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Protein

Baculoviral IAP repeat-containing protein 2

Gene

Birc2

Organism
Mus musculus (Mouse)
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, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO, IKBKE 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.1 Publication

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.1 Publication

Enzyme regulationi

The CARD domain inhibits the activation of E3 ubiquitin ligase activity by preventing RING domain dimerization and E2 ubiquitin donor binding and activation. The CARD domain-mediated autoinhibition of the E3 ubiquitin-protein ligase activity suppresses cell proliferation and migration. USP19 regulates the stability of BIRC2/c-IAP1 by preventing its ubiquitination (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi299ZincPROSITE-ProRule annotation1
Metal bindingi302ZincPROSITE-ProRule annotation1
Metal bindingi319ZincPROSITE-ProRule annotation1
Metal bindingi326ZincPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri565 – 600RING-typePROSITE-ProRule annotationAdd BLAST36

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, Transferase
Biological processApoptosis, Transcription, Transcription regulation, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-111465 Apoptotic cleavage of cellular proteins
R-MMU-168638 NOD1/2 Signaling Pathway
R-MMU-5213460 RIPK1-mediated regulated necrosis
R-MMU-5357905 Regulation of TNFR1 signaling
R-MMU-5357956 TNFR1-induced NFkappaB signaling pathway
R-MMU-5668541 TNFR2 non-canonical NF-kB pathway
R-MMU-5675482 Regulation of necroptotic cell death
R-MMU-5676594 TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
R-MMU-5689880 Ub-specific processing proteases
R-MMU-937041 IKK complex recruitment mediated by RIP1

Protein family/group databases

MEROPSiI32.007

Names & Taxonomyi

Protein namesi
Recommended name:
Baculoviral IAP repeat-containing protein 2 (EC:2.3.2.271 Publication)
Alternative name(s):
Cellular inhibitor of apoptosis 1
Short name:
C-IAP11 Publication
Inhibitor of apoptosis protein 21 Publication
Short name:
mIAP21 Publication
RING-type E3 ubiquitin transferase BIRC2Curated
Gene namesi
Name:Birc2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1197009 Birc2

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001223481 – 612Baculoviral IAP repeat-containing protein 2Add BLAST612

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei143Omega-N-methylarginineCombined sources1
Modified residuei153PhosphoserineCombined sources1

Post-translational modificationi

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

Keywords - PTMi

Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ62210
MaxQBiQ62210
PaxDbiQ62210
PRIDEiQ62210

PTM databases

iPTMnetiQ62210
PhosphoSitePlusiQ62210

Expressioni

Tissue specificityi

Expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.

Gene expression databases

BgeeiENSMUSG00000057367
CleanExiMM_BIRC2
MM_BIRC3
ExpressionAtlasiQ62210 baseline and differential
GenevisibleiQ62210 MM

Interactioni

Subunit structurei

Interacts with DIABLO/SMAC and with PRSS25; these interactions inhibit apoptotic suppressor activity. Interacts with CASP9. Interacts (via BIR domains) with TRAF2; the interaction is required for IKBKE ubiquitination. Interacts with E2F1, RIPK1, RIPK2, RIPK3, RIPK4, BIRC5/survivin and USP19 (By similarity). Interacts with HSP90AB1 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198148, 6 interactors
CORUMiQ62210
IntActiQ62210, 3 interactors
MINTiQ62210
STRINGi10090.ENSMUSP00000091422

Structurei

3D structure databases

ProteinModelPortaliQ62210
SMRiQ62210
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati46 – 113BIR 1Add BLAST68
Repeati177 – 243BIR 2Add BLAST67
Repeati262 – 329BIR 3Add BLAST68
Domaini447 – 537CARDPROSITE-ProRule annotationAdd BLAST91

Domaini

The BIR domains mediate nuclear localization.By similarity
The CARD domain is necessary to stabilize the protein and inhibit the activation of E3 ubiquitin-protein ligase activity of BIRC2/c-IAP1 by preventing RING domain dimerization and E2 ubiquitin donor binding and activation.By similarity

Sequence similaritiesi

Belongs to the IAP family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri565 – 600RING-typePROSITE-ProRule annotationAdd BLAST36

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1101 Eukaryota
ENOG410YPNM LUCA
GeneTreeiENSGT00500000044782
HOGENOMiHOG000232059
HOVERGENiHBG004848
InParanoidiQ62210
KOiK16060
OMAiCSMVLAP
OrthoDBiEOG091G0CXH
PhylomeDBiQ62210
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.

Q62210-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDKTVSQRLG QGTLHQKLKR IMEKSTILSN WTKESEEKMK FDFSCELYRM
60 70 80 90 100
STYSAFPRGV PVSERSLARA GFYYTGVNDK VKCFCCGLML DNWKQGDSPV
110 120 130 140 150
EKHRQFYPSC SFVQTLLSAS LQSPSKNMSP VKSRFAHSSP LERGGIHSNL
160 170 180 190 200
CSSPLNSRAV EDFSSRMDPC SYAMSTEEAR FLTYSMWPLS FLSPAELARA
210 220 230 240 250
GFYYIGPGDR VACFACGGKL SNWEPKDDAM SEHRRHFPHC PFLENTSETQ
260 270 280 290 300
RFSISNLSMQ THSARLRTFL YWPPSVPVQP EQLASAGFYY VDRNDDVKCF
310 320 330 340 350
CCDGGLRCWE PGDDPWIEHA KWFPRCEFLI RMKGQEFVDE IQARYPHLLE
360 370 380 390 400
QLLSTSDTPG EENADPTETV VHFGPGESSE DVVMMSTPVV KAALEMGFSR
410 420 430 440 450
SLVRQTVQRQ ILATGENYRT VNDIVSVLLN AEDERREEEK ERQTEEMASG
460 470 480 490 500
DLSLIRKNRM ALFQQLTHVL PILDNLLEAS VITKQEHDII RQKTQIPLQA
510 520 530 540 550
RELIDTVLVK GNAAANIFKN SLKEIDSTLY ENLFVEKNMK YIPTEDVSGL
560 570 580 590 600
SLEEQLRRLQ EERTCKVCMD REVSIVFIPC GHLVVCQECA PSLRKCPICR
610
GTIKGTVRTF LS
Length:612
Mass (Da):69,676
Last modified:November 1, 1996 - v1
Checksum:iE08969D93C6C610D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti380E → K in AAC53532 (PubMed:9441758).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L49433 mRNA Translation: AAC42078.1
U88909 mRNA Translation: AAC53532.1
BC145985 mRNA Translation: AAI45986.1
CCDSiCCDS22811.1
RefSeqiNP_001278432.1, NM_001291503.1
NP_031491.2, NM_007465.3
XP_017168599.1, XM_017313110.1
UniGeneiMm.335659
Mm.400826

Genome annotation databases

EnsembliENSMUST00000074246; ENSMUSP00000091422; ENSMUSG00000057367
ENSMUST00000190341; ENSMUSP00000140049; ENSMUSG00000057367
GeneIDi11797
KEGGimmu:11797
UCSCiuc009ocz.2 mouse

Similar proteinsi

Entry informationi

Entry nameiBIRC2_MOUSE
AccessioniPrimary (citable) accession number: Q62210
Secondary accession number(s): A6H6S7, O08864
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: May 23, 2018
This is version 166 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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