InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PTEN

Summary

InnateDB Protein

IDBP-81411.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PTEN

Protein Name

phosphatase and tensin homolog

Synonyms

10q23del; BZS; CWS1; DEC; GLM2; MHAM; MMAC1; PTEN1; TEP1;

Species

Homo sapiens

Ensembl Protein

ENSP00000361021

InnateDB Gene

IDBG-81409 (PTEN)

Protein Structure

UniProt Annotation

Function

Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine- phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3- phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K- AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with AIP1 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement.Isoform alpha: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1.

Subcellular Localization

Cytoplasm. Nucleus. Nucleus, PML body. Note=Monoubiquitinated form is nuclear. Nonubiquitinated form is cytoplasmic. Colocalized with PML and USP7 in PML nuclear bodies. XIAP/BIRC4 promotes its nuclear localization.Isoform alpha: Secreted {ECO:0000269PubMed:23744781, ECO:0000269PubMed:24768297}. Note=May be secreted via a classical signal peptide and reenter into cells with the help of a poly-Arg motif.

Disease Associations

Cowden syndrome 1 (CWS1) [MIM:158350]: An autosomal dominant hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. {ECO:0000269PubMed:10051160, ECO:0000269PubMed:10234502, ECO:0000269PubMed:11494117, ECO:0000269PubMed:9140396, ECO:0000269PubMed:9259288, ECO:0000269PubMed:9345101, ECO:0000269PubMed:9399897, ECO:0000269PubMed:9425889, ECO:0000269PubMed:9600246, ECO:0000269PubMed:9735393, ECO:0000269PubMed:9797362, ECO:0000269PubMed:9832031, ECO:0000269PubMed:9915974}. Note=The disease is caused by mutations affecting the gene represented in this entry.Lhermitte-Duclos disease (LDD) [MIM:158350]: A rare disease characterized by the occurrence of a slowly enlarging mass within the cerebellar cortex corresponding histologically to a cerebellar hamartoma. It manifests, most commonly in the third and fourth decades of life, with increased intracranial pressure, headache, nausea, cerebellar dysfunction, occlusive hydrocephalus, ataxia, visual disturbances and other cranial nerve palsies. Various associated abnormalities may be present such as megalencephaly, microgyria, hydromyelia, polydactyly, partial gigantism, macroglossia. LDD is part of the PTEN hamartoma tumor syndromes spectrum that also includes Cowden syndrome. Note=The disease is caused by mutations affecting the gene represented in this entry.Bannayan-Riley-Ruvalcaba syndrome (BRRS) [MIM:153480]: A rare hamartomatous disorder characterized by macrocephaly and multiple hemangiomas as well as subcutaneous and visceral lipomas. It belongs to the family of hamartomatous polyposis syndromes that includes Peutz Jeghers syndrome, juvenile polyposis, and Cowden syndrome. {ECO:0000269PubMed:10400993, ECO:0000269PubMed:11494117, ECO:0000269PubMed:9241266, ECO:0000269PubMed:9467011}. Note=The disease is caused by mutations affecting the gene represented in this entry.Squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355]: A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. {ECO:0000269PubMed:11801303}. Note=The disease is caused by mutations affecting the gene represented in this entry.Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Note=PTEN mutations are found in a subset of patients with Proteus syndrome, a genetically heterogeneous condition. The molecular diagnosis of PTEN mutation positive cases classifies Proteus syndrome patients as part of the PTEN hamartoma syndrome spectrum. As such, patients surviving the early years of Proteus syndrome are likely at a greater risk of developing malignancies.Glioma 2 (GLM2) [MIM:613028]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.VACTERL association with hydrocephalus (VACTERL-H) [MIM:276950]: VACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects. Note=The disease is caused by mutations affecting the gene represented in this entry.Prostate cancer (PC) [MIM:176807]: A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. {ECO:0000269PubMed:9072974}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Macrocephaly/autism syndrome (MCEPHAS) [MIM:605309]: Patients have autism spectrum disorders and macrocephaly, with head circumferences ranging from +2.5 to +8 SD for age and sex (average head circumference +4.0 SD). {ECO:0000269PubMed:15805158}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome, which shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome.

Tissue Specificity

Expressed at a relatively high level in all adult tissues, including heart, brain, placenta, lung, liver, muscle, kidney and pancreas. {ECO:0000269PubMed:9090379}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 139 experimentally validated interaction(s) in this database.
They are also associated with 13 interaction(s) predicted by orthology.

Experimentally validated
Total	139 [view]
Protein-Protein	135 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	13 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004438	phosphatidylinositol-3-phosphatase activity
GO:0004721	phosphoprotein phosphatase activity
GO:0004722	protein serine/threonine phosphatase activity
GO:0004725	protein tyrosine phosphatase activity
GO:0005161	platelet-derived growth factor receptor binding
GO:0005515	protein binding
GO:0008138	protein tyrosine/serine/threonine phosphatase activity
GO:0008289	lipid binding
GO:0010997	anaphase-promoting complex binding
GO:0016314	phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
GO:0016791	phosphatase activity
GO:0019899	enzyme binding
GO:0019901	protein kinase binding
GO:0030165	PDZ domain binding
GO:0051717	inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
GO:0051800	phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity

Biological Process

GO:0000079	regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0001525	angiogenesis
GO:0001933	negative regulation of protein phosphorylation
GO:0002902	regulation of B cell apoptotic process
GO:0006470	protein dephosphorylation
GO:0006644	phospholipid metabolic process
GO:0006661	phosphatidylinositol biosynthetic process
GO:0006915	apoptotic process
GO:0007092	activation of mitotic anaphase-promoting complex activity
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007270	neuron-neuron synaptic transmission
GO:0007416	synapse assembly
GO:0007417	central nervous system development
GO:0007507	heart development
GO:0007568	aging
GO:0007584	response to nutrient
GO:0007611	learning or memory
GO:0007613	memory
GO:0007626	locomotory behavior
GO:0008283	cell proliferation
GO:0008284	positive regulation of cell proliferation
GO:0008285	negative regulation of cell proliferation
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0009749	response to glucose
GO:0010033	response to organic substance
GO:0010035	response to inorganic substance
GO:0010043	response to zinc ion
GO:0010975	regulation of neuron projection development
GO:0014067	negative regulation of phosphatidylinositol 3-kinase signaling
GO:0014070	response to organic cyclic compound
GO:0016311	dephosphorylation
GO:0016477	cell migration
GO:0021542	dentate gyrus development
GO:0021955	central nervous system neuron axonogenesis
GO:0030336	negative regulation of cell migration
GO:0031175	neuron projection development
GO:0031642	negative regulation of myelination
GO:0031647	regulation of protein stability
GO:0031658	negative regulation of cyclin-dependent protein kinase activity involved in G1/S
GO:0032286	central nervous system myelin maintenance
GO:0032355	response to estradiol
GO:0032535	regulation of cellular component size
GO:0033032	regulation of myeloid cell apoptotic process
GO:0033198	response to ATP
GO:0033555	multicellular organismal response to stress
GO:0035176	social behavior
GO:0035335	peptidyl-tyrosine dephosphorylation
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0042493	response to drug
GO:0042711	maternal behavior
GO:0043065	positive regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0043491	protein kinase B signaling
GO:0043542	endothelial cell migration
GO:0043647	inositol phosphate metabolic process
GO:0044281	small molecule metabolic process
GO:0045087	innate immune response (InnateDB)
GO:0045471	response to ethanol
GO:0045475	locomotor rhythm
GO:0045792	negative regulation of cell size
GO:0046621	negative regulation of organ growth
GO:0046685	response to arsenic-containing substance
GO:0046855	inositol phosphate dephosphorylation
GO:0046856	phosphatidylinositol dephosphorylation
GO:0048008	platelet-derived growth factor receptor signaling pathway
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0048738	cardiac muscle tissue development
GO:0048853	forebrain morphogenesis
GO:0048854	brain morphogenesis
GO:0050680	negative regulation of epithelial cell proliferation
GO:0050765	negative regulation of phagocytosis
GO:0050771	negative regulation of axonogenesis
GO:0050821	protein stabilization
GO:0050852	T cell receptor signaling pathway
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051726	regulation of cell cycle
GO:0051895	negative regulation of focal adhesion assembly
GO:0051898	negative regulation of protein kinase B signaling
GO:0060024	rhythmic synaptic transmission
GO:0060070	canonical Wnt signaling pathway
GO:0060074	synapse maturation
GO:0060134	prepulse inhibition
GO:0060179	male mating behavior
GO:0060291	long-term synaptic potentiation
GO:0060292	long term synaptic depression
GO:0060736	prostate gland growth
GO:0060997	dendritic spine morphogenesis
GO:0061002	negative regulation of dendritic spine morphogenesis
GO:0090071	negative regulation of ribosome biogenesis
GO:0090344	negative regulation of cell aging
GO:0090394	negative regulation of excitatory postsynaptic membrane potential
GO:0097105	presynaptic membrane assembly
GO:0097107	postsynaptic density assembly
GO:2000060	positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2000134	negative regulation of G1/S transition of mitotic cell cycle
GO:2000463	positive regulation of excitatory postsynaptic membrane potential
GO:2000808	negative regulation of synaptic vesicle clustering
GO:2001235	positive regulation of apoptotic signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0009898	cytoplasmic side of plasma membrane
GO:0016605	PML body
GO:0035749	myelin sheath adaxonal region
GO:0042995	cell projection
GO:0043005	neuron projection
GO:0043197	dendritic spine
GO:0043220	Schmidt-Lanterman incisure
GO:0045211	postsynaptic membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000008 C2 domain
IPR000242 Protein-tyrosine phosphatase, receptor/non-receptor type
IPR000340 Dual specificity phosphatase, catalytic domain
IPR000387 Protein-tyrosine/Dual specificity phosphatase
IPR003595 Protein-tyrosine phosphatase, catalytic
IPR014020 Tensin phosphatase, C2 domain
IPR017361 Bifunctional phosphatidylinositol trisphosphate phosphatase/dual specificity phosphatase PTEN
IPR029021 Protein-tyrosine phosphatase-like
IPR029023 Tensin phosphatase, lipid phosphatase domain

PFAM

PF00168
PF00102
PF00782
PF10409

PRINTS

PR00360
PR00700

PIRSF

PIRSF038025

SMART

SM00239
SM00194
SM00404

TIGRFAMs

Post-translational Modifications

Modification

Cross-References