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Database: UniProt
Entry: O75365
LinkDB: O75365
Original site: O75365 
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-OCT-2014, entry version 119.
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. {ECO:0000269|PubMed:11355880,
CC       ECO:0000269|PubMed:12782572}.
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       {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         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       {ECO:0000269|PubMed:11355880}.
CC   -!- PTM: Farnesylated. Farnesylation is required for membrane
CC       targeting (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC       {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 tyrosine-protein phosphatase domain.
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_005250819.1; XM_005250762.2. [O75365-1]
DR   RefSeq; XP_005250820.1; XM_005250763.1. [O75365-1]
DR   RefSeq; XP_005250821.1; XM_005250764.1. [O75365-1]
DR   RefSeq; XP_005250824.1; XM_005250767.2. [O75365-2]
DR   RefSeq; XP_006716562.1; XM_006716499.1. [O75365-1]
DR   RefSeq; XP_006725163.1; XM_006725100.1. [O75365-1]
DR   RefSeq; XP_006725164.1; XM_006725101.1. [O75365-1]
DR   RefSeq; XP_006725165.1; XM_006725102.1. [O75365-1]
DR   RefSeq; XP_006725166.1; XM_006725103.1. [O75365-1]
DR   UniGene; Hs.43666; -.
DR   UniGene; Hs.744870; -.
DR   PDB; 1R6H; NMR; -; A=1-169.
DR   PDB; 1V3A; NMR; -; A=1-173.
DR   PDB; 2MBC; NMR; -; A=1-162.
DR   PDBsum; 1R6H; -.
DR   PDBsum; 1V3A; -.
DR   PDBsum; 2MBC; -.
DR   DisProt; DP00254; -.
DR   ProteinModelPortal; O75365; -.
DR   SMR; O75365; 1-169.
DR   BioGrid; 116327; 37.
DR   IntAct; O75365; 4.
DR   STRING; 9606.ENSP00000332274; -.
DR   BindingDB; O75365; -.
DR   ChEMBL; CHEMBL4162; -.
DR   PhosphoSite; O75365; -.
DR   MaxQB; O75365; -.
DR   PaxDb; O75365; -.
DR   PRIDE; O75365; -.
DR   DNASU; 11156; -.
DR   Ensembl; ENST00000329397; ENSP00000332274; ENSG00000184489. [O75365-1]
DR   Ensembl; ENST00000349124; ENSP00000331730; ENSG00000184489. [O75365-2]
DR   Ensembl; ENST00000520105; ENSP00000428758; ENSG00000184489. [O75365-2]
DR   Ensembl; ENST00000521578; ENSP00000428976; ENSG00000184489. [O75365-1]
DR   GeneID; 11156; -.
DR   KEGG; hsa:11156; -.
DR   UCSC; uc003ywg.1; human. [O75365-1]
DR   UCSC; uc003ywh.1; human. [O75365-2]
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; K18041; -.
DR   OMA; KAKFCDD; -.
DR   OrthoDB; EOG7C8GJD; -.
DR   PhylomeDB; O75365; -.
DR   TreeFam; TF313384; -.
DR   EvolutionaryTrace; O75365; -.
DR   GeneWiki; PTP4A3; -.
DR   GenomeRNAi; 11156; -.
DR   NextBio; 42423; -.
DR   PRO; PR:O75365; -.
DR   ArrayExpress; O75365; -.
DR   Bgee; O75365; -.
DR   CleanEx; HS_PTP4A3; -.
DR   Genevestigator; O75365; -.
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   GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; TAS:GOC.
DR   Gene3D; 3.90.190.10; -; 1.
DR   InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR   InterPro; IPR000387; Tyr/Dual-sp_Pase.
DR   InterPro; IPR000242; Tyr_Pase_rcpt/non-rcpt.
DR   Pfam; PF00102; Y_phosphatase; 1.
DR   SUPFAM; SSF52799; SSF52799; 1.
DR   PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
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. {ECO:0000250}.
FT                                /FTId=PRO_0000396735.
FT   DOMAIN       82    148       Tyrosine-protein phosphatase.
FT   ACT_SITE     72     72       Proton donor. {ECO:0000305}.
FT   ACT_SITE    104    104       Phosphocysteine intermediate.
FT   BINDING     110    110       Substrate.
FT   MOD_RES     170    170       Cysteine methyl ester. {ECO:0000250}.
FT   LIPID       170    170       S-farnesyl cysteine. {ECO:0000250}.
FT   DISULFID     49    104       {ECO:0000269|PubMed:14704153}.
FT   VAR_SEQ      39    124       Missing (in isoform 3).
FT                                {ECO:0000303|Ref.2}.
FT                                /FTId=VSP_014406.
FT   VAR_SEQ     111    135       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:15489334,
FT                                ECO:0000303|Ref.3}.
FT                                /FTId=VSP_014407.
FT   MUTAGEN      49     49       C->A: No effect on enzymatic activity.
FT                                {ECO:0000269|PubMed:14704153}.
FT   MUTAGEN      71     71       D->A: No effect on enzymatic activity.
FT                                {ECO:0000269|PubMed:14704153}.
FT   MUTAGEN      72     72       D->A: Abolishes enzymatic activity.
FT                                {ECO:0000269|PubMed:14704153}.
FT   MUTAGEN     104    104       C->A,S: 95% loss of enzymatic activity.
FT                                {ECO:0000269|PubMed:11355880,
FT                                ECO:0000269|PubMed:12782572}.
FT   MUTAGEN     104    104       C->S: Reduces migration-promoting
FT                                activity. {ECO:0000269|PubMed:11355880,
FT                                ECO:0000269|PubMed:12782572}.
FT   MUTAGEN     111    111       A->S: Enhances catalytic activity.
FT                                {ECO:0000269|PubMed:14704153}.
FT   CONFLICT    140    140       A -> R (in Ref. 1; AAC29314).
FT                                {ECO:0000305}.
FT   STRAND       10     14
FT   STRAND       17     22
FT   STRAND       23     26
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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