DB code: M00149

RLCP classification 1.15.36030.52 : Hydrolysis
CATH domain 2.60.40.- : Immunoglobulin-like
2.60.40.- : Immunoglobulin-like
2.60.40.- : Immunoglobulin-like
2.60.40.30 : Immunoglobulin-like
2.60.40.30 : Immunoglobulin-like
2.60.40.30 : Immunoglobulin-like
2.60.40.30 : Immunoglobulin-like
2.60.40.30 : Immunoglobulin-like
2.60.40.30 : Immunoglobulin-like
2.60.40.30 : Immunoglobulin-like
2.60.40.30 : Immunoglobulin-like
3.90.190.10 : Protein-Tyrosine Phosphatase; Chain A Catalytic domain
3.90.190.10 : Protein-Tyrosine Phosphatase; Chain A
E.C. 3.1.3.48
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.90.190.10 : Protein-Tyrosine Phosphatase; Chain A M00169 S00458 D00154 T00221
2.60.40.30 : Immunoglobulin-like M00124 M00134 M00129 M00136 M00192

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P10586 Receptor-type tyrosine-protein phosphatase F
EC 3.1.3.48
Leukocyte common antigen related
LAR
NP_002831.2 (Protein)
NM_002840.3 (DNA/RNA sequence)
NP_569707.2 (Protein)
NM_130440.2 (DNA/RNA sequence)
PF00041 (fn3)
PF07679 (I-set)
PF00102 (Y_phosphatase)
[Graphical View]

KEGG enzyme name
protein-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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P10586 PTPRF_HUMAN Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. Interacts with GRIP1 (By similarity). Interacts with PPFIA1, PPFIA2 and PPFIA3. Membrane, Single-pass type I membrane protein.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00001 C01167 C00009 C00585
E.C.
Compound H2O Protein tyrosine phosphate Orthophosphate Protein tyrosine
Type H2O aromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion phosphate group/phosphate ion aromatic ring (only carbon atom),peptide/protein
ChEBI 15377
26078
PubChem 22247451
962
1004
22486802
1larA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1larB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1larA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1larB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P10586

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1larA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 1490;CYS 1522;ARG 1528;THR 1529 SER 1523;ALA 1524;VAL 1526;GLY 1527;ARG 1528
1larB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 1490;CYS 1522;ARG 1528;THR 1529 SER 1523;ALA 1524;VAL 1526;GLY 1527;ARG 1528
1larA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 1813;ARG 1819;THR 1820 SER 1814;ALA 1815;VAL 1817;GLY 1818;ARG 1819 No catalytic activity
1larB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 1813;ARG 1819;THR 1820 SER 1814;ALA 1815;VAL 1817;GLY 1818;ARG 1819 No catalytic activity

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[6]
Scheme 2 p.5640
[8]
p.451-454

References
[1]
Resource
Comments MUTAGENESIS.
Medline ID 90316093
PubMed ID 1695146
Journal EMBO J
Year 1990
Volume 9
Pages 2399-407
Authors Streuli M, Krueger NX, Thai T, Tang M, Saito H
Title Distinct functional roles of the two intracellular phosphatase like domains of the receptor-linked protein tyrosine phosphatases LCA and LAR.
Related PDB
Related UniProtKB P10586
[2]
Resource
Comments
Medline ID
PubMed ID 1318316
Journal J Biol Chem
Year 1992
Volume 267
Pages 12356-63
Authors Itoh M, Streuli M, Krueger NX, Saito H
Title Purification 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).
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1303753
Journal Protein Sci
Year 1992
Volume 1
Pages 1353-62
Authors Lee JP, Cho H, Bannwarth W, Kitas EA, Walsh CT
Title NMR analysis of regioselectivity in dephosphorylation of a triphosphotyrosyl dodecapeptide autophosphorylation site of the insulin receptor by a catalytic fragment of LAR phosphotyrosine phosphatase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8068021
Journal Biochem J
Year 1994
Volume 302
Pages 39-47
Authors Zhang WR, Hashimoto N, Ahmad F, Ding W, Goldstein BJ
Title Molecular cloning and expression of a unique receptor-like protein-tyrosine-phosphatase in the leucocyte-common-antigen-related phosphate family.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 7665159
Journal Genomics
Year 1995
Volume 27
Pages 124-30
Authors Schaapveld RQ, van den Maagdenberg AM, Schepens JT, Weghuis DO, Geurts van Kessel A, Wieringa B, Hendriks WJ
Title The mouse gene Ptprf encoding the leukocyte common antigen-related molecule LAR: cloning, characterization, and chromosomal localization.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9548949
Journal Biochemistry
Year 1998
Volume 37
Pages 5633-42
Authors Denu JM, Tanner KG
Title Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide: evidence for a sulfenic acid intermediate and implications for redox regulation.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 9882618
Journal Biochem J
Year 1999
Volume 337
Pages 219-23
Authors Desmarais S, Friesen RW, Zamboni R, Ramachandran C
Title Difluro(phosphono)methyl]phenylalanine-containing peptide inhibitors of protein tyrosine phosphatases.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10338209
Journal Cell
Year 1999
Volume 97
Pages 449-57
Authors Nam HJ, Poy F, Krueger NX, Saito H, Frederick CA
Title Crystal structure of the tandem phosphatase domains of RPTP LAR.
Related PDB 1lar
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10735562
Journal Biochem Cell Biol
Year 2000
Volume 78
Pages 39-50
Authors Glover NR, Tracey AS
Title The phosphatase domains of LAR, CD45, and PTP1B: structural correlations with peptide-based inhibitors.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10777529
Journal J Biol Chem
Year 2000
Volume 275
Pages 12446-52
Authors Blanchetot C, den Hertog J
Title Multiple interactions between receptor protein-tyrosine phosphatase (RPTP) alpha and membrane-distal protein-tyrosine phosphatase domains of various RPTPs.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11241288
Journal Eur J Immunol
Year 2001
Volume 31
Pages 832-40
Authors Terszowski G, Jankowski A, Hendriks WJ, Rolink AG, Kisielow P
Title Within 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.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 11158333
Journal Mol Endocrinol
Year 2001
Volume 15
Pages 271-80
Authors Tsujikawa K, Kawakami N, Uchino Y, Ichijo T, Furukawa T, Saito H, Yamamoto H
Title Distinct functions of the two protein tyrosine phosphatase domains of LAR (leukocyte common antigen-related) on tyrosine dephosphorylation of insulin receptor.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 12376545
Journal J Biol Chem
Year 2002
Volume 277
Pages 47263-9
Authors Blanchetot C, Tertoolen LG, Overvoorde J, den Hertog J
Title Intra- and intermolecular interactions between intracellular domains of receptor protein-tyrosine phosphatases.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 11806712
Journal J Med Chem
Year 2002
Volume 45
Pages 598-622
Authors Larsen SD, Barf T, Liljebris C, May PD, Ogg D, O'Sullivan TJ, Palazuk BJ, Schostarez HJ, Stevens FC, Bleasdale JE
Title Synthesis and biological activity of a novel class of small molecular weight peptidomimetic competitive inhibitors of protein tyrosine phosphatase 1B.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 12176037
Journal Biochem Biophys Res Commun
Year 2002
Volume 296
Pages 692-7
Authors Caselli A, Mazzinghi B, Camici G, Manao G, Ramponi G
Title Some protein tyrosine phosphatases target in part to lipid rafts and interact with caveolin-1.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 9566880
Journal Mol Cell Biol
Year 1998
Volume 18
Pages 2608-16
Authors Wallace MJ, Fladd C, Batt J, Rotin D
Title The second catalytic domain of protein tyrosine phosphatase delta (PTP delta) binds to and inhibits the first catalytic domain of PTP sigma.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 1730581
Journal J Biol Chem
Year 1992
Volume 267
Pages 140-3
Authors Pot DA, Dixon JE
Title Active site labeling of a receptor-like protein tyrosine phosphatase.
Related PDB
Related UniProtKB

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.

Created Updated
2004-08-18 2009-02-26