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)
2.60.40.30 : Immunoglobulin-like	M00124 M00134 M00129 M00136 M00192
3.90.190.10 : Protein-Tyrosine Phosphatase; Chain A	M00169 S00458 D00154 T00221

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	RefSeq	Pfam
P10586	Receptor-type tyrosine-protein phosphatase F	EC 3.1.3.48 LAR protein Leukocyte antigen related	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 15377		26078 26078
PubChem	22247451 962 22247451 962		1004 22486802 1004 22486802

1larA01		Unbound	Unbound	Unbound
1larB01		Unbound	Unbound	Unbound
1larA02		Unbound	Unbound	Unbound
1larB02		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	ASP 1490;CYS 1522;ARG 1528;THR 1529			SER 1523;ALA 1524;VAL 1526;GLY 1527;ARG 1528
1larB01	ASP 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
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.

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