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Protein

Baculoviral IAP repeat-containing protein 2

Gene

BIRC2

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, 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.6 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.4 Publications

Activity 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.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi306Zinc1
Metal bindingi309Zinc1
Metal bindingi326Zinc1
Metal bindingi333Zinc1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri571 – 606RING-typePROSITE-ProRule annotationAdd BLAST36

GO - Molecular functioni

  • chaperone binding Source: UniProtKB
  • cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: GO_Central
  • FBXO family protein binding Source: ParkinsonsUK-UCL
  • identical protein binding Source: IntAct
  • protein N-terminus binding Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB
  • transferase activity Source: Reactome
  • ubiquitin binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase activity Source: GO_Central
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-111465 Apoptotic cleavage of cellular proteins
R-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
SignaLinkiQ13490
SIGNORiQ13490

Protein family/group databases

MEROPSiI32.007

Names & Taxonomyi

Protein namesi
Recommended name:
Baculoviral IAP repeat-containing protein 2 (EC:2.3.2.274 Publications)
Alternative name(s):
Cellular inhibitor of apoptosis 1
Short name:
C-IAP11 Publication
IAP homolog B
Inhibitor of apoptosis protein 2
Short name:
hIAP-2
Short name:
hIAP2
RING finger protein 48
RING-type E3 ubiquitin transferase BIRC2Curated
TNFR2-TRAF-signaling complex protein 2
Gene namesi
Name:BIRC2
Synonyms:API1, MIHB, RNF48
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000110330.8
HGNCiHGNC:590 BIRC2
MIMi601712 gene
neXtProtiNX_Q13490

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

Organism-specific databases

DisGeNETi329
OpenTargetsiENSG00000110330
PharmGKBiPA25359

Chemistry databases

ChEMBLiCHEMBL5462
GuidetoPHARMACOLOGYi2791

Polymorphism and mutation databases

BioMutaiBIRC2
DMDMi2497238

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001223471 – 618Baculoviral IAP repeat-containing protein 2Add BLAST618

Post-translational modificationi

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

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ13490
MaxQBiQ13490
PaxDbiQ13490
PeptideAtlasiQ13490
PRIDEiQ13490
ProteomicsDBi59484

PTM databases

CarbonylDBiQ13490
iPTMnetiQ13490
PhosphoSitePlusiQ13490

Miscellaneous databases

PMAP-CutDBiQ13490

Expressioni

Tissue specificityi

Present in many fetal and adult tissues. Mainly expressed in adult skeletal muscle, thymus, testis, ovary, and pancreas, low or absent in brain and peripheral blood leukocytes.

Gene expression databases

BgeeiENSG00000110330 Expressed in 235 organ(s), highest expression level in cartilage tissue
CleanExiHS_BIRC2
ExpressionAtlasiQ13490 baseline and differential
GenevisibleiQ13490 HS

Organism-specific databases

HPAiCAB020661
HPA005513

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. Interacts with HSP90AB1 (PubMed:25486457). Interacts with UBXN1 (PubMed:25681446).7 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106826, 162 interactors
CORUMiQ13490
DIPiDIP-33485N
IntActiQ13490, 75 interactors
MINTiQ13490
STRINGi9606.ENSP00000227758

Chemistry databases

BindingDBiQ13490

Structurei

Secondary structure

1618
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ13490
SMRiQ13490
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13490

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati46 – 113BIR 1Add BLAST68
Repeati184 – 250BIR 2Add BLAST67
Repeati269 – 336BIR 3Add BLAST68
Domaini453 – 543CARDPROSITE-ProRule annotationAdd BLAST91

Domaini

The BIR domains mediate nuclear localization.1 Publication
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.1 Publication

Sequence similaritiesi

Belongs to the IAP family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri571 – 606RING-typePROSITE-ProRule annotationAdd BLAST36

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1101 Eukaryota
ENOG410YPNM LUCA
GeneTreeiENSGT00500000044782
HOGENOMiHOG000232059
HOVERGENiHBG004848
InParanoidiQ13490
KOiK16060
OMAiYFCGVEI
OrthoDBiEOG091G0CXH
PhylomeDBiQ13490
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

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q13490-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MHKTASQRLF PGPSYQNIKS IMEDSTILSD WTNSNKQKMK YDFSCELYRM
60 70 80 90 100
STYSTFPAGV PVSERSLARA GFYYTGVNDK VKCFCCGLML DNWKLGDSPI
110 120 130 140 150
QKHKQLYPSC SFIQNLVSAS LGSTSKNTSP MRNSFAHSLS PTLEHSSLFS
160 170 180 190 200
GSYSSLSPNP LNSRAVEDIS SSRTNPYSYA MSTEEARFLT YHMWPLTFLS
210 220 230 240 250
PSELARAGFY YIGPGDRVAC FACGGKLSNW EPKDDAMSEH RRHFPNCPFL
260 270 280 290 300
ENSLETLRFS ISNLSMQTHA ARMRTFMYWP SSVPVQPEQL ASAGFYYVGR
310 320 330 340 350
NDDVKCFCCD GGLRCWESGD DPWVEHAKWF PRCEFLIRMK GQEFVDEIQG
360 370 380 390 400
RYPHLLEQLL STSDTTGEEN ADPPIIHFGP GESSSEDAVM MNTPVVKSAL
410 420 430 440 450
EMGFNRDLVK QTVQSKILTT GENYKTVNDI VSALLNAEDE KREEEKEKQA
460 470 480 490 500
EEMASDDLSL IRKNRMALFQ QLTCVLPILD NLLKANVINK QEHDIIKQKT
510 520 530 540 550
QIPLQARELI DTILVKGNAA ANIFKNCLKE IDSTLYKNLF VDKNMKYIPT
560 570 580 590 600
EDVSGLSLEE QLRRLQEERT CKVCMDKEVS VVFIPCGHLV VCQECAPSLR
610
KCPICRGIIK GTVRTFLS
Length:618
Mass (Da):69,900
Last modified:November 1, 1997 - v2
Checksum:iC1778D328063586D
GO
Isoform 2 (identifier: Q13490-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: Missing.

Show »
Length:569
Mass (Da):64,098
Checksum:iB678A4C2069F0A22
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PMH5E9PMH5_HUMAN
Baculoviral IAP repeat-containing p...
BIRC2
597Annotation score:
A0A087X2B2A0A087X2B2_HUMAN
Baculoviral IAP repeat-containing p...
BIRC2
534Annotation score:
E9PIW1E9PIW1_HUMAN
Baculoviral IAP repeat-containing p...
BIRC2
182Annotation score:
E9PI77E9PI77_HUMAN
Baculoviral IAP repeat-containing p...
BIRC2
139Annotation score:
E9PQZ9E9PQZ9_HUMAN
Baculoviral IAP repeat-containing p...
BIRC2
79Annotation score:
E9PNM6E9PNM6_HUMAN
Baculoviral IAP repeat-containing p...
BIRC2
149Annotation score:
H0YDY3H0YDY3_HUMAN
Baculoviral IAP repeat-containing p...
BIRC2
262Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti157S → P in AAC50372 (PubMed:8552191).Curated1
Sequence conflicti308C → G in AAC50372 (PubMed:8552191).Curated1
Sequence conflicti414Q → L in AAC50372 (PubMed:8552191).Curated1
Sequence conflicti514L → W in AAC50372 (PubMed:8552191).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049535453M → I. Corresponds to variant dbSNP:rs34749508Ensembl.1
Natural variantiVAR_025016453M → V1 PublicationCorresponds to variant dbSNP:rs370745983Ensembl.1
Natural variantiVAR_025017506A → V1 PublicationCorresponds to variant dbSNP:rs34510872Ensembl.1
Natural variantiVAR_025018549P → S1 PublicationCorresponds to variant dbSNP:rs35494784Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0453141 – 49Missing in isoform 2. 1 PublicationAdd BLAST49

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L49431 mRNA Translation: AAC41942.1
U45879 mRNA Translation: AAC50372.1
U37547 mRNA Translation: AAC50508.1
AK303197 mRNA Translation: BAG64288.1
AP000942 Genomic DNA No translation available.
DQ068066 Genomic DNA Translation: AAY46158.1
BC016174 mRNA Translation: AAH16174.1
BC028578 mRNA Translation: AAH28578.1
CCDSiCCDS58169.1 [Q13490-2]
CCDS8316.1 [Q13490-1]
PIRiS68450
RefSeqiNP_001157.1, NM_001166.4 [Q13490-1]
NP_001243092.1, NM_001256163.1 [Q13490-1]
NP_001243095.1, NM_001256166.1 [Q13490-2]
UniGeneiHs.696238
Hs.731943

Genome annotation databases

EnsembliENST00000227758; ENSP00000227758; ENSG00000110330 [Q13490-1]
ENST00000530675; ENSP00000431723; ENSG00000110330 [Q13490-2]
ENST00000613397; ENSP00000477613; ENSG00000110330 [Q13490-1]
GeneIDi329
KEGGihsa:329
UCSCiuc001pgy.5 human [Q13490-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L49431 mRNA Translation: AAC41942.1
U45879 mRNA Translation: AAC50372.1
U37547 mRNA Translation: AAC50508.1
AK303197 mRNA Translation: BAG64288.1
AP000942 Genomic DNA No translation available.
DQ068066 Genomic DNA Translation: AAY46158.1
BC016174 mRNA Translation: AAH16174.1
BC028578 mRNA Translation: AAH28578.1
CCDSiCCDS58169.1 [Q13490-2]
CCDS8316.1 [Q13490-1]
PIRiS68450
RefSeqiNP_001157.1, NM_001166.4 [Q13490-1]
NP_001243092.1, NM_001256163.1 [Q13490-1]
NP_001243095.1, NM_001256166.1 [Q13490-2]
UniGeneiHs.696238
Hs.731943

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1QBHNMR-A266-363[»]
2L9MNMR-A435-562[»]
3D9TX-ray1.50A/B260-352[»]
3D9UX-ray2.30A260-352[»]
3M1DX-ray2.00A/B40-119[»]
3MUPX-ray2.60A/B/C/D251-363[»]
3OZ1X-ray3.00A/B/C/D251-363[»]
3T6PX-ray1.90A265-618[»]
3UW4X-ray1.79A266-343[»]
4EB9X-ray2.60A/B/C/D251-363[»]
4HY4X-ray1.25A/B260-352[»]
4HY5X-ray1.75A/B260-352[»]
4KMNX-ray1.52A260-357[»]
4LGEX-ray1.55A/B260-352[»]
4LGUX-ray2.00A/B260-352[»]
4MTIX-ray2.15A/B260-352[»]
4MU7X-ray1.79A/B260-352[»]
5M6NX-ray1.80A/B266-363[»]
6EXWX-ray2.20A/C250-363[»]
ProteinModelPortaliQ13490
SMRiQ13490
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106826, 162 interactors
CORUMiQ13490
DIPiDIP-33485N
IntActiQ13490, 75 interactors
MINTiQ13490
STRINGi9606.ENSP00000227758

Chemistry databases

BindingDBiQ13490
ChEMBLiCHEMBL5462
GuidetoPHARMACOLOGYi2791

Protein family/group databases

MEROPSiI32.007

PTM databases

CarbonylDBiQ13490
iPTMnetiQ13490
PhosphoSitePlusiQ13490

Polymorphism and mutation databases

BioMutaiBIRC2
DMDMi2497238

Proteomic databases

EPDiQ13490
MaxQBiQ13490
PaxDbiQ13490
PeptideAtlasiQ13490
PRIDEiQ13490
ProteomicsDBi59484

Protocols and materials databases

DNASUi329
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000227758; ENSP00000227758; ENSG00000110330 [Q13490-1]
ENST00000530675; ENSP00000431723; ENSG00000110330 [Q13490-2]
ENST00000613397; ENSP00000477613; ENSG00000110330 [Q13490-1]
GeneIDi329
KEGGihsa:329
UCSCiuc001pgy.5 human [Q13490-1]

Organism-specific databases

CTDi329
DisGeNETi329
EuPathDBiHostDB:ENSG00000110330.8
GeneCardsiBIRC2
HGNCiHGNC:590 BIRC2
HPAiCAB020661
HPA005513
MIMi601712 gene
neXtProtiNX_Q13490
OpenTargetsiENSG00000110330
PharmGKBiPA25359
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1101 Eukaryota
ENOG410YPNM LUCA
GeneTreeiENSGT00500000044782
HOGENOMiHOG000232059
HOVERGENiHBG004848
InParanoidiQ13490
KOiK16060
OMAiYFCGVEI
OrthoDBiEOG091G0CXH
PhylomeDBiQ13490
TreeFamiTF105356

Enzyme and pathway databases

ReactomeiR-HSA-111465 Apoptotic cleavage of cellular proteins
R-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
SignaLinkiQ13490
SIGNORiQ13490

Miscellaneous databases

ChiTaRSiBIRC2 human
EvolutionaryTraceiQ13490
GeneWikiiBIRC2
GenomeRNAii329
PMAP-CutDBiQ13490
PROiPR:Q13490
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000110330 Expressed in 235 organ(s), highest expression level in cartilage tissue
CleanExiHS_BIRC2
ExpressionAtlasiQ13490 baseline and differential
GenevisibleiQ13490 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiBIRC2_HUMAN
AccessioniPrimary (citable) accession number: Q13490
Secondary accession number(s): B4E026, Q16516, Q4TTG0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 7, 2018
This is version 197 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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