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0  structures 312  species 0  interactions 686  sequences 16  architectures

Family: PTPLA (PF04387)

Summary: Protein tyrosine phosphatase-like protein, PTPLA

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This is the Wikipedia entry entitled "Protein tyrosine phosphatase". More...

Protein tyrosine phosphatase Edit Wikipedia article

Protein-tyrosine-phosphatase
Identifiers
EC number 3.1.3.48
CAS number 79747-53-8
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum

Protein tyrosine phosphatases (EC 3.1.3.48, PTPs, phosphotyrosine phosphatase, phosphoprotein phosphatase (phosphotyrosine), phosphotyrosine histone phosphatase, protein phosphotyrosine phosphatase, tyrosylprotein phosphatase, phosphotyrosine protein phosphatase, phosphotyrosylprotein phosphatase, tyrosine O-phosphate phosphatase, PPT-phosphatase, PTPase, [phosphotyrosine]protein phosphatase, PTP-phosphatase) are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins. Protein tyrosine (pTyr) phosphorylation is a common post-translational modification that can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. As a consequence, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase; EC 3.1.3.48) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation.[1][2]

Functions[edit]

Together with tyrosine kinases, PTPs regulate the phosphorylation state of many important signalling molecules, such as the MAP kinase family. PTPs are increasingly viewed as integral components of signal transduction cascades, despite less study and understanding compared to tyrosine kinases.

PTPs have been implicated in regulation of many cellular processes, including, but not limited to:

Classification[edit]

By mechanism[edit]

The PTP superfamily can be divided into four subfamilies.[3][4]

Links to all 107 members of the protein tyrosine phosphatase family can be found in the template at the bottom of this article.

Class I[edit]

The class I PTPs, are the largest group of PTPs with 99 members, which can be further subdivided into

Dual-specificity phosphatases (dTyr and dSer/dThr) dual-specificity protein-tyrosine phosphatases. Ser/Thr and Tyr dual-specificity phosphatases are a group of enzymes with both Ser/Thr (EC 3.1.3.16) and tyrosine-specific protein phosphatase (EC 3.1.3.48) activity able to remove the serine/threonine or the tyrosine-bound phosphate group from a wide range of phosphoproteins, including a number of enzymes that have been phosphorylated under the action of a kinase. Dual-specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle.

LEOPARD syndrome, Noonan syndrome, and Metachondromatosis are associated with PTPN11.

Class II[edit]

LMW (low-molecular-weight) phosphatases, or acid phosphatases, act on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates.[5][6]

The class II PTPs contain only one member, low-molecular-weight phosphotyrosine phosphatase (LMPTP).

Class III[edit]

Cdc25 phosphatases (dTyr and/or dThr)

The Class III PTPs contains three members, CDC25 A, B, and C

Class IV[edit]

pTyr-specific phosphatases

The class IV PTPs contains four members, Eya1-4.

This class is believed to have evolved separately from the other three.[7]

By location[edit]

Based on their cellular localization, PTPases are also classified as:

Common elements[edit]

All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and possess a similar core structure made of a central parallel beta-sheet with flanking alpha-helices containing a beta-loop-alpha-loop that encompasses the PTP signature motif.[10] Functional diversity between PTPases is endowed by regulatory domains and subunits.

Low-molecular-weight phosphotyrosine protein phosphatase
PDB 1phr EBI.jpg
Structure of a low-molecular-weight phosphotyrosine protein phosphatase.[11]
Identifiers
Symbol LMWPc
Pfam PF01451
InterPro IPR017867
SMART SM00226
SCOP 1phr
SUPERFAMILY 1phr
Protein-tyrosine phosphatase
PDB 1ypt EBI.jpg
Structure of Yersinia protein tyrosine phosphatase.[12]
Identifiers
Symbol Y_phosphatase
Pfam PF00102
Pfam clan CL0031
InterPro IPR000242
SMART SM00194
PROSITE PS50055
SCOP 1ypt
SUPERFAMILY 1ypt
Dual-specificity phosphatase, catalytic domain
PDB 1vhr EBI.jpg
Structure of the dual-specificity protein phosphatase VHR.[13]
Identifiers
Symbol DSPc
Pfam PF00782
Pfam clan CL0031
InterPro IPR000340
PROSITE PDOC00323
SCOP 1vhr
SUPERFAMILY 1vhr
Protein-tyrosine phosphatase, SIW14-like
PDB 1xri EBI.jpg
Structure of a putative phosphoprotein phosphatase from Arabidopsis thaliana.[14]
Identifiers
Symbol Y_phosphatase2
Pfam PF03162
Pfam clan CL0031
InterPro IPR004861
Protein-tyrosine phosphatase-like, PTPLA
Identifiers
Symbol PTPLA
Pfam PF04387
InterPro IPR007482

Expression pattern[edit]

Individual PTPs may be expressed by all cell types, or their expression may be strictly tissue-specific. Most cells express 30% to 60% of all the PTPs, however hematopoietic and neuronal cells express a higher number of PTPs in comparison to other cell types. T cells and B cells of hematopoietic origin express around 60 to 70 different PTPs. The expression of several PTPS is restricted to hematopoietic cells, for example, LYP, SHP1, CD45, and HePTP.[15]

References[edit]

  1. ^ Dixon JE, Denu JM (1998). "Protein tyrosine phosphatases: mechanisms of catalysis and regulation". Curr Opin Chem Biol 2 (5): –. PMID 9818190. 
  2. ^ Paul S, Lombroso PJ (2003). "Receptor and nonreceptor protein tyrosine phosphatases in the nervous system". Cell. Mol. Life Sci. 60 (11): –. doi:10.1007/s00018-003-3123-7. PMID 14625689. 
  3. ^ Sun JP, Zhang ZY, Wang WQ (2003). "An overview of the protein tyrosine phosphatase superfamily". Curr Top Med Chem 3 (7): –. PMID 12678841. 
  4. ^ Alonso A, Sasin J, et al. (2004). "Protein tyrosine phosphatases in the human genome". Cell 117 (6): 699–711. doi:10.1016/j.cell.2004.05.018. PMID 15186772. 
  5. ^ Wo YY, Shabanowitz J, Hunt DF, Davis JP, Mitchell GL, Van Etten RL, McCormack AL (1992). "Sequencing, cloning, and expression of human red cell-type acid phosphatase, a cytoplasmic phosphotyrosyl protein phosphatase". J. Biol. Chem. 267 (15): 10856–10865. PMID 1587862. 
  6. ^ Shekels LL, Smith AJ, Bernlohr DA, Van Etten RL (1992). "Identification of the adipocyte acid phosphatase as a PAO-sensitive tyrosyl phosphatase". Protein Sci. 1 (6): 710–721. doi:10.1002/pro.5560010603. PMC 2142247. PMID 1304913. 
  7. ^ William C. Plaxton; Michael T. McManus (2006). Control of primary metabolism in plants. Wiley-Blackwell. pp. 130–. ISBN 978-1-4051-3096-7. Retrieved 12 December 2010. 
  8. ^ Knapp S, Longman E, Debreczeni JE, Eswaran J, Barr AJ (2006). "The crystal structure of human receptor protein tyrosine phosphatase kappa phosphatase domain 1". Protein Sci. 15 (6): –. doi:10.1110/ps.062128706. PMC 2242534. PMID 16672235. 
  9. ^ Perrimon N, Johnson MR, Perkins LA, Melnick MB (1996). "The nonreceptor protein tyrosine phosphatase corkscrew functions in multiple receptor tyrosine kinase pathways in Drosophila". Dev. Biol. 180 (1): –. doi:10.1006/dbio.1996.0285. PMID 8948575. 
  10. ^ Barford D, Das AK, Egloff MP (1998). "The structure and mechanism of protein phosphatase s: insights into catalysis and regulation". Annu. Rev. Biophys. Biomol. Struct. 27 (1): –. doi:10.1146/annurev.biophys.27.1.133. PMID 9646865. 
  11. ^ Su XD, Taddei N, Stefani M, Ramponi G, Nordlund P (August 1994). "The crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase". Nature 370 (6490): 575–8. doi:10.1038/370575a0. PMID 8052313. 
  12. ^ Stuckey JA, Schubert HL, Fauman EB, Zhang ZY, Dixon JE, Saper MA (August 1994). "Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 A and the complex with tungstate". Nature 370 (6490): 571–5. doi:10.1038/370571a0. PMID 8052312. 
  13. ^ Yuvaniyama J, Denu JM, Dixon JE, Saper MA (May 1996). "Crystal structure of the dual specificity protein phosphatase VHR". Science 272 (5266): 1328–31. doi:10.1126/science.272.5266.1328. PMID 8650541. 
  14. ^ Aceti DJ, Bitto E, Yakunin AF, et al. (October 2008). "Structural and functional characterization of a novel phosphatase from the Arabidopsis thaliana gene locus At1g05000". Proteins 73 (1): 241–53. doi:10.1002/prot.22041. PMID 18433060. 
  15. ^ Mustelin T, Vang T and Bottini N. (2005). "Protein tyrosine phosphatases and the immune response". Nat. Rev. Immunol. 5 (1): 43–57. doi:10.1038/nri1530. PMID 15630428. 

External links[edit]

This article incorporates text from the public domain Pfam and InterPro IPR000106

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Protein tyrosine phosphatase-like protein, PTPLA Provide feedback

This family includes the mammalian protein tyrosine phosphatase-like protein, PTPLA. A significant variation of PTPLA from other protein tyrosine phosphatases is the presence of proline instead of catalytic arginine at the active site. It is thought that PTPLA proteins have a role in the development, differentiation, and maintenance of a number of tissue types [1].

Literature references

  1. Uwanogho DA, Hardcastle Z, Balogh P, Mirza G, Thornburg KL, Ragoussis J, Sharpe PT; , Genomics 1999;62:406-416.: Molecular cloning, chromosomal mapping, and developmental expression of a novel protein tyrosine phosphatase-like gene. PUBMED:10644438 EPMC:10644438

  2. Li D, Gonzalez O, Bachinski LL, Roberts R; , Gene 2000;256:237-243.: Human protein tyrosine phosphatase-like gene: expression profile, genomic structure, and mutation analysis in families with ARVD. PUBMED:11054553 EPMC:11054553


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR007482

Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. Consequently, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase; EC) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation [PUBMED:9818190, PUBMED:14625689]. The PTP superfamily can be divided into four subfamilies [PUBMED:12678841]:

  • (1) pTyr-specific phosphatases
  • (2) dual specificity phosphatases (dTyr and dSer/dThr)
  • (3) Cdc25 phosphatases (dTyr and/or dThr)
  • (4) LMW (low molecular weight) phosphatases

Based on their cellular localisation, PTPases are also classified as:

  • Receptor-like, which are transmembrane receptors that contain PTPase domains [PUBMED:16672235]
  • Non-receptor (intracellular) PTPases [PUBMED:8948575]

All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and share a similar core structure made of a central parallel beta-sheet with flanking alpha-helices containing a beta-loop-alpha-loop that encompasses the PTP signature motif [PUBMED:9646865]. Functional diversity between PTPases is endowed by regulatory domains and subunits.

This family includes the mammalian protein tyrosine phosphatase-like protein, PTPLA. A significant variation of PTPLA from other protein tyrosine phosphatases is the presence of proline instead of catalytic arginine at the active site. It is thought that PTPLA proteins have a role in the development, differentiation, and maintenance of a number of tissue types [PUBMED:10644438].

Domain organisation

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Seed source: Pfam-B_1525 (release 7.3)
Previous IDs: none
Type: Family
Author: Mifsud, W
Number in seed: 70
Number in full: 686
Average length of the domain: 151.90 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 59.31 %

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build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.2 21.2
Trusted cut-off 23.8 22.0
Noise cut-off 19.5 19.5
Model length: 164
Family (HMM) version: 9
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