Programmed cell death protein 10 (PDCD10)

The protein contains 212 amino acids for an estimated molecular weight of 24702 Da.

 

Promotes cell proliferation. Modulates apoptotic pathways. Increases mitogen-activated protein kinase activity and STK26 activity (PubMed:27807006). Important for cell migration, and for normal structure and assembly of the Golgi complex (PubMed:27807006). Important for KDR/VEGFR2 signaling. Increases the stability of KDR/VEGFR2 and prevents its breakdown. Required for normal cardiovascular development. Required for normal angiogenesis, vasculogenesis and hematopoiesis during embryonic development (By similarity). (updated: Oct. 25, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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VariantDescription
dbSNP:rs1129087

The reference OMIM entry for this protein is 603285

Cerebral cavernous malformations 3; ccm3

A number sign (#) is used with this entry because of evidence that this form of cerebral cavernous malformations (CCM3) can be caused by mutation in the PDCD10 gene (609118). Evidence suggests that a 2-hit mechanism involving biallelic germline and somatic mutations is responsible for CCM3 pathogenesis, see

PATHOGENESIS

and

MOLECULAR GENETICS

sections. For a phenotypic description and discussion of genetic heterogeneity of cerebral cavernous malformations, see CCM1 (116860).

CLINICAL FEATURES

Denier et al. (2006) compared the clinical features of mutation carriers from 86 families with CCM1, 25 families with CCM2 (603284), and 17 families with CCM3, ascertained from academic medical centers in France. Of the 3 groups, CCM3 families had the lowest number of affected individuals per family, and the highest proportion of patients with onset of symptoms before age 15 years. Cerebral hemorrhage was the most common initial presentation in patients with CCM3.

PATHOGENESIS

For each of the 3 CCM genes, Pagenstecher et al. (2009) showed complete localized loss of either KRIT1 (604214), CCM2/malcavernin (607929), or PDCD10 protein expression depending on the respective inherited mutation. Cavernous but not adjacent normal or reactive endothelial cells of known germline mutation carriers displayed immunohistochemical negativity only for the corresponding CCM protein, but stained positively for the 2 other proteins. Immunohistochemical studies demonstrated endothelial cell mosaicism as neoangiogenic vessels within caverns from a CCM1 patient, normal brain endothelium from a CCM2 patient, and capillary endothelial cells of vessels in a revascularized thrombosed cavern from a CCM3 patient stained positively for KRIT1, CCM2/malcavernin, and PDCD10 respectively. Pagenstecher et al. (2009) suggested that complete lack of CCM protein in affected endothelial cells from CCM germline mutation carriers supports a 2-hit mechanism for CCM formation.

MAPPING

Among Hispanic Americans, virtually all cerebral cavernous malformation (CCM) is attributable to a founder mutation localized to 7q (CCM1; 116860). Craig et al. (1998) reported analysis of linkage in 20 non-Hispanic Caucasian kindreds with familial CCM. Linkage to new loci, CCM2 at 7p15-p13 and CCM3 at 3q25.2-q27, was demonstrated. Multilocus analysis yielded a maximum lod score of 14.11, with 14% of kindreds linked to CCM1, 20% linked to CCM2, and 40% linked to CCM3, with highly significant evidence for linkage to 3 loci; linkage to 3 loci was supported with an odds ratio of 2.6 x 10(5):1 over linkage to 2 loci, and 1.6 x 10(9):1 over linkage to 1 locus. Multipoint analysis among families with high posterior probabilities of linkage to each of the 3 loci refined the locations of CCM2 and CCM3 to approximately 22 cM intervals. Linkage to these 3 loci can account for inheritance of CCM in all kindreds studied. Significant locus-specific differences in penetrance were identified.

MOLECULAR GENETICS

Bergametti et al. (2005) reported the identification of the PDCD10 gene (609118) as the CCM3 gene. The CCM3 locus had been mapped to 3q26-q27 within a 22-cM interval bracketed by D3S1763 and D3S1262. They hypothesized that genomic deletions might occur at the CCM3 locus as had been reported at the CCM2 locus. Therefore, through high-density microsatellite genotyping of 20 families, they identified, in 1 family, null alleles that resulted from a deleti ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603285 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed