Programmed cell death 6-interacting protein (PDCD6IP)

The protein contains 868 amino acids for an estimated molecular weight of 96023 Da.

 

Multifunctional protein involved in endocytosis, multivesicular body biogenesis, membrane repair, cytokinesis, apoptosis and maintenance of tight junction integrity. Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway requires the sequential function of ESCRT-O, -I,-II and -III complexes (PubMed:14739459). The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:17853893, PubMed:17556548). Adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis (PubMed:17853893, PubMed:17556548, PubMed:18641129). May play a role in the regulation of both apoptosis and cell proliferation. Regulates exosome biogenesis in concert with SDC1/4 and SDCBP (PubMed:22660413). By interacting with F-actin, PARD3 and TJP1 secures the proper assembly and positioning of actomyosin-tight junction complex at the apical sides of adjacent epithelial cells that defines a spatial membrane domain essential for the maintenance of epithelial cell polarity and barrier (By similarity).', '(Microbial infection) Involved in HIV-1 virus budding. Ca (updated: Dec. 20, 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. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. 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.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 82%
Model score: 100
MODL_MODELLER-9.18

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VariantDescription
dbSNP:rs11554560
dbSNP:rs3792594
dbSNP:rs3203777
dbSNP:rs76608858
dbSNP:rs9813017
dbSNP:rs3183982
dbSNP:rs1127732

The reference OMIM entry for this protein is 608074

Programmed cell death 6-interacting protein; pdcd6ip
Pdcd6-interacting protein
Alg2-interacting protein 1; aip1
Alg2-interacting protein x; alix
Kiaa1375

DESCRIPTION

PDCD6IP interacts with proteins associated with apoptosis, including PDCD6 (601057), and with endophilins, which regulate membrane shape (Chatellard-Causse et al., 2002).

CLONING

By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) cloned PDCD6IP, which they designated KIAA1375. RT-PCR ELISA detected moderate expression in all adult and fetal tissues tested except adult lung, spleen, and pancreas and fetal brain, which all showed low expression. Moderate expression was detected in all individual brain regions examined. Wu et al. (2001) cloned full-length PDCD6IP, which they designated p95, by searching databases for sequences similar to YNK1, the C. elegans PDCD6IP homolog, followed by 5-prime and 3-prime RACE of a placenta cDNA library. The deduced 868-amino acid PDCD6IP protein has a calculated molecular mass of 96 kD. It has a proline-rich C terminus containing several PxxP motifs, which are SRC (190090) homology domain-3 (SH3)-binding domains. PDCD6IP also contains a tyrosine autophosphorylation consensus sequence that is conserved with SRC family members, as well as several additional conserved tyrosines. PDCD6IP shares significant homology with proteins from mouse, Xenopus, Drosophila, several yeast species, and Arabidopsis. Northern blot analysis detected an endogenous 3.5-kb transcript in HeLa cell RNA. Western blot analysis of HeLa cell lysates determined that the PDCD6IP protein has an apparent molecular mass of 95 kD. Missotten et al. (1999) cloned mouse Pdcd6ip, which they called Alix, in a yeast 2-hybrid screen of a brain cDNA library using Alg2 (PDCD6) as bait. The deduced 869-amino acid protein has a calculated molecular mass of about 96 kD. The authors noted that, in addition to several SH3-binding domains, the C terminus of Alix contains a WW-binding domain. Northern blot analysis detected 3.5- and 6.5-kb transcripts in all adult mouse tissues tested.

GENE FUNCTION

Normal epithelial cells stop proliferating in culture following cell-cell contact due to induction of G1 phase arrest in the cell cycle. However, malignant HeLa cells do not inhibit proliferation upon cell-cell contact and proceed toward multilayer growth. Wu et al. (2001) determined that overexpression of PDCD6IP restored the ability of HeLa cells to undergo G1 phase arrest and form a monolayer culture after confluence. Overexpression of PDCD6IP did not inhibit HeLa cell growth in sparse cultures. Wu et al. (2002) found that overexpression of PDCD6IP in HeLa cells promoted detachment-induced apoptosis, inhibited detachment of viable cells from the substratum, and reduced tumorigenicity following injection into nude mice. Overexpression in mouse fibroblasts promoted flat cell morphology and slowed cell proliferation. Transfection of antisense PDCD6IP had the opposite effects, with more rounded fibroblast morphology and dense growth. Missotten et al. (1999) determined that interaction between mouse Alix and Alg2 is calcium-dependent. Vito et al. (1999) determined that mouse Alix and Alg2 colocalized in the cytosol of fibroblasts and required calcium for their association. Overexpression of the C terminus of Alix protected HeLa and COS cells from apoptosis induced by withdrawal of trophic factors. By yeast 2-hybrid analysis, Chatellard-Causse et al. (2002) determined that mouse Alix binds to the endophilins Sh3p4 (604465), Sh3p8 (601768), and Sh3p13 (603362). Coimmunop ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

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

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 608074 was added.

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

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