Reviewed, UniProtKB/Swiss-Prot Q96CA5 (BIRC7_HUMAN)

Names and origin

Protein names

Recommended name:
    Baculoviral IAP repeat-containing protein 7
Alternative name(s):
    Kidney inhibitor of apoptosis protein
      Short name=KIAP
    Melanoma inhibitor of apoptosis protein
      Short name=ML-IAP
    Livin
    RING finger protein 50

Gene names

Name:	BIRC7
Synonyms:	KIAP, LIVIN, MLIAP, RNF50
ORF Names:	UNQ5800/PRO19607/PRO21344

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	298 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Protects against apoptosis induced by TNF or by chemical agents such as adriamycin, etoposide or staurosporine. Suppression of apoptosis is mediated by activation of MAPK8/JNK1, and possibly also of MAPK9/JNK2. This activation depends on TAB1 and NR2C2/TAK1. In vitro, inhibits caspase-3 and proteolytic activation of pro-caspase-9. Isoform 1 blocks staurosporine-induced apoptosis and isoform 2 blocks etoposide-induced apoptosis. Ref.7
Subunit structure	Binds to caspase-9. Interaction with SMAC via the BIR domain disrupts binding to caspase-9 and apoptotic suppressor activity. Interacts with TAB1. In vitro, interacts with caspase-3 and caspase-7 via its BIR domain. Ref.8
Subcellular location	Nucleus. Cytoplasm. Note: Nuclear, and in a filamentous pattern throughout the cytoplasm.
Tissue specificity	Very low levels or not detectable in most adult tissues. Detected in adult heart, placenta, lung, lymph node, spleen and ovary, and in several carcinoma cell lines (isoform 1 and isoform 2). Isoform 2 (but not isoform 1) is detected in fetal kidney, heart and spleen, and at lower levels in adult brain, skeletal muscle and peripheral blood leukocytes.
Sequence similarities	Belongs to the IAP family. Contains 1 BIR repeat. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	DNA fragmentation involved in apoptosis Ref.3 Non-traceable author statement. Source: UniProtKB activation of JUN kinase activity Ref.9 Non-traceable author statement. Source: UniProtKB anti-apoptosis Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	enzyme binding Ref.8 Non-traceable author statement. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CASP3	P42574	1	EBI-517623,EBI-524064
CASP9	P55211	5	EBI-517623,EBI-516799
DIABLO	Q9NR28	5	EBI-517623,EBI-517508
HTRA2	O43464	2	EBI-517623,EBI-517086

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: Q96CA5-1)

Also known as: Livin alpha;

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.

Isoform 1 (identifier: Q96CA5-2)

Also known as: Livin beta;

The sequence of this isoform differs from the canonical sequence as follows:
     216-233: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 298

298

Baculoviral IAP repeat-containing protein 7

PRO_0000122362

Regions

Repeat

90 – 155

66

BIR

Zinc finger

252 – 286

35

RING-type

Compositional bias

64 – 69

6

Poly-Glu

Sites

Metal binding

124

1

Zinc

Metal binding

127

1

Zinc

Metal binding

144

1

Zinc

Metal binding

151

1

Zinc

Natural variations

Alternative sequence

216 – 233

18

Missing in isoform 1.

VSP_002459

Natural variant

223

1

E → Q: dbSNP rs1077019. Ref.6

VAR_020253

Experimental info

Mutagenesis

87 – 88

2

EE → AA: No change in SMAC interaction and anti-apoptotic activity.

Mutagenesis

120

1

D → A: Abolishes inhibition of caspases, SMAC binding and anti-apoptotic activity. Ref.7

Mutagenesis

124

1

C → A: Abolishes inhibition of caspases and anti-apoptotic activity. Ref.7

Mutagenesis

138

1

D → A: Abolishes inhibition of caspases, SMAC binding and anti-apoptotic activity. Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

298

Helix Strand Turn

Details...

Helix

82 – 85

4

Helix

87 – 93

7

Helix

94 – 96

3

Helix

105 – 110

6

Beta strand

113 – 115

3

Beta strand

117 – 120

4

Beta strand

122 – 124

3

Turn

125 – 127

3

Beta strand

130 – 132

3

Helix

140 – 147

8

Helix

152 – 167

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (Livin alpha) [UniParc]. Last modified July 11, 2002. Version 2. Checksum: B2EAAEE531BEC101	FASTA	298	32,798
	10 20 30 40 50 60 MGPKDSAKCL HRGPQPSHWA AGDGPTQERC GPRSLGSPVL GLDTCRAWDH VDGQILGQLR 70 80 90 100 110 120 PLTEEEEEEG AGATLSRGPA FPGMGSEELR LASFYDWPLT AEVPPELLAA AGFFHTGHQD 130 140 150 160 170 180 KVRCFFCYGG LQSWKRGDDP WTEHAKWFPS CQFLLRSKGR DFVHSVQETH SQLLGSWDPW 190 200 210 220 230 240 EEPEDAAPVA PSVPASGYPE LPTPRREVQS ESAQEPGGVS PAEAQRAWWV LEPPGARDVE 250 260 270 280 290 AQLRRLQEER TCKVCLDRAV SIVFVPCGHL VCAECAPGLQ LCPICRAPVR SRVRTFLS
	Isoform 1 (Livin beta). Checksum: 630BE9C0737F7952	FASTA	280	30,866
	10 20 30 40 50 60 MGPKDSAKCL HRGPQPSHWA AGDGPTQERC GPRSLGSPVL GLDTCRAWDH VDGQILGQLR 70 80 90 100 110 120 PLTEEEEEEG AGATLSRGPA FPGMGSEELR LASFYDWPLT AEVPPELLAA AGFFHTGHQD 130 140 150 160 170 180 KVRCFFCYGG LQSWKRGDDP WTEHAKWFPS CQFLLRSKGR DFVHSVQETH SQLLGSWDPW 190 200 210 220 230 240 EEPEDAAPVA PSVPASGYPE LPTPRREVQS ESAQEPGARD VEAQLRRLQE ERTCKVCLDR 250 260 270 280 AVSIVFVPCG HLVCAECAPG LQLCPICRAP VRSRVRTFLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"KIAP, a novel member of the inhibitor of apoptosis protein family." Lin J.-H., Deng G., Huang Q., Morser J. Biochem. Biophys. Res. Commun. 279:820-831(2000) [PubMed: 11162435] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Fetal kidney.
[2]	"Two splicing variants of a new inhibitor of apoptosis gene with different biological properties and tissue distribution pattern." Ashhab Y., Alian A., Polliack A., Panet A., Yehuda D.B. FEBS Lett. 495:56-60(2001) [PubMed: 11322947] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1 AND 2). Tissue: Melanoma.
[3]	"Livin, a novel inhibitor of apoptosis protein family member." Kasof G.M., Gomes B.C. J. Biol. Chem. 276:3238-3246(2001) [PubMed: 11024045] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Kidney.
[4]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[5]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT GLN-223. Tissue: Skin.
[7]	"ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas." Vucic D., Stennicke H.R., Pisabarro M.T., Salvesen G.S., Dixit V.M. Curr. Biol. 10:1359-1366(2000) [PubMed: 11084335] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF 87-GLU--GLU-88; ASP-120; CYS-124 AND ASP-138.
[8]	"SMAC negatively regulates the anti-apoptotic activity of melanoma inhibitor of apoptosis (ML-IAP)." Vucic D., Deshayes K., Ackerly H., Pisabarro M.T., Kadkhodayan S., Fairbrother W.J., Dixit V.M. J. Biol. Chem. 277:12275-12279(2002) [PubMed: 11801603] [Abstract] Cited for: INTERACTION WITH SMAC.
[9]	"IAP suppression of apoptosis involves distinct mechanisms: the TAK1/JNK1 signaling cascade and caspase inhibition." Sanna M.G., da Silva Correia J., Ducrey O., Lee J., Nomoto K., Schrantz N., Deveraux Q.L., Ulevitch R.J. Mol. Cell. Biol. 22:1754-1766(2002) [PubMed: 11865055] [Abstract] Cited for: ACTIVATION OF MAP KINASES.
[10]	"Structure and function analysis of peptide antagonists of melanoma inhibitor of apoptosis (ML-IAP)." Franklin M.C., Kadkhodayan S., Ackerly H., Alexandru D., Distefano M.D., Elliott L.O., Flygare J.A., Mausisa G., Okawa D.C., Ong D., Vucic D., Deshayes K., Fairbrother W.J. Biochemistry 42:8223-8231(2003) [PubMed: 12846571] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 63-179 IN COMPLEX WITH PHAGE-AND SMAC-DERIVED PEPTIDES, ZINC-BINDING SITES.
[11]	"Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IAP." Vucic D., Franklin M.C., Wallweber H.J., Das K., Eckelman B.P., Shin H., Elliott L.O., Kadkhodayan S., Deshayes K., Salvesen G.S., Fairbrother W.J. Biochem. J. 385:11-20(2005) [PubMed: 15485396] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) OF 63-159, ZINC-BINDING SITES.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF301009 mRNA. Translation: AAG37878.1.
AJ309298 Genomic DNA. Translation: CAC37337.1.
AJ309298 Genomic DNA. Translation: CAC37338.1.
AF311388 mRNA. Translation: AAG33622.1.
AY358835 mRNA. Translation: AAQ89194.1.
AY358836 mRNA. Translation: AAQ89195.1.
AL121827 Genomic DNA. No translation available.
BC014475 mRNA. Translation: AAH14475.1.

IPI

IPI00152993.
IPI00219046.

PIR

JC7568.

RefSeq

NP_071444.1.
NP_647478.1.

UniGene

Hs.256126

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1OXN	X-ray	2.20	A/B/C/D/E	63-179	[»]
1OXQ	X-ray	2.30	A/B/C/D/E	63-179	[»]
1OY7	X-ray	2.70	A/B/C/D/E	63-179	[»]
1TW6	X-ray	1.71	A/B	63-159	[»]
2I3H	X-ray	1.62	A/B	63-159	[»]
2I3I	X-ray	2.30	A/B	63-159	[»]
3F7G	X-ray	2.30	A/B/C/D/E	63-179	[»]
3F7H	X-ray	1.80	A/B	63-159	[»]
3F7I	X-ray	1.90	A/B	63-159	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96CA5. 4 interactions.

Protein family/group databases

MEROPS

I32.007.

Proteomic databases

PRIDE

Q96CA5.

Genome annotation databases

Ensembl

ENSG00000101197. Homo sapiens. [Contig view]

GeneID

79444.

KEGG

hsa:79444.

UCSC

uc002yei.1. human.
uc002yej.1. human.

Organism-specific databases

GeneCards

GC20P061337.

H-InvDB

HIX0015996.

HGNC

HGNC:13702. BIRC7.

MIM

605737. gene.

PharmGKB

PA25364.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q96CA5.

HOVERGEN

Q96CA5.

OMA

Q96CA5. YDWPLTA.

Gene expression databases

ArrayExpress

Q96CA5.

Bgee

Q96CA5.

CleanEx

HS_BIRC7.

GermOnline

ENSG00000101197. Homo sapiens.

Family and domain databases

InterPro

IPR001370. Prot_inh_I32_IAP.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR017907. Znf_RING_CS.
[Graphical view]

Pfam

PF00653. BIR. 1 hit.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]

SMART

SM00238. BIR. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]

PROSITE

PS01282. BIR_REPEAT_1. 1 hit.
PS50143. BIR_REPEAT_2. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

68407.

PMAP-CutDB

Q96CA5.

SOURCE

Search...

Entry information

Entry name

BIRC7_HUMAN

Accession

Primary (citable) accession number: Q96CA5
Secondary accession number(s): Q9BQV0, Q9H2A8, Q9HAP7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2002
Last sequence update:	July 11, 2002
Last modified:	July 7, 2009
This is version 86 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)