BIRC3 (Homo sapiens)
Description [+]
- Synonyms: BIRC3, CIAP2, HIAP-1, MIHC, RNF49, MALT2
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Baculoviral IAP repeat-containing protein 3 (Inhibitor of apoptosis protein 1)(HIAP-1)(HIAP1)(C-IAP2)(TNFR2-TRAF-signaling complex protein 1)(IAP homolog C)(Apoptosis inhibitor 2)(API2)(RING finger protein 49) [Source:UniProtKB/Swiss-Prot;Acc:Q13489]
- Family: BIR-containing protein : IAP
- Process: apoptosis, immunity,
- Pathways: TNF/NF-kappaB signaling,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): cIAP2 Birc3
- WIKI: BIRC3-H_sapiens
References [+]
- The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases.
- Eckelman BP, Salvesen GS
- cIAPs (cellular inhibitor of apoptosis proteins) 1 and 2 are able to regulate apoptosis when ectopically expressed in recipient cells and probably also in vivo. Previous work suggested that this is at least partially due to direct caspase inhibition, mediated by two of the three baculovirus IAP repeat (BIR) domains that are contained in these proteins. In support of this we show that the BIR domains 2 and 3 of the two cIAPs are able to bind caspases-7 and -9. However, we demonstrate that neither of these BIR domains is able to inhibit caspases because of critical substitutions in the regions that target caspase inhibition in the X-linked IAP, a tight binding caspase inhibitor. The cIAP BIR domains can be converted to tight binding caspase inhibitors by substituting these critical residues with XIAP residues. Thus, cIAPs maintain protein scaffolds suitable for direct caspase inhibition but have lost or never acquired specific caspase inhibitory interaction sites. Consequently, although the binding function of the cIAP BIRs may be important for their physiologic function, caspase inhibition is not. J Biol Chem. 2006 Feb 10;281(6):3254-60. Epub 2005 Dec 8.
- References from Mouse ortholog(s):
- Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2.
- Bertrand MJ, Doiron K, Labbe K, Korneluk RG, Barker PA, Saleh M
- Cellular inhibitor of apoptosis proteins (cIAPs) block apoptosis, but their physiological functions are still under investigation. Here, we report that cIAP1 and cIAP2 are E3 ubiquitin ligases that are required for receptor-interacting protein 2 (RIP2) ubiquitination and for nucleotide-binding and oligomerization (NOD) signaling. Macrophages derived from Birc2(-/-) or Birc3(-/-) mice, or colonocytes depleted of cIAP1 or cIAP2 by RNAi, were defective in NOD signaling and displayed sharp attenuation of cytokine and chemokine production. This blunted response was observed in vivo when Birc2(-/-) and Birc3(-/-) mice were challenged with NOD agonists. Defects in NOD2 signaling are associated with Crohn's disease, and muramyl dipeptide (MDP) activation of NOD2 signaling protects mice from experimental colitis. Here, we show that administration of MDP protected wild-type but not Ripk2(-/-) or Birc3(-/-) mice from colitis, confirming the role of the cIAPs in NOD2 signaling in vivo. This discovery provides therapeutic opportunities in the treatment of NOD-dependent immunologic and inflammatory diseases. Immunity. 2009 Jun 19;30(6):789-801. Epub 2009 May 21.
- The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins.
- Rothe M, Pan MG, Henzel WJ, Ayres TM, Goeddel DV
- The 75 kDa tumor necrosis factor receptor (TNFR2) transduces extracellular signals via receptor-associated cytoplasmic proteins. Two of these signal transducers, TRAF1 and TRAF2, were isolated and characterized previously. We report here the biochemical purification and subsequent molecular cloning of two novel TNFR2-associated proteins, designated c-IAP1 and c-IAP2, that are closely related mammalian members of the inhibitor of apoptosis protein (IAP) family originally identified in baculoviruses. The viral and cellular IAPs contain N-terminal baculovirus IAP repeat (BIR) motifs and a C-terminal RING finger. The c-IAPs do not directly contact TNFR2, but rather associate with TRAF1 and TRAF2 through their N-terminal BIR motif-comprising domain. The recruitment of c-IAP1 or c-IAP2 to the TNFR2 signaling complex requires a TRAF2-TRAF1 heterocomplex. Cell. 1995 Dec 29;83(7):1243-52.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | BIR | 32 | 97 |
| PFAM A | BIR | 172 | 236 |
| PFAM A | BIR | 258 | 323 |
| PFAM A | CARD | 444 | 528 |
Protein sequence [+]
BIRC3 | Homo sapiens | 9606 | length:604
MNIVENSIFLSNLMKSANTFELKYDLSCELYRMSTYSTFPAGVPVSERSLARAGFYYTGV
NDKVKCFCCGLMLDNWKRGDSPTEKHKKLYPSCRFVQSLNSVNNLEATSQPTFPSSVTNS
THSLLPGTENSGYFRGSYSNSPSNPVNSRANQDFSALMRSSYHCAMNNENARLLTFQTWP
LTFLSPTDLAKAGFYYIGPGDRVACFACGGKLSNWEPKDNAMSEHLRHFPKCPFIENQLQ
DTSRYTVSNLSMQTHAARFKTFFNWPSSVLVNPEQLASAGFYYVGNSDDVKCFCCDGGLR
CWESGDDPWVQHAKWFPRCEYLIRIKGQEFIRQVQASYPHLLEQLLSTSDSPGDENAESS
IIHFEPGEDHSEDAIMMNTPVINAAVEMGFSRSLVKQTVQRKILATGENYRLVNDLVLDL
LNAEDEIREEERERATEEKESNDLLLIRKNRMALFQHLTCVIPILDSLLTAGIINEQEHD
VIKQKTQTSLQARELIDTILVKGNIAATVFRNSLQEAEAVLYEHLFVQQDIKYIPTEDVS
DLPVEEQLRRLQEERTCKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRSTIKGTVR
TFLS
NDKVKCFCCGLMLDNWKRGDSPTEKHKKLYPSCRFVQSLNSVNNLEATSQPTFPSSVTNS
THSLLPGTENSGYFRGSYSNSPSNPVNSRANQDFSALMRSSYHCAMNNENARLLTFQTWP
LTFLSPTDLAKAGFYYIGPGDRVACFACGGKLSNWEPKDNAMSEHLRHFPKCPFIENQLQ
DTSRYTVSNLSMQTHAARFKTFFNWPSSVLVNPEQLASAGFYYVGNSDDVKCFCCDGGLR
CWESGDDPWVQHAKWFPRCEYLIRIKGQEFIRQVQASYPHLLEQLLSTSDSPGDENAESS
IIHFEPGEDHSEDAIMMNTPVINAAVEMGFSRSLVKQTVQRKILATGENYRLVNDLVLDL
LNAEDEIREEERERATEEKESNDLLLIRKNRMALFQHLTCVIPILDSLLTAGIINEQEHD
VIKQKTQTSLQARELIDTILVKGNIAATVFRNSLQEAEAVLYEHLFVQQDIKYIPTEDVS
DLPVEEQLRRLQEERTCKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRSTIKGTVR
TFLS
Structure links:
- Smartdomain prediction information: SM00238
- Smartdomain prediction information: SM00114
- Smartdomain prediction information: SM00184
- Prosite motif and domain information: PS01282
- Profile motif and domain profile information: PS50209
- Profile motif and domain profile information: PS50143
- Profile motif and domain profile information: PS50089
- Interpro domain information: Q13489
- PFAM domain and domain family information: Q13489
- Protein 3D structures from PDB: 3EB6 2UVL 3EB5
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| Q5MM83_AEDAE | orthology | Aedes |
| A_aegypti_AAEL006633-PA | orthology | Aedes |
| IAP4 | orthology | Anopheles |
| IAP1 | orthology | Anopheles |
| IAP3 | orthology | Anopheles |
| A_gambiae_AGAP007293-PA | orthology | Anopheles |
| BIR_CHICK | orthology | Chicken |
| BIR_CHICK | orthology | Chicken |
| BIRC3 | orthology | Chimpanzee |
| BIRC3 | orthology | Chimpanzee |
| C_intestinalis_ENSCINP00000020067 | orthology | Ciona |
| NA | orthology | Ciona |
| C_intestinalis_ENSCINP00000000466 | orthology | Ciona |
| NA | orthology | Ciona |
| C_intestinalis_ENSCINP00000011648 | orthology | Ciona |
| C_intestinalis_ENSCINP00000009820 | orthology | Ciona |
| C_intestinalis_ENSCINP00000000045 | orthology | Ciona |
| C_intestinalis_ENSCINP00000002256 | orthology | Ciona |
| C_intestinalis_ENSCINP00000005161 | orthology | Ciona |
| C_intestinalis_ENSCINP00000000510 | orthology | Ciona |
| C_intestinalis_ENSCINP00000002312 | orthology | Ciona |
| C_intestinalis_ENSCINP00000010449 | orthology | Ciona |
| C_intestinalis_ENSCINP00000000487 | orthology | Ciona |
| C_intestinalis_ENSCINP00000021651 | orthology | Ciona |
| NP_001030370.1 | orthology | Cow |
| NP_001030370.1 | orthology | Cow |
| BIRC3_CANFA | orthology | Dog |
| BIRC3_CANFA | orthology | Dog |
| Iap2 | orthology | Fly |
| Iap2 | orthology | Fly |
| th | orthology | Fly |
| BIRC3 | orthology | Fugu |
| BIRC3 | orthology | Fugu |
| BIRC3 | orthology | Gasterosteus |
| BIRC3 | orthology | Gasterosteus |
| BIRC3 | orthology | Gorilla |
| BIRC3 | orthology | Horse |
| BIRC3 | orthology | Horse |
| A_carolinensis_ENSACAP00000012475 | orthology | Lyzard |
| A_carolinensis_ENSACAP00000012475 | orthology | Lyzard |
| BIRC3 | orthology | Macaca |
| BIRC3 | orthology | Macaca |
| BIRC3 | orthology | Medaka |
| cIAP2 | orthology | Mouse |
| Birc3 | orthology | Mouse |
| BIRC3 | orthology | Orangutan |
| BIRC3 | orthology | Orangutan |
| O_anatinus_ENSOANP00000016616 | orthology | Ornithorhynchus |
| O_anatinus_ENSOANP00000016616 | orthology | Ornithorhynchus |
| BIRC3 | orthology | Rabbit |
| BIRC3 | orthology | Rabbit |
| Birc3 | orthology | Rat |
| NP_076477.2 | orthology | Rat |
| BIRC3 | orthology | Tetraodon |
| birc3 | orthology | Xenopus |
| birc3 | orthology | Xenopus |
| X_tropicalis_ENSXETP00000030727 | orthology | Xenopus |
| X_tropicalis_ENSXETP00000030727 | orthology | Xenopus |
| T_guttata_ENSTGUP00000013125 | orthology | Zebra finch |
| BIRC2 | orthology | Zebra finch |
| birc2 | orthology | Zebrafish |
| birc2 | orthology | Zebrafish |
| NP_989919.1 | paralogy | Chicken |
| NP_989919.1 | paralogy | Chicken |
| BIRC7 | paralogy | Chicken |
| IPI00603248.2 | paralogy | Chicken |
| XIAP | paralogy | Chimpanzee |
| XIAP | paralogy | Chimpanzee |
| P_troglodytes_ENSPTRP00000048273 | paralogy | Chimpanzee |
| BIRC2 | paralogy | Chimpanzee |
| XM_001156604.1 | paralogy | Chimpanzee |
| BIRC2 | paralogy | Chimpanzee |
| XR_021305.1 | paralogy | Chimpanzee |
| XR_021305.1 | paralogy | Chimpanzee |
| BIRC8_PANTR | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000013345 | paralogy | Ciona |
| IPI00689691.3 | paralogy | Cow |
| IPI00689691.3 | paralogy | Cow |
| IPI00824732.2 | paralogy | Cow |
| Q8WMY4_BOVIN | paralogy | Cow |
| Q8WMY4_BOVIN | paralogy | Cow |
| BIRC7 | paralogy | Dog |
| BIRC7 | paralogy | Dog |
| Q38JA8_CANFA | paralogy | Dog |
| Q38JA8_CANFA | paralogy | Dog |
| Q38IV1_CANFA | paralogy | Dog |
| Q38IV1_CANFA | paralogy | Dog |
| BIRC7 | paralogy | Fugu |
| BIRC7 | paralogy | Fugu |
| BIRC8 | paralogy | Fugu |
| XIAP | paralogy | Fugu |
| BIRC7 | paralogy | Gasterosteus |
| BIRC8 | paralogy | Gasterosteus |
| XIAP | paralogy | Gasterosteus |
| BIRC7 | paralogy | Gasterosteus |
| BIRC2 | paralogy | Gorilla |
| BIRC2 | paralogy | Gorilla |
| XIAP | paralogy | Gorilla |
| XIAP | paralogy | Gorilla |
| BIRC7 | paralogy | Gorilla |
| BIRC7 | paralogy | Gorilla |
| BIRC8 | paralogy | Gorilla |
| BIRC7 | paralogy | Horse |
| BIRC7 | paralogy | Horse |
| E_caballus_ENSECAP00000002314 | paralogy | Horse |
| XP_001504091.2 | paralogy | Horse |
| BIRC2 | paralogy | Horse |
| BIRC2 | paralogy | Horse |
| BIRC8 | paralogy | Horse |
| XIAP | paralogy | Horse |
| cIAP1 | paralogy | Human |
| BIRC2 | paralogy | Human |
| BIRC8 | paralogy | Human |
| BIRC8 | paralogy | Human |
| BIRC7 | paralogy | Human |
| BIRC7 | paralogy | Human |
| XIAP | paralogy | Human |
| BIRC1 | paralogy | Human |
| XIAP | paralogy | Human |
| NAIP | paralogy | Human |
| BIRC7 | paralogy | Lyzard |
| BIRC7 | paralogy | Lyzard |
| A_carolinensis_ENSACAP00000009897 | paralogy | Lyzard |
| A_carolinensis_ENSACAP00000009897 | paralogy | Lyzard |
| A_carolinensis_ENSACAP00000011315 | paralogy | Lyzard |
| A_carolinensis_ENSACAP00000011315 | paralogy | Lyzard |
| M_mulatta_ENSMMUP00000040836 | paralogy | Macaca |
| BIRC7 | paralogy | Macaca |
| BIRC7 | paralogy | Macaca |
| BIRC2 | paralogy | Macaca |
| BIRC2 | paralogy | Macaca |
| BIRC8 | paralogy | Medaka |
| XIAP | paralogy | Medaka |
| BIRC7 | paralogy | Medaka |
| BIRC7 | paralogy | Medaka |
| M_domestica_ENSMODP00000000728 | paralogy | Monodelphis |
| BIRC7 | paralogy | Monodelphis |
| XM_001362587.1 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000000705 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000000705 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000018715 | paralogy | Monodelphis |
| BIRC7 | paralogy | Monodelphis |
| XM_001364568.1 | paralogy | Monodelphis |
| Naip2 | paralogy | Mouse |
| Naip2 | paralogy | Mouse |
| Birc1-rs1 | paralogy | Mouse |
| Naip6 | paralogy | Mouse |
| Xiap | paralogy | Mouse |
| Xiap | paralogy | Mouse |
| cIAP1 | paralogy | Mouse |
| Birc2 | paralogy | Mouse |
| Birc7 | paralogy | Mouse |
| Birc7 | paralogy | Mouse |
| Naip1 | paralogy | Mouse |
| Naip4 | paralogy | Mouse |
| Naip5 | paralogy | Mouse |
| Naip5 | paralogy | Mouse |
| Q5R9T1_PONPY | paralogy | Orangutan |
| Q5R9T1_PONPY | paralogy | Orangutan |
| P_pygmaeus_ENSPPYP00000017359 | paralogy | Orangutan |
| P_pygmaeus_ENSPPYP00000017359 | paralogy | Orangutan |
| BIRC7 | paralogy | Orangutan |
| BIRC7 | paralogy | Orangutan |
| XIAP | paralogy | Orangutan |
| XIAP | paralogy | Orangutan |
| O_anatinus_ENSOANP00000006435 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000006435 | paralogy | Ornithorhynchus |
| BIRC7 | paralogy | Rabbit |
| O_cuniculus_ENSOCUP00000014265 | paralogy | Rabbit |
| O_cuniculus_ENSOCUP00000011948 | paralogy | Rabbit |
| O_cuniculus_ENSOCUP00000011948 | paralogy | Rabbit |
| O_cuniculus_ENSOCUP00000008505 | paralogy | Rabbit |
| XIAP | paralogy | Rabbit |
| Birc4 | paralogy | Rat |
| XIAP_RAT | paralogy | Rat |
| RGD1559914_predicted | paralogy | Rat |
| Q8R4U8_RAT | paralogy | Rat |
| Birc2 | paralogy | Rat |
| NP_068520.2 | paralogy | Rat |
| BIRC8 | paralogy | Tetraodon |
| XIAP | paralogy | Tetraodon |
| BIRC7 | paralogy | Tetraodon |
| BIRC7 | paralogy | Tetraodon |
| X_tropicalis_ENSXETP00000016315 | paralogy | Xenopus |
| X_tropicalis_ENSXETP00000057704 | paralogy | Xenopus |
| X_tropicalis_ENSXETP00000016312 | paralogy | Xenopus |
| birc4 | paralogy | Xenopus |
| birc4 | paralogy | Xenopus |
| BIRC7 | paralogy | Xenopus |
| BIRC7 | paralogy | Xenopus |
| X_tropicalis_ENSXETP00000034890 | paralogy | Xenopus |
| T_guttata_ENSTGUP00000003825 | paralogy | Zebra finch |
| XIAP | paralogy | Zebra finch |
| BIRC7 | paralogy | Zebra finch |
| BIRC7 | paralogy | Zebra finch |
| birc4 | paralogy | Zebrafish |
| xiap | paralogy | Zebrafish |
| BIRC7 | paralogy | Zebrafish |
| zgc:165605 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006916 | anti-apoptosis | biological_proccess | TAS |
| GO:0007166 | cell surface receptor linked signal transduction | biological_proccess | TAS |
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0007283 | spermatogenesis | biological_proccess | IEA |
| GO:0051291 | protein heterooligomerization | biological_proccess | IEA |
| GO:0046872 | metal ion binding | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0004842 | ubiquitin-protein ligase activity | mollecular_function | IDA |
| GO:0008270 | zinc ion binding | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0005634 | nucleus | cell_component | IDA |
| GO:0005737 | cytoplasm | cell_component | IDA |
| GO:0005622 | intracellular | cell_component | IEA |
| GO:0043234 | protein complex | cell_component | IEA |
| GO:0045121 | membrane raft | cell_component | IEA |
Check GO Evidence Codes here
KEGG Pathways [+]
Information from other databases [+]
- Gene info from HGNC [?] :591
- Gene related info from GeneCards [?] : BIRC3
- Ensembl genome browser [?] : ENSG00000023445
- Expression info from Arrayexpress [?] : ENSG00000023445
- Protein expression from Protein Atlas: [?] ENSG00000023445
- Community gene edition from Wikigenes: [?] 330
- OMIM gene information: 601721
- OMIM disease information:
Click on [?] for more information.
