DUS7_HUMAN
ID DUS7_HUMAN Reviewed; 419 AA.
AC Q16829; Q2M3J7; Q8NFJ0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 4.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Dual specificity protein phosphatase 7 {ECO:0000312|HGNC:HGNC:3073};
DE EC=3.1.3.16 {ECO:0000269|PubMed:9788880};
DE EC=3.1.3.48 {ECO:0000269|PubMed:9788880};
DE AltName: Full=Dual specificity protein phosphatase PYST2 {ECO:0000303|PubMed:9788880};
GN Name=DUSP7 {ECO:0000312|HGNC:HGNC:3073};
GN Synonyms=PYST2 {ECO:0000303|PubMed:9788880};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH MAPK1,
RP AND SUBCELLULAR LOCATION.
RX PubMed=9788880; DOI=10.1242/jcs.111.22.3389;
RA Dowd S., Sneddon A.A., Keyse S.M.;
RT "Isolation of the human genes encoding the Pyst1 and Pyst2 phosphatases:
RT characterisation of Pyst2 as a cytosolic dual-specificity MAP kinase
RT phosphatase and its catalytic activation by both MAP and SAP kinases.";
RL J. Cell Sci. 111:3389-3399(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND ALTERNATIVE PROMOTER
RP USAGE.
RC TISSUE=Monocyte;
RX PubMed=14603440; DOI=10.1002/gcc.10295;
RA Levy-Nissenbaum O., Sagi-Assif O., Witz I.P.;
RT "Characterization of the dual-specificity phosphatase PYST2 and its
RT transcripts.";
RL Genes Chromosomes Cancer 39:37-47(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-235 (ISOFORM 1).
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 83-419 (ISOFORM 1).
RC TISSUE=Brain, and Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 149-419 (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=8670865; DOI=10.1002/j.1460-2075.1996.tb00731.x;
RA Groom L.A., Sneddon A.A., Alessi D.R., Dowd S., Keyse S.M.;
RT "Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a
RT novel cytosolic dual-specificity phosphatase.";
RL EMBO J. 15:3621-3632(1996).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=14576828; DOI=10.1038/sj.onc.1206971;
RA Levy-Nissenbaum O., Sagi-Assif O., Kapon D., Hantisteanu S., Burg T.,
RA Raanani P., Avigdor A., Ben-Bassat I., Witz I.P.;
RT "Dual-specificity phosphatase Pyst2-L is constitutively highly expressed in
RT myeloid leukemia and other malignant cells.";
RL Oncogene 22:7649-7660(2003).
RN [8] {ECO:0007744|PDB:4Y2E}
RP X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) OF 240-388 OF MUTANT SER-331 IN
RP COMPLEX WITH PHOSPHATE.
RX PubMed=26057789; DOI=10.1107/s2053230x1500504x;
RA Lountos G.T., Austin B.P., Tropea J.E., Waugh D.S.;
RT "Structure of human dual-specificity phosphatase 7, a potential cancer drug
RT target.";
RL Acta Crystallogr. F 71:650-656(2015).
CC -!- FUNCTION: Dual specificity protein phosphatase (PubMed:9788880). Shows
CC high activity towards MAPK1/ERK2 (PubMed:9788880). Also has lower
CC activity towards MAPK14 and MAPK8 (PubMed:9788880). In arrested
CC oocytes, plays a role in meiotic resumption (By similarity). Promotes
CC nuclear envelope breakdown and activation of the CDK1/Cyclin-B complex
CC in oocytes, probably by dephosphorylating and inactivating the
CC conventional protein kinase C (cPKC) isozyme PRKCB (By similarity). May
CC also inactivate PRKCA and/or PRKCG (By similarity). Also important in
CC oocytes for normal chromosome alignment on the metaphase plate and
CC progression to anaphase, where it might regulate activity of the
CC spindle-assembly checkpoint (SAC) complex (By similarity).
CC {ECO:0000250|UniProtKB:Q91Z46, ECO:0000269|PubMed:9788880}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48;
CC Evidence={ECO:0000269|PubMed:9788880};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:83421; EC=3.1.3.16;
CC Evidence={ECO:0000269|PubMed:9788880};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:61977; EC=3.1.3.16;
CC Evidence={ECO:0000269|PubMed:9788880};
CC -!- ACTIVITY REGULATION: Strongly inhibited by sodium orthovanadate.
CC {ECO:0000269|PubMed:9788880}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.82 mM for p-nitrophenyl phosphate {ECO:0000269|PubMed:9788880};
CC KM=0.76 mM for p-nitrophenyl phosphate (in the presence of MAPK1)
CC {ECO:0000269|PubMed:9788880};
CC -!- SUBUNIT: Interacts with MAPK1/ERK2; the interaction enhances DUSP7
CC phosphatase activity. {ECO:0000269|PubMed:9788880}.
CC -!- INTERACTION:
CC Q16829; Q9H6Z9: EGLN3; NbExp=3; IntAct=EBI-1265847, EBI-1175354;
CC Q16829; P10912: GHR; NbExp=2; IntAct=EBI-1265847, EBI-286316;
CC Q16829; Q14005-2: IL16; NbExp=3; IntAct=EBI-1265847, EBI-17178971;
CC Q16829; O43791: SPOP; NbExp=5; IntAct=EBI-1265847, EBI-743549;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9788880}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1; Synonyms=PYST2-L;
CC IsoId=Q16829-1; Sequence=Displayed;
CC Name=2; Synonyms=PYST2-S;
CC IsoId=Q16829-2; Sequence=VSP_012822;
CC -!- TISSUE SPECIFICITY: Strongly expressed in liver (PubMed:8670865).
CC Expressed at significantly higher levels in malignant hematopoietic
CC cells than in corresponding non-malignant cells (PubMed:14576828).
CC {ECO:0000269|PubMed:14576828, ECO:0000269|PubMed:8670865}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class dual specificity subfamily. {ECO:0000305}.
CC -!- CAUTION: An out-of-frame translation product, PYST2SB, has been
CC experimentally demonstrated to be formed from the alternative promoter.
CC The expression of the in-frame product has not yet been shown.
CC {ECO:0000305}.
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DR EMBL; AF508727; AAM77606.1; -; mRNA.
DR EMBL; AF508728; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC115284; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL556300; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC019107; AAH19107.2; -; mRNA.
DR EMBL; BC104880; AAI04881.1; -; mRNA.
DR EMBL; BC104882; AAI04883.1; -; mRNA.
DR EMBL; X93921; CAA63814.1; -; mRNA.
DR CCDS; CCDS33766.2; -. [Q16829-1]
DR RefSeq; NP_001938.2; NM_001947.3. [Q16829-1]
DR PDB; 4Y2E; X-ray; 1.67 A; A/B/C/D=240-388.
DR PDBsum; 4Y2E; -.
DR AlphaFoldDB; Q16829; -.
DR SMR; Q16829; -.
DR BioGRID; 108182; 65.
DR IntAct; Q16829; 17.
DR MINT; Q16829; -.
DR STRING; 9606.ENSP00000417183; -.
DR DEPOD; DUSP7; -.
DR iPTMnet; Q16829; -.
DR PhosphoSitePlus; Q16829; -.
DR BioMuta; DUSP7; -.
DR DMDM; 338817906; -.
DR EPD; Q16829; -.
DR jPOST; Q16829; -.
DR MassIVE; Q16829; -.
DR MaxQB; Q16829; -.
DR PaxDb; Q16829; -.
DR PeptideAtlas; Q16829; -.
DR PRIDE; Q16829; -.
DR ProteomicsDB; 61091; -. [Q16829-1]
DR ProteomicsDB; 61092; -. [Q16829-2]
DR TopDownProteomics; Q16829-2; -. [Q16829-2]
DR Antibodypedia; 31149; 180 antibodies from 25 providers.
DR DNASU; 1849; -.
DR Ensembl; ENST00000495880.2; ENSP00000417183.1; ENSG00000164086.10. [Q16829-1]
DR GeneID; 1849; -.
DR KEGG; hsa:1849; -.
DR MANE-Select; ENST00000495880.2; ENSP00000417183.1; NM_001947.4; NP_001938.2.
DR UCSC; uc003dct.4; human. [Q16829-1]
DR CTD; 1849; -.
DR DisGeNET; 1849; -.
DR GeneCards; DUSP7; -.
DR HGNC; HGNC:3073; DUSP7.
DR HPA; ENSG00000164086; Tissue enhanced (esophagus).
DR MIM; 602749; gene.
DR neXtProt; NX_Q16829; -.
DR OpenTargets; ENSG00000164086; -.
DR PharmGKB; PA27530; -.
DR VEuPathDB; HostDB:ENSG00000164086; -.
DR eggNOG; KOG1717; Eukaryota.
DR GeneTree; ENSGT00940000157262; -.
DR HOGENOM; CLU_027074_0_0_1; -.
DR InParanoid; Q16829; -.
DR OMA; TAEWQQD; -.
DR OrthoDB; 911920at2759; -.
DR PhylomeDB; Q16829; -.
DR TreeFam; TF105122; -.
DR PathwayCommons; Q16829; -.
DR Reactome; R-HSA-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-HSA-202670; ERKs are inactivated.
DR Reactome; R-HSA-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-HSA-9652817; Signaling by MAPK mutants.
DR SignaLink; Q16829; -.
DR SIGNOR; Q16829; -.
DR BioGRID-ORCS; 1849; 18 hits in 1083 CRISPR screens.
DR ChiTaRS; DUSP7; human.
DR GeneWiki; DUSP7; -.
DR GenomeRNAi; 1849; -.
DR Pharos; Q16829; Tbio.
DR PRO; PR:Q16829; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q16829; protein.
DR Bgee; ENSG00000164086; Expressed in oocyte and 198 other tissues.
DR ExpressionAtlas; Q16829; baseline and differential.
DR Genevisible; Q16829; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0017017; F:MAP kinase tyrosine/serine/threonine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IBA:GO_Central.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; TAS:Reactome.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; TAS:Reactome.
DR GO; GO:0008330; F:protein tyrosine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; TAS:Reactome.
DR GO; GO:0000165; P:MAPK cascade; TAS:Reactome.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IDA:UniProtKB.
DR Gene3D; 3.40.250.10; -; 1.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR000340; Dual-sp_phosphatase_cat-dom.
DR InterPro; IPR008343; MKP.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR001763; Rhodanese-like_dom.
DR InterPro; IPR036873; Rhodanese-like_dom_sf.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR Pfam; PF00782; DSPc; 1.
DR Pfam; PF00581; Rhodanese; 1.
DR PIRSF; PIRSF000939; MAPK_Ptase; 1.
DR PRINTS; PR01764; MAPKPHPHTASE.
DR SMART; SM00195; DSPc; 1.
DR SMART; SM00450; RHOD; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR SUPFAM; SSF52821; SSF52821; 1.
DR PROSITE; PS50206; RHODANESE_3; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative promoter usage; Cytoplasm; Hydrolase;
KW Protein phosphatase; Reference proteome.
FT CHAIN 1..419
FT /note="Dual specificity protein phosphatase 7"
FT /id="PRO_0000094807"
FT DOMAIN 68..187
FT /note="Rhodanese"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT DOMAIN 244..387
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 216..240
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 331
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT BINDING 331..337
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26057789,
FT ECO:0007744|PDB:4Y2E"
FT VAR_SEQ 1..51
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14603440"
FT /id="VSP_012822"
FT VARIANT 235
FT /note="S -> N (in dbSNP:rs34821455)"
FT /id="VAR_051752"
FT CONFLICT 87..90
FT /note="HIET -> THRD (in Ref. 1; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT STRAND 246..249
FT /evidence="ECO:0007829|PDB:4Y2E"
FT STRAND 252..255
FT /evidence="ECO:0007829|PDB:4Y2E"
FT HELIX 257..260
FT /evidence="ECO:0007829|PDB:4Y2E"
FT HELIX 263..268
FT /evidence="ECO:0007829|PDB:4Y2E"
FT STRAND 271..276
FT /evidence="ECO:0007829|PDB:4Y2E"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:4Y2E"
FT STRAND 287..290
FT /evidence="ECO:0007829|PDB:4Y2E"
FT STRAND 292..295
FT /evidence="ECO:0007829|PDB:4Y2E"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:4Y2E"
FT HELIX 310..322
FT /evidence="ECO:0007829|PDB:4Y2E"
FT STRAND 326..330
FT /evidence="ECO:0007829|PDB:4Y2E"
FT STRAND 332..336
FT /evidence="ECO:0007829|PDB:4Y2E"
FT HELIX 337..349
FT /evidence="ECO:0007829|PDB:4Y2E"
FT HELIX 354..364
FT /evidence="ECO:0007829|PDB:4Y2E"
FT HELIX 372..385
FT /evidence="ECO:0007829|PDB:4Y2E"
SQ SEQUENCE 419 AA; 44957 MW; 434467AC16A3F8BA CRC64;
MKNQLRGPPA RAHMSTSGAA AAGGTRAGSE PGAGSGSGAG TGAGAATGAG AMPCKSAEWL
QEELEARGGA SLLLLDCRPH ELFESSHIET AINLAIPGLM LRRLRKGNLP IRSIIPNHAD
KERFATRCKA ATVLLYDEAT AEWQPEPGAP ASVLGLLLQK LRDDGCQAYY LQGGFNKFQT
EYSEHCETNV DSSSSPSSSP PTSVLGLGGL RISSDCSDGE SDRELPSSAT ESDGSPVPSS
QPAFPVQILP YLYLGCAKDS TNLDVLGKYG IKYILNVTPN LPNAFEHGGE FTYKQIPISD
HWSQNLSQFF PEAISFIDEA RSKKCGVLVH CLAGISRSVT VTVAYLMQKM NLSLNDAYDF
VKRKKSNISP NFNFMGQLLD FERTLGLSSP CDNHASSEQL YFSTPTNHNL FPLNTLEST
