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Information on EC 3.1.3.48 - protein-tyrosine-phosphatase and Organism(s) Mus musculus and UniProt Accession Q62130
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EC Tree
3.1.3.48 protein-tyrosine-phosphataseIUBMB Comments
Dephosphorylates O-phosphotyrosine groups in phosphoproteins, such as the products of EC 2.7.10.2, non-specific protein-tyrosine kinase.
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Word Map
- 3.1.3.48
- pp2a
- mapks
- autoimmune
- erk
- cyclin
- leukemia
- endothelial
- ras
-
signal-regulated
- lysosomal
-
okadaic
- t-cells
- metastasis
-
checkpoint
- sirna
- obesity
- myeloid
- 3-kinase
- adaptor
- arthritis
- vanadate
- stat3
- tumorigenesis
- prostate
- mellitus
- phosphatidylinositol
-
cyclin-dependent
- c-jun
- pkc
-
rheumatoid
-
tyrosine-phosphorylated
-
hyperphosphorylation
-
nonreceptor
- chk1
-
cytochemical
- autophosphorylation
-
receptor-like
- genistein
- irs-1
-
insulin-stimulated
- phosphopeptide
-
tartrate-resistant
- grb2
- c-src
- jak2
- fyn
- paxillin
- substrate-1
-
myelomonocytic
-
polo-like
- medicine
- pharmacology
- diagnostics
- drug development
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
ptp1b, protein tyrosine phosphatase, shp-1, shp-2, tyrosine phosphatase, protein phosphatase 2a, acid phosphatase activity, mkp-1, cdc25a, ptpn22, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
70Z-SHP
-
-
-
-
Brain-derived phosphatase
-
-
-
-
BVP
-
-
-
-
CD148 antigen
-
-
-
-
CD45
-
-
-
-
CD45 antigen
-
-
-
-
Cdc25-like protein
-
-
-
-
CDK2-associated dual specificity phosphatase
-
-
-
-
Ch-1PTPase
-
-
-
-
CPTP1
-
-
-
-
DLAR
-
-
-
-
Dual specificity phosphatase Cdc25A
-
-
-
-
Dual specificity phosphatase Cdc25B
-
-
-
-
Dual specificity phosphatase Cdc25C
-
-
-
-
Dual specificity protein phosphatase hVH1
-
-
-
-
Dual specificity protein phosphatase hVH2
-
-
-
-
Dual specificity protein phosphatase hVH3
-
-
-
-
Dual specificity protein phosphatase PYST1
-
-
-
-
Dual specificity protein phosphatase PYST2
-
-
-
-
Dual specificity protein phosphatase VHR
-
-
-
-
Dual-specificity tyrosine phosphatase TS-DSP6
-
-
-
-
Dual-specificity tyrosine phosphatase YVH1
-
-
-
-
ES cell phosphatase
-
-
-
-
HCP
-
-
-
-
Hematopoietic cell protein-tyrosine phosphatase
-
-
-
-
Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP
-
-
-
-
Hematopoietic protein-tyrosine phosphatase
-
-
-
-
HEPTP
HPTP beta-like tyrosine phosphatase
-
-
-
-
HPTP eta
-
-
-
-
hPTPE1
-
-
-
-
ICAAR
-
-
-
-
Islet cell autoantigen related protein
-
-
-
-
kinase associated phosphatase
-
-
-
-
L-CA
-
-
-
-
Late protein H1
-
-
-
-
LCA
-
-
-
-
LCA-related phosphatase
-
-
-
-
Leukocyte antigen related
-
-
-
-
Low molecular weight cytosolic acid phosphatase
-
-
-
-
LRP
-
-
-
-
Lymphoid phosphatase
-
-
-
-
LyP
-
-
-
-
M1851
-
-
-
-
MAP-kinase phosphatase CPG21
-
-
-
-
MEG
-
-
-
-
Mitosis initiation protein
-
-
-
-
Mitosis initiation protein MIH1
-
-
-
-
Mitotic inducer homolog
-
-
-
-
MKP-1 like protein tyrosine phosphatase
-
-
-
-
MPTP
-
-
-
-
MPTP-PEST
-
-
-
-
NC-PTPCOM1
-
-
-
-
Neural-specific protein-tyrosine phosphatase
-
-
-
-
ORF5
-
-
-
-
OST-PTP
-
-
-
-
P19-PTP
-
-
-
-
P80
-
-
-
-
PC12-PTP1
-
-
-
-
Phogrin
-
-
-
-
Phosphacan
-
-
-
-
phosphatase, phosphoprotein (phosphotyrosine)
-
-
-
-
phosphatase, phosphotyrosine
-
-
-
-
phosphoprotein phosphatase (phosphotyrosine)
-
-
-
-
phosphotyrosine histone phosphatase
-
-
-
-
phosphotyrosine phosphatase
-
-
-
-
Phosphotyrosine phosphatase 13
-
-
-
-
phosphotyrosine protein phosphatase
-
-
-
-
phosphotyrosylprotein phosphatase
-
-
-
-
protein phosphotyrosine phosphatase
-
-
-
-
protein tyrosine phosphatase
Protein tyrosine phosphatase-NP
-
-
-
-
Protein-protein-tyrosine phosphatase HA2
-
-
-
-
protein-tyrosine phosphatase
Protein-tyrosine phosphatase 1B
-
-
-
-
Protein-tyrosine phosphatase 1C
-
-
-
-
Protein-tyrosine phosphatase 1E
-
-
-
-
Protein-tyrosine phosphatase 2C
-
-
-
-
Protein-tyrosine phosphatase 2E
-
-
-
-
Protein-tyrosine phosphatase 3CH134
-
-
-
-
Protein-tyrosine phosphatase CL100
-
-
-
-
Protein-tyrosine phosphatase D1
-
-
-
-
Protein-tyrosine phosphatase ERP
-
-
-
-
Protein-tyrosine phosphatase G1
-
-
-
-
Protein-tyrosine phosphatase H1
-
-
-
-
Protein-tyrosine phosphatase LC-PTP
-
-
-
-
Protein-tyrosine phosphatase MEG1
-
-
-
-
Protein-tyrosine phosphatase MEG2
-
-
-
-
Protein-tyrosine phosphatase P19
-
-
-
-
Protein-tyrosine phosphatase PCPTP1
-
-
-
-
Protein-tyrosine phosphatase pez
-
-
-
-
Protein-tyrosine phosphatase PTP-RL10
-
-
-
-
Protein-tyrosine phosphatase PTP36
-
-
-
-
Protein-tyrosine phosphatase PTPL1
-
-
-
-
Protein-tyrosine phosphatase striatum-enriched
-
-
-
-
Protein-tyrosine phosphatase SYP
-
-
-
-
Protein-tyrosine-phosphatase SL
-
-
-
-
Protein-tyrosine-phosphate phosphohydrolase
-
-
-
-
PTP
PTP IA-2beta
-
-
-
-
PTP-1B
PTP-1C
-
-
-
-
PTP-1D
-
-
-
-
PTP-2C
-
-
-
-
PTP-BAS
-
-
-
-
PTP-E1
-
-
-
-
PTP-H1
-
-
-
-
PTP-HA2
-
-
-
-
PTP-NP
-
-
-
-
PTP-PEST
PTP-SH2beta
-
-
-
-
PTP1C
-
-
-
-
PTP1D
-
-
-
-
PTP2C
-
-
-
-
PTPalpha
PTPase YVH1
-
-
-
-
PTPase-MEG1
-
-
-
-
PTPase-MEG2
-
-
-
-
PTPBR7
PTPepsilon
PTPG1
-
-
-
-
PTPN1
PTPN4
PTPN6
PTPNE6
-
-
-
-
PY protein phosphatase
-
-
-
-
R-PTP-alpha
-
-
-
-
R-PTP-beta
-
-
-
-
R-PTP-delta
-
-
-
-
R-PTP-epsilon
-
-
-
-
R-PTP-eta
-
-
-
-
R-PTP-gamma
-
-
-
-
R-PTP-kappa
-
-
-
-
R-PTP-mu
-
-
-
-
R-PTP-zeta
-
-
-
-
Receptor-linked protein-tyrosine phosphatase 10D
-
-
-
-
Receptor-linked protein-tyrosine phosphatase 99A
-
-
-
-
RNA/RNP complex-intereracting phosphatase
-
-
-
-
ROL B protein
-
-
-
-
RPTPalpha
-
-
-
-
SH-PTP1
-
-
-
-
SH-PTP2
-
-
-
-
SH-PTP3
-
-
-
-
SHP
-
-
-
-
Small tyrosine phosphatase
-
-
-
-
Small, acidic phosphotyrosine protein phosphatase
-
-
-
-
STEP
String protein
-
-
-
-
Syp
-
-
-
-
T-cell protein-tyrosine phosphatase
-
-
-
-
T-DSP11
-
-
-
-
T200
-
-
-
-
TCPTP
Testis-and skeletal-muscle-specific DSP
-
-
-
-
tyrosine O-phosphate phosphatase
-
-
-
-
Tyrosine phosphatase CBPTP
-
-
-
-
tyrosylprotein phosphatase
-
-
-
-
[phosphotyrosine]protein phosphatase
-
-
-
-
additional information
-
SHP-1 is a member of SH2 domain-containing PTP subfamily
HEPTP
-
-
-
-
protein tyrosine phosphatase
-
-
PTP-1B
-
-
-
-
PTPN6
-
-
-
-
STEP
-
-
-
-
TCPTP
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
[a protein]-tyrosine phosphate + H2O = [a protein]-tyrosine + phosphate
for both alkyl and aryl substrates, including the activated substrate 4-nitrophenyl phosphate with its particularly good leaving group, general acid catalysis in PTPs is highly efficient and fully neutralizes the leaving group in the transition state. Mutating the conserved aspartic acid to glutamine causes the expected reductions in rate of several orders of magnitude and loss of the basic limb in pH-rate profiles, kinetic isotope effects, general acid catalysis mechanism, overview
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
protein-tyrosine-phosphate phosphohydrolase
Dephosphorylates O-phosphotyrosine groups in phosphoproteins, such as the products of EC 2.7.10.2, non-specific protein-tyrosine kinase.
CAS REGISTRY NUMBER
COMMENTARY
79747-53-8
-
97162-86-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
6,8-difluoro-4-methylumbelliferyl phosphate + H2O
6,8-difluoro-4-methylumbelliferol + phosphate
-
-
-
-
?
phosphorylated AMP-activated protein kinase + H2O
AMP-activated protein kinase + phosphate
phosphorylated c-Kit + H2O
c-Kit + phosphate
-
dephosphorylation occurs at tyrosines 567/569 and 719
-
-
?
phosphorylated c-Src + H2O
c-Src + phosphate
-
dephosphorylation activates c-Src
-
-
?
phosphorylated colony-stimulating factor 1 receptor + H2O
colony-stimulating factor 1 + phosphate
-
-
-
-
?
phosphorylated epidermal growth factor receptor + H2O
epidermal growth factor receptor + phosphate
-
-
-
-
?
phosphorylated extracellular signal-regulated kinase 1 + H2O
extracellular signal-regulated kinase 1 + phosphate
-
-
-
-
?
phosphorylated extracellular signal-regulated kinase 2 + H2O
extracellular signal-regulated kinase 2 + phosphate
-
-
-
-
?
phosphorylated insulin receptor + H2O
insulin receptor + phosphate
-
-
preferential dephosphorylation of Y1162/1163 of insulin receptor
-
?
phosphorylated insulin receptor substrate-1 + H2O
insulin receptor substrate-1 + phosphate
-
-
-
-
?
phosphorylated insulin receptor substrate-2 + H2O
insulin receptor substrate-2 + phosphate
-
-
-
-
?
phosphorylated mitogen-activated protein kinase + H2O
mitogen-activated protein kinase + phosphate
-
-
-
-
?
phosphorylated p190B Rho-GTPase-activating protein + H2O
p190B Rho-GTPase-activating protein + phosphate
-
-
-
-
?
phosphorylated phospholipase Cgamma + H2O
phospholipase Cgamma + phosphate
-
dephosphorylation occurs at Tyr-783
-
-
?
phosphorylated proline serine threonine-rich phosphatase interacting protein + H2O
proline serine threonine-rich phosphatase interacting protein + phosphate
-
-
-
-
?
phosphorylated proline-rich tyrosine kinase 2 + H2O
proline-rich tyrosine kinase 2 + phosphate
-
the enzyme directly binds to and dephosphorylates proline-rich tyrosine kinase 2 at Tyr402
-
-
?
phosphorylated T cell antigen receptor chain zeta + H2O
T cell antigen receptor chain zeta + phosphate
-
-
-
-
?
phosphorylated T-cell receptor-zeta subunit + H2O
T-cell receptor-zeta subunit + phosphate
-
dephosphorylates ITAMs of the T-cell receptor-zeta subunit
-
-
?
phosphorylated TCRzeta + H2O
TCRzeta + phosphate
-
PTPH1 dephosphorylates TCRzeta in vitro, inhibiting the downstream inflammatory signaling pathway
-
-
?
phosphorylated vascular endothelial growth factor receptor 2 + H2O
vascular endothelial growth factor receptor 2 + phosphate
-
dephosphorylation occurs at Tyr-1175, PTP1B binds to vascular endothelial growth factor receptor 2 cytoplasmic domain and directly dephosphorylates activated vascular endothelial growth factor receptor 2 immunoprecipitates
-
-
?
phosphorylated voltage-gated potassium channel subunit Kv2.1 + H2O
voltage-gated potassium channel subunit Kv2.1 + phosphate
-
-
-
-
?
phosphorylated AMP-activated protein kinase + H2O
AMP-activated protein kinase + phosphate
-
PTPB1 is involved in AMPK regulation through its phosphorylation in a tissue-specific manner, overview
-
-
?
phosphorylated AMP-activated protein kinase + H2O
AMP-activated protein kinase + phosphate
-
phosphorylation of the AMPK alpha subunit at Thr172
-
-
?
[a protein]-tyrosine phosphate + H2O
[a protein]-tyrosine + phosphate
-
-
-
-
?
[a protein]-tyrosine phosphate + H2O
[a protein]-tyrosine + phosphate
-
-
-
?
[a protein]-tyrosine phosphate + H2O
[a protein]-tyrosine + phosphate
-
-
-
?
[a protein]-tyrosine phosphate + H2O
[a protein]-tyrosine + phosphate
-
-
-
?
additional information
?
-
the isoforms of PRP36 may function as adapter molecules rather than as a phosphatase
-
-
?
additional information
?
-
-
protein tyrosine phosphatase alpha regulates the activity of raft Fyn
-
-
?
additional information
?
-
-
N-cadherin, VE-cadherin, desmoglein, alpha-catenin, beta-catenin, gamma-catenin, and alpha-actinin are not dephosphorylated by RPTPrho
-
-
?
additional information
?
-
-
PTP-PEST most likely also participates in regulating osteoclast differentiation and adhesion to bone matrix
-
-
?
additional information
?
-
-
PTPalpha is required for stem cell factor-stimulated Src family kinase activation and signaling, and for mast cell migration
-
-
?
additional information
?
-
-
SHP-1 is a negative regulator of osteoclastogenic signalling
-
-
?
additional information
?
-
-
phospho-p38 mitogen-activated protein kinase and Akt are not dephosphorylated
-
-
?
additional information
?
-
-
HePTP plays a role in regulating the level of p38 MAPK phosphorylation in B-lymphocytes, HePTP can be phosphorylated by PKA, which inactivates the phosphatase and causes it to release p38 MAPK into the cytoplasm
-
-
?
additional information
?
-
-
PTPN4 does not dephosphorylate Lck at tyrosine residue 394
-
-
?
additional information
?
-
in vivo phagocytosis assay and in vivo microglial migration assay, overview
-
-
?
additional information
?
-
enzyme additionally catalyzes the hydrolysis of 2-phosphoglycolate, reaction of EC 3.1.3.18
-
-
?
additional information
?
-
PTP1 is a classical PTP with a deep active site pocket suited for phosphotyrosine, that also efficiently hydrolyzes other phosphorylated phenols
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
phosphorylated AMP-activated protein kinase + H2O
AMP-activated protein kinase + phosphate
-
PTPB1 is involved in AMPK regulation through its phosphorylation in a tissue-specific manner, overview
-
-
?
[a protein]-tyrosine phosphate + H2O
[a protein]-tyrosine + phosphate
-
-
-
-
?
[a protein]-tyrosine phosphate + H2O
[a protein]-tyrosine + phosphate
-
-
-
?
[a protein]-tyrosine phosphate + H2O
[a protein]-tyrosine + phosphate
-
-
-
?
[a protein]-tyrosine phosphate + H2O
[a protein]-tyrosine + phosphate
-
-
-
?
additional information
?
-
the isoforms of PRP36 may function as adapter molecules rather than as a phosphatase
-
-
?
additional information
?
-
-
protein tyrosine phosphatase alpha regulates the activity of raft Fyn
-
-
?
additional information
?
-
-
PTP-PEST most likely also participates in regulating osteoclast differentiation and adhesion to bone matrix
-
-
?
additional information
?
-
-
PTPalpha is required for stem cell factor-stimulated Src family kinase activation and signaling, and for mast cell migration
-
-
?
additional information
?
-
-
SHP-1 is a negative regulator of osteoclastogenic signalling
-
-
?
additional information
?
-
in vivo phagocytosis assay and in vivo microglial migration assay, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
JTT-551
-
i.e. monosodium (([5-(1,1-dimethylethyl)thiazol-2-yl]methyl)([(4-(4-[4-(1-propylbutyl)phenoxy]methyl)phenyl)thiazol-2-yl]methyl)amino)acetate, a specific protein tyrosine phosphatase 1B inhibitor in vitro and in vivo, mixed-type inhibition mode versus PTPB1, overview. The inhibitor shows a hypoglycaemic effect in ob/ob mice, overview
additional information
-
beta2AR stimulation on a B cell phosphorylates and inactivates HePTP in a Gs/cAMP/PKA-dependent manner
-
additional information
-
inhibition of PTP-PEST by RNAi reduces formation of podosomal structures at the cell periphery and reduces bone resorption indicating a positive functional role for this PTP in promoting osteoclast activity
-
additional information
-
interaction between the alpha-cytoplasmic tail of a1beta1 integrin and TCPTP activates TCPTP by disrupting an inhibitory intramolecular bond in TCPTP, screening of screened 64280 small molecules for TCPTP inhibition, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Mitoxantrone
-
activates isozyme TC45 via a mechanism similar to alpha1-cyt, i.e. integrin alpha1 cytoplasmic tail residues 1164-1179, molecular mechanism, overview
spermidine
-
activates isozyme TC45 via a mechanism similar to alpha1-cyt, i.e. integrin alpha1 cytoplasmic tail residues 1164-1179, molecular mechanism, overview. Spermidine inhibits serum-induced cell proliferation in a TC45-dependent manner, and regulates EGFR and PDGFRb signalling via TC45
additional information
-
interaction between the alpha-cytoplasmic tail of a1beta1 integrin and TCPTP activates TCPTP by disrupting an inhibitory intramolecular bond in TCPTP
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
kinetic isotope effects. The active form of the substrate is the dianion
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GenBank accession numbers are PTP36-A: AF170902, PTP36-B: AF170903, PTP36-C: AF170904
Uniprot
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
during cerebellar maturation, PTPBR7 expression in developing Purkinje cells ceases and is replaced by PTP-SL expression in the mature Purkinje cells
-
highest transcriptional level in embryo at day 10, lowest transcriptional level in embryo at day 15
murine microglia are isolated from newborn mice, DEP-1 is expressed in microglial cells in a cell density-dependent manner
additional information
-
cyt-PTPepsilon is expressed strongly in osteoclasts and is virtually absent from osteoblasts, RPTPepsilon is not expressed in either cell type, function of cyt-PTPepsilon is critical for proper organization of podosomes in osteoclasts
-
of enzyme-deficient animal, cells develop normally, but show increased tyrosine phosphorylation of specific proteins, increased Fyn activity due to enhanced phosphorylation of Y528 and Y417, and hyperphosphorylation of Cbp/PAG
additional information
DEP-1 protein levels increase in several cell types at high-cell density. DEP-1 is a widely expressed in cells of the immune system
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the enzyme is a member of the PTP superfamily. The Trp residue is highly conserved in the PTP family and is one of the residues in the flexible loop that bears the general acid
malfunction
metabolism
physiological function
additional information
phosphatases do not alter the transition state for phosphoryl transfer
malfunction
-
bone marrow-derived macrophages lacking significant SHP-1 activity display a profound defect in interleukin-12p40 synthesis in response to lipopolysaccharide, peptidoglycan, and synthetic Toll-like receptor ligands, while producing normal amounts of other proinflammatory cytokines, such as TNFalpha and interleukin-6
malfunction
-
neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMP-activated protein kinase, AMPK, and isoform-specific activation of AMPK in peripheral tissues, overview
malfunction
-
the enzyme is involved in the negative regulation of several cancer relevant cellular signalling pathways
malfunction
-
loss of SHP-1 expression strongly augments the ability of regulatory T cells to suppress inflammation in a mouse model. Specific pharmacological inhibition of SHP-1 enzymatic activity via the cancer drug sodium stibogluconate potently augmented regulatory T cell suppressor activity both in vivo and ex vivo. SHP-1-deficient regulatory T cells are more efficient suppressors T-cell activation than wild-type regulatory T-cells
malfunction
in the microglial cell line BV-2, DEP-1 depletion by shRNA-mediated knockdown results in enhanced phosphorylation of the Fyn activating tyrosine (Tyr420) and elevated specific Fyn-kinase activity in immunoprecipitates. Fyn mRNA and protein levels are reduced in DEP-1-deficient microglia cells. Knockdown of DEP-1 causes a small but significant decrease of phagocytosis of unstimulated microglial BV-2 cells. And the stimulatory effect on phagocytosis is significantly reduced in cells depleted for DEP-1, reduced phagocytic activity of microglial cells in DEP-1-/- mice brains
malfunction
the C1858T polymorphism within the protein tyrosine phosphatase PTPN22 (encoding PTPN22R619W) is a major risk factor for the development of multiple autoimmune diseases, including rheumatoid arthritis (RA), type I diabetes, lupus and juvenile idiopathic arthritis (JIA). The autoimmune associated PTPN22R619W variant displays reduced binding to the tyrosine kinase Csk, due to a missense mutation in the P1 domain. Ptpn22 variants do not alter BMDC receptor mediated phagocytosis
metabolism
-
striatal-enriched protein-tyrosine phosphatase regulates proline-rich tyrosine kinase 2 activity
metabolism
cysteine residues Cys35, Cys104 and Cys243 in the catalytic core domain of PGP mediate the reversible inhibition of PGP activity and the associated, redox-dependent conformational changes. Cys35 oxidation weakens van-der-Waals interactions with Thr67, a conserved catalytic residue required for substrate coordination. Cys104 and Cys243 form a redox-dependent disulfide bridge between the PGP catalytic core and cap domains. Cys297 in the PGP cap domain is essential for redox-dependent PGP oligomerization, and PGP oxidation/oligomerization occurs in response to stimulation of cells with EGF
physiological function
-
PTPH1 might play a role in the positive regulation of the LPS-induced cytokines release in vivo, in contrast to previous reports indicating PTPH1 as potential negative regulator of immune response
physiological function
-
SHP-1 plays critical roles in regulation of many receptor-mediated signaling cascades in the immune system, and it represents a mechanism for host regulation of a specific proinflammatory cytokine important in both innate and adaptive immunity. It is required for SHP-1 in interleukin-12/23 p40 production in response to Toll-like receptor stimulation in macrophages. SHP-1 regulation of interleukin-12p40 transcription requires both its catalytic activity and phosphotyrosine binding by its N-terminal SH2 domain and is mediated via repression of, and interaction with, phosphatidylinositol 3-kinase, without affecting c-Rel activation, overview
physiological function
-
the cytoplasmic tyrosine phosphatase Src homology region 2 domain-containing phosphatase 1, SHP-1, acts as an endogenous brake and modifier of the suppressive ability of regulatory T cells, which are important for immune tolerance. Regulatory T cells prevent the activation of conventional T cells. Regulatory T cell -mediated suppression of Tcon activation occurs by multiple mechanisms and is regulated by SHP-1, overview
physiological function
-
protein tyrosine phosphatase (PTP) alpha regulates integrin signaling, focal adhesion formation, and migration. PTPalpha-Tyr789 is necessary for efficient integrin-induced Cas tyrosine phosphorylation and Cas-Crk association, and regulates Cas downstream signaling events and Cas localization to focal adhesions
physiological function
-
protein tyrosine phosphatase 1B is a negative regulator of systemic glucose and insulin homeostasis and inhibits adipocyte differentiation and mediates TNFalpha action in obesity
physiological function
-
the enzyme is capable of rescuing the effects of v-Src toxicity
physiological function
density-enhanced phosphatase-1 (DEP-1), also designated PTPRJ, receptor-type PTP eta or CD148, is a transmembrane PTP endowed with one intracellular catalytic domain, and an extracellular domain harboring eight fibronectin-like repeats. The protein-tyrosine phosphatase DEP-1 promotes migration and phagocytic activity of microglial cells in part through negative regulation of fyn tyrosine kinase. DEP-1 protein levels increase in several cell types at high-cell density, suggesting a role of the molecule in density-dependent growth control. A negative regulatory role of Fyn for microglial functions is inhibited by DEP-1. Determination of a role of DEP-1 in a potential DEP-1-Fyn axis in the regulation of microglial functions. Enzyme DEP-1 stimulates microglial phagocytosis and microglial cell migration, overview
physiological function
PGP depletion facilitates fatty acid flux through the intracellular triacylglycerol/fatty acid cycle, and phosphatidylinositol-4,5-bisphosphate is critical for the impact of PGP activity on EGF-induced signaling. Loss of endogenous PGP expression amplifies both EGF-induced EGF receptor autophosphorylation and Src-dependent tyrosine phosphorylation of phospholipase C-gamma1. EGF enhances the formation of circular dorsal ruffles in PGP-depleted cells via Src/PLCgamma1/protein kinase C (PKC)-dependent signaling to the cytoskeleton
physiological function
Ptpn22 in the mouse negatively regulates Src and Syk family kinase (SFK) activity downstream of the T-cell antigen receptor (TCR). In addition to TCR signalling, PTPN22 regulates many pathways in different cell types including the B-cell receptor, the alphaLbeta2 integrin LFA-1 and Toll-Like Receptor (TLR) signalling pathways. Ptpn22 also functions to alter SFK independent signalling events by modulating TRAF ubiquitination. Macropinocytosis does not require Ptpn22. Splenic dendritic cell uptake of ovalbumin occurs independently of Ptpn22. Ptpn22 is dispensable for antigen processing and presentation and is redundant for dendritic cell activation of antigen specific T-cells. Ptpn22 variants do not modulate BMDC dependent OT-II T-cell activation
physiological function
replacement of murine Pgp with its phosphatase-inactive PgpD34N mutant is embryonically lethal due to intrauterine growth arrest and developmental delay in midgestation. PGP inactivation attenuates triosephosphate isomerase activity, increases triglyceride levels at the expense of the cellular phosphatidylcholine content, and inhibits cell proliferation. These effects are prevented under hypoxic conditions or by blocking phosphoglycolate release from damaged DNA
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PTN14_MOUSE
1189
0
135042
Swiss-Prot
Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
SHP-1 has two SH2 domains at its N terminus and a C-terminal tail containing at least two tyrosine phosphorylation sites
additional information
SEC-multi angle light scattering analysis, the mass fractions show a tetramer/dimer distribution of 13.8/ 84.5% for untreated PGP, and of 6.6/92.5% for the tris(2-carboxyethyl)phosphine-treated enzyme
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
-
phosphorylation of Y131 and Y132 during platelet-derived growth factor signaling, physiological role
phosphoprotein
-
SHP-1 has a C-terminal tail containing at least two tyrosine phosphorylation sites
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
protein-ligand interaction analysis. The Cys26 thiol group can engage in a van-der-Waals interaction with Ser58. The reduction-induced conformational change in wild-type is likely triggered by loss of the Cys104/Cys243 disulfide bridge between the PGP core and cap domains
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D245A
D34N
phosphatase-inactive mutant. Knockin replacement of murine Pgp with its D34N mutant is embryonically lethal
R283M
R619W
naturally occuring polymorphisms, phenotype, overview. Ptpn22-/- mice and Ptpn22R619W mutant mice are backcrossed for more than 10 generations to the C57BL/6 strain, genotyping and phenotyping in bone marrow derived dendritic cell culture, overview
Y131A
-
residue phosphorylated during platelet-derived growth factor signaling, physiological role
Y132A
-
residue phosphorylated during platelet-derived growth factor signaling, physiological role
additional information
additional information
-
in thymocytes of enzyme-deficient animal, cells develop normally, but show increased tyrosine phosphorylation of specific proteins, increased Fyn activity due to enhanced phosphorylation of Y528 and Y417, and hyperphosphorylation of Cbp/PAG
additional information
-
construction of PTPH1 knockout mice, no immunological phenotype in primary T cells derived from PTPH1-KO mice, carrageenan induces a trend of slightly increased spontaneous pain sensitivity in PTPH1-KO mice compared to wild-type littermates, but no differences in cytokine release, induced pain perception and cellular infiltration, but LPS-induced TNFalpha, MCP-1, and IL10 release is significantly reduced in PTPH1-KO plasma compared to wild-type plasma, overview
additional information
-
generation of PTP1B-/- mice, neuron-specific PTP1B-/- mice, and muscle specific-PTP1B-/- mice. Neuronal PTP1B-deficient mutant mice show inhibition of hypothalamic AMP-activated protein kinase, AMPK, and isoform-specific activation of AMPK in peripheral tissues, e.g. muscle and adipose tissue, overview
additional information
generation of specific shRNA cell lines for DEP-1 knockout
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli DH5alpha cells and HEK-293 cells as GST fusion protein
-
expressed in HUVEC cells, overexpression of PTP1B stabilizes VE-cadherin-mediated cell-cell adhesions by reducing VE-cadherin tyrosine phosphorylation
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
homozygous enzyme-deficient animal, hyperresponsive to insulin and leptin and resistant to diet-induced obesity. Liver-specific re-expression of PTP1B leads to marked attenuation of their enhanced insulin sensitivity in correlation with decreased insulin-stimulated tyrosyl phosphorylation of the insulin receptor and insulin receptor substrate 2-associated phosphatidylinositide 3-kinase activity. Preferential dephosphorylation of Y1162/1163 of insulin receptor
pharmacology
-
inhibition of the regulatory interaction in TCPTP is a desirable strategy for TCPTP activation and attenuation of oncogenic receptor tyrosine kinase signalling
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hrlein, D.; Gallis, B.; Brautigan, D.L.; Bornstein, P.
Partial purification and characterization of phosphotyrosyl-protein phosphatase from Ehrlich ascites tumor cells
Biochemistry
21
5577-5584
1982
Mus musculus
Aoyama, K.; Matsuda, T.; Aoki, N.
Characterization of newly identified four isoforms for a putative cytosolic protein tyrosine phosphatase PTP36
Biochem. Biophys. Res. Commun.
266
523-531
1999
Mus musculus (Q62130)
Foulkes, J.G.
Phosphotyrosyl-protein phosphatases
Curr. Top. Microbiol. Immunol.
107
163-180
1983
Gallus gallus, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus
Lau, K.H.W.; Farley, J.R.; Baylink, D.J.
Phosphotyrosyl protein phosphatases
Biochem. J.
257
23-36
1989
Gallus gallus, Homo sapiens, Mus musculus
Ohsugi, M.; Kuramochi, S.; Matsuda, S.; Yamamoto, T.
Molecular cloning and characterization of a novel cytoplasmic protein-tyrosine phosphatase that is specifically expressed in spermatocytes
J. Biol. Chem.
272
33092-33099
1997
Mus musculus
Dosil, M.; Leibman, N.; Lemischka, I.R.
Cloning and characterization of fetal liver phosphatase1, a nuclear protein tyrosine phosphatase isolated from hematopoietic stem cells
Blood
88
4510-4525
1996
Mus musculus
Chida, D.; Kume, T.; Mukouyama, Y.; Tabata, S.; Nomura, N.; Thomas, M.L.; Watanabe, T.; Oishi, M.
Characterization of a protein tyrosine phosphatase (RIP) expressed in a very early stage of differentiation in both mouse erythroleukemia and embryonal carcinoma cells
FEBS Lett.
358
233-239
1995
Mus musculus
Chiarugi, P.; Cirri, P.; Taddei, L.; Giannoni, E.; Camici, G.; Manao, G.; Raugei, G.; Ramponi, G.
The low Mr protein-tyrosine phosphatase is involved in Rho-mediated cytoskeleton rearrangement after integrin and platelet-derived growth factor stimulation
J. Biol. Chem.
275
4640-4646
2000
Mus musculus
Haj, F.G.; Zabolotny, J.M.; Kim, Y.B.; Kahn, B.B.; Neel, B.G.
Liver-specific protein-tyrosine phosphatase 1B (PTP1B) re-expression alters glucose homeostasis of PTP1B-/-mice
J. Biol. Chem.
280
15038-15046
2005
Mus musculus
Maksumova, L.; Le, H.T.; Muratkhodjaev, F.; Davidson, D.; Veillette, A.; Pallen, C.J.
Protein tyrosine phosphatase alpha regulates Fyn activity and Cbp/PAG phosphorylation in thymocyte lipid rafts
J. Immunol.
175
7947-7956
2005
Mus musculus
Tiganis, T.; Bennett, A.M.
Protein tyrosine phosphatase function: the substrate perspective
Biochem. J.
402
1-15
2007
Mus musculus
Besco, J.A.; Hooft van Huijsduijnen, R.; Frostholm, A.; Rotter, A.
Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT)
Brain Res.
1116
50-57
2006
Mus musculus, Mus musculus C57/BL6J
Kraut-Cohen, J.; Muller, W.J.; Elson, A.
Protein tyrosine phosphatase epsilon regulates Shc signaling in a kinase-specific manner: increasing coherence in tyrosine phosphatase signaling
J. Biol. Chem.
283
4612-4621
2008
Mus musculus
Noordman, Y.E.; Jansen, P.A.; Hendriks, W.J.
Tyrosine-specific MAPK phosphatases and the control of ERK signaling in PC12 cells
J. Mol. Signal.
1
2006
2006
Mus musculus, Rattus norvegicus
Tiran, Z.; Peretz, A.; Sines, T.; Shinder, V.; Sap, J.; Attali, B.; Elson, A.
Tyrosine phosphatases epsilon and alpha perform specific and overlapping functions in regulation of voltage-gated potassium channels in Schwann cells
Mol. Biol. Cell
17
4330-4342
2006
Mus musculus
Hendriks, W.J.; Dilaver, G.; Noordman, Y.E.; Kremer, B.; Fransen, J.A.
PTPRR protein tyrosine phosphatase isoforms and locomotion of vesicles and mice
Cerebellum
8
80-88
2009
Mus musculus
Nakamura, Y.; Patrushev, N.; Inomata, H.; Mehta, D.; Urao, N.; Kim, H.W.; Razvi, M.; Kini, V.; Mahadev, K.; Goldstein, B.J.; McKinney, R.; Fukai, T.; Ushio-Fukai, M.
Role of protein tyrosine phosphatase 1B in vascular endothelial growth factor signaling and cell-cell adhesions in endothelial cells
Circ. Res.
102
1182-1191
2008
Mus musculus
Granot-Attas, S.; Elson, A.
Protein tyrosine phosphatases in osteoclast differentiation, adhesion, and bone resorption
Eur. J. Cell Biol.
87
479-490
2008
Oryctolagus cuniculus, Mus musculus
Samayawardhena, L.A.; Pallen, C.J.
Protein-tyrosine phosphatase alpha regulates stem cell factor-dependent c-Kit activation and migration of mast cells
J. Biol. Chem.
283
29175-29185
2008
Mus musculus
McAlees, J.W.; Sanders, V.M.
Hematopoietic protein tyrosine phosphatase mediates beta2-adrenergic receptor-induced regulation of p38 mitogen-activated protein kinase in B lymphocytes
Mol. Cell. Biol.
29
675-686
2009
Mus musculus
Young, J.A.; Becker, A.M.; Medeiros, J.J.; Shapiro, V.S.; Wang, A.; Farrar, J.D.; Quill, T.A.; Hooft van Huijsduijnen, R.; van Oers, N.S.
The protein tyrosine phosphatase PTPN4/PTP-MEG1, an enzyme capable of dephosphorylating the TCR ITAMs and regulating NF-kappaB, is dispensable for T cell development and/or T cell effector functions
Mol. Immunol.
45
3756-3766
2008
Mus musculus
Bauler, T.J.; Hendriks, W.J.; King, P.D.
The FERM and PDZ domain-containing protein tyrosine phosphatases, PTPN4 and PTPN3, are both dispensable for T cell receptor signal transduction
PLoS ONE
3
e4014
2008
Mus musculus
Mattila, E.; Marttila, H.; Sahlberg, N.; Kohonen, P.; Taehtinen, S.; Halonen, P.; Peraelae, M.; Ivaska, J.
Inhibition of receptor tyrosine kinase signalling by small molecule agonist of T-cell protein tyrosine phosphatase
BMC Cancer
10
7
2010
Mus musculus
Fukuda, S.; Ohta, T.; Sakata, S.; Morinaga, H.; Ito, M.; Nakagawa, Y.; Tanaka, M.; Matsushita, M.
Pharmacological profiles of a novel protein tyrosine phosphatase 1B inhibitor, JTT-551
Diabetes Obes. Metab.
12
299-306
2010
Homo sapiens, Mus musculus, Rattus norvegicus
Patrignani, C.; Lafont, D.T.; Muzio, V.; Greco, B.; Hooft van Huijsduijnen, R.; Zaratin, P.F.
Characterization of protein tyrosine phosphatase H1 knockout mice in animal models of local and systemic inflammation
J. Inflamm.
7
16
2010
Mus musculus
Zhou, D.; Collins, C.A.; Wu, P.; Brown, E.J.
Protein tyrosine phosphatase SHP-1 positively regulates TLR-induced IL-12p40 production in macrophages through inhibition of phosphatidylinositol 3-kinase
J. Leukoc. Biol.
87
845-855
2010
Mus musculus
Xue, B.; Pulinilkunnil, T.; Murano, I.; Bence, K.K.; He, H.; Minokoshi, Y.; Asakura, K.; Lee, A.; Haj, F.; Furukawa, N.; Catalano, K.J.; Delibegovic, M.; Balschi, J.A.; Cinti, S.; Neel, B.G.; Kahn, B.B.
Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues
Mol. Cell. Biol.
29
4563-4573
2009
Mus musculus
Iype, T.; Sankarshanan, M.; Mauldin, I.S.; Mullins, D.W.; Lorenz, U.
The protein tyrosine phosphatase SHP-1 modulates the suppressive activity of regulatory T cells
J. Immunol.
185
6115-6127
2010
Mus musculus, Mus musculus BALB/c
Harris, L.K.; Frumm, S.M.; Bishop, A.C.
A general assay for monitoring the activities of protein tyrosine phosphatases in living eukaryotic cells
Anal. Biochem.
435
99-105
2013
Homo sapiens, Mus musculus
Song, D.D.; Chen, Y.; Li, Z.Y.; Guan, Y.F.; Zou, D.J.; Miao, C.Y.
Protein tyrosine phosphatase 1B inhibits adipocyte differentiation and mediates TNFalpha action in obesity
Biochim. Biophys. Acta
1831
1368-1376
2013
Mus musculus
Xu, J.; Kurup, P.; Bartos, J.A.; Patriarchi, T.; Hell, J.W.; Lombroso, P.J.
Striatal-enriched protein-tyrosine phosphatase (STEP) regulates Pyk2 kinase activity
J. Biol. Chem.
287
20942-20956
2012
Mus musculus
Sun, G.; Cheng, S.Y.; Chen, M.; Lim, C.J.; Pallen, C.J.
Protein tyrosine phosphatase alpha phosphotyrosyl-789 binds BCAR3 to position Cas for activation at integrin-mediated focal adhesions
Mol. Cell. Biol.
32
3776-3789
2012
Mus musculus
Hengge, A.C.
Kinetic isotope effects in the characterization of catalysis by protein tyrosine phosphatases
Biochim. Biophys. Acta
1854
1768-1775
2015
Yersinia sp., Homo sapiens (P18031), Homo sapiens (P51452), Homo sapiens (Q9BVJ7), Mus musculus (P35821), Schizosaccharomyces pombe (P41893), Schizosaccharomyces pombe ATCC 24843 (P41893)
Segerer, G.; Engelmann, D.; Kaestner, A.; Troetzmueller, M.; Koefeler, H.; Stigloher, C.; Thiele, C.; Jeanclos, E.; Gohla, A.
A phosphoglycolate phosphatase/AUM-dependent link between triacylglycerol turnover and epidermal growth factor signaling
Biochim. Biophys. Acta
1863
584-594
2018
Mus musculus (Q8CHP8)
Seifried, A.; Bergeron, A.; Boivin, B.; Gohla, A.
Reversible oxidation controls the activity and oligomeric state of the mammalian phosphoglycolate phosphatase AUM
Free Radic. Biol. Med.
97
75-84
2016
Mus musculus (Q8CHP8)
Schneble, N.; Mueller, J.; Kliche, S.; Bauer, R.; Wetzker, R.; Boehmer, F.D.; Wang, Z.Q.; Mueller, J.P.
The protein-tyrosine phosphatase DEP-1 promotes migration and phagocytic activity of microglial cells in part through negative regulation of fyn tyrosine kinase
Glia
65
416-428
2017
Mus musculus (Q64455), Mus musculus C57BL/6 (Q64455)
Clarke, F.; Jordan, C.K.; Gutierrez-Martinez, E.; Bibby, J.A.; Sanchez-Blanco, C.; Cornish, G.H.; Dai, X.; Rawlings, D.J.; Zamoyska, R.; Guermonprez, P.; Cope, A.P.; Purvis, H.A.
Protein tyrosine phosphatase PTPN22 is dispensable for dendritic cell antigen processing and promotion of T-cell activation by dendritic cells
PLoS ONE
12
e0186625
2017
Mus musculus (E9QAS3), Mus musculus, Mus musculus C57BL/6 (E9QAS3)
Segerer, G.; Hadamek, K.; Zundler, M.; Fekete, A.; Seifried, A.; Mueller, M.J.; Koentgen, F.; Gessler, M.; Jeanclos, E.; Gohla, A.
An essential developmental function for murine phosphoglycolate phosphatase in safeguarding cell proliferation
Sci. Rep.
6
35160
2016
Mus musculus (Q8CHP8)
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