Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q93096 (TP4A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein tyrosine phosphatase type IVA 1

EC=3.1.3.48
Alternative name(s):
PTP(CAAXI)
Protein-tyrosine phosphatase 4a1
Protein-tyrosine phosphatase of regenerating liver 1
Short name=PRL-1
Gene names
Name:PTP4A1
Synonyms:PRL1, PTPCAAX1
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. May play a role in the development and maintenance of differentiating epithelial tissues. Enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. Ref.10 Ref.12 Ref.13

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.1

Enzyme regulation

Inhibited by sodium orthovanadate and pentamidine. Ref.11

Subunit structure

Homotrimer. Interacts with ATF5 By similarity. Interacts with tubulin. Ref.10 Ref.16

Subcellular location

Cell membrane. Early endosome. Endoplasmic reticulum. Cytoplasm. Cytoplasmcytoskeletonspindle. Note: And mitotic spindle. Ref.9 Ref.10 Ref.16

Tissue specificity

Expressed in bone marrow, lymph nodes, T lymphocytes, spleen, thymus and tonsil. Overexpressed in tumor cell lines. Ref.9 Ref.10

Developmental stage

Expressed in fetal liver. Ref.9

Induction

Strongly down-regulated upon tetrodotoxin treatment. Ref.11 Ref.14

Post-translational modification

Farnesylated. Farnesylation is required for membrane targeting. Unfarnesylated forms are shifted into the nucleus.

Sequence similarities

Belongs to the protein-tyrosine phosphatase family.

Contains 1 tyrosine-protein phosphatase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 170170Protein tyrosine phosphatase type IVA 1
PRO_0000094780
Propeptide171 – 1733Removed in mature form Probable
PRO_0000396726

Regions

Domain82 – 14867Tyrosine-protein phosphatase
Region97 – 13236Interaction with ATF5 By similarity
Region105 – 1106Phosphate binding

Sites

Active site721Proton donor Probable
Active site1041Phosphocysteine intermediate
Binding site1101Substrate

Amino acid modifications

Modified residue1701Cysteine methyl ester Probable
Lipidation1701S-farnesyl cysteine Ref.1
Disulfide bond49 ↔ 104 Ref.16

Experimental info

Mutagenesis131T → F: Reduces trimerization. Ref.16
Mutagenesis711D → A: No effect on catalytic activity. Ref.10
Mutagenesis721D → A: 80% loss of catalytic activity; delay in progression through G2/M. Ref.10
Mutagenesis1041C → S: Abolishes enzymatic activity. Ref.10
Mutagenesis1311Q → A: Reduces trimerization. Ref.16
Mutagenesis1701C → S: Redistributes to the nucleus in resting cells, but still locates to the mitotic spindle in dividing cells. Induces defects in cytokinesis. Ref.10
Mutagenesis1711C → S: No effect on subcellular location. Ref.10

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Q93096 [UniParc].

Last modified July 5, 2005. Version 2.
Checksum: 702008013D3F3835

FASTA17319,815
        10         20         30         40         50         60 
MARMNRPAPV EVTYKNMRFL ITHNPTNATL NKFIEELKKY GVTTIVRVCE ATYDTTLVEK 

        70         80         90        100        110        120 
EGIHVLDWPF DDGAPPSNQI VDDWLSLVKI KFREEPGCCI AVHCVAGLGR APVLVALALI 

       130        140        150        160        170 
EGGMKYEDAV QFIRQKRRGA FNSKQLLYLE KYRPKMRLRF KDSNGHRNNC CIQ 

« Hide

References

« Hide 'large scale' references
[1]"Prenylation of oncogenic human PTP(CAAX) protein tyrosine phosphatases."
Cates C.A., Michael R.L., Stayrook K.R., Harvey K.A., Burke Y.D., Randall S.K., Crowell P.L., Crowell D.N.
Cancer Lett. 110:49-55(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY, ISOPRENYLATION AT CYS-170.
Tissue: Mammary carcinoma.
[2]"The gene encoding human nuclear protein tyrosine phosphatase, PRL-1. Cloning, chromosomal localization, and identification of an intron enhancer."
Peng Y., Genin A., Spinner N.B., Diamond R.H., Taub R.
J. Biol. Chem. 273:17286-17295(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Regenerating liver.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Thalamus.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Fetal liver.
[5]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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].
Tissue: Muscle and Testis.
[8]"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 80-163.
Tissue: Lung fibroblast.
[9]"Subcellular localization of intracellular protein tyrosine phosphatases in T cells."
Gjoerloff-Wingren A., Saxena M., Han S., Wang X., Alonso A., Renedo M., Oh P., Williams S., Schnitzer J., Mustelin T.
Eur. J. Immunol. 30:2412-2421(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[10]"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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-71; ASP-72; CYS-104; CYS-170 AND CYS-171, INTERACTION WITH TUBULIN, FUNCTION.
[11]"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.
[12]"Enhanced cell cycle progression and down regulation of p21(Cip1/Waf1) by PRL tyrosine phosphatases."
Werner S.R., Lee P.A., DeCamp M.W., Crowell D.N., Randall S.K., Crowell P.L.
Cancer Lett. 202:201-211(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"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.
[14]"Potential effects of tetrodotoxin exposure to human glial cells postulated using microarray approach."
Raghavendra Prasad H.S., Qi Z., Srinivasan K.N., Gopalakrishnakone P.
Toxicon 44:597-608(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Trimeric structure of PRL-1 phosphatase reveals an active enzyme conformation and regulation mechanisms."
Jeong D.G., Kim S.J., Kim J.H., Son J.H., Park M.R., Lim S.M., Yoon T.-S., Ryu S.E.
J. Mol. Biol. 345:401-413(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF MUTANT SER-104, DISULFIDE BOND, SUBCELLULAR LOCATION, SUBUNIT, MUTAGENESIS OF THR-13 AND GLN-131, IDENTIFICATION BY MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U48296 mRNA. Translation: AAB40597.1.
AF051160 Genomic DNA. Translation: AAC39836.1.
AK312526 mRNA. Translation: BAG35425.1.
CR749458 mRNA. Translation: CAH18292.1.
AL135905 Genomic DNA. Translation: CAC12761.1.
CH471143 Genomic DNA. Translation: EAW88494.1.
BC023975 mRNA. Translation: AAH23975.1.
BC045571 mRNA. Translation: AAH45571.1.
U69701 mRNA. Translation: AAB09080.1.
CCDSCCDS4965.1.
RefSeqNP_003454.1. NM_003463.4.
XP_006715626.1. XM_006715563.1.
UniGeneHs.227777.
Hs.706850.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1RXDX-ray1.90A/B/C2-160[»]
1XM2X-ray2.70A/B/C/D/E/F1-173[»]
DisProtDP00255.
ProteinModelPortalQ93096.
SMRQ93096. Positions 9-160.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113578. 10 interactions.
IntActQ93096. 4 interactions.
MINTMINT-194351.
STRING9606.ENSP00000359685.

Chemistry

BindingDBQ93096.
ChEMBLCHEMBL1075169.

PTM databases

PhosphoSiteQ93096.

Polymorphism databases

DMDM68566217.

Proteomic databases

MaxQBQ93096.
PaxDbQ93096.
PRIDEQ93096.

Protocols and materials databases

DNASU7803.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000370651; ENSP00000359685; ENSG00000112245.
GeneID7803.
KEGGhsa:7803.
UCSCuc003pek.3. human.

Organism-specific databases

CTD7803.
GeneCardsGC06P064279.
HGNCHGNC:9634. PTP4A1.
HPAHPA003281.
MIM601585. gene.
neXtProtNX_Q93096.
PharmGKBPA33977.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG265664.
HOGENOMHOG000231265.
HOVERGENHBG071295.
InParanoidQ93096.
KOK18041.
OMADKSIAVH.
OrthoDBEOG7C8GJD.
PhylomeDBQ93096.
TreeFamTF313384.

Gene expression databases

ArrayExpressQ93096.
BgeeQ93096.
CleanExHS_PTP4A1.
GenevestigatorQ93096.

Family and domain databases

Gene3D3.90.190.10. 1 hit.
InterProIPR029021. Prot-tyrosine_phosphatase-like.
IPR000387. Tyr/Dual-sp_Pase.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
[Graphical view]
PfamPF00102. Y_phosphatase. 1 hit.
[Graphical view]
SUPFAMSSF52799. SSF52799. 1 hit.
PROSITEPS50056. TYR_PHOSPHATASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ93096.
GeneWikiPTP4A1.
GenomeRNAi7803.
NextBio30184.
PROQ93096.
SOURCESearch...

Entry information

Entry nameTP4A1_HUMAN
AccessionPrimary (citable) accession number: Q93096
Secondary accession number(s): B2R6C8, O00648, Q49A54
Entry history
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: July 9, 2014
This is version 122 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 6

Human chromosome 6: entries, gene names and cross-references to MIM