LMWPc

Low molecular weight phosphatase family

• SMART accession number: SM00226
• Description: -
• Interpro abstract (IPR023485):

  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 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 [ (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 entry represents the low molecular weight (LMW) protein-tyrosine phosphatases (or acid phosphatase), which act on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates [ (PUBMED:1587862) (PUBMED:1304913) ]. The structure of a LMW PTPase has been solved by X-ray crystallography [ (PUBMED:8052313) ] and is found to form a single structural domain. It belongs to the alpha/beta class, with 6 alpha-helices and 4 beta-strands forming a 3-layer alpha-beta-alpha sandwich architecture.

There are 43599 LMWPc domains in 43553 proteins in SMART's nrdb database.

Disease (disease genes where sequence variants are found in this domain)

SwissProt sequences and OMIM curated human diseases associated with missense mutations within the LMWPc domain.

Protein	Disease
Low molecular weight phosphotyrosine protein phosphatase (P24666) (SMART)	OMIM:171500: ACID PHOSPHATASE 1, SOLUBLE; ACP1

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
43.24	map00740	Riboflavin metabolism
40.54	map00361	gamma-Hexachlorocyclohexane degradation
2.70	map00710	Carbon fixation
2.70	map00760	Nicotinate and nicotinamide metabolism
2.70	map00530	Aminosugars metabolism
2.70	map00030	Pentose phosphate pathway
2.70	map00730	Thiamine metabolism
2.70	map00051	Fructose and mannose metabolism

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with LMWPc domain which could be assigned to a KEGG orthologous group, and not all proteins containing LMWPc domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of LMWPc domains in PDB

PDB code	Title
1bvh	SOLUTION STRUCTURE OF A LOW MOLECULAR WEIGHT PROTEIN TYROSINE PHOSPHATASE
1c0e	Active Site S19A Mutant of Bovine Heart Phosphotyrosyl Phosphatase
1d1p	CRYSTAL STRUCTURE OF A YEAST LOW MOLECULAR WEIGHT PROTEIN TYROSINE PHOSPHATASE (LTP1)
1d1q	CRYSTAL STRUCTURE OF A YEAST LOW MOLECULAR WEIGHT PROTEIN TYROSINE PHOSPHATASE (LTP1) COMPLEXED WITH THE SUBSTRATE PNPP
1d2a	CRYSTAL STRUCTURE OF A YEAST LOW MOLECULAR WEIGHT PROTEIN TYROSINE PHOSPHATASE (LTP1) COMPLEXED WITH THE ACTIVATOR ADENINE
1dg9	CRYSTAL STRUCTURE OF BOVINE LOW MOLECULAR WEIGHT PTPASE COMPLEXED WITH HEPES
1jf8	X-ray structure of reduced C10S, C15A arsenate reductase from pI258
1jfv	X-Ray Structure of oxidised C10S, C15A arsenate reductase from pI258
1jl3	Crystal Structure of B. subtilis ArsC
1ljl	Wild Type pI258 S. aureus arsenate reductase
1lju	X-RAY STRUCTURE OF C15A ARSENATE REDUCTASE FROM PI258 COMPLEXED WITH ARSENITE
1lk0	Disulfide intermediate of C89L Arsenate reductase from pI258
1p8a	Solution structure of the low molecular weight protein tyrosine phosphatase from Tritrichomonas foetus
1phr	THE CRYSTAL STRUCTURE OF A LOW MOLECULAR PHOSPHOTYROSINE PROTEIN PHOSPHATASE
1pnt	CRYSTAL STRUCTURE OF BOVINE HEART PHOSPHOTYROSYL PHOSPHATASE AT 2.2 ANGSTROMS RESOLUTION
1rxe	ArsC complexed with MNB
1rxi	pI258 arsenate reductase (ArsC) triple mutant C10S/C15A/C82S
1u2p	Crystal structure of Mycobacterium tuberculosis Low Molecular Protein Tyrosine Phosphatase (MPtpA) at 1.9A resolution
1u2q	Crystal structure of Mycobacterium tuberculosis Low Molecular Weight Protein Tyrosine Phosphatase (MPtpA) at 2.5A resolution with glycerol in the active site
1xww	Crystal Structure of Human B-form Low Molecular Weight Phosphotyrosyl Phosphatase at 1.6 Angstrom Resolution
1y1l	crystal stracture of arsenate reductase from Archaeoglobus fulgidus DSM 4304, structural genomics
1z12	Crystal Structure of Bovine Low Molecular Weight PTPase Complexed with Vanadate
1z13	Crystal Structure of Bovine Low Molecular Weight PTPase Complexed with Molybdate
1z2d	Solution Structure of Bacillus subtilis ArsC in reduced state
1z2e	Solution Structure of Bacillus subtilis ArsC in oxidized state
1zgg	Solution structure of a low molecular weight protein tyrosine phosphatase from Bacillus subtilis
2cd7	Staphylococcus aureus pI258 arsenate reductase (ArsC) H62Q mutant
2cwd	Crystal Structure of TT1001 protein from Thermus thermophilus HB8
2fek	Structure of a protein tyrosine phosphatase
2fxi	Arsenate reductase (ArsC from pI258) C10S/C15A double mutant with sulfate in its active site
2gi4	Solution Structure of the Low Molecular Weight Protein Tyrosine Phosphatase from Campylobacter jejuni.
2ipa	solution structure of Trx-ArsC complex
2l17	An arsenate reductase in the reduced state
2l18	An arsenate reductase in the phosphate binding state
2l19	An arsenate reductase in the intermediate state
2luo	NMR solution structure of apo-MptpA
2myn	2MYN
2myp	2MYP
2myt	2MYT
2myu	2MYU
2p4u	Crystal structure of acid phosphatase 1 (Acp1) from Mus musculus
2wja	Crystal structure of the tyrosine phosphatase Wzb from Escherichia coli K30 in complex with phosphate.
2wmy	Crystal structure of the tyrosine phosphatase Wzb from Escherichia coli K30 in complex with sulphate.
3ido	Crystal structure of protein tyrosine phosphatase from Entamoeba histolytica with a phosphotyrosine crude mimic HEPES molecule in the active site
3ily	Apo crystal structure of protein tyrosine phosphatase from Entamoeba histolytica featuring a disordered active site
3js5	Crystal structure of protein tyrosine phosphatase from Entamoeba histolytica with Hepes in the active site. High resolution, alternative crystal form with 1 molecule in asymmetric unit
3jvi	Product state mimic crystal structure of protein tyrosine phosphatase from Entamoeba histolytica
3n8i	Crystal structure of the A isoform of human cytoplasmic protein tyrosine phosphatase (HCPTP-A) in complex with 1-naphtylacetic acid
3rh0	Corynebacterium glutamicum mycothiol/mycoredoxin1-dependent arsenate reductase Cg_ArsC2
3rof	Crystal Structure of the S. aureus Protein Tyrosine Phosphatase PtpA
3t38	Corynebacterium glutamicum thioredoxin-dependent arsenate reductase Cg_ArsC1'
4d74	4D74
4egs	Crystal Structure Analysis of Low Molecular Weight Protein Tyrosine Phosphatase from T. tengcongensis
4eti	Crystal Structure of YwlE from Bacillus subtilis
4etm	Crystal structure of YfkJ from Bacillus subtilis
4etn	Crystal structure of YwlE mutant from Bacillus subtilis
4kk3	YwlE arginine phosphatase - wildtype
4kk4	YwlE arginine phosphatase - C7S mutant with phosphorylated active site serine
4lrq	4LRQ
4pic	4PIC
4z99	4Z99
4z9a	4Z9A
4z9b	4Z9B
5got	5GOT
5kqg	5KQG
5kql	5KQL
5kqm	5KQM
5kqp	5KQP
5pnt	CRYSTAL STRUCTURE OF A HUMAN LOW MOLECULAR WEIGHT PHOSPHOTYROSYL PHOSPHATASE. IMPLICATIONS FOR SUBSTRATE SPECIFICITY

Links (links to other resources describing this domain)

• INTERPRO: IPR023485