EzCatDB: M00149
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DB codeM00149
RLCP classification1.15.36030.52 : Hydrolysis
CATH domainDomain 12.60.40.- : Immunoglobulin-like
Domain 22.60.40.- : Immunoglobulin-like
Domain 32.60.40.- : Immunoglobulin-like
Domain 42.60.40.30 : Immunoglobulin-like
Domain 52.60.40.30 : Immunoglobulin-like
Domain 62.60.40.30 : Immunoglobulin-like
Domain 72.60.40.30 : Immunoglobulin-like
Domain 82.60.40.30 : Immunoglobulin-like
Domain 92.60.40.30 : Immunoglobulin-like
Domain 102.60.40.30 : Immunoglobulin-like
Domain 112.60.40.30 : Immunoglobulin-like
Domain 123.90.190.10 : Protein-Tyrosine Phosphatase; Chain ACatalytic domain
Domain 133.90.190.10 : Protein-Tyrosine Phosphatase; Chain A
E.C.3.1.3.48

CATH domainRelated DB codes (homologues)
2.60.40.30 : Immunoglobulin-likeM00124,M00134,M00129,M00136,M00192
3.90.190.10 : Protein-Tyrosine Phosphatase; Chain AM00169,S00458,D00154,T00221

Enzyme Name
UniProtKBKEGG

P10586
Protein nameReceptor-type tyrosine-protein phosphatase Fprotein-tyrosine-phosphatase
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
SynonymsEC 3.1.3.48
LAR protein
Leukocyte antigen related
RefSeqNP_002831.2 (Protein)
NM_002840.3 (DNA/RNA sequence)
NP_569707.2 (Protein)
NM_130440.2 (DNA/RNA sequence)
PfamPF00041 (fn3)
PF07679 (I-set)
PF00102 (Y_phosphatase)
[Graphical view]


UniProtKB:Accession NumberP10586
Entry namePTPRF_HUMAN
ActivityProtein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.
SubunitInteracts with GRIP1 (By similarity). Interacts with PPFIA1, PPFIA2 and PPFIA3.
Subcellular locationMembrane, Single-pass type I membrane protein.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00001C01167C00009C00585
CompoundH2OProtein tyrosine phosphateOrthophosphateProtein tyrosine
TypeH2Oaromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ionphosphate group/phosphate ionaromatic ring (only carbon atom),peptide/protein
ChEBI15377

26078

PubChem962
22247451

22486802
1004

            
1larA01 UnboundUnboundUnbound
1larB01 UnboundUnboundUnbound
1larA02 UnboundUnboundUnbound
1larB02 UnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P10586
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
1larA01ASP 1490;CYS 1522;ARG 1528;THR 1529
SER 1523;ALA 1524;VAL 1526;GLY 1527;ARG 1528
 
1larB01ASP 1490;CYS 1522;ARG 1528;THR 1529
SER 1523;ALA 1524;VAL 1526;GLY 1527;ARG 1528
 
1larA02         CYS 1813;ARG 1819;THR 1820
SER 1814;ALA 1815;VAL 1817;GLY 1818;ARG 1819
No catalytic activity
1larB02         CYS 1813;ARG 1819;THR 1820
SER 1814;ALA 1815;VAL 1817;GLY 1818;ARG 1819
No catalytic activity

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[6]Scheme 2p.5640
[8]p.451-454

references
[1]
CommentsMUTAGENESIS.
Medline ID90316093
PubMed ID1695146
JournalEMBO J
Year1990
Volume9
Pages2399-407
AuthorsStreuli M, Krueger NX, Thai T, Tang M, Saito H
TitleDistinct functional roles of the two intracellular phosphatase like domains of the receptor-linked protein tyrosine phosphatases LCA and LAR.
Related UniProtKBP10586
[2]
PubMed ID1318316
JournalJ Biol Chem
Year1992
Volume267
Pages12356-63
AuthorsItoh M, Streuli M, Krueger NX, Saito H
TitlePurification and characterization of the catalytic domains of the human receptor-linked protein tyrosine phosphatases HPTP beta, leukocyte common antigen (LCA), and leukocyte common antigen-related molecule (LAR).
[3]
PubMed ID1303753
JournalProtein Sci
Year1992
Volume1
Pages1353-62
AuthorsLee JP, Cho H, Bannwarth W, Kitas EA, Walsh CT
TitleNMR analysis of regioselectivity in dephosphorylation of a triphosphotyrosyl dodecapeptide autophosphorylation site of the insulin receptor by a catalytic fragment of LAR phosphotyrosine phosphatase.
[4]
PubMed ID8068021
JournalBiochem J
Year1994
Volume302
Pages39-47
AuthorsZhang WR, Hashimoto N, Ahmad F, Ding W, Goldstein BJ
TitleMolecular cloning and expression of a unique receptor-like protein-tyrosine-phosphatase in the leucocyte-common-antigen-related phosphate family.
[5]
PubMed ID7665159
JournalGenomics
Year1995
Volume27
Pages124-30
AuthorsSchaapveld RQ, van den Maagdenberg AM, Schepens JT, Weghuis DO, Geurts van Kessel A, Wieringa B, Hendriks WJ
TitleThe mouse gene Ptprf encoding the leukocyte common antigen-related molecule LAR: cloning, characterization, and chromosomal localization.
[6]
PubMed ID9548949
JournalBiochemistry
Year1998
Volume37
Pages5633-42
AuthorsDenu JM, Tanner KG
TitleSpecific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide: evidence for a sulfenic acid intermediate and implications for redox regulation.
[7]
PubMed ID9882618
JournalBiochem J
Year1999
Volume337
Pages219-23
AuthorsDesmarais S, Friesen RW, Zamboni R, Ramachandran C
TitleDifluro(phosphono)methyl]phenylalanine-containing peptide inhibitors of protein tyrosine phosphatases.
[8]
CommentsX-ray crystallography
PubMed ID10338209
JournalCell
Year1999
Volume97
Pages449-57
AuthorsNam HJ, Poy F, Krueger NX, Saito H, Frederick CA
TitleCrystal structure of the tandem phosphatase domains of RPTP LAR.
Related PDB1lar
[9]
PubMed ID10735562
JournalBiochem Cell Biol
Year2000
Volume78
Pages39-50
AuthorsGlover NR, Tracey AS
TitleThe phosphatase domains of LAR, CD45, and PTP1B: structural correlations with peptide-based inhibitors.
[10]
PubMed ID10777529
JournalJ Biol Chem
Year2000
Volume275
Pages12446-52
AuthorsBlanchetot C, den Hertog J
TitleMultiple interactions between receptor protein-tyrosine phosphatase (RPTP) alpha and membrane-distal protein-tyrosine phosphatase domains of various RPTPs.
[11]
PubMed ID11241288
JournalEur J Immunol
Year2001
Volume31
Pages832-40
AuthorsTerszowski G, Jankowski A, Hendriks WJ, Rolink AG, Kisielow P
TitleWithin the hemopoietic system, LAR phosphatase is a T cell lineage-specific adhesion receptor-like protein whose phosphatase activity appears dispensable for T cell development, repertoire selection and function.
[12]
PubMed ID11158333
JournalMol Endocrinol
Year2001
Volume15
Pages271-80
AuthorsTsujikawa K, Kawakami N, Uchino Y, Ichijo T, Furukawa T, Saito H, Yamamoto H
TitleDistinct functions of the two protein tyrosine phosphatase domains of LAR (leukocyte common antigen-related) on tyrosine dephosphorylation of insulin receptor.
[13]
PubMed ID12376545
JournalJ Biol Chem
Year2002
Volume277
Pages47263-9
AuthorsBlanchetot C, Tertoolen LG, Overvoorde J, den Hertog J
TitleIntra- and intermolecular interactions between intracellular domains of receptor protein-tyrosine phosphatases.
[14]
PubMed ID11806712
JournalJ Med Chem
Year2002
Volume45
Pages598-622
AuthorsLarsen SD, Barf T, Liljebris C, May PD, Ogg D, O'Sullivan TJ, Palazuk BJ, Schostarez HJ, Stevens FC, Bleasdale JE
TitleSynthesis and biological activity of a novel class of small molecular weight peptidomimetic competitive inhibitors of protein tyrosine phosphatase 1B.
[15]
PubMed ID12176037
JournalBiochem Biophys Res Commun
Year2002
Volume296
Pages692-7
AuthorsCaselli A, Mazzinghi B, Camici G, Manao G, Ramponi G
TitleSome protein tyrosine phosphatases target in part to lipid rafts and interact with caveolin-1.
[16]
PubMed ID9566880
JournalMol Cell Biol
Year1998
Volume18
Pages2608-16
AuthorsWallace MJ, Fladd C, Batt J, Rotin D
TitleThe second catalytic domain of protein tyrosine phosphatase delta (PTP delta) binds to and inhibits the first catalytic domain of PTP sigma.
[17]
PubMed ID1730581
JournalJ Biol Chem
Year1992
Volume267
Pages140-3
AuthorsPot DA, Dixon JE
TitleActive site labeling of a receptor-like protein tyrosine phosphatase.

comments
This enzyme is composed of the N-terminal extracellular region, the transmembrane region, and the C-terminal cytoplasmic region. The C-terminal region contains two protein tyrosine phosphatase domains. Whilst the structures of the catalytic domains have been determined, the remainder has not been determined yet. However, according to the literature [4], homology search suggested that the N-terminal extracellular region seems to be composed of three immunoglobulin-like domains and eight fibronectin type III domains.
According to the literature [8], the second phosphatase domain has no catalytic activity, whereas the first domain retains the activily. Considering the active site residues and mutational analysis, the loss of catalytic activity is due to two residues, Leu1644 and Glu1779. When these residues are mutated into Tyr and Asp, respectively, the activity was restored (see [8]). The corresponding tyrosine may interact with phosphorylated tyrosine (see [8]).
According to the literature [8], in the first phosphatase domain, Cys1522 acts as a nucleophile, which will make an attack on an incoming phosphopeptide, whilst Asp1490 acts as a general acid.
Moreover, the catalytic domain is homologous to other phosphatase enzyme domains (S00458, D00154 in EzCatDB). These domains has Ser or Thr next to the catalytic Arg, and it acts as a modulator interacting with catalytic Cys. As this enzyme also has got the residue at the position, it may play the same role as the counterparts.

createdupdated
2004-08-182009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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