PYCARD (Homo sapiens)
Description [+]
- Synonyms: PYCARD, TMS-1, CARD5, ASC
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Apoptosis-associated speck-like protein containing a CARD (hASC)(PYD and CARD domain-containing protein)(Target of methylation-induced silencing 1)(Caspase recruitment domain-containing protein 5) [Source:UniProtKB/Swiss-Prot;Acc:Q9ULZ3]
- Family: CARD-containing protein : CARD adapter protein
- Process: immunity,
- Pathways: inflammasome,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Pycard
- WIKI: PYCARD-H_sapiens
References [+]
- ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells.
- Masumoto J, Taniguchi S, Ayukawa K, Sarvotham H, Kishino T, Niikawa N, Hidaka E, Katsuyama T, Higuchi T, Sagara J
- The cytoskeletal and/or nuclear matrix molecules responsible for morphological changes associated with apoptosis were identified using monoclonal antibodies (mAbs). We developed mAbs against Triton X-100-insoluble components of HL-60 cells pretreated with all-trans retinoic acid. In particular, one mAb recognized a 22-kDa protein that exhibited intriguing behavior by forming an aggregate and appearing as a speck during apoptosis induced by retinoic acid and other anti-tumor drugs. Cloning and sequencing of its cDNA revealed that this protein comprises 195 amino acids and that its C-terminal half has a caspase recruitment domain (CARD) motif, characteristic of numerous proteins involved in apoptotic signaling. We referred to this protein as ASC (apoptosis-associated speck-like protein containing a CARD). The ASC gene was mapped on chromosome 16p11.2-12. The antisense oligonucleotides of ASC were found to reduce the expression of ASC, and consequently, etoposide-mediated apoptosis of HL-60 cells was suppressed. Our results indicate that ASC is a novel member of the CARD-containing adaptor protein family. J Biol Chem. 1999 Nov 26;274(48):33835-8.
- TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers.
- Conway KE, McConnell BB, Bowring CE, Donald CD, Warren ST, Vertino PM
- Gene silencing associated with aberrant methylation of promoter region CpG islands is an acquired epigenetic alteration that serves as an alternative to genetic defects in the inactivation of tumor suppressor and other genes in human cancers. The hypothesis that aberrant methylation plays a direct causal role in carcinogenesis hinges on the question of whether aberrant methylation is sufficient to drive gene silencing. To identify downstream targets of methylation-induced gene silencing, we used a human cell model in which aberrant CpG island methylation is induced by ectopic expression of DNA methyltransferase. Here we report the isolation and characterization of TMS1 (target of methylation-induced silencing), a novel CpG island-associated gene that becomes hypermethylated and silenced in cells overexpressing DNA cytosine-5-methyltransferase-1. We also show that TMS1 is aberrantly methylated and silenced in human breast cancer cells. Forty percent (11 of 27) of primary breast tumors exhibited aberrant methylation of TMS1. TMS1 is localized to chromosome 16p11.2-12.1 and encodes a 22-kDa predicted protein containing a COOH-terminal caspase recruitment domain, a recently described protein interaction motif found in apoptotic signaling molecules. Ectopic expression of TMS1 induced apoptosis in 293 cells and inhibited the survival of human breast cancer cells. The data suggest that methylation-mediated silencing of TMS1 confers a survival advantage by allowing cells to escape from apoptosis, supporting a new role for aberrant methylation in breast tumorigenesis. Cancer Res. 2000 Nov 15;60(22):6236-42.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | PAAD_DAPIN | 4 | 87 |
| PFAM A | CARD | 112 | 195 |
Protein sequence [+]
PYCARD | Homo sapiens | 9606 | length:195
MGRARDAILDALENLTAEELKKFKLKLLSVPLREGYGRIPRGALLSMDALDLTDKLVSFY
LETYGAELTANVLRDMGLQEMAGQLQAATHQGSGAAPAGIQAPPQSAAKPGLHFIDQHRA
ALIARVTNVEWLLDALYGKVLTDEQYQAVRAEPTNPSKMRKLFSFTPAWNWTCKDLLLQA
LRESQSYLVEDLERS
LETYGAELTANVLRDMGLQEMAGQLQAATHQGSGAAPAGIQAPPQSAAKPGLHFIDQHRA
ALIARVTNVEWLLDALYGKVLTDEQYQAVRAEPTNPSKMRKLFSFTPAWNWTCKDLLLQA
LRESQSYLVEDLERS
Structure links:
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| PYCARD | orthology | Chimpanzee |
| ASC_BOVIN | orthology | Cow |
| C_familiaris_ENSCAFP00000024803 | orthology | Dog |
| PYCARD | orthology | Fugu |
| G_aculeatus_ENSGACP00000016318 | orthology | Gasterosteus |
| G_aculeatus_ENSGACP00000016321 | orthology | Gasterosteus |
| G_aculeatus_ENSGACP00000016327 | orthology | Gasterosteus |
| G_aculeatus_ENSGACP00000016325 | orthology | Gasterosteus |
| PYCARD | orthology | Gorilla |
| E_caballus_ENSECAP00000008035 | orthology | Horse |
| A_carolinensis_ENSACAP00000006535 | orthology | Lyzard |
| PYCARD | orthology | Macaca |
| PYCARD | orthology | Medaka |
| M_domestica_ENSMODP00000037463 | orthology | Monodelphis |
| Pycard | orthology | Mouse |
| PYCARD | orthology | Orangutan |
| O_anatinus_ENSOANP00000002200 | orthology | Ornithorhynchus |
| O_cuniculus_ENSOCUP00000003881 | orthology | Rabbit |
| Pycard | orthology | Rat |
| CARD8 | orthology | Xenopus |
| X_tropicalis_ENSXETP00000024833 | orthology | Xenopus |
| X_tropicalis_ENSXETP00000004042 | orthology | Xenopus |
| pycard | orthology | Zebrafish |
| NLRP1 | paralogy | Chimpanzee |
| PYDC1 | paralogy | Chimpanzee |
| Q95N50_PANTR | paralogy | Chimpanzee |
| IPI00686327.3 | paralogy | Cow |
| IPI00713942.2 | paralogy | Cow |
| NALP6 | paralogy | Dog |
| Q95N30_CANFA | paralogy | Dog |
| NLRP13 | paralogy | Dog |
| NLRP1 | paralogy | Dog |
| NLRP1 | paralogy | Gorilla |
| MEFV | paralogy | Gorilla |
| MEFV | paralogy | Horse |
| NLRP1 | paralogy | Horse |
| MEFV | paralogy | Human |
| NLRP1 | paralogy | Human |
| PYDC1 | paralogy | Human |
| MEFV | paralogy | Macaca |
| PYDC1 | paralogy | Macaca |
| NLRP10 | paralogy | Macaca |
| NLRP8 | paralogy | Monodelphis |
| NLRP1 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000037465 | paralogy | Monodelphis |
| MEFV | paralogy | Monodelphis |
| Nlrp1a | paralogy | Mouse |
| Nlrp1b | paralogy | Mouse |
| Nlrp6 | paralogy | Mouse |
| Mefv | paralogy | Mouse |
| Q95N48_PONPY | paralogy | Orangutan |
| NLRP1 | paralogy | Orangutan |
| PYDC1 | paralogy | Orangutan |
| O_anatinus_ENSOANP00000018610 | paralogy | Ornithorhynchus |
| Q95N29_RABIT | paralogy | Rabbit |
| Mefv | paralogy | Rat |
| Nlrp6 | paralogy | Rat |
| LOC687766 | paralogy | Rat |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0050718 | positive regulation of interleukin-1 beta secretion | biological_proccess | IDA |
| GO:0051092 | positive regulation of NF-kappaB transcription factor activity | biological_proccess | IDA |
| GO:0033209 | tumor necrosis factor-mediated signaling pathway | biological_proccess | IDA |
| GO:0006508 | proteolysis | biological_proccess | IEA |
| GO:0006917 | induction of apoptosis | biological_proccess | TAS |
| GO:0006919 | activation of caspase activity | biological_proccess | NAS |
| GO:0007165 | signal transduction | biological_proccess | NAS |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0042803 | protein homodimerization activity | mollecular_function | IDA |
| GO:0032090 | Pyrin domain binding | mollecular_function | IPI |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | IEA |
| GO:0008656 | caspase activator activity | mollecular_function | NAS |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0005622 | intracellular | cell_component | IEA |
| GO:0008385 | IkappaB kinase complex | cell_component | TAS |
| GO:0005737 | cytoplasm | cell_component | NAS |
Check GO Evidence Codes here
Curated Isoforms [+]
| Transcript | Translation |
|---|---|
| OTTHUMT00000255539 * | OTTHUMP00000163239 * |
| OTTHUMT00000255540 | OTTHUMP00000163240 |
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :16608
- Gene related info from GeneCards [?] : PYCARD
- Ensembl genome browser [?] : ENSG00000103490
- Expression info from Arrayexpress [?] : ENSG00000103490
- Protein expression from Protein Atlas: [?] ENSG00000103490
- Community gene edition from Wikigenes: [?] 29108
- OMIM gene information: 606838
- OMIM disease information:
Click on [?] for more information.
