UniProt Accession

 BIRC2_HUMAN; Q13490; B4E026; Q16516; Q4TTG0 

Genbank Protein ID

 L49431; U45879; U37547; AK303197; AP000942; DQ068066; BC016174; BC028578 

Genbank Nucleotide ID

 AAC41942.1; AAC50372.1; AAC50508.1; BAG64288.1; AAY46158.1; AAH16174.1; AAH28578.1 

Protein Name

 Baculoviral IAP repeat-containing protein 2 

Protein Synonyms/Alias

 C-IAP1; IAP homolog B; Inhibitor of apoptosis protein 2; IAP-2; hIAP-2; hIAP2; RING finger protein 48; TNFR2-TRAF-signaling complex protein 2 

Gene Name

 BIRC2 

Gene Synonyms/Alias

 API1; IAP2; MIHB; RNF48 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
19	GPSYQNIKSIMEDST	ubiquitination	[1, 2, 3]
36	SDWTNSNKQKMKYDF	ubiquitination	[4, 5]
38	WTNSNKQKMKYDFSC	ubiquitination	[2]
40	NSNKQKMKYDFSCEL	ubiquitination	[4, 5]
94	GLMLDNWKLGDSPIQ	ubiquitination	[2]
102	LGDSPIQKHKQLYPS	ubiquitination	[2]
126	ASLGSTSKNTSPMRN	ubiquitination	[2, 4, 5]
226	ACFACGGKLSNWEPK	ubiquitination	[4, 5]
233	KLSNWEPKDDAMSEH	ubiquitination	[2, 3, 4, 5, 6]
305	VGRNDDVKCFCCDGG	ubiquitination	[2, 7]
340	CEFLIRMKGQEFVDE	ubiquitination	[2, 6, 7]
410	GFNRDLVKQTVQSKI	ubiquitination	[2, 6]
416	VKQTVQSKILTTGEN	ubiquitination	[2, 4, 5]
425	LTTGENYKTVNDIVS	ubiquitination	[3, 4, 5, 6]
441	LLNAEDEKREEEKEK	ubiquitination	[3, 6]
446	DEKREEEKEKQAEEM	ubiquitination	[6]
448	KREEEKEKQAEEMAS	ubiquitination	[6]
490	LKANVINKQEHDIIK	ubiquitination	[2]
497	KQEHDIIKQKTQIPL	ubiquitination	[3]
516	LIDTILVKGNAAANI	ubiquitination	[2]
537	EIDSTLYKNLFVDKN	ubiquitination	[4, 5]
546	LFVDKNMKYIPTEDV	ubiquitination	[3]
610	PICRGIIKGTVRTFL	ubiquitination	[2]

Reference

 [1] A data set of human endogenous protein ubiquitination sites.
 Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
 Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [6] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [7] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 

Functional Description

 Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling, and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin- protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin- protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO and MXD1/MAD1. Can also function as an E3 ubiquitin- protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Can stimulate the transcriptional activity of E2F1. Plays a role in the modulation of the cell cycle. 

Sequence Annotation

 REPEAT 46 113 BIR 1.
 REPEAT 184 250 BIR 2.
 REPEAT 269 336 BIR 3.
 DOMAIN 453 543 CARD.
 ZN_FING 571 606 RING-type.
 METAL 306 306 Zinc.
 METAL 309 309 Zinc.
 METAL 326 326 Zinc.
 METAL 333 333 Zinc.  

Keyword

 3D-structure; Activator; Alternative splicing; Apoptosis; Complete proteome; Cytoplasm; Ligase; Metal-binding; Nucleus; Polymorphism; Reference proteome; Repeat; Transcription; Transcription regulation; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 618 AA 

Protein Sequence

Gene Ontology

 GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0009898; C:internal side of plasma membrane; ISS:BHF-UCL.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0003713; F:transcription coactivator activity; IMP:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
 GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0070266; P:necroptosis; IEA:Compara.
 GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
 GO:0038061; P:NIK/NF-kappaB cascade; TAS:UniProtKB.
 GO:0001890; P:placenta development; IEA:Compara.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IEP:UniProtKB.
 GO:0043161; P:proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
 GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
 GO:0051726; P:regulation of cell cycle; IDA:UniProtKB.
 GO:0045595; P:regulation of cell differentiation; TAS:UniProtKB.
 GO:0042127; P:regulation of cell proliferation; TAS:UniProtKB.
 GO:2000116; P:regulation of cysteine-type endopeptidase activity; TAS:UniProtKB.
 GO:0050727; P:regulation of inflammatory response; TAS:UniProtKB.
 GO:0070424; P:regulation of nucleotide-binding oligomerization domain containing signaling pathway; TAS:UniProtKB.
 GO:0039535; P:regulation of RIG-I signaling pathway; TAS:UniProtKB.
 GO:0034121; P:regulation of toll-like receptor signaling pathway; TAS:UniProtKB.
 GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. 

Interpro

 IPR001370; BIR.
 IPR001315; CARD.
 IPR011029; DEATH-like_dom.
 IPR001841; Znf_RING. 

Pfam

 PF00653; BIR
 PF00619; CARD 

SMART

 SM00238; BIR
 SM00114; CARD
 SM00184; RING 

PROSITE

 PS01282; BIR_REPEAT_1
 PS50143; BIR_REPEAT_2
 PS50209; CARD
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 

PRINTS