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Protein

Baculoviral IAP repeat-containing protein 3

Gene

BIRC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 CASP8.2 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.2 Publications

Enzyme regulationi

USP19 regulates the stability of BIRC3/c-IAP2 by preventing its ubiquitination.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi292ZincPROSITE-ProRule annotation1
Metal bindingi295ZincPROSITE-ProRule annotation1
Metal bindingi312ZincPROSITE-ProRule annotation1
Metal bindingi319ZincPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri557 – 592RING-typePROSITE-ProRule annotationAdd BLAST36

GO - Molecular functioni

GO - Biological processi

  • cell surface receptor signaling pathway Source: ProtInc
  • I-kappaB kinase/NF-kappaB signaling Source: Reactome
  • inhibition of cysteine-type endopeptidase activity involved in apoptotic process Source: GO_Central
  • negative regulation of apoptotic process Source: ProtInc
  • negative regulation of necroptotic process Source: GO_Central
  • NIK/NF-kappaB signaling Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of protein ubiquitination Source: UniProtKB
  • protein deubiquitination Source: Reactome
  • protein heterooligomerization Source: Ensembl
  • regulation of apoptotic process Source: UniProtKB
  • regulation of cysteine-type endopeptidase activity Source: UniProtKB
  • regulation of inflammatory response Source: UniProtKB
  • regulation of innate immune response Source: UniProtKB
  • regulation of necroptotic process Source: UniProtKB
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway Source: UniProtKB
  • regulation of RIG-I signaling pathway Source: UniProtKB
  • regulation of toll-like receptor signaling pathway Source: UniProtKB
  • regulation of tumor necrosis factor-mediated signaling pathway Source: Reactome
  • spermatogenesis Source: Ensembl
  • tumor necrosis factor-mediated signaling pathway Source: Reactome

Keywordsi

Molecular functionTransferase
Biological processApoptosis, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-5213460 RIPK1-mediated regulated necrosis
R-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-5668541 TNFR2 non-canonical NF-kB pathway
R-HSA-5675482 Regulation of necroptotic cell death
R-HSA-5676594 TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
R-HSA-5689880 Ub-specific processing proteases
R-HSA-937041 IKK complex recruitment mediated by RIP1
SignaLinkiQ13489
SIGNORiQ13489

Protein family/group databases

MEROPSiI32.007

Names & Taxonomyi

Protein namesi
Recommended name:
Baculoviral IAP repeat-containing protein 3 (EC:2.3.2.272 Publications)
Alternative name(s):
Apoptosis inhibitor 2
Short name:
API2
Cellular inhibitor of apoptosis 2
Short name:
C-IAP21 Publication
IAP homolog C
Inhibitor of apoptosis protein 1
Short name:
hIAP-1
Short name:
hIAP1
RING finger protein 49
RING-type E3 ubiquitin transferase BIRC3Curated
TNFR2-TRAF-signaling complex protein 1
Gene namesi
Name:BIRC3
Synonyms:API2, MIHC, RNF49
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000023445.13
HGNCiHGNC:591 BIRC3
MIMi601721 gene
neXtProtiNX_Q13489

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei442 – 443Breakpoint for translocation to form BIRC3-MALT12

Organism-specific databases

DisGeNETi330
MalaCardsiBIRC3
OpenTargetsiENSG00000023445
Orphaneti52417 MALT lymphoma
PharmGKBiPA25360

Chemistry databases

ChEMBLiCHEMBL5335
GuidetoPHARMACOLOGYi2792

Polymorphism and mutation databases

BioMutaiBIRC3
DMDMi2497236

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001223491 – 604Baculoviral IAP repeat-containing protein 3Add BLAST604

Post-translational modificationi

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

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ13489
MaxQBiQ13489
PaxDbiQ13489
PeptideAtlasiQ13489
PRIDEiQ13489
ProteomicsDBi59483

PTM databases

iPTMnetiQ13489
PhosphoSitePlusiQ13489

Miscellaneous databases

PMAP-CutDBiQ13489

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000023445
CleanExiHS_BIRC3
ExpressionAtlasiQ13489 baseline and differential
GenevisibleiQ13489 HS

Organism-specific databases

HPAiHPA002317

Interactioni

Subunit structurei

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 USP19.2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi106827, 81 interactors
CORUMiQ13489
DIPiDIP-33720N
IntActiQ13489, 40 interactors
MINTiQ13489
STRINGi9606.ENSP00000263464

Chemistry databases

BindingDBiQ13489

Structurei

Secondary structure

1604
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi28 – 34Combined sources7
Helixi35 – 38Combined sources4
Helixi47 – 52Combined sources6
Beta strandi55 – 57Combined sources3
Beta strandi64 – 66Combined sources3
Turni67 – 69Combined sources3
Helixi82 – 89Combined sources8
Turni94 – 97Combined sources4
Helixi250 – 252Combined sources3
Helixi255 – 260Combined sources6
Helixi261 – 264Combined sources4
Helixi273 – 278Combined sources6
Beta strandi281 – 285Combined sources5
Turni286 – 288Combined sources3
Beta strandi289 – 292Combined sources4
Turni293 – 295Combined sources3
Beta strandi298 – 301Combined sources4
Helixi308 – 315Combined sources8
Helixi320 – 334Combined sources15
Helixi544 – 555Combined sources12
Turni558 – 560Combined sources3
Beta strandi561 – 564Combined sources4
Beta strandi567 – 570Combined sources4
Beta strandi575 – 577Combined sources3
Turni579 – 581Combined sources3
Helixi582 – 584Combined sources3
Beta strandi589 – 591Combined sources3
Beta strandi597 – 600Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2UVLX-ray1.91A/B244-337[»]
3EB5X-ray2.00A536-604[»]
3EB6X-ray3.40A536-604[»]
3M0AX-ray2.61D26-99[»]
3M0DX-ray2.80D26-99[»]
ProteinModelPortaliQ13489
SMRiQ13489
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13489

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati29 – 96BIR 1Add BLAST68
Repeati169 – 235BIR 2Add BLAST67
Repeati255 – 322BIR 3Add BLAST68
Domaini439 – 529CARDPROSITE-ProRule annotationAdd BLAST91

Sequence similaritiesi

Belongs to the IAP family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri557 – 592RING-typePROSITE-ProRule annotationAdd BLAST36

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1101 Eukaryota
ENOG410YPNM LUCA
GeneTreeiENSGT00500000044782
HOGENOMiHOG000232059
HOVERGENiHBG004848
InParanoidiQ13489
KOiK16060
OMAiCAMNTEK
OrthoDBiEOG091G0CXH
PhylomeDBiQ13489
TreeFamiTF105356

Family and domain databases

CDDicd00022 BIR, 3 hits
InterProiView protein in InterPro
IPR001370 BIR_rpt
IPR001315 CARD
IPR011029 DEATH-like_dom_sf
IPR001841 Znf_RING
PfamiView protein in Pfam
PF00653 BIR, 3 hits
PF00619 CARD, 1 hit
SMARTiView protein in SMART
SM00238 BIR, 3 hits
SM00114 CARD, 1 hit
SM00184 RING, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
PROSITEiView protein in PROSITE
PS01282 BIR_REPEAT_1, 3 hits
PS50143 BIR_REPEAT_2, 3 hits
PS50209 CARD, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q13489-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNIVENSIFL SNLMKSANTF ELKYDLSCEL YRMSTYSTFP AGVPVSERSL
60 70 80 90 100
ARAGFYYTGV NDKVKCFCCG LMLDNWKRGD SPTEKHKKLY PSCRFVQSLN
110 120 130 140 150
SVNNLEATSQ PTFPSSVTNS THSLLPGTEN SGYFRGSYSN SPSNPVNSRA
160 170 180 190 200
NQDFSALMRS SYHCAMNNEN ARLLTFQTWP LTFLSPTDLA KAGFYYIGPG
210 220 230 240 250
DRVACFACGG KLSNWEPKDN AMSEHLRHFP KCPFIENQLQ DTSRYTVSNL
260 270 280 290 300
SMQTHAARFK TFFNWPSSVL VNPEQLASAG FYYVGNSDDV KCFCCDGGLR
310 320 330 340 350
CWESGDDPWV QHAKWFPRCE YLIRIKGQEF IRQVQASYPH LLEQLLSTSD
360 370 380 390 400
SPGDENAESS IIHFEPGEDH SEDAIMMNTP VINAAVEMGF SRSLVKQTVQ
410 420 430 440 450
RKILATGENY RLVNDLVLDL LNAEDEIREE ERERATEEKE SNDLLLIRKN
460 470 480 490 500
RMALFQHLTC VIPILDSLLT AGIINEQEHD VIKQKTQTSL QARELIDTIL
510 520 530 540 550
VKGNIAATVF RNSLQEAEAV LYEHLFVQQD IKYIPTEDVS DLPVEEQLRR
560 570 580 590 600
LQEERTCKVC MDKEVSIVFI PCGHLVVCKD CAPSLRKCPI CRSTIKGTVR

TFLS
Length:604
Mass (Da):68,372
Last modified:November 1, 1997 - v2
Checksum:i8581A00BA9AAB4A7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti18N → Y in AAC83232 (PubMed:10233894).Curated1
Sequence conflicti119N → H in AAC50371 (PubMed:8552191).Curated1
Sequence conflicti153D → E in AAC50371 (PubMed:8552191).Curated1
Sequence conflicti163H → P in AAC50371 (PubMed:8552191).Curated1
Sequence conflicti165A → P in AAC50371 (PubMed:8552191).Curated1
Sequence conflicti191K → R in AAC50371 (PubMed:8552191).Curated1
Sequence conflicti364F → L in AAC50371 (PubMed:8552191).Curated1
Sequence conflicti552Q → P in AAC50371 (PubMed:8552191).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021069260K → R1 PublicationCorresponds to variant dbSNP:rs2276113Ensembl.1
Natural variantiVAR_049536386V → M. Corresponds to variant dbSNP:rs12222256Ensembl.1
Natural variantiVAR_021070401R → K1 PublicationCorresponds to variant dbSNP:rs17881197Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS8315.1
PIRiS68449
RefSeqiNP_001156.1, NM_001165.4
NP_892007.1, NM_182962.2
XP_016873132.1, XM_017017643.1
UniGeneiHs.127799

Genome annotation databases

EnsembliENST00000263464; ENSP00000263464; ENSG00000023445
ENST00000532808; ENSP00000432907; ENSG00000023445
ENST00000615299; ENSP00000481903; ENSG00000023445
GeneIDi330
KEGGihsa:330
UCSCiuc001pgx.5 human

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiBIRC3_HUMAN
AccessioniPrimary (citable) accession number: Q13489
Secondary accession number(s): Q16628, Q9HC27, Q9UP46
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: June 20, 2018
This is version 191 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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