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Reviewed, UniProtKB/Swiss-Prot O75365 (TP4A3_HUMAN)

Last modified June 16, 2009. Version 65. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Protein tyrosine phosphatase type IVA 3
    EC=3.1.3.48
Alternative name(s):
    Protein-tyrosine phosphatase 4a3
    Protein-tyrosine phosphatase of regenerating liver 3
      Short name=PRL-3
      Short name=PRL-R
Gene names
Name: PTP4A3
Synonyms: PRL3
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length173 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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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.

Involvement in disease

Significantly overexpressed in liver metastasis of colorectal cancer.

Sequence similarities

Belongs to the protein-tyrosine phosphatase family.

Contains 1 tyrosine-protein phosphatase domain.

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Ontologies

Keywords
   Cellular componentCell membrane
Endosome
Membrane
   Coding sequence diversityAlternative splicing
   Molecular functionHydrolase
Protein phosphatase
   PTMDisulfide bond
Lipoprotein
Prenylation
   Technical term3D-structure
Gene Ontology (GO)
   Biological processprotein amino acid dephosphorylation

Inferred from electronic annotation. Source: InterPro

   Cellular componentearly endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionidentical protein binding

Inferred from physical interaction. Source: IntAct

prenylated protein tyrosine phosphatase activity

Traceable author statement. Source: ProtInc

Complete GO annotation...

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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.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 173173Protein tyrosine phosphatase type IVA 3
PRO_0000094788

Regions

Domain82 – 14867Tyrosine-protein phosphatase

Sites

Active site721Proton donor Probable
Active site1041Phosphocysteine intermediate
Binding site1101Substrate

Amino acid modifications

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

1 ........................... 173
Helix Strand Turn

Details...

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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.

Checksum: E9B7DB82575DF7CD
Show »

FASTA14816,777
Isoform 3 (short).

Checksum: DE4A4D64102DC8CF
Show »

FASTA8710,494

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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: 15489334] [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: 9633825] [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: 11355880] [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: 11598267] [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: 12235145] [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: 12516958] [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: 12782572] [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: 15135076] [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: 14704153] [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.

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Cross-references

Sequence databases

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.
IPIIPI00026647.
IPI00217075.
IPI00289328.
RefSeqNP_009010.2.
NP_116000.1.
XP_001717100.1.
UniGeneHs.43666

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1R6HNMR-A1-169[»]
1V3ANMR-A1-173[»]
DisProtDP00254.
ModBaseSearch...

Protein-protein interaction databases

IntActO75365. 111 interactions.

Genome annotation databases

EnsemblENSG00000184489. Homo sapiens. [Contig view]
GeneID100131062.
11156.
KEGGhsa:100131062.
hsa:11156.

Organism-specific databases

GeneCardsGC08P142501.
GC08P142502.
H-InvDBHIX0019234.
HGNCHGNC:9636. PTP4A3.
HPAHPA003281.
MIM606449. gene.
PharmGKBPA33979.
GenAtlasSearch...

Phylogenomic databases

HOGENOMO75365.
HOVERGENO75365.
OMAO75365. KAPLEKD.

Enzyme and pathway databases

BRENDA3.1.3.48. 247.
Pathway_Interaction_DBprlsignalingeventspathway. Signaling events mediated by PRL.

Gene expression databases

ArrayExpressO75365.
BgeeO75365.
CleanExHS_PTP4A3.
GermOnlineENSG00000184489. Homo sapiens.

Family and domain databases

InterProIPR000387. Tyr_Pase.
IPR016130. Tyr_Pase_AS.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
[Graphical view]
PfamPF00102. Y_phosphatase. 1 hit.
[Graphical view]
PROSITEPS00383. TYR_PHOSPHATASE_1. False negative.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. False negative.
[Graphical view]
ProtoNetSearch...

Other Resources

SOURCESearch...

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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: June 16, 2009
This is version 65 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 8

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

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents