DUSP_VAR67
ID DUSP_VAR67 Reviewed; 171 AA.
AC P0DOQ5; P33064;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2019, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=Dual specificity protein phosphatase H1;
DE EC=3.1.3.-;
DE EC=3.1.3.48 {ECO:0000269|PubMed:16793284, ECO:0000269|PubMed:17505108};
DE AltName: Full=Late protein H1;
GN ORFNames=H1L, I1L;
OS Variola virus (isolate Human/India/Ind3/1967) (VARV) (Smallpox virus).
OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus.
OX NCBI_TaxID=587200;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8383392; DOI=10.1016/0168-1702(93)90110-9;
RA Shchelkunov S.N., Blinov V.M., Totmenin A.V., Marennikova S.S.,
RA Kolykhalov A.A., Frolov I.V., Chizhikov V.E., Gytorov V.V., Gashikov P.V.,
RA Belanov E.F., Belavin P.A., Resenchuk S.M., Andzhaparidze O.G.,
RA Sandakhchiev L.S.;
RT "Nucleotide sequence analysis of variola virus HindIII M, L, I genome
RT fragments.";
RL Virus Res. 27:25-35(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=8384129; DOI=10.1016/0014-5793(93)80041-r;
RA Shchelkunov S.N., Blinov V.M., Sandakhchiev L.S.;
RT "Genes of variola and vaccinia viruses necessary to overcome the host
RT protective mechanisms.";
RL FEBS Lett. 319:80-83(1993).
RN [3]
RP CATALYTIC ACTIVITY, SUBUNIT, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16793284; DOI=10.1016/j.pep.2006.05.007;
RA Tropea J.E., Phan J., Waugh D.S.;
RT "Overproduction, purification, and biochemical characterization of the dual
RT specificity H1 protein phosphatase encoded by variola major virus.";
RL Protein Expr. Purif. 50:31-36(2006).
RN [4] {ECO:0007744|PDB:2P4D}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS), CATALYTIC ACTIVITY, SUBUNIT,
RP ACTIVITY REGULATION, AND ACTIVE SITE.
RX PubMed=17505108; DOI=10.1107/s0907444907014904;
RA Phan J., Tropea J.E., Waugh D.S.;
RT "Structure-assisted discovery of Variola major H1 phosphatase inhibitors.";
RL Acta Crystallogr. D 63:698-704(2007).
CC -!- FUNCTION: Serine/Tyrosine phosphatase which down-regulates cellular
CC antiviral response by dephosphorylating activated host STAT1 and
CC blocking interferon (IFN)-stimulated innate immune responses.
CC Dephosphorylates the A17 protein (By similarity). {ECO:0000250}.
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; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10044, ECO:0000269|PubMed:16793284,
CC ECO:0000269|PubMed:17505108};
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;
CC -!- ACTIVITY REGULATION: Inhibited by NSC-62914, NSC-28086, NSC-105687,
CC NSC-23173, 540211 and 217691 with IC50 values of 48, 51, 212, 342, 4
CC and 11 uM, respectively. {ECO:0000269|PubMed:17505108}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=228 uM for para-nitrophenyl phosphate
CC {ECO:0000269|PubMed:16793284};
CC pH dependence:
CC Optimum pH is 6.5-7.0. {ECO:0000269|PubMed:16793284};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16793284,
CC ECO:0000269|PubMed:17505108}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000250}. Host cytoplasm
CC {ECO:0000250}. Note=Approximately 200 molecules of H1 are packaged
CC within the virion and are essential for the viability of the virus.
CC {ECO:0000250}.
CC -!- INDUCTION: Expressed in the late phase of the viral replicative cycle.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class dual specificity subfamily. {ECO:0000305}.
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DR EMBL; X67119; CAA47583.1; -; Genomic_DNA.
DR EMBL; S55844; AAB24680.1; -; Genomic_DNA.
DR EMBL; X69198; CAA49025.1; -; Genomic_DNA.
DR PIR; I36845; I36845.
DR RefSeq; NP_042128.1; NC_001611.1.
DR PDB; 2P4D; X-ray; 1.80 A; A=1-171.
DR PDBsum; 2P4D; -.
DR SMR; P0DOQ5; -.
DR GeneID; 1486439; -.
DR KEGG; vg:1486439; -.
DR Proteomes; UP000002060; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IEA:RHEA.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IEA:InterPro.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
DR GO; GO:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR000340; Dual-sp_phosphatase_cat-dom.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR Pfam; PF00782; DSPc; 1.
DR SMART; SM00195; DSPc; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host cytoplasm; Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host STAT1 by virus; Late protein; Protein phosphatase;
KW Reference proteome; Viral immunoevasion; Virion.
FT CHAIN 1..171
FT /note="Dual specificity protein phosphatase H1"
FT /id="PRO_0000094869"
FT DOMAIN 23..171
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT ACT_SITE 110
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000269|PubMed:17505108"
FT HELIX 6..14
FT /evidence="ECO:0007829|PDB:2P4D"
FT STRAND 31..37
FT /evidence="ECO:0007829|PDB:2P4D"
FT HELIX 39..44
FT /evidence="ECO:0007829|PDB:2P4D"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:2P4D"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:2P4D"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:2P4D"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:2P4D"
FT STRAND 80..83
FT /evidence="ECO:0007829|PDB:2P4D"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:2P4D"
FT HELIX 89..102
FT /evidence="ECO:0007829|PDB:2P4D"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:2P4D"
FT STRAND 111..115
FT /evidence="ECO:0007829|PDB:2P4D"
FT HELIX 116..128
FT /evidence="ECO:0007829|PDB:2P4D"
FT HELIX 134..149
FT /evidence="ECO:0007829|PDB:2P4D"
FT HELIX 156..166
FT /evidence="ECO:0007829|PDB:2P4D"
SQ SEQUENCE 171 AA; 19746 MW; 1D58C54FF17BADF7 CRC64;
MDKKSLYKYL LLRSTGDMRR AKSPTIMTRV TNNVYLGNYK NAMNAPSSEV KFKYVLNLTM
DKYTLPNSNI NIIHIPLVDD TTTDISKYFD DVTAFLSKCD QRNEPVLVHC VAGVNRSGAM
ILAYLMSKNK ESSPMLYFLY VYHSMRDLRG AFVENPSFKR QIIEKYVIDK N
