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O75365 (TP4A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein tyrosine phosphatase type IVA 3

EC=3.1.3.48
Alternative name(s):
PRL-R
Protein-tyrosine phosphatase 4a3
Protein-tyrosine phosphatase of regenerating liver 3
Short name=PRL-3
Gene names
Name:PTP4A3
Synonyms:PRL3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length173 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. May be involved in the progression of cardiac hypertrophy by inhibiting intracellular calcium mobilization in response to angiotensin II. Ref.6 Ref.10

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.12

Enzyme regulation

Inhibited by sodium orthovanadate and peroxovanadium compounds, and by pentamidine. Ref.6 Ref.9

Subunit structure

Interacts with tubulin. Ref.8

Subcellular location

Cell membrane. Early endosome Ref.10.

Tissue specificity

Mainly expressed in cardiomyocytes and skeletal muscle; also found in pancreas. Consistently overexpressed in colon cancer metastasis. Ref.6

Post-translational modification

Farnesylated. Farnesylation is required for membrane targeting By similarity.

Sequence similarities

Belongs to the protein-tyrosine phosphatase family.

Contains 1 tyrosine-protein phosphatase domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: O75365-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O75365-2)

The sequence of this isoform differs from the canonical sequence as follows:
     111-135: Missing.
Note: Unstructured and inactive.
Isoform 3 (identifier: O75365-3)

Also known as: short;

The sequence of this isoform differs from the canonical sequence as follows:
     39-124: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 170170Protein tyrosine phosphatase type IVA 3
PRO_0000094788
Propeptide171 – 1733Removed in mature form By similarity
PRO_0000396735

Regions

Domain82 – 14867Tyrosine-protein phosphatase

Sites

Active site721Proton donor Probable
Active site1041Phosphocysteine intermediate
Binding site1101Substrate

Amino acid modifications

Modified residue1701Cysteine methyl ester By similarity
Lipidation1701S-farnesyl cysteine By similarity
Disulfide bond49 ↔ 104 Ref.12

Natural variations

Alternative sequence39 – 12486Missing in isoform 3.
VSP_014406
Alternative sequence111 – 13525Missing in isoform 2.
VSP_014407

Experimental info

Mutagenesis491C → A: No effect on enzymatic activity. Ref.12
Mutagenesis711D → A: No effect on enzymatic activity. Ref.12
Mutagenesis721D → A: Abolishes enzymatic activity. Ref.12
Mutagenesis1041C → A or S: 95% loss of enzymatic activity. Ref.6 Ref.10
Mutagenesis1041C → S: Reduces migration-promoting activity. Ref.6 Ref.10
Mutagenesis1111A → S: Enhances catalytic activity. Ref.12
Sequence conflict1401A → R in AAC29314. Ref.1

Secondary structure

............................... 173
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 5, 2005. Version 2.
Checksum: 15DF01999A9A3573

FASTA17319,535
        10         20         30         40         50         60 
MARMNRPAPV EVSYKHMRFL ITHNPTNATL STFIEDLKKY GATTVVRVCE VTYDKTPLEK 

        70         80         90        100        110        120 
DGITVVDWPF DDGAPPPGKV VEDWLSLVKA KFCEAPGSCV AVHCVAGLGR APVLVALALI 

       130        140        150        160        170 
ESGMKYEDAI QFIRQKRRGA INSKQLTYLE KYRPKQRLRF KDPHTHKTRC CVM 

« Hide

Isoform 2 [UniParc].

Checksum: E9B7DB82575DF7CD
Show »

FASTA14816,777
Isoform 3 (short) [UniParc].

Checksum: DE4A4D64102DC8CF
Show »

FASTA8710,494

References

« Hide 'large scale' references
[1]Zeng Q., Tan Y.H., Hong W.
Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Full-length of some muscular transcripts, Telethon (Italy) project B41."
Ievolella C., Stanchi F., Pacchioni B., Silvia T., Frigimelica E., Scannapieco P., Corso V., Biasio B., Lanfranchi G.
Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Skeletal muscle.
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Eye.
[5]"Multiple phosphotyrosine phosphatase mRNAs are expressed in the human lung fibroblast cell line WI-38."
Dayton M.A., Knobloch T.J.
Recept. Signal Transduct. 7:241-256(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 93-148 (ISOFORM 1).
Tissue: Lung fibroblast.
[6]"Role of PRL-3, a human muscle-specific tyrosine phosphatase, in angiotensin-II signaling."
Matter W.F., Estridge T., Zhang C., Belagaje R., Stancato L., Dixon J., Johnson B., Bloem L., Pickard T., Donaghue M., Acton S., Jeyaseelan R., Kadambi V., Vlahos C.J.
Biochem. Biophys. Res. Commun. 283:1061-1068(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, MUTAGENESIS OF CYS-104, ENZYME REGULATION, FUNCTION.
[7]"A phosphatase associated with metastasis of colorectal cancer."
Saha S., Bardelli A., Buckhaults P., Velculescu V.E., Rago C., St Croix B., Romans K.E., Choti M.A., Lengauer C., Kinzler K.W., Vogelstein B.
Science 294:1343-1346(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: OVEREXPRESSION IN COLON CANCER.
[8]"The tyrosine phosphatase PRL-1 localizes to the endoplasmic reticulum and the mitotic spindle and is required for normal mitosis."
Wang J., Kirby C.E., Herbst R.
J. Biol. Chem. 277:46659-46668(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TUBULIN.
[9]"Pentamidine is an inhibitor of PRL phosphatases with anticancer activity."
Pathak M.K., Dhawan D., Lindner D.J., Borden E.C., Farver C., Yi T.
Mol. Cancer Ther. 1:1255-1264(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[10]"PRL-3 and PRL-1 promote cell migration, invasion, and metastasis."
Zeng Q., Dong J.-M., Guo K., Li J., Tan H.-X., Koh V., Pallen C.J., Manser E., Hong W.
Cancer Res. 63:2716-2722(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-104.
[11]"Structure of human PRL-3, the phosphatase associated with cancer metastasis."
Kim K.-A., Song J.-S., Jee J., Sheen M.R., Lee C., Lee T.G., Ro S., Cho J.M., Lee W., Yamazaki T., Jeon Y.H., Cheong C.
FEBS Lett. 565:181-187(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-173 (ISOFORM 1).
[12]"Structural insights into molecular function of the metastasis-associated phosphatase PRL-3."
Kozlov G., Cheng J., Ziomek E., Banville D., Gehring K., Ekiel I.
J. Biol. Chem. 279:11882-11889(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-169 (ISOFORM 1), DISULFIDE BOND, ENZYME ACTIVITY (ISOFORMS 1 AND 2), MUTAGENESIS OF CYS-49; ASP-71; ASP-72 AND ALA-111.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF041434 mRNA. Translation: AAC29314.1.
AJ276554 mRNA. Translation: CAC81757.1.
BT007303 mRNA. Translation: AAP35967.1.
BC003105 mRNA. Translation: AAH03105.1.
U87168 mRNA. Translation: AAB47560.1.
RefSeqNP_009010.2. NM_007079.3.
NP_116000.1. NM_032611.2.
XP_005250819.1. XM_005250762.2.
XP_005250820.1. XM_005250763.1.
XP_005250821.1. XM_005250764.1.
XP_005250824.1. XM_005250767.2.
UniGeneHs.43666.
Hs.744870.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1R6HNMR-A1-169[»]
1V3ANMR-A1-173[»]
2MBCNMR-A1-162[»]
DisProtDP00254.
ProteinModelPortalO75365.
SMRO75365. Positions 1-169.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116327. 37 interactions.
IntActO75365. 4 interactions.
STRING9606.ENSP00000332274.

Chemistry

BindingDBO75365.
ChEMBLCHEMBL4162.

PTM databases

PhosphoSiteO75365.

Proteomic databases

PaxDbO75365.
PRIDEO75365.

Protocols and materials databases

DNASU11156.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000329397; ENSP00000332274; ENSG00000184489. [O75365-1]
ENST00000349124; ENSP00000331730; ENSG00000184489. [O75365-2]
ENST00000520105; ENSP00000428758; ENSG00000184489. [O75365-2]
ENST00000521578; ENSP00000428976; ENSG00000184489. [O75365-1]
GeneID11156.
KEGGhsa:11156.
UCSCuc003ywg.1. human. [O75365-1]
uc003ywh.1. human. [O75365-2]

Organism-specific databases

CTD11156.
GeneCardsGC08P142432.
HGNCHGNC:9636. PTP4A3.
HPAHPA003281.
MIM606449. gene.
neXtProtNX_O75365.
PharmGKBPA33979.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG265664.
HOGENOMHOG000231265.
HOVERGENHBG071295.
InParanoidO75365.
KOK18041.
OMAKAKFCDD.
OrthoDBEOG7C8GJD.
PhylomeDBO75365.
TreeFamTF313384.

Gene expression databases

ArrayExpressO75365.
BgeeO75365.
CleanExHS_PTP4A3.
GenevestigatorO75365.

Family and domain databases

InterProIPR000387. Tyr/Dual-sp_Pase.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
[Graphical view]
PfamPF00102. Y_phosphatase. 1 hit.
[Graphical view]
PROSITEPS50056. TYR_PHOSPHATASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO75365.
GeneWikiPTP4A3.
GenomeRNAi11156.
NextBio42423.
PROO75365.
SOURCESearch...

Entry information

Entry nameTP4A3_HUMAN
AccessionPrimary (citable) accession number: O75365
Secondary accession number(s): Q8IVN5, Q99849, Q9BTW5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: April 16, 2014
This is version 115 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM