Property Summary

NCBI Gene PubMed Count 75
PubMed Score 74.12
PubTator Score 83.06

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (5)

Disease log2 FC p
Waldenstrons macroglobulinemia 1.411 1.6e-02
Multiple myeloma 1.111 2.8e-02
psoriasis 1.400 7.3e-05
hereditary spastic paraplegia -1.072 4.0e-03
lung cancer 1.600 3.2e-05

Protein-protein Interaction (11)

Gene RIF (56)

PMID Text
26771762 The proto-oncogene PDCD10 is direct target of miR-103 that can suppress Prostate cancer proliferation and migration by down-regulating the PDCD10.
26490252 We report for the first time that PDCD10 expression is downregulated in GBM, which is associated with the activation of Akt signaling protein
26385474 Study highlights the potential role of CCM3 in regulating tight junction complex organization and brain endothelial barrier permeability through CCM3-ERK1/2-cortactin cross-talk
26356566 Studies suggest that the 3 proteins of the Cerebral Cavernous Malformations (CCM) complex KRIT1/CCM1, CCM2/malcavernin and CCM3/PDCD10 not only require one another for reciprocal stabilization, but also act as a platform for signal transduction.
26246098 A causative mutation in the PDCD10 gene (p.Gln112PhefsX13) was identified in an Italian family with cerebral cavernous malformations associated with meningioma.
26115622 A novel CCM3 missense mutation (c.422T>G) detected in 2 Greek brothers with cerebral cavernous malformations causes a loss of function in Pdcd10 protein due to its localization in the 8th helix. It affects Leu141. It may play a role in angiogenesis.
25872572 miR-181b was upregulated by hypoxia in retinoblastoma in an HIF-1a-independent manner. Additionally, miR-181b exerts its angiogenic function, at least in part, by inhibiting PDCD10 and GATA6.
25825518 both CCM2 and CCM3 are required for normal endothelial cell network formation.
25655101 Results broaden our knowledge on the mechanisms by which CCM3 deficiency results in disease and open new avenues of research into both CCM3 and senescence biology.
25550858 Our results suggest that MST4, STK25 and PDCD10 are upregulated in prostate cancer and may play roles in prostate tumorigenesis.
25451273 Identification of genetic variants in the CCM3/PDCD10 gene which are critical indicators of cerebral cavernous malformations in humans.
25354366 DNA mutational analysis in 87 Italian affected individuals with Cerebral cavernous malformations identified mutations in over 97.7% of cases, and PDCD10/CCM3 mutations account for 13.1% four of which already known and four novel ones.
25122144 Study shows that PDCD10 mutations result in vascular permeability mediated by ROCK activity and a particularly severe clinical phenotype of patients and mouse model for cerebral cavernous malformation disease.
24466005 Prevalence, frequency and characterization of CCM1, CCM2 and CCM3 variants in cerebral cavernous malformation Spanish patients.
24058906 The identification of other four new mutations in 40 sporadic patients with either single or multiple cerebral cavernous malformations, is reported.
24007869 DNA sequencing and deletion/duplication testing of the CCM1, CCM2, and CCM3 genes in the proband revealed a CCM1 c.601CNG mutation.
23541896 CCM3 forms a stable complex with MST4 in vivo to promote cell proliferation and migration synergistically in a manner dependent on MST4 kinase activity.
23485406 CCM3 mutations are associated with cerebral cavernous malformation in some Japanese patients.
23388056 Loss of CCM3 impairs DLL4-Notch signalling and is associated with impaired endothelial angiogenesis and inherited cerebral cavernous malformations.
22750858 crystal of the CCM3-MST4 C-terminal domain complex belonged to space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = 69.10, b = 69.10, c = 117.57 A
22652780 PDCD10 might be a regulatory adaptor required for STK25 functions, which differ distinctly depending on the redox status of the cells that may be potentially related to tumor progression.
22291017 role of CCM3 and ezrin/radixin/moesin family of proteins in cell's response to oxidative stress
21632544 the crystal structures of CCM3 in complex with three different leucine-aspartate repeat (LD) motifs (LD1, LD2, and LD4) from the scaffolding protein paxillin
21041308 PDCD10/CCM3 acts as a critical regulator of neuronal survival during development
21029238 Among familial cases of Cerebral cavernous malformations 67% had a mutation in CCM1, 5.5% in CCM2, and 5.5% in CCM3
20862502 adenoviral CCM3 expression inhibits endothelial cell migration, proliferation, and tube formation while downregulation of endogenous CCM3 results in increased formation of tube-like structures
20854465 PDCD10 can form complexes with other members of the CCM family, including CCM2, a key mediator of receptor tyrosine kinase-dependent cell death in neuroblastic tumors.
20682288 The crystal structure of human PDCD10 complexed with inositol-(1,3,4,5)-tetrakisphosphate has been determined at 2.3A resolution.
20677014 Observational study of gene-disease association. (HuGE Navigator)
20668527 Study propose that the Cerebral cavernous malformations protein complex functions in the PI3K signaling pathway through the interaction between PDCD10 and PtdIns(3,4,5)P3.
20623299 A novel large CCM3 deletion is identified with typical magnetic resonance imaging in a patient and her daughter.
20592472 In cultured human endothelial cells, CCM3 and STK25 regulated barrier function in a manner similar to CCM2, and STKs negatively regulated Rho by directly activating moesin.
20489202 CCM3 is a cerebral cavernous malformation protein critical for vascular integrity
20438785 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20419355 Genetic variations could interfere with the proper CCM1/CCM2/CCM3 protein complex, thus explaining the observed clinical variability in cerebral cavernous malformations in a large family.
20406964 Observational study of gene-disease association. (HuGE Navigator)
20332113 CCM3 is located on the Golgi apparatus, forming a complex with proteins of the germinal center kinase III (GCKIII) family and GM130, a Golgi-resident protein.
19688696 CCM3 protein contributes to vasculogenesis and angiogenesis in human placenta.
19506228 We report multiple dural lesions mimicking meningiomas in patients with CCM3/PDCD10 mutations.
19423540 Observational study of gene-disease association. (HuGE Navigator)
19370760 The newly mapped STK25 and MST4 interaction domain within the CCM3 protein plays a crucial role for vascular development in zebrafish.
19246713 CCM3 is both necessary and sufficient to induce apoptosis in vitro in well-defined cell culture systems
19199464 Multiplex Ligation-dependent Probe Amplification analysis integrates the consecutive sequence analysis of the 3 genes (Krit1/CCM1, MGC4607/CCM2, and PDCD10/CCM3) known to be responsible for cerebral cavernous malformation lesions.
19088124 Complete localized loss of either CCM1, CCM2 or CCM3 protein expression depend on the inherited mutation in cerebral cavernous malformations.
19088123 Biallelic germline and somatic mutations were identified in CCM1, CCM2 or PDCD10 from all forms of inherited cerebral cavernous malformations.
18300272 data are in agreement with a loss-of-function mechanism for CCM mutations, uncover an N-terminal CCM2 domain required for CCM1 binding, and demonstrate full-length CCM2 as the essential core protein in the CCM1/CCM2/CCM3 complex
18035376 To the best of our knowledge, this is the first report of an association between a mutation in the PDCD10 gene and spinal cavernous malformations.
17657516 CCM3 (PDCD10) coprecipitates and colocalizes with CCM2. CCM3 directly binds to serine/threonine kinase 25 (STK25, YSK1, SOK1) and the phosphatase domain of Fas-associated phosphatase-1 (FAP-1, PTPN13, PTP-Bas, PTP-BL).
17360971 Results show that PDCD10 modulation of ERK signaling is mediated by MST4, and that PDCD10 may be a regulatory adaptor necessary for MST4 function, suggesting a link between cerebral cavernous malformation and the ERK-MAPK cascade via PDCD10/MST4.
17212813 intergenic region of the head-to-head PDCD10-SERPINI1 gene pair provides an interesting and informative example of a complex regulatory system
16769843 Five percent of patients with familial cerebral cavernomas have retinal cavernomas. These lesions are clinically asymptomatic. They can be associated with any of the 3 cerebral cavernous malformation genes.
16380626 The authors screened the PCDC10 gene in 15 families that did not have a CCM1 or CCM2 mutation. Only two novel mutations were found, suggesting that mutations in this gene may only account for a small percentage of CCM familial cases.
16329096 Sequence analysis of PDCD10 in a panel of 29 probands lacking Krit1 and MGC4607 mutations revealed only three mutations.
16284570 Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3.
16239636 KRIT1, Malcavernin, and PDCD10 are differentially expressed in cerebral venous malformations and cerebral cavernous malformations
15543491 We report herein the identification of PDCD10 (programmed cell death 10) as the CCM3 gene.

AA Sequence

MRMTMEEMKNEAETTSMVSMPLYAVMYPVFNELERVNLSAAQTLRAAFIKAEKENPGLTQDIIMKILEKK      1 - 70
SVEVNFTESLLRMAADDVEEYMIERPEPEFQDLNEKARALKQILSKIPDEINDRVRFLQTIKDIASAIKE     71 - 140
LLDTVNNVFKKYQYQNRRALEHQKKEFVKYSKSFSDTLKTYFKDGKAINVFVSANRLIHQTNLILQTFKT    141 - 210
VA                                                                        211 - 212
//

Text Mined References (79)

PMID Year Title
26771762 2016 MicroRNA-103 suppresses tumor cell proliferation by targeting PDCD10 in prostate cancer.
26496610 2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
26490252 2015 Downregulation of programmed cell death 10 is associated with tumor cell proliferation, hyperangiogenesis and peritumoral edema in human glioblastoma.
26385474 2015 PDCD10 (CCM3) regulates brain endothelial barrier integrity in cerebral cavernous malformation type 3: role of CCM3-ERK1/2-cortactin cross-talk.
26356566 2015 The cerebral cavernous malformations proteins.
26246098 2015 Cerebral cavernous malformations associated to meningioma: High penetrance in a novel family mutated in the PDCD10 gene.
26115622 2015 Detection of Novel Mutation in Ccm3 Causes Familial Cerebral Cavernous Malformations.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25872572 2015 Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6.
25825518 2015 CCM2-CCM3 interaction stabilizes their protein expression and permits endothelial network formation.
25655101 2015 The cerebral cavernous malformation 3 gene is necessary for senescence induction.
25550858 2014 Differential expression of MST4, STK25 and PDCD10 between benign prostatic hyperplasia and prostate cancer.
25451273 2014 Surveying genetic variants and molecular phylogeny of cerebral cavernous malformation gene, CCM3/PDCD10.
25416956 2014 A proteome-scale map of the human interactome network.
25354366 2014 PDCD10 gene mutations in multiple cerebral cavernous malformations.
25122144 2015 Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations.
24466005 2014 Mutation prevalence of cerebral cavernous malformation genes in Spanish patients.
24366813 2013 Interaction proteome of human Hippo signaling: modular control of the co-activator YAP1.
24058906 2013 Sporadic cerebral cavernous malformations: report of further mutations of CCM genes in 40 Italian patients.
24007869 2013 Identification of a c.601C>G mutation in the CCM1 gene in a kindred with multiple skin, spinal and cerebral cavernous malformations.
23541896 2013 Structural mechanism of CCM3 heterodimerization with GCKIII kinases.
23533145 2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
23485406 2013 Genomic causes of multiple cerebral cavernous malformations in a Japanese population.
23455922 2013 Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized AP-MS.
23388056 2013 Loss of CCM3 impairs DLL4-Notch signalling: implication in endothelial angiogenesis and in inherited cerebral cavernous malformations.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23266514 2013 Structural studies of cerebral cavernous malformations 2 (CCM2) reveal a folded helical domain at its C-terminus.
22750858 2012 Crystallization and preliminary crystallographic studies of CCM3 in complex with the C-terminal domain of MST4.
22652780 2012 PDCD10 interacts with STK25 to accelerate cell apoptosis under oxidative stress.
22291017 2012 Adaptor protein cerebral cavernous malformation 3 (CCM3) mediates phosphorylation of the cytoskeletal proteins ezrin/radixin/moesin by mammalian Ste20-4 to protect cells from oxidative stress.
21632544 2011 Molecular recognition of leucine-aspartate repeat (LD) motifs by the focal adhesion targeting homology domain of cerebral cavernous malformation 3 (CCM3).
21561863 2011 CCM3/PDCD10 heterodimerizes with germinal center kinase III (GCKIII) proteins using a mechanism analogous to CCM3 homodimerization.
21516116 2011 Next-generation sequencing to generate interactome datasets.
21269460 2011 Initial characterization of the human central proteome.
21041308 2010 PDCD10/CCM3 acts downstream of {gamma}-protocadherins to regulate neuronal survival.
21029238 2011 Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian patients with cerebral cavernous malformation.
20862502 2011 Evidence for anti-angiogenic and pro-survival functions of the cerebral cavernous malformation protein 3.
20854465 2010 Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis.
20682288 2010 Crystal structure of human programmed cell death 10 complexed with inositol-(1,3,4,5)-tetrakisphosphate: a novel adaptor protein involved in human cerebral cavernous malformation.
20677014 2010 An approach based on a genome-wide association study reveals candidate loci for narcolepsy.
20668527 2010 Defining the functional domain of programmed cell death 10 through its interactions with phosphatidylinositol-3,4,5-trisphosphate.
20623299 2010 Multiple cerebral cavernous malformations and a novel CCM3 germline deletion in a German family.
20592472 2010 CCM3 signaling through sterile 20-like kinases plays an essential role during zebrafish cardiovascular development and cerebral cavernous malformations.
20489202 2010 Crystal structure of CCM3, a cerebral cavernous malformation protein critical for vascular integrity.
20458337 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
20438785 2010 Polymorphisms in innate immunity genes and risk of childhood leukemia.
20419355 2010 Genetic variations within KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3 in a large Italian family harbouring a Krit1/CCM1 mutation.
20406964 2010 Risk of meningioma and common variation in genes related to innate immunity.
20332113 2010 CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation.
19688696 2009 CCM2 and CCM3 proteins contribute to vasculogenesis and angiogenesis in human placenta.
19608861 2009 Lysine acetylation targets protein complexes and co-regulates major cellular functions.
19506228 2009 Multiple dural lesions mimicking meningiomas in patients with CCM3/PDCD10 mutations.
19423540 2009 Common variation in genes related to innate immunity and risk of adult glioma.
19370760 2009 Functional analyses of human and zebrafish 18-amino acid in-frame deletion pave the way for domain mapping of the cerebral cavernous malformation 3 protein.
19246713 2009 Apoptotic functions of PDCD10/CCM3, the gene mutated in cerebral cavernous malformation 3.
19199464 2009 Molecular screening test in familial forms of cerebral cavernous malformation: the impact of the Multiplex Ligation-dependent Probe Amplification approach.
19088124 2009 A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells.
19088123 2009 Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis.
19056867 2009 Large-scale proteomics and phosphoproteomics of urinary exosomes.
18782753 2009 A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein.
18300272 2008 Novel CCM1, CCM2, and CCM3 mutations in patients with cerebral cavernous malformations: in-frame deletion in CCM2 prevents formation of a CCM1/CCM2/CCM3 protein complex.
18035376 2008 Identification of an Arg35X mutation in the PDCD10 gene in a patient with cerebral and multiple spinal cavernous malformations.
17657516 2007 CCM3 interacts with CCM2 indicating common pathogenesis for cerebral cavernous malformations.
17360971 2007 PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway.
17353931 2007 Large-scale mapping of human protein-protein interactions by mass spectrometry.
17212813 2007 Two non-homologous brain diseases-related genes, SERPINI1 and PDCD10, are tightly linked by an asymmetric bidirectional promoter in an evolutionarily conserved manner.
16769843 2006 Frequency of retinal cavernomas in 60 patients with familial cerebral cavernomas: a clinical and genetic study.
16730941 2006 A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex.
16641997 2006 The DNA sequence, annotation and analysis of human chromosome 3.
16380626 2005 CCM3 mutations are uncommon in cerebral cavernous malformations.
16329096 2006 Low frequency of PDCD10 mutations in a panel of CCM3 probands: potential for a fourth CCM locus.
16284570 2005 Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3.
16239636 2005 Cerebral venous malformations have distinct genetic origin from cerebral cavernous malformations.
16189514 2005 Towards a proteome-scale map of the human protein-protein interaction network.
15543491 2005 Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
9811928 1998 Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27.