DUS12_HUMAN
ID DUS12_HUMAN Reviewed; 340 AA.
AC Q9UNI6; Q5VXA8;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Dual specificity protein phosphatase 12;
DE EC=3.1.3.16 {ECO:0000250|UniProtKB:Q9JIM4};
DE EC=3.1.3.48 {ECO:0000250|UniProtKB:Q9JIM4};
DE AltName: Full=Dual specificity tyrosine phosphatase YVH1;
GN Name=DUSP12;
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], CHARACTERIZATION, ZINC-BINDING, AND SUBCELLULAR
RP LOCATION.
RX PubMed=10446167; DOI=10.1074/jbc.274.34.23991;
RA Muda M., Manning E.R., Orth K., Dixon J.E.;
RT "Identification of the human YVH1 protein-tyrosine phosphatase orthologue
RT reveals a novel zinc binding domain essential for in vivo function.";
RL J. Biol. Chem. 274:23991-23995(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-335, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10] {ECO:0007744|PDB:4JNB, ECO:0007744|PDB:4KI9}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 27-189 IN COMPLEX WITH PHOSPHATE,
RP FUNCTION, AND SUBUNIT.
RX PubMed=24531476; DOI=10.1107/s1399004713029866;
RA Jeong D.G., Wei C.H., Ku B., Jeon T.J., Chien P.N., Kim J.K., Park S.Y.,
RA Hwang H.S., Ryu S.Y., Park H., Kim D.S., Kim S.J., Ryu S.E.;
RT "The family-wide structure and function of human dual-specificity protein
RT phosphatases.";
RL Acta Crystallogr. D 70:421-435(2014).
CC -!- FUNCTION: Dual specificity phosphatase; can dephosphorylate both
CC phosphotyrosine and phosphoserine or phosphothreonine residues. Can
CC dephosphorylate glucokinase (in vitro) (By similarity). Has phosphatase
CC activity with the synthetic substrate 6,8-difluoro-4-methylumbelliferyl
CC phosphate and other in vitro substrates (PubMed:10446167,
CC PubMed:24531476). {ECO:0000250|UniProtKB:Q9JIM4,
CC ECO:0000269|PubMed:10446167, ECO:0000269|PubMed:24531476}.
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:0000250|UniProtKB:Q9JIM4};
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:0000250|UniProtKB:Q9JIM4};
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:0000250|UniProtKB:Q9JIM4};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 2 Zn(2+) ions per subunit.;
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:24531476}.
CC -!- INTERACTION:
CC Q9UNI6; Q13137: CALCOCO2; NbExp=5; IntAct=EBI-715161, EBI-739580;
CC Q9UNI6; P51946: CCNH; NbExp=7; IntAct=EBI-715161, EBI-741406;
CC Q9UNI6; P55010: EIF5; NbExp=6; IntAct=EBI-715161, EBI-286450;
CC Q9UNI6; Q9UJY1: HSPB8; NbExp=3; IntAct=EBI-715161, EBI-739074;
CC Q9UNI6; P20645: M6PR; NbExp=3; IntAct=EBI-715161, EBI-2907262;
CC Q9UNI6; Q9Y5P8: PPP2R3B; NbExp=4; IntAct=EBI-715161, EBI-2479826;
CC Q9UNI6; Q9UI14: RABAC1; NbExp=7; IntAct=EBI-715161, EBI-712367;
CC Q9UNI6; O60763: USO1; NbExp=3; IntAct=EBI-715161, EBI-356164;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10446167}. Cytoplasm,
CC cytosol {ECO:0000269|PubMed:10446167}. Note=Primarily nuclear. Detected
CC in a mesh-like pattern in the cytosol. {ECO:0000269|PubMed:10446167}.
CC -!- TISSUE SPECIFICITY: Ubiquitous, highest expression in spleen, testis,
CC ovary, and peripheral blood leukocytes and lower expression in liver
CC and lung.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class dual specificity subfamily. {ECO:0000305}.
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DR EMBL; AF119226; AAD51134.1; -; mRNA.
DR EMBL; BT006633; AAP35279.1; -; mRNA.
DR EMBL; AL359541; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006286; AAH06286.1; -; mRNA.
DR CCDS; CCDS1234.1; -.
DR RefSeq; NP_009171.1; NM_007240.2.
DR PDB; 4JNB; X-ray; 3.00 A; A=27-193.
DR PDB; 4KI9; X-ray; 2.00 A; A=27-189.
DR PDBsum; 4JNB; -.
DR PDBsum; 4KI9; -.
DR AlphaFoldDB; Q9UNI6; -.
DR SMR; Q9UNI6; -.
DR BioGRID; 116424; 58.
DR IntAct; Q9UNI6; 13.
DR MINT; Q9UNI6; -.
DR STRING; 9606.ENSP00000356920; -.
DR DEPOD; DUSP12; -.
DR iPTMnet; Q9UNI6; -.
DR PhosphoSitePlus; Q9UNI6; -.
DR BioMuta; DUSP12; -.
DR DMDM; 9973073; -.
DR EPD; Q9UNI6; -.
DR jPOST; Q9UNI6; -.
DR MassIVE; Q9UNI6; -.
DR MaxQB; Q9UNI6; -.
DR PaxDb; Q9UNI6; -.
DR PeptideAtlas; Q9UNI6; -.
DR PRIDE; Q9UNI6; -.
DR ProteomicsDB; 85298; -.
DR Antibodypedia; 1653; 226 antibodies from 25 providers.
DR DNASU; 11266; -.
DR Ensembl; ENST00000367943.5; ENSP00000356920.4; ENSG00000081721.12.
DR GeneID; 11266; -.
DR KEGG; hsa:11266; -.
DR MANE-Select; ENST00000367943.5; ENSP00000356920.4; NM_007240.3; NP_009171.1.
DR UCSC; uc001gbo.4; human.
DR CTD; 11266; -.
DR DisGeNET; 11266; -.
DR GeneCards; DUSP12; -.
DR HGNC; HGNC:3067; DUSP12.
DR HPA; ENSG00000081721; Low tissue specificity.
DR MIM; 604835; gene.
DR neXtProt; NX_Q9UNI6; -.
DR OpenTargets; ENSG00000081721; -.
DR PharmGKB; PA27522; -.
DR VEuPathDB; HostDB:ENSG00000081721; -.
DR eggNOG; KOG1716; Eukaryota.
DR GeneTree; ENSGT00930000151041; -.
DR HOGENOM; CLU_023312_1_0_1; -.
DR InParanoid; Q9UNI6; -.
DR OMA; RIMLNTQ; -.
DR OrthoDB; 1482182at2759; -.
DR PhylomeDB; Q9UNI6; -.
DR TreeFam; TF105123; -.
DR PathwayCommons; Q9UNI6; -.
DR SignaLink; Q9UNI6; -.
DR BioGRID-ORCS; 11266; 57 hits in 1084 CRISPR screens.
DR ChiTaRS; DUSP12; human.
DR GeneWiki; DUSP12; -.
DR GenomeRNAi; 11266; -.
DR Pharos; Q9UNI6; Tbio.
DR PRO; PR:Q9UNI6; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UNI6; protein.
DR Bgee; ENSG00000081721; Expressed in oocyte and 193 other tissues.
DR ExpressionAtlas; Q9UNI6; baseline and differential.
DR Genevisible; Q9UNI6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0019900; F:kinase binding; IEA:Ensembl.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0016791; F:phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; TAS:ProtInc.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0016311; P:dephosphorylation; IDA:UniProtKB.
DR GO; GO:0033133; P:positive regulation of glucokinase activity; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; IBA:GO_Central.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR000340; Dual-sp_phosphatase_cat-dom.
DR InterPro; IPR016278; DUSP12.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00782; DSPc; 1.
DR PIRSF; PIRSF000941; DUSP12; 1.
DR SMART; SM00195; DSPc; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Hydrolase; Metal-binding; Nucleus;
KW Phosphoprotein; Protein phosphatase; Reference proteome; Zinc.
FT CHAIN 1..340
FT /note="Dual specificity protein phosphatase 12"
FT /id="PRO_0000094818"
FT DOMAIN 26..171
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT ACT_SITE 115
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT BINDING 116..121
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:24531476,
FT ECO:0007744|PDB:4KI9"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 51
FT /note="A -> E (in dbSNP:rs35106830)"
FT /id="VAR_033899"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:4KI9"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:4KI9"
FT HELIX 39..43
FT /evidence="ECO:0007829|PDB:4KI9"
FT HELIX 45..51
FT /evidence="ECO:0007829|PDB:4KI9"
FT STRAND 53..62
FT /evidence="ECO:0007829|PDB:4KI9"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:4KI9"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:4KI9"
FT HELIX 94..106
FT /evidence="ECO:0007829|PDB:4KI9"
FT STRAND 110..114
FT /evidence="ECO:0007829|PDB:4KI9"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:4KI9"
FT HELIX 121..134
FT /evidence="ECO:0007829|PDB:4KI9"
FT HELIX 138..148
FT /evidence="ECO:0007829|PDB:4KI9"
FT HELIX 156..167
FT /evidence="ECO:0007829|PDB:4KI9"
FT HELIX 177..186
FT /evidence="ECO:0007829|PDB:4KI9"
SQ SEQUENCE 340 AA; 37687 MW; 56B52192B42C73EB CRC64;
MLEAPGPSDG CELSNPSASR VSCAGQMLEV QPGLYFGGAA AVAEPDHLRE AGITAVLTVD
SEEPSFKAGP GVEDLWRLFV PALDKPETDL LSHLDRCVAF IGQARAEGRA VLVHCHAGVS
RSVAIITAFL MKTDQLPFEK AYEKLQILKP EAKMNEGFEW QLKLYQAMGY EVDTSSAIYK
QYRLQKVTEK YPELQNLPQE LFAVDPTTVS QGLKDEVLYK CRKCRRSLFR SSSILDHREG
SGPIAFAHKR MTPSSMLTTG RQAQCTSYFI EPVQWMESAL LGVMDGQLLC PKCSAKLGSF
NWYGEQCSCG RWITPAFQIH KNRVDEMKIL PVLGSQTGKI
