1.
CH471100 Genomic DNA. Translation: EAW93283.1.
CH471100 Genomic DNA. Translation: EAW93285.1.
CH471100 Genomic DNA. Translation: EAW93286.1.
CH471100 Genomic DNA. Translation: EAW93287.1.
BC020608 mRNA. Translation: AAH20608.1.
BC031405 mRNA. Translation: AAH31405.1.
BC063826 mRNA. Translation: AAH63826.1.

IPI

IPI00026987.
IPI00939755.

RefSeq

NP_009138.1. NM_007207.4.
NP_653329.1. NM_144728.2.
NP_653330.1. NM_144729.2.

UniGene

Hs.497822.
Hs.732301.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZZW	X-ray	1.60	A/B	320-467	[»]
2OUC	X-ray	2.20	A/B	148-287	[»]
2OUD	X-ray	2.80	A	315-482	[»]
3TG1	X-ray	2.71	B	139-288	[»]

ProteinModelPortal

Q9Y6W6.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y6W6. 7 interactions.

MINT

MINT-8208613.

STRING

9606.ENSP00000355866.

PTM databases

PhosphoSite

Q9Y6W6.

Polymorphism databases

DMDM

20138090.

Proteomic databases

PaxDb

Q9Y6W6.

PRIDE

Q9Y6W6.

Protocols and materials databases

DNASU

11221.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000323825; ENSP00000322015; ENSG00000143507.
ENST00000366899; ENSP00000355866; ENSG00000143507.
ENST00000544095; ENSP00000441302; ENSG00000143507.

GeneID

11221.

KEGG

hsa:11221.

UCSC

uc001hmx.2. human.
uc001hmy.2. human.

Organism-specific databases

CTD

11221.

GeneCards

GC01M221874.

HGNC

HGNC:3065. DUSP10.

HPA

HPA016758.

MIM

608867. gene.

neXtProt

NX_Q9Y6W6.

PharmGKB

PA27520.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2453.

HOGENOM

HOG000069871.

HOVERGEN

HBG102158.

InParanoid

Q9Y6W6.

KO

K04459.

OMA

NEHDAQD.

OrthoDB

EOG4W0XD5.

PhylomeDB

Q9Y6W6.

Enzyme and pathway databases

BRENDA

3.1.3.48. 2681.

Pathway_Interaction_DB

p38alphabetapathway. Regulation of p38-alpha and p38-beta.

SignaLink

Q9Y6W6.

Gene expression databases

Bgee

Q9Y6W6.

CleanEx

HS_DUSP10.

Genevestigator

Q9Y6W6.

GermOnline

ENSG00000143507. Homo sapiens.

Family and domain databases

Gene3D

3.40.250.10. 1 hit.

InterPro

IPR020417. Atypical_DUSP.
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.
IPR016130. Tyr_Pase_AS.
[Graphical view]

PANTHER

PTHR10159. PTHR10159. 1 hit.

Pfam

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

PRINTS

PR01908. ADSPHPHTASE.
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. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9Y6W6.

GenomeRNAi

11221.

NextBio

42707.

SOURCE

Search...

Entry information

Entry name

DUS10_HUMAN

Accession

Primary (citable) accession number: Q9Y6W6
Secondary accession number(s): D3DTB4, Q6GSI4, Q9H9Z5

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 23, 2002
Last sequence update:	November 1, 1999
Last modified:	May 29, 2013
This is version 121 of the entry and version 1 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.