Protein: UV radiation resistance-associated gene protein (p63) (Q9P2Y5)
Organism: Homo sapiens (Human)
Function: Versatile protein that is involved in regulation of different cellular pathways implicated in membrane trafficking. Involved in regulation of the COPI-dependent retrograde transport from Golgi and the endoplasmic reticulum by associating with the NRZ complex; the function is dependent on its binding to phosphatidylinositol 3-phosphate (PtdIns(3)P). During autophagy acts as regulatory subunit of the alternative PI3K complex II (PI3KC3-C2) that mediates formation of phosphatidylinositol 3-phosphate and is believed to be involved in maturation of autophagosomes and endocytosis. Activates lipid kinase activity of PIK3C3. Involved in the regulation of degradative endocytic trafficking and cytokinesis, and in regulation of ATG9A transport from the Golgi to the autophagosome; the functions seems to implicate its association with PI3KC3-C2. Involved in maturation of autophagosomes and degradative endocytic trafficking independently of BECN1 but depending on its association with a class C Vps complex (possibly the HOPS complex); the association is also proposed to promote autophagosome recruitment and activation of Rab7 and endosome-endosome fusion events. Enhances class C Vps complex (possibly HOPS complex) association with a SNARE complex and promotes fusogenic SNARE complex formation during late endocytic membrane fusion. In case of negative-strand RNA virus infection is required for efficient virus entry, promotes endocytic transport of virions and is implicated in a VAMP8-specific fusogenic SNARE complex assembly.
Subcellular location: Late endosome {ECO:0000269|PubMed:18843052}. Lysosome {ECO:0000269|PubMed:18843052}. Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:28306502}. Early endosome {ECO:0000269|PubMed:18552835, ECO:0000269|PubMed:18843052}. Endoplasmic reticulum {ECO:0000269|PubMed:24056303}. Midbody {ECO:0000269|PubMed:20643123}. Chromosome, centromere {ECO:0000269|PubMed:22542840}. Note=Colocalizes with RAB9-positive compartments involved in retrograde transport from late endosomes to trans-Golgi network. Colocalization with early endosomes is only partial (PubMed:24056303). Recruited to autophagosome following interaction with RUBCNL/PACER (PubMed:28306502). {ECO:0000269|PubMed:24056303, ECO:0000269|PubMed:28306502}.
Interaction partners:
- Run domain Beclin-1-interacting and cysteine-rich domain-containing protein
- Beclin-1
- Phosphoinositide 3-kinase regulatory subunit 4
- Phosphatidylinositol 3-kinase catalytic subunit type 3
- Beclin 1-associated autophagy-related key regulator
- Endophilin-B1
- Activating molecule in BECN1-regulated autophagy protein 1
- Beclin-2
- Apoptosis regulator Bcl-2
- Vacuolar protein sorting-associated protein 16 homolog
Sequence:
MSASASVGGPVPQPPPGPAAALPPGSAARALHVELPSQQRRLRHLRNIAARNIVNRNGHQLLDTYFTLHLCSTEKIYKEFYRSEVIKNSLNPTWRSLDFGIMPDRLDTSVSCFVVKIWGGKENIYQLLIEWKVCLDGLKYLGQQIHARNQNEIIFGLNDGYYGAPFEHKGYSNAQKTILLQVDQNCVRNSYDVFSLLRLHRAQCAIKQTQVTVQKIGKEIEEKLRLTSTSNELKKKSECLQLKILVLQNELERQKKALGREVALLHKQQIALQDKGSAFSAEHLKLQLQKESLNELRKECTAKRELFLKTNAQLTIRCRQLLSELSYIYPIDLNEHKDYFVCGVKLPNSEDFQAKDDGSIAVALGYTAHLVSMISFFLQVPLRYPIIHKGSRSTIKDNINDKLTEKEREFPLYPKGGEKLQFDYGVYLLNKNIAQLRYQHGLGTPDLRQTLPNLKNFMEHGLMVRCDRHHTSSAIPVPKRQSSIFGGADVGFSGGIPSPDKGHRKRASSENERLQYKTPPPSYNSALAQPVTTVPSMGETERKITSLSSSLDTSLDFSKENKKKGEDLVGSLNGGHANVHPSQEQGEALSGHRATVNGTLLPSEQAGSASVQLPGEFHPVSEAELCCTVEQAEEIIGLEATGFASGDQLEAFNCIPVDSAVAVECDEQVLGEFEEFSRRIYALNENVSSFRRPRRSSDK