Protein: Pyrin (Marenostrin) (O15553)
Organism: Homo sapiens (Human)
Function: Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1, ATG16L1, and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy. Acts as an autophagy receptor for the degradation of several inflammasome components, including CASP1, NLRP1 and NLRP3, hence preventing excessive IL1B- and IL18-mediated inflammation. However, it can also have a positive effect in the inflammatory pathway, acting as an innate immune sensor that triggers PYCARD/ASC specks formation, caspase-1 activation, and IL1B and IL18 production. Together with AIM2, also acts as a mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, in response to bacterial infection (By similarity). It is required for PSTPIP1-induced PYCARD/ASC oligomerization and inflammasome formation. Recruits PSTPIP1 to inflammasomes, and is required for PSTPIP1 oligomerization.
Subcellular location: [Isoform 1]: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:11468188, ECO:0000269|PubMed:19109554}. Cell projection, ruffle {ECO:0000269|PubMed:11468188}. Cell projection, lamellipodium {ECO:0000269|PubMed:11468188}. Nucleus {ECO:0000269|PubMed:11115844}. Cytoplasm {ECO:0000269|PubMed:10666224, ECO:0000269|PubMed:11498534, ECO:0000269|PubMed:18577712, ECO:0000269|PubMed:19584923, ECO:0000269|PubMed:26347139}. Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:26347139}. Note=Associated with microtubules and with the filamentous actin of perinuclear filaments and peripheral lamellar ruffles (PubMed:11468188). In pre-apoptotic cells, colocalizes with PYCARD/ASC in large specks (inflammasomes) (PubMed:11468188). In migrating monocytes, strongly polarized at the leading edge of the cell where it colocalizes with polymerizing actin and PYCARD/ASC (PubMed:11468188). {ECO:0000269|PubMed:11468188}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:11115844}.
Interaction partners:
- Apoptosis-associated speck-like protein containing a CARD
- Interferon-inducible protein AIM2
- NLR family CARD domain-containing protein 4
- Proline-serine-threonine phosphatase-interacting protein 1
- Caspase-1
- NACHT, LRR and PYD domains-containing protein 1
- NACHT, LRR and PYD domains-containing protein 3
- NACHT, LRR and PYD domains-containing protein 6
- Baculoviral IAP repeat-containing protein 1
- NACHT, LRR and PYD domains-containing protein 12
Sequence:
MAKTPSDHLLSTLEELVPYDFEKFKFKLQNTSVQKEHSRIPRSQIQRARPVKMATLLVTYYGEEYAVQLTLQVLRAINQRLLAEELHRAAIQEYSTQENGTDDSAASSSLGENKPRSLKTPDHPEGNEGNGPRPYGGGAASLRCSQPEAGRGLSRKPLSKRREKASEGLDAQGKPRTRSPALPGGRSPGPCRALEGGQAEVRLRRNASSAGRLQGLAGGAPGQKECRPFEVYLPSGKMRPRSLEVTISTGEKAPANPEILLTLEEKTAANLDSATEPRARPTPDGGASADLKEGPGNPEHSVTGRPPDTAASPRCHAQEGDPVDGTCVRDSCSFPEAVSGHPQASGSRSPGCPRCQDSHERKSPGSLSPQPLPQCKRHLKQVQLLFCEDHDEPICLICSLSQEHQGHRVRPIEEVALEHKKKIQKQLEHLKKLRKSGEEQRSYGEEKAVSFLKQTEALKQRVQRKLEQVYYFLEQQEHFFVASLEDVGQMVGQIRKAYDTRVSQDIALLDALIGELEAKECQSEWELLQDIGDILHRAKTVPVPEKWTTPQEIKQKIQLLHQKSEFVEKSTKYFSETLRSEMEMFNVPELIGAQAHAVNVILDAETAYPNLIFSDDLKSVRLGNKWERLPDGPQRFDSCIIVLGSPSFLSGRRYWEVEVGDKTAWILGACKTSISRKGNMTLSPENGYWVVIMMKENEYQASSVPPTRLLIKEPPKRVGIFVDYRVGSISFYNVTARSHIYTFASCSFSGPLQPIFSPGTRDGGKNTAPLTICPVGGQGPD