BIRC7
Domain
The RING domain is essential for autoubiquitination.
Function
Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control (PubMed:11024045, PubMed:11084335, PubMed:11162435, PubMed:16729033, PubMed:17294084). Its anti-apoptotic activity is mediated through the inhibition of CASP3, CASP7 and CASP9, as well as by its E3 ubiquitin-protein ligase activity (PubMed:11024045, PubMed:16729033). As it is a weak caspase inhibitor, its anti-apoptotic activity is thought to be due to its ability to ubiquitinate DIABLO/SMAC targeting it for degradation thereby promoting cell survival (PubMed:16729033). May contribute to caspase inhibition, by blocking the ability of DIABLO/SMAC to disrupt XIAP/BIRC4-caspase interactions (PubMed:16729033). Protects against apoptosis induced by TNF or by chemical agents such as adriamycin, etoposide or staurosporine (PubMed:11084335, PubMed:11162435, PubMed:11865055). Suppression of apoptosis is mediated by activation of MAPK8/JNK1, and possibly also of MAPK9/JNK2 (PubMed:11865055). This activation depends on TAB1 and MAP3K7/TAK1 (PubMed:11865055). In vitro, inhibits CASP3 and proteolytic activation of pro-CASP9 (PubMed:11024045).
Isoform 1
Blocks staurosporine-induced apoptosis (PubMed:11322947). Promotes natural killer (NK) cell-mediated killing (PubMed:18034418).
Isoform 2
Blocks etoposide-induced apoptosis (PubMed:11162435, PubMed:11322947). Protects against natural killer (NK) cell-mediated killing (PubMed:18034418).
Post-translational modifications
Autoubiquitinated and undergoes proteasome-mediated degradation.
The truncated protein (tLivin) not only loses its anti-apoptotic effect but also acquires a pro-apoptotic effect.
Sequence Similarities
Belongs to the IAP family.
Tissue Specificity
Isoform 1 and isoform 2 are expressed at very low levels or not detectable in most adult tissues. Detected in adult heart, placenta, lung, lymph node, spleen and ovary, and in several carcinoma cell lines. Isoform 2 is detected in fetal kidney, heart and spleen, and at lower levels in adult brain, skeletal muscle and peripheral blood leukocytes.
Cellular localization
- Nucleus
- Cytoplasm
- Golgi apparatus
- Nuclear, and in a filamentous pattern throughout the cytoplasm. Full-length livin is detected exclusively in the cytoplasm, whereas the truncated form (tLivin) is found in the peri-nuclear region with marked localization to the Golgi apparatus; the accumulation of tLivin in the nucleus shows positive correlation with the increase in apoptosis.
Alternative names
KIAP, LIVIN, MLIAP, RNF50, UNQ5800/PRO19607/PRO21344, BIRC7, Baculoviral IAP repeat-containing protein 7, Kidney inhibitor of apoptosis protein, Livin, Melanoma inhibitor of apoptosis protein, RING finger protein 50, RING-type E3 ubiquitin transferase BIRC7, ML-IAP