Q13490 (BIRC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Baculoviral IAP repeat-containing protein 2

Alternative name(s):
C-IAP1
IAP homolog B
Inhibitor of apoptosis protein 2
Short name=IAP-2
Short name=hIAP-2
Short name=hIAP2
RING finger protein 48
TNFR2-TRAF-signaling complex protein 2

Gene names

Name:	BIRC2
Synonyms:	API1, IAP2, MIHB, RNF48

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	618 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Apoptotic suppressor. The BIR motifs region interacts with TNF receptor associated factors 1 and 2 (TRAF1 and TRAF2) to form an heteromeric complex, which is then recruited to the tumor necrosis factor receptor 2 (TNFR2).
Subunit structure	Interacts with DIABLO/SMAC and with PRSS25; these interactions inhibit apoptotic suppressor activity. Interacts with CASP9. Ref.7
Subcellular location	Cytoplasm Potential.
Tissue specificity	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.
Sequence similarities	Belongs to the IAP family. Contains 3 BIR repeats. Contains 1 CARD domain. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell surface receptor linked signaling pathway Traceable author statement. Source: ProtInc cellular component disassembly involved in apoptosis Traceable author statement. Source: Reactome negative regulation of apoptotic process Inferred from direct assay. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern. Source: UniProtKB proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay. Source: UniProtKB protein polyubiquitination Inferred from direct assay. Source: UniProtKB
Cellular component	CD40 receptor complex Inferred from sequence or structural similarity. Source: BHF-UCL cytosol Traceable author statement. Source: Reactome internal side of plasma membrane Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular function	protein N-terminus binding Inferred from physical interaction Ref.7. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CASP7	P55210	2	EBI-514538,EBI-523958
DIABLO	Q9NR28	4	EBI-514538,EBI-517508
RIPK1	Q13546	3	EBI-514538,EBI-358507
RIPK2	O43353	3	EBI-514538,EBI-358522
RIPK3	Q9Y572	3	EBI-514538,EBI-298250
RIPK4	P57078	3	EBI-514538,EBI-4422308
TNFRSF12A	Q9NP84	2	EBI-514538,EBI-2851995
TRAF2	Q12933	8	EBI-514538,EBI-355744

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 618

618

Baculoviral IAP repeat-containing protein 2

PRO_0000122347

Regions

Repeat

46 – 113

68

BIR 1

Repeat

184 – 250

67

BIR 2

Repeat

269 – 336

68

BIR 3

Domain

453 – 543

91

CARD

Zinc finger

571 – 606

36

RING-type

Sites

Metal binding

306

1

Zinc

Metal binding

309

1

Zinc

Metal binding

326

1

Zinc

Metal binding

333

1

Zinc

Natural variations

Natural variant

453

1

M → I.
Corresponds to variant rs34749508 [ dbSNP | Ensembl ].

VAR_049535

Natural variant

453

1

M → V. Ref.4

VAR_025016

Natural variant

506

1

A → V. Ref.4
Corresponds to variant rs34510872 [ dbSNP | Ensembl ].

VAR_025017

Natural variant

549

1

P → S. Ref.4
Corresponds to variant rs35494784 [ dbSNP | Ensembl ].

VAR_025018

Experimental info

Sequence conflict

157

1

S → P in AAC50372. Ref.2

Sequence conflict

308

1

C → G in AAC50372. Ref.2

Sequence conflict

414

1

Q → L in AAC50372. Ref.2

Sequence conflict

514

1

L → W in AAC50372. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

618

Helix Strand Turn

Details...

Helix

264 – 266

3

Helix

269 – 274

6

Helix

275 – 278

4

Beta strand

283 – 285

3

Helix

287 – 292

6

Beta strand

295 – 297

3

Beta strand

304 – 306

3

Turn

307 – 309

3

Beta strand

312 – 314

3

Helix

322 – 329

8

Helix

334 – 340

7

Helix

342 – 348

7

Sequences

	Sequence		Length	Mass (Da)
	Q13490 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: C1778D328063586D	FASTA	618	69,900
	10 20 30 40 50 60 MHKTASQRLF PGPSYQNIKS IMEDSTILSD WTNSNKQKMK YDFSCELYRM STYSTFPAGV 70 80 90 100 110 120 PVSERSLARA GFYYTGVNDK VKCFCCGLML DNWKLGDSPI QKHKQLYPSC SFIQNLVSAS 130 140 150 160 170 180 LGSTSKNTSP MRNSFAHSLS PTLEHSSLFS GSYSSLSPNP LNSRAVEDIS SSRTNPYSYA 190 200 210 220 230 240 MSTEEARFLT YHMWPLTFLS PSELARAGFY YIGPGDRVAC FACGGKLSNW EPKDDAMSEH 250 260 270 280 290 300 RRHFPNCPFL ENSLETLRFS ISNLSMQTHA ARMRTFMYWP SSVPVQPEQL ASAGFYYVGR 310 320 330 340 350 360 NDDVKCFCCD GGLRCWESGD DPWVEHAKWF PRCEFLIRMK GQEFVDEIQG RYPHLLEQLL 370 380 390 400 410 420 STSDTTGEEN ADPPIIHFGP GESSSEDAVM MNTPVVKSAL EMGFNRDLVK QTVQSKILTT 430 440 450 460 470 480 GENYKTVNDI VSALLNAEDE KREEEKEKQA EEMASDDLSL IRKNRMALFQ QLTCVLPILD 490 500 510 520 530 540 NLLKANVINK QEHDIIKQKT QIPLQARELI DTILVKGNAA ANIFKNCLKE IDSTLYKNLF 550 560 570 580 590 600 VDKNMKYIPT EDVSGLSLEE QLRRLQEERT CKVCMDKEVS VVFIPCGHLV VCQECAPSLR 610 KCPICRGIIK GTVRTFLS

References

	« Hide 'large scale' referencesShow '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: 8548810] [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: 8552191] [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: 8643514] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal liver.
[4]	NIEHS SNPs program Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-453; VAL-506 AND SER-549.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis and Uterus.
[6]	"Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat." Hinds M.G., Norton R.S., Vaux D.L., Day C.L. Nat. Struct. Biol. 6:648-651(1999) [PubMed: 10404221] [Abstract] Cited for: STRUCTURE BY NMR OF 266-363.
[7]	"The structure of the BIR3 domain of cIAP1 in complex with the N-terminal peptides of SMAC and caspase-9." Kulathila R., Vash B., Sage D., Cornell-Kennon S., Wright K., Koehn J., Stams T., Clark K., Price A. Acta Crystallogr. D 65:58-66(2009) [PubMed: 19153467] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 260-352 IN COMPLEXES WITH ZINC IONS; DIABLO AND CASP9 PEPTIDES, SUBUNIT.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L49431 mRNA. Translation: AAC41942.1.
U45879 mRNA. Translation: AAC50372.1.
U37547 mRNA. Translation: AAC50508.1.
DQ068066 Genomic DNA. Translation: AAY46158.1.
BC016174 mRNA. Translation: AAH16174.1.
BC028578 mRNA. Translation: AAH28578.1.

IPI

IPI00013418.

PIR

S68450.

RefSeq

NP_001157.1. NM_001166.3.

UniGene

Hs.696238.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QBH	NMR	-	A	266-363	[»]
2L9M	NMR	-	A	435-562	[»]
3D9T	X-ray	1.50	A/B	260-352	[»]
3D9U	X-ray	2.30	A	260-352	[»]
3M1D	X-ray	2.00	A/B	40-119	[»]
3MUP	X-ray	2.60	A/B/C/D	251-363	[»]
3OZ1	X-ray	3.00	A/B/C/D	251-363	[»]
3T6P	X-ray	1.90	A	265-618	[»]

ProteinModelPortal

Q13490.

SMR

Q13490. Positions 41-362, 379-618.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13490. 25 interactions.

MINT

MINT-216174.

STRING

Q13490.

Protein family/group databases

MEROPS

I32.002.

PTM databases

PhosphoSite

Q13490.

Polymorphism databases

DMDM

2497238.

Proteomic databases

PRIDE

Q13490.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000227758; ENSP00000227758; ENSG00000110330.

GeneID

329.

KEGG

hsa:329.

UCSC

uc001pgy.1. human.

Organism-specific databases

CTD

329.

GeneCards

GC11P102252.

H-InvDB

HIX0010063.

HGNC

HGNC:590. BIRC2.

HPA

CAB020661.
HPA005513.

MIM

601712. gene.

neXtProt

NX_Q13490.

PharmGKB

PA25359.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08896.

HOGENOM

HBG714776.

HOVERGEN

HBG004848.

InParanoid

Q13490.

OMA

SPMRNSF.

OrthoDB

EOG4K3KVW.

PhylomeDB

Q13490.

Enzyme and pathway databases

Pathway_Interaction_DB

nfkappabcanonicalpathway. Canonical NF-kappaB pathway.
caspase_pathway. Caspase cascade in apoptosis.
p75ntrpathway. p75(NTR)-mediated signaling.
tnfpathway. TNF receptor signaling pathway.

Reactome

REACT_578. Apoptosis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q13490.

Bgee

Q13490.

CleanEx

HS_BIRC2.

Genevestigator

Q13490.

GermOnline

ENSG00000110330. Homo sapiens.

Family and domain databases

InterPro

IPR001370. BIR.
IPR001315. CARD.
IPR011029. DEATH-like.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

Gene3D

G3DSA:1.10.1170.10. BIR. 4 hits.
G3DSA:1.10.533.10. DEATH_like. 1 hit.
G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.

KO

K04725.

Pfam

PF00653. BIR. 3 hits.
PF00619. CARD. 1 hit.
[Graphical view]

SMART

SM00238. BIR. 3 hits.
SM00114. CARD. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]

SUPFAM

SSF47986. DEATH_like. 1 hit.

PROSITE

PS01282. BIR_REPEAT_1. 3 hits.
PS50143. BIR_REPEAT_2. 3 hits.
PS50209. CARD. 1 hit.
PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

1355.

PMAP-CutDB

Q13490.

SOURCE

Search...

Entry information

Entry name

BIRC2_HUMAN

Accession

Primary (citable) accession number: Q13490
Secondary accession number(s): Q16516, Q4TTG0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	January 25, 2012
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.