Programmed cell death protein 6 (O75340)

Uniprot ID O75340
Protein Name Programmed cell death protein 6
Gene Name PDCD6
Species Homo sapiens (Human)
Signal peptide(a) N Secretome P(b) 0.951
Function Calcium sensor that plays a key role in processes such as endoplasmic reticulum (ER)-Golgi vesicular transport, endosomal biogenesis or membrane repair. Acts as an adapter that bridges unrelated proteins or stabilizes weak protein-protein complexes in response to calcium: calcium-binding triggers exposure of apolar surface, promoting interaction with different sets of proteins thanks to 3 different hydrophobic pockets, leading to translocation to membranes (PubMed:20691033, PubMed:25667979). Involved in ER-Golgi transport by promoting the association between PDCD6IP and TSG101, thereby bridging together the ESCRT-III and ESCRT-I complexes (PubMed:19520058). Together with PEF1, acts as calcium-dependent adapter for the BCR(KLHL12) complex, a complex involved in ER-Golgi transport by regulating the size of COPII coats (PubMed:27716508). In response to cytosolic calcium increase, the heterodimer formed with PEF1 interacts with, and bridges together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export, which is required for neural crest specification (PubMed:27716508). Involved in the regulation of the distribution and function of MCOLN1 in the endosomal pathway (PubMed:19864416). Promotes localization and polymerization of TFG at endoplasmic reticulum exit site (PubMed:27813252). Required for T-cell receptor-, Fas-, and glucocorticoid-induced apoptosis (By similarity). May mediate Ca(2+)-regulated signals along the death pathway: interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity (PubMed:16132846). Its role in apoptosis may however be indirect, as suggested by knockout experiments (By similarity). May inhibit KDR/VEGFR2-dependent angiogenesis; the function involves inhibition of VEGF-induced phosphorylation of the Akt signaling pathway (PubMed:21893193). In case of infection by HIV-1 virus, indirectly inhibits HIV-1 production by affecting viral Gag expression and distribution (PubMed:27784779). .Isoform 2: Has a lower Ca(2+) affinity than isoform 1 (By similarity). {ECO:0000250|UniProtKB:P12815}.
GO - Molecular function
  • calcium ion binding : IDA:UniProtKB
  • calcium-dependent cysteine-type endopeptidase activity : IBA:GO_Central
  • calcium-dependent protein binding : IPI:UniProtKB
  • identical protein binding : IPI:IntAct
  • magnesium ion binding : ISS:UniProtKB
  • molecular adaptor activity : IMP:UniProtKB
  • protein dimerization activity : IPI:UniProtKB
  • protein homodimerization activity : IDA:UniProtKB
  • protein membrane anchor : IMP:UniProtKB
GO - Biological process
  • activation of cysteine-type endopeptidase activity involved in apoptotic process : IEA:Ensembl
  • angiogenesis : IEA:UniProtKB-KW
  • apoptotic signaling pathway : TAS:ProtInc
  • cellular response to heat : IDA:UniProtKB
  • COPII vesicle coating : IMP:UniProtKB
  • ER to Golgi vesicle-mediated transport : IMP:UniProtKB
  • intracellular protein transport : IDA:UniProtKB
  • negative regulation of protein kinase B signaling : IDA:UniProtKB
  • negative regulation of TOR signaling : IDA:UniProtKB
  • negative regulation of vascular endothelial growth factor receptor signaling pathway : IDA:UniProtKB
  • neural crest cell development : IMP:UniProtKB
  • neural crest formation : IMP:UniProtKB
  • positive regulation of angiogenesis : IDA:UniProtKB
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process : IDA:UniProtKB
  • positive regulation of endothelial cell migration : IDA:UniProtKB
  • positive regulation of endothelial cell proliferation : IDA:UniProtKB
  • positive regulation of protein monoubiquitination : IMP:UniProtKB
  • response to calcium ion : ISS:UniProtKB
  • vascular endothelial growth factor receptor-2 signaling pathway : IDA:UniProtKB
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(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.
(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.