4o1v

<StructureSection load='4o1v' size='340' side='right' caption='[[4o1v]], [[Resolution|resolution]] 2.00&Aring;' scene=''>

<table><tr><td colspan='2'>[[4o1v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O1V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O1V FirstGlance]. <br>

</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SPOP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4o1v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o1v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o1v RCSB], [http://www.ebi.ac.uk/pdbsum/4o1v PDBsum]</span></td></tr>

== Disease ==

[[http://www.uniprot.org/uniprot/PTEN_HUMAN PTEN_HUMAN]] Defects in PTEN are a cause of Cowden disease (CD) [MIM:[http://omim.org/entry/158350 158350]]; also known as Cowden syndrome (CS). CD is an autosomal dominant cancer predisposition syndrome associated with elevated risk for tumors of the breast, thyroid and skin. The predominant phenotype for CD is multiple hamartoma syndrome, in many organ systems including the breast (70% of CD patients), thyroid (40-60%), skin, CNS (40%), gastrointestinal tract. Affected individuals are at an increased risk of both breast and thyroid cancers. Trichilemmomas (benign tumors of the hair follicle infundibulum), and mucocutaneous papillomatosis (99%) are hallmarks of CD.<ref>PMID:9256433</ref> <ref>PMID:9811831</ref> <ref>PMID:9345101</ref> <ref>PMID:9399897</ref> <ref>PMID:9259288</ref> <ref>PMID:9140396</ref> <ref>PMID:9797362</ref> <ref>PMID:9600246</ref> <ref>PMID:9467011</ref> <ref>PMID:9735393</ref> <ref>PMID:9832031</ref> <ref>PMID:9425889</ref> <ref>PMID:9915974</ref> <ref>PMID:10051160</ref> <ref>PMID:10234502</ref> <ref>PMID:10866302</ref> <ref>PMID:11230179</ref> <ref>PMID:11494117</ref> Defects in PTEN are the cause of Lhermitte-Duclos disease (LDD) [MIM:[http://omim.org/entry/158350 158350]]; also known as cerebelloparenchymal disorder VI. LDD is characterized by dysplastic gangliocytoma of the cerebellum which often results in cerebellar signs and seizures. LDD and CD seem to be the same entity, and are considered as hamartoma-neoplasia syndromes. Defects in PTEN are a cause of Bannayan-Zonana syndrome (BZS) [MIM:[http://omim.org/entry/153480 153480]]; also known as Ruvalcaba-Myhre-Smith syndrome (RMSS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS). In BZS there seems not to be an increased risk of malignancy. It has a partial clinical overlap with CD. BZS is characterized by the classic triad of macrocephaly, lipomatosis and pigmented macules of the gland penis.<ref>PMID:9467011</ref> <ref>PMID:10866302</ref> <ref>PMID:11494117</ref> <ref>PMID:9241266</ref> <ref>PMID:10400993</ref> Defects in PTEN are a cause of head and neck squamous cell carcinomas (HNSCC) [MIM:[http://omim.org/entry/275355 275355]]; also known as squamous cell carcinoma of the head and neck.<ref>PMID:11801303</ref> Defects in PTEN are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[http://omim.org/entry/608089 608089]]. 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. Defects in PTEN are a cause of susceptibility to glioma type 2 (GLM2) [MIM:[http://omim.org/entry/613028 613028]]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Defects in PTEN are a cause of VACTERL association with hydrocephalus (VACTERL-H) [MIM:[http://omim.org/entry/276950 276950]]. VACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects. Defects in PTEN may be a cause of susceptibility to prostate cancer (PC) [MIM:[http://omim.org/entry/176807 176807]]. It is 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. Defects in PTEN are a cause of macrocephaly/autism syndrome (MCEPHAS) [MIM:[http://omim.org/entry/605309 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).<ref>PMID:15805158</ref> 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.

[[http://www.uniprot.org/uniprot/SPOP_HUMAN SPOP_HUMAN]] Inhibits IPF1/PDX1 transactivation of established target promoters, such as insulin, may be by recruiting a repressor complex (By similarity). In complex with CUL3, involved in ubiquitination of BMI1, H2AFY and DAXX, and probably also in ubiquitination and proteasomal degradation of Gli2 or Gli3.<ref>PMID:14528312</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref> [[http://www.uniprot.org/uniprot/PTEN_HUMAN PTEN_HUMAN]] 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.<ref>PMID:9187108</ref> <ref>PMID:9256433</ref> <ref>PMID:9593664</ref> <ref>PMID:9811831</ref> <ref>PMID:9616126</ref> <ref>PMID:10468583</ref> <ref>PMID:11707428</ref> <ref>PMID:18716620</ref>

[[Category: Human]]

[[Category: Calabrese, M F]]

[[Category: Schulman, B A]]

[[Category: Watson, E R]]

[[Category: E3]]

[[Category: Ubl conjugation pathway]]