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 01-MAY-2013, entry version 105.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT 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
RT 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
RT project: 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
RT lung fibroblast cell line WI-38.";
RL Recept. Signal Transduct. 7:241-256(1997).
RN [6]
RP TISSUE SPECIFICITY, MUTAGENESIS OF CYS-104, ENZYME 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.,
RA Dixon J., Johnson B., Bloem L., Pickard T., Donaghue M., Acton S.,
RA Jeyaseelan R., 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.,
RA St Croix B., Romans K.E., Choti M.A., Lengauer C., Kinzler K.W.,
RA 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
RT and the mitotic spindle and is required for normal mitosis.";
RL J. Biol. Chem. 277:46659-46668(2002).
RN [9]
RP ENZYME 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
RP 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-
RT associated phosphatase PRL-3.";
RL J. Biol. Chem. 279:11882-11889(2004).
CC -!- FUNCTION: Protein tyrosine phosphatase which stimulates
CC progression from G1 into S phase during mitosis. Enhances cell
CC proliferation, cell motility and invasive activity, and promotes
CC cancer metastasis. May be involved in the progression of cardiac
CC hypertrophy by inhibiting intracellular calcium mobilization in
CC response to angiotensin II.
CC -!- CATALYTIC ACTIVITY: Protein tyrosine phosphate + H(2)O = protein
CC tyrosine + phosphate.
CC -!- ENZYME REGULATION: Inhibited by sodium orthovanadate and
CC peroxovanadium compounds, and by pentamidine.
CC -!- SUBUNIT: Interacts with tubulin.
CC -!- SUBCELLULAR LOCATION: Cell membrane. Early endosome.
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 Note=Unstructured and inactive;
CC Name=3; Synonyms=short;
CC IsoId=O75365-3; Sequence=VSP_014406;
CC -!- TISSUE SPECIFICITY: Mainly expressed in cardiomyocytes and
CC skeletal muscle; also found in pancreas. Consistently
CC overexpressed in colon cancer metastasis.
CC -!- PTM: Farnesylated. Farnesylation is required for membrane
CC targeting (By similarity).
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC -!- SIMILARITY: Contains 1 tyrosine-protein phosphatase domain.
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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 IPI; IPI00026647; -.
DR IPI; IPI00217075; -.
DR IPI; IPI00289328; -.
DR RefSeq; NP_009010.2; NM_007079.2.
DR RefSeq; NP_116000.1; NM_032611.1.
DR UniGene; Hs.741196; -.
DR PDB; 1R6H; NMR; -; A=1-169.
DR PDB; 1V3A; NMR; -; A=1-173.
DR PDBsum; 1R6H; -.
DR PDBsum; 1V3A; -.
DR DisProt; DP00254; -.
DR ProteinModelPortal; O75365; -.
DR IntAct; O75365; 4.
DR STRING; 9606.ENSP00000332274; -.
DR PhosphoSite; O75365; -.
DR PaxDb; O75365; -.
DR PRIDE; O75365; -.
DR DNASU; 11156; -.
DR Ensembl; ENST00000329397; ENSP00000332274; ENSG00000184489.
DR Ensembl; ENST00000349124; ENSP00000331730; ENSG00000184489.
DR Ensembl; ENST00000520105; ENSP00000428758; ENSG00000184489.
DR Ensembl; ENST00000521578; ENSP00000428976; ENSG00000184489.
DR GeneID; 11156; -.
DR KEGG; hsa:11156; -.
DR UCSC; uc003ywg.1; human.
DR UCSC; uc003ywh.1; human.
DR CTD; 11156; -.
DR GeneCards; GC08P142432; -.
DR HGNC; HGNC:9636; PTP4A3.
DR HPA; HPA003281; -.
DR MIM; 606449; gene.
DR neXtProt; NX_O75365; -.
DR PharmGKB; PA33979; -.
DR eggNOG; NOG265664; -.
DR HOGENOM; HOG000231265; -.
DR HOVERGEN; HBG071295; -.
DR InParanoid; O75365; -.
DR KO; K01104; -.
DR OMA; KAKFCDD; -.
DR OrthoDB; EOG415GFJ; -.
DR PhylomeDB; O75365; -.
DR Pathway_Interaction_DB; prlsignalingeventspathway; Signaling events mediated by PRL.
DR BindingDB; O75365; -.
DR ChEMBL; CHEMBL4162; -.
DR EvolutionaryTrace; O75365; -.
DR GenomeRNAi; 11156; -.
DR NextBio; 42423; -.
DR ArrayExpress; O75365; -.
DR Bgee; O75365; -.
DR CleanEx; HS_PTP4A3; -.
DR Genevestigator; O75365; -.
DR GermOnline; ENSG00000184489; Homo sapiens.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004727; F:prenylated protein tyrosine phosphatase activity; TAS:ProtInc.
DR InterPro; IPR000387; Tyr/Dual-sp_Pase.
DR InterPro; IPR000242; Tyr_Pase_rcpt/non-rcpt.
DR Pfam; PF00102; Y_phosphatase; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; FALSE_NEG.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50055; TYR_PHOSPHATASE_PTP; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Complete proteome;
KW Disulfide bond; Endosome; Hydrolase; Lipoprotein; Membrane;
KW Methylation; Prenylation; Protein phosphatase; Reference proteome.
FT CHAIN 1 170 Protein tyrosine phosphatase type IVA 3.
FT /FTId=PRO_0000094788.
FT PROPEP 171 173 Removed in mature form (By similarity).
FT /FTId=PRO_0000396735.
FT DOMAIN 82 148 Tyrosine-protein phosphatase.
FT ACT_SITE 72 72 Proton donor (Probable).
FT ACT_SITE 104 104 Phosphocysteine intermediate.
FT BINDING 110 110 Substrate.
FT MOD_RES 170 170 Cysteine methyl ester (By similarity).
FT LIPID 170 170 S-farnesyl cysteine (By similarity).
FT DISULFID 49 104
FT VAR_SEQ 39 124 Missing (in isoform 3).
FT /FTId=VSP_014406.
FT VAR_SEQ 111 135 Missing (in isoform 2).
FT /FTId=VSP_014407.
FT MUTAGEN 49 49 C->A: No effect on enzymatic activity.
FT MUTAGEN 71 71 D->A: No effect on enzymatic activity.
FT MUTAGEN 72 72 D->A: Abolishes enzymatic activity.
FT MUTAGEN 104 104 C->A,S: 95% loss of enzymatic activity.
FT MUTAGEN 104 104 C->S: Reduces migration-promoting
FT activity.
FT MUTAGEN 111 111 A->S: Enhances catalytic activity.
FT CONFLICT 140 140 A -> R (in Ref. 1; AAC29314).
FT STRAND 10 14
FT STRAND 17 22
FT TURN 27 29
FT HELIX 30 40
FT STRAND 45 49
FT HELIX 55 61
FT STRAND 65 68
FT STRAND 69 71
FT HELIX 79 94
FT STRAND 99 103
FT STRAND 107 110
FT HELIX 111 119
FT HELIX 120 122
FT HELIX 125 135
FT STRAND 137 139
FT HELIX 144 152
FT TURN 156 158
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
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