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Q13489 (BIRC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Baculoviral IAP repeat-containing protein 3

EC=6.3.2.-
Alternative name(s):
Apoptosis inhibitor 2
Short name=API2
C-IAP2
IAP homolog C
Inhibitor of apoptosis protein 1
Short name=IAP-1
Short name=hIAP-1
Short name=hIAP1
RING finger protein 49
TNFR2-TRAF-signaling complex protein 1
Gene names
Name:BIRC3
Synonyms:API2, IAP1, MIHC, RNF49
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length604 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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, IKBKE, TRAF1, and BCL10. 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. Ref.14 Ref.16

Enzyme regulation

USP19 regulates the stability of BIRC3/c-IAP2 by preventing its ubiquitination. Ref.13

Subunit structure

Interacts with DIABLO/SMAC and with PRSS25; these interactions inhibit apoptotic suppressor activity. The BIR motifs region interacts with TNF receptor associated factors 1 and 2 (TRAF1 and TRAF2) to form a heteromeric complex, which is then recruited to the tumor necrosis factor receptor 2 (TNFR2). Interaction with TRAF2 is required for ubiquitination of IKBKE, degradation of NFKBIA and activation of NF-kappa-B. Interacts with RIP1, RIP2, RIP3, RIP4 and USP19. Ref.13 Ref.14

Subcellular location

Cytoplasm. Nucleus Ref.8.

Tissue specificity

Highly expressed in fetal lung, and kidney. In the adult, expression is mainly seen in lymphoid tissues, including spleen, thymus and peripheral blood lymphocytes.

Post-translational modification

Auto-ubiquitinated and degraded by the proteasome in apoptotic cells.

Involvement in disease

A chromosomal aberration involving BIRC3 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with MALT1. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma.

Sequence similarities

Belongs to the IAP family.

Contains 3 BIR repeats.

Contains 1 CARD domain.

Contains 1 RING-type zinc finger.

Ontologies

Keywords
   Biological processApoptosis
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityChromosomal rearrangement
Polymorphism
   DomainRepeat
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
   PTMUbl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

NIK/NF-kappaB signaling

Traceable author statement Ref.11. Source: UniProtKB

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell surface receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

innate immune response

Traceable author statement. Source: Reactome

necroptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Traceable author statement Ref.2. Source: ProtInc

negative regulation of necroptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of phosphorylation

Inferred from electronic annotation. Source: Ensembl

negative regulation of reactive oxygen species metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of I-kappaB kinase/NF-kappaB signaling

Traceable author statement Ref.11. Source: UniProtKB

positive regulation of protein ubiquitination

Inferred from direct assay Ref.14. Source: UniProtKB

protein heterooligomerization

Inferred from electronic annotation. Source: Ensembl

protein ubiquitination

Inferred from direct assay PubMed 16395405Ref.14. Source: GOC

regulation of RIG-I signaling pathway

Traceable author statement Ref.10. Source: UniProtKB

regulation of apoptotic process

Inferred from mutant phenotype PubMed 21737330. Source: UniProtKB

regulation of cysteine-type endopeptidase activity

Traceable author statement Ref.11. Source: UniProtKB

regulation of inflammatory response

Traceable author statement Ref.12. Source: UniProtKB

regulation of innate immune response

Traceable author statement Ref.12. Source: UniProtKB

regulation of necroptotic process

Inferred from mutant phenotype PubMed 21737330. Source: UniProtKB

regulation of nucleotide-binding oligomerization domain containing signaling pathway

Traceable author statement Ref.10. Source: UniProtKB

regulation of toll-like receptor signaling pathway

Traceable author statement Ref.10. Source: UniProtKB

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay Ref.8PubMed 16123224. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

membrane raft

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.8PubMed 16123224. Source: UniProtKB

protein complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionubiquitin-protein ligase activity

Inferred from direct assay PubMed 16395405Ref.14. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 604604Baculoviral IAP repeat-containing protein 3
PRO_0000122349

Regions

Repeat29 – 9668BIR 1
Repeat169 – 23567BIR 2
Repeat255 – 32268BIR 3
Domain439 – 52991CARD
Zinc finger557 – 59236RING-type

Sites

Metal binding2921Zinc By similarity
Metal binding2951Zinc By similarity
Metal binding3121Zinc By similarity
Metal binding3191Zinc By similarity
Site442 – 4432Breakpoint for translocation to form BIRC3-MALT1

Natural variations

Natural variant2601K → R. Ref.5
Corresponds to variant rs2276113 [ dbSNP | Ensembl ].
VAR_021069
Natural variant3861V → M.
Corresponds to variant rs12222256 [ dbSNP | Ensembl ].
VAR_049536
Natural variant4011R → K. Ref.5
Corresponds to variant rs17881197 [ dbSNP | Ensembl ].
VAR_021070

Experimental info

Sequence conflict181N → Y in AAC83232. Ref.4
Sequence conflict1191N → H in AAC50371. Ref.2
Sequence conflict1531D → E in AAC50371. Ref.2
Sequence conflict1631H → P in AAC50371. Ref.2
Sequence conflict1651A → P in AAC50371. Ref.2
Sequence conflict1911K → R in AAC50371. Ref.2
Sequence conflict3641F → L in AAC50371. Ref.2
Sequence conflict5521Q → P in AAC50371. Ref.2

Secondary structure

................................................. 604
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q13489 [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: 8581A00BA9AAB4A7

FASTA60468,372
        10         20         30         40         50         60 
MNIVENSIFL SNLMKSANTF ELKYDLSCEL YRMSTYSTFP AGVPVSERSL ARAGFYYTGV 

        70         80         90        100        110        120 
NDKVKCFCCG LMLDNWKRGD SPTEKHKKLY PSCRFVQSLN SVNNLEATSQ PTFPSSVTNS 

       130        140        150        160        170        180 
THSLLPGTEN SGYFRGSYSN SPSNPVNSRA NQDFSALMRS SYHCAMNNEN ARLLTFQTWP 

       190        200        210        220        230        240 
LTFLSPTDLA KAGFYYIGPG DRVACFACGG KLSNWEPKDN AMSEHLRHFP KCPFIENQLQ 

       250        260        270        280        290        300 
DTSRYTVSNL SMQTHAARFK TFFNWPSSVL VNPEQLASAG FYYVGNSDDV KCFCCDGGLR 

       310        320        330        340        350        360 
CWESGDDPWV QHAKWFPRCE YLIRIKGQEF IRQVQASYPH LLEQLLSTSD SPGDENAESS 

       370        380        390        400        410        420 
IIHFEPGEDH SEDAIMMNTP VINAAVEMGF SRSLVKQTVQ RKILATGENY RLVNDLVLDL 

       430        440        450        460        470        480 
LNAEDEIREE ERERATEEKE SNDLLLIRKN RMALFQHLTC VIPILDSLLT AGIINEQEHD 

       490        500        510        520        530        540 
VIKQKTQTSL QARELIDTIL VKGNIAATVF RNSLQEAEAV LYEHLFVQQD IKYIPTEDVS 

       550        560        570        580        590        600 
DLPVEEQLRR LQEERTCKVC MDKEVSIVFI PCGHLVVCKD CAPSLRKCPI CRSTIKGTVR 


TFLS 

« Hide

References

« Hide 'large scale' references
[1]"The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins."
Rothe M., Pan M.-G., Henzel W.J., Ayres T.M., Goeddel D.V.
Cell 83:1243-1252(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes."
Liston P., Roy N., Tamai K., Lefebvre C., Baird S., Cherton-Horvat G., Farahani R., McLean M., Ikeda J., Mackenzie A., Korneluk R.G.
Nature 379:349-353(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]"Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors."
Uren A.G., Pakusch M., Hawkins C.J., Puls K.L., Vaux D.L.
Proc. Natl. Acad. Sci. U.S.A. 93:4974-4978(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal liver.
[4]"Vascular endothelial genes that are responsive to tumor necrosis factor-alpha in vitro are expressed in atherosclerotic lesions, including inhibitor of apoptosis protein-1, stannin, and two novel genes."
Horrevoets A.J.G., Fontijn R.D., van Zonneveld A.J., de Vries C.J.M., ten Cate J.W., Pannekoek H.
Blood 93:3418-3431(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]NIEHS SNPs program
Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-260 AND LYS-401.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lymph.
[7]"Structure of the MLT gene and molecular characterization of the genomic breakpoint junctions in the t(11;18)(q21;q21) of marginal zone B-cell lymphomas of MALT type."
Baens M., Steyls A., Dierlamm J., De Wolf-Peeters C., Marynen P.
Genes Chromosomes Cancer 29:281-291(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 362-441.
[8]"cIAP1 Localizes to the nuclear compartment and modulates the cell cycle."
Samuel T., Okada K., Hyer M., Welsh K., Zapata J.M., Reed J.C.
Cancer Res. 65:210-218(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[9]"IAPs: more than just inhibitors of apoptosis proteins."
Dubrez-Daloz L., Dupoux A., Cartier J.
Cell Cycle 7:1036-1046(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[10]"To fight or die - inhibitor of apoptosis proteins at the crossroad of innate immunity and death."
Lopez J., Meier P.
Curr. Opin. Cell Biol. 22:872-881(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[11]"IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer."
Gyrd-Hansen M., Meier P.
Nat. Rev. Cancer 10:561-574(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[12]"Inhibitor of apoptosis (IAP) proteins in regulation of inflammation and innate immunity."
Damgaard R.B., Gyrd-Hansen M.
Discov. Med. 11:221-231(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[13]"The USP19 deubiquitinase regulates the stability of c-IAP1 and c-IAP2."
Mei Y., Hahn A.A., Hu S., Yang X.
J. Biol. Chem. 286:35380-35387(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, INTERACTION WITH USP19.
[14]"cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4)."
Bertrand M.J., Lippens S., Staes A., Gilbert B., Roelandt R., De Medts J., Gevaert K., Declercq W., Vandenabeele P.
PLoS ONE 6:E22356-E22356(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE UBIQUITINATION OF RIPK1; RIPK2; RIPK3 AND RIPK4, INTERACTION WITH RIPK1; RIPK2; RIPK3 AND RIPK4.
[15]"IAPs: guardians of RIPK1."
Darding M., Meier P.
Cell Death Differ. 19:58-66(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[16]"IKKepsilon-mediated tumorigenesis requires K63-linked polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex."
Zhou A.Y., Shen R.R., Kim E., Lock Y.J., Xu M., Chen Z.J., Hahn W.C.
Cell Rep. 3:724-733(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN IKBKE UBIQUITINATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L49432 mRNA. Translation: AAC41943.1.
U45878 mRNA. Translation: AAC50371.1.
U37546 mRNA. Translation: AAC50507.1.
AF070674 mRNA. Translation: AAC83232.1.
AY764389 Genomic DNA. Translation: AAU88144.1.
BC037420 mRNA. Translation: AAH37420.1.
AF178945 Genomic DNA. Translation: AAG09369.1.
PIRS68449.
RefSeqNP_001156.1. NM_001165.4.
NP_892007.1. NM_182962.2.
UniGeneHs.127799.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2UVLX-ray1.91A/B244-337[»]
3EB5X-ray2.00A536-604[»]
3EB6X-ray3.40A536-604[»]
3M0AX-ray2.61D26-99[»]
3M0DX-ray2.80D26-99[»]
ProteinModelPortalQ13489.
SMRQ13489. Positions 26-604.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106827. 65 interactions.
DIPDIP-33720N.
IntActQ13489. 34 interactions.
MINTMINT-216139.
STRING9606.ENSP00000263464.

Chemistry

BindingDBQ13489.
ChEMBLCHEMBL5335.

Protein family/group databases

MEROPSI32.003.

PTM databases

PhosphoSiteQ13489.

Polymorphism databases

DMDM2497236.

Proteomic databases

PaxDbQ13489.
PRIDEQ13489.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263464; ENSP00000263464; ENSG00000023445.
ENST00000532808; ENSP00000432907; ENSG00000023445.
GeneID330.
KEGGhsa:330.
UCSCuc001pgx.3. human.

Organism-specific databases

CTD330.
GeneCardsGC11P102188.
HGNCHGNC:591. BIRC3.
HPAHPA002317.
MIM601721. gene.
neXtProtNX_Q13489.
Orphanet52417. MALT lymphoma.
PharmGKBPA25360.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG243347.
HOGENOMHOG000232059.
HOVERGENHBG004848.
InParanoidQ13489.
KOK16060.
OMAENSGYFS.
OrthoDBEOG78H3TF.
PhylomeDBQ13489.
TreeFamTF105356.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkQ13489.

Gene expression databases

ArrayExpressQ13489.
BgeeQ13489.
CleanExHS_BIRC3.
GenevestigatorQ13489.

Family and domain databases

Gene3D1.10.1170.10. 4 hits.
1.10.533.10. 1 hit.
InterProIPR001370. BIR.
IPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR001841. Znf_RING.
[Graphical view]
PfamPF00653. BIR. 3 hits.
PF00619. CARD. 1 hit.
[Graphical view]
SMARTSM00238. BIR. 3 hits.
SM00114. CARD. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
PROSITEPS01282. BIR_REPEAT_1. 3 hits.
PS50143. BIR_REPEAT_2. 3 hits.
PS50209. CARD. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSBIRC3. human.
EvolutionaryTraceQ13489.
GeneWikiBaculoviral_IAP_repeat-containing_protein_3.
GenomeRNAi330.
NextBio1359.
PMAP-CutDBQ13489.
PROQ13489.
SOURCESearch...

Entry information

Entry nameBIRC3_HUMAN
AccessionPrimary (citable) accession number: Q13489
Secondary accession number(s): Q16628, Q9HC27, Q9UP46
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: April 16, 2014
This is version 145 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM