O75365 (TP4A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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. 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.

Ontologies

Keywords
Cellular component	Cell membrane Endosome Membrane
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protein phosphatase
PTM	Disulfide bond Lipoprotein Methylation Prenylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	early endosome Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	prenylated protein tyrosine phosphatase activity Traceable author statement. Source: ProtInc protein tyrosine/serine/threonine phosphatase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 170

170

Protein tyrosine phosphatase type IVA 3

PRO_0000094788

Propeptide

171 – 173

3

Removed in mature form By similarity

PRO_0000396735

Regions

Domain

82 – 148

67

Tyrosine-protein phosphatase

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 By similarity

Lipidation

170

1

S-farnesyl cysteine By similarity

Disulfide bond

49 ↔ 104

Ref.12

Natural variations

Alternative sequence

39 – 124

86

Missing in isoform 3.

VSP_014406

Alternative sequence

111 – 135

25

Missing in isoform 2.

VSP_014407

Experimental info

Mutagenesis

49

1

C → A: No effect on enzymatic activity. Ref.12

Mutagenesis

71

1

D → A: No effect on enzymatic activity. Ref.12

Mutagenesis

72

1

D → A: Abolishes enzymatic activity. Ref.12

Mutagenesis

104

1

C → A or S: 95% loss of enzymatic activity. Ref.6 Ref.10

Mutagenesis

104

1

C → S: Reduces migration-promoting activity. Ref.6 Ref.10

Mutagenesis

111

1

A → S: Enhances catalytic activity. Ref.12

Sequence conflict

140

1

A → R in AAC29314. Ref.1

Secondary structure

1

.

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.

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173

Helix Strand Turn

Details...

Beta strand

10 – 14

5

Beta strand

17 – 22

6

Helix

30 – 40

11

Beta strand

45 – 49

5

Helix

55 – 61

7

Beta strand

65 – 68

4

Helix

79 – 94

16

Beta strand

99 – 103

5

Beta strand

107 – 110

4

Helix

111 – 119

9

Helix

120 – 122

3

Helix

125 – 135

11

Helix

144 – 152

9

Turn

156 – 158

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2005. Version 2. Checksum: 15DF01999A9A3573	FASTA	173	19,535
	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
	Isoform 2 [UniParc]. Checksum: E9B7DB82575DF7CD	FASTA	148	16,777
	10 20 30 40 50 60 MARMNRPAPV EVSYKHMRFL ITHNPTNATL STFIEDLKKY GATTVVRVCE VTYDKTPLEK 70 80 90 100 110 120 DGITVVDWPF DDGAPPPGKV VEDWLSLVKA KFCEAPGSCV AVHCVAGLGR KRRGAINSKQ 130 140 LTYLEKYRPK QRLRFKDPHT HKTRCCVM
	Isoform 3 (short) [UniParc]. Checksum: DE4A4D64102DC8CF	FASTA	87	10,494
	10 20 30 40 50 60 MARMNRPAPV EVSYKHMRFL ITHNPTNATL STFIEDLKKY EDAIQFIRQK RRGAINSKQL 70 80 TYLEKYRPKQ RLRFKDPHTH KTRCCVM

References

	« Hide 'large scale' referencesShow '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.

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.

IPI

IPI00026647.
IPI00217075.
IPI00289328.

RefSeq

NP_009010.2. NM_007079.2.
NP_116000.1. NM_032611.1.

UniGene

Hs.43666.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1R6H	NMR	-	A	1-169	[»]
1V3A	NMR	-	A	1-173	[»]

ProteinModelPortal

O75365.

SMR

O75365. Positions 1-169.

DisProt

DP00254.

ModBase

Search...

Protein-protein interaction databases

IntAct

O75365. 4 interactions.

STRING

O75365.

PTM databases

PhosphoSite

O75365.

Proteomic databases

PRIDE

O75365.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000329397; ENSP00000332274; ENSG00000184489.

GeneID

11156.

KEGG

hsa:11156.

UCSC

uc003ywg.1. human.
uc003ywh.1. human.

Organism-specific databases

CTD

11156.

GeneCards

GC08P142432.

HGNC

HGNC:9636. PTP4A3.

HPA

HPA003281.

MIM

606449. gene.

neXtProt

NX_O75365.

PharmGKB

PA33979.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07609.

GeneTree

ENSGT00390000009788.

HOGENOM

HBG314303.

HOVERGEN

HBG071295.

InParanoid

O75365.

OMA

KAKFCDD.

OrthoDB

EOG415GFJ.

PhylomeDB

O75365.

Enzyme and pathway databases

Pathway_Interaction_DB

prlsignalingeventspathway. Signaling events mediated by PRL.

Gene expression databases

ArrayExpress

O75365.

Bgee

O75365.

CleanEx

HS_PTP4A3.

Genevestigator

O75365.

GermOnline

ENSG00000184489. Homo sapiens.

Family and domain databases

InterPro

IPR000340. Dual-sp_phosphatase_cat-dom.
IPR000387. Tyr/Dual-specificity_Pase.
[Graphical view]

KO

K01104.

Pfam

PF00782. DSPc. 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

SOURCE

Search...

Entry information

Entry name

TP4A3_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 92 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.