Q93096 (TP4A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	173 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Cytoplasm › cytoskeleton › spindle. 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.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cell membrane Cytoplasm Cytoskeleton Endoplasmic reticulum Endosome Membrane
Molecular function	Developmental protein Hydrolase Protein phosphatase
PTM	Disulfide bond Lipoprotein Methylation Prenylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell migration Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from direct assay Ref.9. Source: UniProtKB early endosome Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell internal side of plasma membrane Inferred from direct assay Ref.9. Source: UniProtKB spindle Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	protein tyrosine phosphatase activity Non-traceable author statement PubMed 10569806. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 170

170

Protein tyrosine phosphatase type IVA 1

PRO_0000094780

Propeptide

171 – 173

3

Removed in mature form Probable

PRO_0000396726

Regions

Domain

82 – 148

67

Tyrosine-protein phosphatase

Region

97 – 132

36

Interaction with ATF5 By similarity

Region

105 – 110

6

Phosphate binding

Sites

Active site

72

1

Proton donor Probable

Active site

104

1

Phosphocysteine intermediate

Binding site

110

1

Substrate

Amino acid modifications

Modified residue

170

1

Cysteine methyl ester Probable

Lipidation

170

1

S-farnesyl cysteine Ref.1

Disulfide bond

49 ↔ 104

Ref.16

Experimental info

Mutagenesis

13

1

T → F: Reduces trimerization. Ref.16

Mutagenesis

71

1

D → A: No effect on catalytic activity. Ref.10

Mutagenesis

72

1

D → A: 80% loss of catalytic activity; delay in progression through G2/M. Ref.10

Mutagenesis

104

1

C → S: Abolishes enzymatic activity. Ref.10

Mutagenesis

131

1

Q → A: Reduces trimerization. Ref.16

Mutagenesis

170

1

C → S: Redistributes to the nucleus in resting cells, but still locates to the mitotic spindle in dividing cells. Induces defects in cytokinesis. Ref.10

Mutagenesis

171

1

C → S: No effect on subcellular location. Ref.10

Secondary structure

1

.

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.

.

.

.

.

.

.

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.

.

.

.

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.

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.

.

.

173

Helix Strand Turn

Details...

Beta strand

10 – 14

5

Beta strand

17 – 21

5

Helix

27 – 29

3

Helix

30 – 39

10

Beta strand

42 – 47

6

Helix

56 – 60

5

Beta strand

64 – 67

4

Beta strand

72 – 74

3

Helix

78 – 94

17

Beta strand

99 – 103

5

Beta strand

105 – 108

4

Turn

109 – 111

3

Helix

112 – 121

10

Helix

126 – 134

9

Helix

143 – 151

9

Sequences

	Sequence		Length	Mass (Da)
	Q93096 [UniParc]. Last modified July 5, 2005. Version 2. Checksum: 702008013D3F3835	FASTA	173	19,815
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, 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.

IPI

IPI00020164.

RefSeq

NP_003454.1. NM_003463.3.

UniGene

Hs.227777.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RXD	X-ray	1.90	A/B/C	2-160	[»]
1XM2	X-ray	2.70	A/B/C/D/E/F	1-173	[»]

DisProt

DP00255.

ProteinModelPortal

Q93096.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q93096. 3 interactions.

STRING

9606.ENSP00000359685.

PTM databases

PhosphoSite

Q93096.

Polymorphism databases

DMDM

68566217.

Proteomic databases

PaxDb

Q93096.

PRIDE

Q93096.

Protocols and materials databases

DNASU

7803.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000370651; ENSP00000359685; ENSG00000112245.

GeneID

7803.

KEGG

hsa:7803.

UCSC

uc003pek.3. human.

Organism-specific databases

CTD

7803.

GeneCards

GC06P064279.

HGNC

HGNC:9634. PTP4A1.

HPA

HPA003281.

MIM

601585. gene.

neXtProt

NX_Q93096.

PharmGKB

PA33977.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG265664.

HOGENOM

HOG000231265.

HOVERGEN

HBG071295.

InParanoid

Q93096.

KO

K01104.

OMA

CEATYDA.

OrthoDB

EOG4ZCT5N.

PhylomeDB

Q93096.

Enzyme and pathway databases

Pathway_Interaction_DB

prlsignalingeventspathway. Signaling events mediated by PRL.

Gene expression databases

ArrayExpress

Q93096.

Bgee

Q93096.

CleanEx

HS_PTP4A1.

Genevestigator

Q93096.

GermOnline

ENSG00000112245. Homo sapiens.

Family and domain databases

InterPro

IPR000387. Tyr/Dual-sp_Pase.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
[Graphical view]

Pfam

PF00102. Y_phosphatase. 1 hit.
[Graphical view]

PROSITE

PS00383. TYR_PHOSPHATASE_1. False negative.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. False negative.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q93096.

ChEMBL

CHEMBL1075169.

EvolutionaryTrace

Q93096.

GenomeRNAi

7803.

NextBio

30184.

SOURCE

Search...

Entry information

Entry name

TP4A1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.