Protein: Programmed cell death protein 6 (Apoptosis-linked gene 2 protein homolog) (ALG-2) (O75340)
Organism: Homo sapiens (Human)
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. Involved in ER-Golgi transport by promoting the association between PDCD6IP and TSG101, thereby bridging together the ESCRT-III and ESCRT-I complexes. 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. 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. Involved in the regulation of the distribution and function of MCOLN1 in the endosomal pathway. Promotes localization and polymerization of TFG at endoplasmic reticulum exit site. 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. 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. In case of infection by HIV-1 virus, indirectly inhibits HIV-1 production by affecting viral Gag expression and distribution.
Subcellular location: Endoplasmic reticulum membrane {ECO:0000269|PubMed:16957052, ECO:0000269|PubMed:27813252}; Peripheral membrane protein {ECO:0000269|PubMed:16957052}. Cytoplasmic vesicle, COPII-coated vesicle membrane {ECO:0000269|PubMed:27716508}. Cytoplasm {ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27784779}. Nucleus {ECO:0000269|PubMed:17045351, ECO:0000269|PubMed:21122810, ECO:0000269|PubMed:27784779}. Endosome {ECO:0000269|PubMed:19864416}. Note=Interaction with RBM22 induces relocalization from the cytoplasm to the nucleus (PubMed:17045351). Translocated from the cytoplasm to the nucleus after heat shock cell treatment. Accumulates in cytoplasmic vesicle-like organelles after heat shock treatment, which may represent stress granules (PubMed:21122810). In response to calcium increase, relocates from cytoplasm to COPII vesicle coat (PubMed:27716508). Localizes to endoplasmic reticulum exit site (ERES) (PubMed:27813252). {ECO:0000269|PubMed:17045351, ECO:0000269|PubMed:21122810, ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27813252}.
Interaction partners:
- Programmed cell death 6-interacting protein
- Protein transport protein Sec31A
- Tumor susceptibility gene 101 protein
- Peflin
- Heme-binding protein 2
- Kelch-like protein 12
- Protein SEC13 homolog
- Protein transport protein Sec24B
- Protein transport protein Sec23A
- Small COPII coat GTPase SAR1A
Sequence:
MAAYSYRPGPGAGPGPAAGAALPDQSFLWNVFQRVDKDRSGVISDTELQQALSNGTWTPFNPVTVRSIISMFDRENKAGVNFSEFTGVWKYITDWQNVFRTYDRDNSGMIDKNELKQALSGFGYRLSDQFHDILIRKFDRQGRGQIAFDDFIQGCIVLQRLTDIFRRYDTDQDGWIQVSYEQYLSMVFSIV