TP4A3_HUMAN
ID TP4A3_HUMAN Reviewed; 173 AA.
AC O75365; Q8IVN5; Q99849; Q9BTW5;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Protein tyrosine phosphatase type IVA 3;
DE EC=3.1.3.48;
DE AltName: Full=PRL-R;
DE AltName: Full=Protein-tyrosine phosphatase 4a3;
DE AltName: Full=Protein-tyrosine phosphatase of regenerating liver 3;
DE Short=PRL-3;
DE Flags: Precursor;
GN Name=PTP4A3; Synonyms=PRL3;
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 1).
RA Zeng Q., Tan Y.H., Hong W.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Skeletal muscle;
RA Ievolella C., Stanchi F., Pacchioni B., Silvia T., Frigimelica E.,
RA Scannapieco P., Corso V., Biasio B., Lanfranchi G.;
RT "Full-length of some muscular transcripts, Telethon (Italy) project B41.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Eye;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 93-148 (ISOFORM 1).
RC TISSUE=Lung fibroblast;
RX PubMed=9633825;
RA Dayton M.A., Knobloch T.J.;
RT "Multiple phosphotyrosine phosphatase mRNAs are expressed in the human lung
RT fibroblast cell line WI-38.";
RL Recept. Signal Transduct. 7:241-256(1997).
RN [6]
RP TISSUE SPECIFICITY, MUTAGENESIS OF CYS-104, ACTIVITY REGULATION, AND
RP FUNCTION.
RX PubMed=11355880; DOI=10.1006/bbrc.2001.4881;
RA Matter W.F., Estridge T., Zhang C., Belagaje R., Stancato L., Dixon J.,
RA Johnson B., Bloem L., Pickard T., Donaghue M., Acton S., Jeyaseelan R.,
RA Kadambi V., Vlahos C.J.;
RT "Role of PRL-3, a human muscle-specific tyrosine phosphatase, in
RT angiotensin-II signaling.";
RL Biochem. Biophys. Res. Commun. 283:1061-1068(2001).
RN [7]
RP OVEREXPRESSION IN COLON CANCER.
RX PubMed=11598267; DOI=10.1126/science.1065817;
RA Saha S., Bardelli A., Buckhaults P., Velculescu V.E., Rago C., St Croix B.,
RA Romans K.E., Choti M.A., Lengauer C., Kinzler K.W., Vogelstein B.;
RT "A phosphatase associated with metastasis of colorectal cancer.";
RL Science 294:1343-1346(2001).
RN [8]
RP INTERACTION WITH TUBULIN.
RX PubMed=12235145; DOI=10.1074/jbc.m206407200;
RA Wang J., Kirby C.E., Herbst R.;
RT "The tyrosine phosphatase PRL-1 localizes to the endoplasmic reticulum and
RT the mitotic spindle and is required for normal mitosis.";
RL J. Biol. Chem. 277:46659-46668(2002).
RN [9]
RP ACTIVITY REGULATION.
RX PubMed=12516958;
RA Pathak M.K., Dhawan D., Lindner D.J., Borden E.C., Farver C., Yi T.;
RT "Pentamidine is an inhibitor of PRL phosphatases with anticancer
RT activity.";
RL Mol. Cancer Ther. 1:1255-1264(2002).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-104.
RX PubMed=12782572;
RA Zeng Q., Dong J.-M., Guo K., Li J., Tan H.-X., Koh V., Pallen C.J.,
RA Manser E., Hong W.;
RT "PRL-3 and PRL-1 promote cell migration, invasion, and metastasis.";
RL Cancer Res. 63:2716-2722(2003).
RN [11]
RP STRUCTURE BY NMR OF 1-173 (ISOFORM 1).
RX PubMed=15135076; DOI=10.1016/j.febslet.2004.03.062;
RA Kim K.-A., Song J.-S., Jee J., Sheen M.R., Lee C., Lee T.G., Ro S.,
RA Cho J.M., Lee W., Yamazaki T., Jeon Y.H., Cheong C.;
RT "Structure of human PRL-3, the phosphatase associated with cancer
RT metastasis.";
RL FEBS Lett. 565:181-187(2004).
RN [12]
RP STRUCTURE BY NMR OF 1-169 (ISOFORM 1), DISULFIDE BOND, ENZYME ACTIVITY
RP (ISOFORMS 1 AND 2), AND MUTAGENESIS OF CYS-49; ASP-71; ASP-72 AND ALA-111.
RX PubMed=14704153; DOI=10.1074/jbc.m312905200;
RA Kozlov G., Cheng J., Ziomek E., Banville D., Gehring K., Ekiel I.;
RT "Structural insights into molecular function of the metastasis-associated
RT phosphatase PRL-3.";
RL J. Biol. Chem. 279:11882-11889(2004).
CC -!- FUNCTION: Protein tyrosine phosphatase which stimulates progression
CC from G1 into S phase during mitosis. Enhances cell proliferation, cell
CC motility and invasive activity, and promotes cancer metastasis. May be
CC involved in the progression of cardiac hypertrophy by inhibiting
CC intracellular calcium mobilization in response to angiotensin II.
CC {ECO:0000269|PubMed:11355880, ECO:0000269|PubMed:12782572}.
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 -!- ACTIVITY REGULATION: Inhibited by sodium orthovanadate and
CC peroxovanadium compounds, and by pentamidine.
CC {ECO:0000269|PubMed:11355880, ECO:0000269|PubMed:12516958}.
CC -!- SUBUNIT: Interacts with tubulin. {ECO:0000269|PubMed:12235145}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12782572}.
CC Early endosome {ECO:0000269|PubMed:12782572}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=O75365-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75365-2; Sequence=VSP_014407;
CC Name=3; Synonyms=short;
CC IsoId=O75365-3; Sequence=VSP_014406;
CC -!- TISSUE SPECIFICITY: Mainly expressed in cardiomyocytes and skeletal
CC muscle; also found in pancreas. Consistently overexpressed in colon
CC cancer metastasis. {ECO:0000269|PubMed:11355880}.
CC -!- PTM: Farnesylated. Farnesylation is required for membrane targeting (By
CC similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 2]: Unstructured and inactive. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC {ECO:0000305}.
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DR EMBL; AF041434; AAC29314.1; -; mRNA.
DR EMBL; AJ276554; CAC81757.1; -; mRNA.
DR EMBL; BT007303; AAP35967.1; -; mRNA.
DR EMBL; BC003105; AAH03105.1; -; mRNA.
DR EMBL; U87168; AAB47560.1; -; mRNA.
DR CCDS; CCDS6382.1; -. [O75365-2]
DR CCDS; CCDS6383.1; -. [O75365-1]
DR RefSeq; NP_009010.2; NM_007079.3. [O75365-2]
DR RefSeq; NP_116000.1; NM_032611.2. [O75365-1]
DR RefSeq; XP_005250821.1; XM_005250764.2. [O75365-1]
DR RefSeq; XP_011515105.1; XM_011516803.1. [O75365-1]
DR RefSeq; XP_011515107.1; XM_011516805.1. [O75365-1]
DR RefSeq; XP_016868487.1; XM_017012998.1. [O75365-2]
DR PDB; 1R6H; NMR; -; A=1-169.
DR PDB; 1V3A; NMR; -; A=1-173.
DR PDB; 2MBC; NMR; -; A=1-162.
DR PDB; 5TSR; X-ray; 3.19 A; A/C=1-169.
DR PDBsum; 1R6H; -.
DR PDBsum; 1V3A; -.
DR PDBsum; 2MBC; -.
DR PDBsum; 5TSR; -.
DR AlphaFoldDB; O75365; -.
DR BMRB; O75365; -.
DR SMR; O75365; -.
DR BioGRID; 116327; 152.
DR IntAct; O75365; 10.
DR MINT; O75365; -.
DR STRING; 9606.ENSP00000332274; -.
DR BindingDB; O75365; -.
DR ChEMBL; CHEMBL4162; -.
DR DrugCentral; O75365; -.
DR DEPOD; PTP4A3; -.
DR iPTMnet; O75365; -.
DR PhosphoSitePlus; O75365; -.
DR BioMuta; PTP4A3; -.
DR EPD; O75365; -.
DR jPOST; O75365; -.
DR MassIVE; O75365; -.
DR MaxQB; O75365; -.
DR PaxDb; O75365; -.
DR PeptideAtlas; O75365; -.
DR PRIDE; O75365; -.
DR ProteomicsDB; 49929; -. [O75365-1]
DR ProteomicsDB; 49930; -. [O75365-2]
DR ProteomicsDB; 49931; -. [O75365-3]
DR Antibodypedia; 27728; 350 antibodies from 35 providers.
DR DNASU; 11156; -.
DR Ensembl; ENST00000329397.6; ENSP00000332274.1; ENSG00000184489.13. [O75365-1]
DR Ensembl; ENST00000349124.3; ENSP00000331730.2; ENSG00000184489.13. [O75365-1]
DR Ensembl; ENST00000520105.5; ENSP00000428758.1; ENSG00000184489.13. [O75365-2]
DR Ensembl; ENST00000521578.6; ENSP00000428976.1; ENSG00000184489.13. [O75365-1]
DR Ensembl; ENST00000614325.2; ENSP00000481205.1; ENSG00000275575.4. [O75365-2]
DR Ensembl; ENST00000622569.3; ENSP00000484500.1; ENSG00000275575.4. [O75365-1]
DR Ensembl; ENST00000633518.1; ENSP00000487595.1; ENSG00000275575.4. [O75365-1]
DR Ensembl; ENST00000633621.1; ENSP00000487610.1; ENSG00000275575.4. [O75365-2]
DR Ensembl; ENST00000680615.1; ENSP00000505068.1; ENSG00000184489.13. [O75365-1]
DR Ensembl; ENST00000681443.1; ENSP00000506615.1; ENSG00000184489.13. [O75365-2]
DR GeneID; 11156; -.
DR KEGG; hsa:11156; -.
DR MANE-Select; ENST00000521578.6; ENSP00000428976.1; NM_032611.3; NP_116000.1.
DR UCSC; uc003ywg.2; human. [O75365-1]
DR CTD; 11156; -.
DR DisGeNET; 11156; -.
DR GeneCards; PTP4A3; -.
DR HGNC; HGNC:9636; PTP4A3.
DR HPA; ENSG00000184489; Group enriched (heart muscle, pituitary gland, skeletal muscle).
DR MIM; 606449; gene.
DR neXtProt; NX_O75365; -.
DR OpenTargets; ENSG00000184489; -.
DR PharmGKB; PA33979; -.
DR VEuPathDB; HostDB:ENSG00000184489; -.
DR eggNOG; KOG2836; Eukaryota.
DR GeneTree; ENSGT00940000159581; -.
DR HOGENOM; CLU_099263_1_0_1; -.
DR InParanoid; O75365; -.
DR OMA; KYRPRQR; -.
DR OrthoDB; 1398550at2759; -.
DR PhylomeDB; O75365; -.
DR TreeFam; TF313384; -.
DR PathwayCommons; O75365; -.
DR SignaLink; O75365; -.
DR SIGNOR; O75365; -.
DR BioGRID-ORCS; 11156; 22 hits in 1072 CRISPR screens.
DR ChiTaRS; PTP4A3; human.
DR EvolutionaryTrace; O75365; -.
DR GeneWiki; PTP4A3; -.
DR GenomeRNAi; 11156; -.
DR Pharos; O75365; Tchem.
DR PRO; PR:O75365; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O75365; protein.
DR Bgee; ENSG00000184489; Expressed in apex of heart and 94 other tissues.
DR ExpressionAtlas; O75365; baseline and differential.
DR Genevisible; O75365; HS.
DR GO; GO:0005737; C:cytoplasm; IMP:CAFA.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IMP:CAFA.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004727; F:prenylated protein tyrosine phosphatase activity; TAS:ProtInc.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IBA:GO_Central.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IEA:InterPro.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0043542; P:endothelial cell migration; IMP:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:1904951; P:positive regulation of establishment of protein localization; IMP:CAFA.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:CAFA.
DR GO; GO:0043117; P:positive regulation of vascular permeability; IEA:Ensembl.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:CAFA.
DR GO; GO:1900746; P:regulation of vascular endothelial growth factor signaling pathway; IEA:Ensembl.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR Pfam; PF00102; Y_phosphatase; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF52799; SSF52799; 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 splicing; Cell membrane; Disulfide bond;
KW Endosome; Hydrolase; Lipoprotein; Membrane; Methylation; Prenylation;
KW Protein phosphatase; Reference proteome.
FT CHAIN 1..170
FT /note="Protein tyrosine phosphatase type IVA 3"
FT /id="PRO_0000094788"
FT PROPEP 171..173
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000396735"
FT DOMAIN 8..161
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT ACT_SITE 72
FT /note="Proton donor"
FT /evidence="ECO:0000305"
FT ACT_SITE 104
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT BINDING 110
FT /ligand="substrate"
FT MOD_RES 170
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 170
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000250"
FT DISULFID 49..104
FT /evidence="ECO:0000269|PubMed:14704153"
FT VAR_SEQ 39..124
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_014406"
FT VAR_SEQ 111..135
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3"
FT /id="VSP_014407"
FT MUTAGEN 49
FT /note="C->A: No effect on enzymatic activity."
FT /evidence="ECO:0000269|PubMed:14704153"
FT MUTAGEN 71
FT /note="D->A: No effect on enzymatic activity."
FT /evidence="ECO:0000269|PubMed:14704153"
FT MUTAGEN 72
FT /note="D->A: Abolishes enzymatic activity."
FT /evidence="ECO:0000269|PubMed:14704153"
FT MUTAGEN 104
FT /note="C->A,S: 95% loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11355880,
FT ECO:0000269|PubMed:12782572"
FT MUTAGEN 104
FT /note="C->S: Reduces migration-promoting activity."
FT /evidence="ECO:0000269|PubMed:11355880,
FT ECO:0000269|PubMed:12782572"
FT MUTAGEN 111
FT /note="A->S: Enhances catalytic activity."
FT /evidence="ECO:0000269|PubMed:14704153"
FT CONFLICT 140
FT /note="A -> R (in Ref. 1; AAC29314)"
FT /evidence="ECO:0000305"
FT STRAND 10..14
FT /evidence="ECO:0007829|PDB:5TSR"
FT STRAND 17..21
FT /evidence="ECO:0007829|PDB:5TSR"
FT STRAND 23..26
FT /evidence="ECO:0007829|PDB:2MBC"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:5TSR"
FT HELIX 30..39
FT /evidence="ECO:0007829|PDB:5TSR"
FT STRAND 42..47
FT /evidence="ECO:0007829|PDB:5TSR"
FT HELIX 56..60
FT /evidence="ECO:0007829|PDB:5TSR"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:5TSR"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:1V3A"
FT HELIX 78..94
FT /evidence="ECO:0007829|PDB:5TSR"
FT STRAND 99..109
FT /evidence="ECO:0007829|PDB:5TSR"
FT HELIX 110..121
FT /evidence="ECO:0007829|PDB:5TSR"
FT HELIX 126..136
FT /evidence="ECO:0007829|PDB:5TSR"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:1V3A"
FT HELIX 144..147
FT /evidence="ECO:0007829|PDB:5TSR"
FT TURN 148..150
FT /evidence="ECO:0007829|PDB:5TSR"
FT TURN 156..158
FT /evidence="ECO:0007829|PDB:1R6H"
SQ SEQUENCE 173 AA; 19535 MW; 15DF01999A9A3573 CRC64;
MARMNRPAPV EVSYKHMRFL ITHNPTNATL STFIEDLKKY GATTVVRVCE VTYDKTPLEK
DGITVVDWPF DDGAPPPGKV VEDWLSLVKA KFCEAPGSCV AVHCVAGLGR APVLVALALI
ESGMKYEDAI QFIRQKRRGA INSKQLTYLE KYRPKQRLRF KDPHTHKTRC CVM
