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Q96CA5 (BIRC7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Baculoviral IAP repeat-containing protein 7
Alternative name(s):
Kidney inhibitor of apoptosis protein
Short name=KIAP
Livin
Melanoma inhibitor of apoptosis protein
Short name=ML-IAP
RING finger protein 50
Gene names
Name:BIRC7
Synonyms:KIAP, LIVIN, MLIAP, RNF50
ORF Names:UNQ5800/PRO19607/PRO21344
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length298 AA.
Sequence statusComplete.
Protein existenceEvidence 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. 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

Isoform 1 and isoform 2 are expressed at 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 2 is detected in fetal kidney, heart and spleen, and at lower levels in adult brain, skeletal muscle and peripheral blood leukocytes. Ref.2

Sequence similarities

Belongs to the IAP family.

Contains 1 BIR repeat.

Contains 1 RING-type zinc finger.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainZinc-finger
   LigandMetal-binding
Zinc
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological processDNA fragmentation involved in apoptotic nuclear change

Non-traceable author statement Ref.3. Source: UniProtKB

activation of JUN kinase activity

Non-traceable author statement Ref.9. Source: UniProtKB

anti-apoptosis

Non-traceable author statement Ref.1. Source: UniProtKB

   Cellular componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionenzyme binding

Non-traceable author statement Ref.8. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CASP9P552115EBI-517623,EBI-516799
DIABLOQ9NR286EBI-517623,EBI-517508
HTRA2O434642EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 298298Baculoviral IAP repeat-containing protein 7
PRO_0000122362

Regions

Repeat90 – 15566BIR
Zinc finger252 – 28635RING-type
Compositional bias64 – 696Poly-Glu

Sites

Metal binding1241Zinc
Metal binding1271Zinc
Metal binding1441Zinc
Metal binding1511Zinc

Natural variations

Alternative sequence216 – 23318Missing in isoform 1.
VSP_002459
Natural variant2231E → Q. Ref.6
Corresponds to variant rs1077019 [ dbSNP | Ensembl ].
VAR_020253

Experimental info

Mutagenesis87 – 882EE → AA: No change in SMAC interaction and anti-apoptotic activity. Ref.7
Mutagenesis1201D → A: Abolishes inhibition of caspases, SMAC binding and anti-apoptotic activity. Ref.7
Mutagenesis1241C → A: Abolishes inhibition of caspases and anti-apoptotic activity. Ref.7
Mutagenesis1381D → A: Abolishes inhibition of caspases, SMAC binding and anti-apoptotic activity. Ref.7

Secondary structure

1 ..................... 298
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 (Livin alpha) [UniParc].

Last modified July 11, 2002. Version 2.
Checksum: B2EAAEE531BEC101

FASTA29832,798
        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

« Hide

Isoform 1 (Livin beta) [UniParc].

Checksum: 630BE9C0737F7952
Show »

FASTA28030,866

References

« Hide '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 SPECIFICITY (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. expand/collapse author list , 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. expand/collapse author list , 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

EMBL
GenBank
DDBJ		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.
IPIIPI00152993.
IPI00219046.
PIRJC7568.
RefSeqNP_071444.1. NM_022161.2.
NP_647478.1. NM_139317.1.
UniGeneHs.256126.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1OXNX-ray2.20A/B/C/D/E63-179[»]
1OXQX-ray2.30A/B/C/D/E63-179[»]
1OY7X-ray2.70A/B/C/D/E63-179[»]
1TW6X-ray1.71A/B63-159[»]
2I3HX-ray1.62A/B63-159[»]
2I3IX-ray2.30A/B63-159[»]
3F7GX-ray2.30A/B/C/D/E63-179[»]
3F7HX-ray1.80A/B63-159[»]
3F7IX-ray1.90A/B63-159[»]
3GT9X-ray1.70A/B63-159[»]
3GTAX-ray1.70A/B63-159[»]
ProteinModelPortalQ96CA5.
SMRQ96CA5. Positions 17-171, 239-298.
ModBaseSearch...

Protein-protein interaction databases

IntActQ96CA5. 5 interactions.
STRINGQ96CA5.

Protein family/group databases

MEROPSI32.007.

Polymorphism databases

DMDM21759008.

Proteomic databases

PRIDEQ96CA5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000217169; ENSP00000217169; ENSG00000101197.
GeneID79444.
KEGGhsa:79444.
UCSCuc002yei.1. human.
uc002yej.1. human.

Organism-specific databases

CTD79444.
GeneCardsGC20P061867.
H-InvDBHIX0015996.
HGNCHGNC:13702. BIRC7.
HPACAB037119.
MIM605737. gene.
neXtProtNX_Q96CA5.
PharmGKBPA25364.
GenAtlasSearch...

Phylogenomic databases

GeneTreeENSGT00500000044782.
HOGENOMHBG714776.
HOVERGENHBG099136.
InParanoidQ96CA5.
OMARAPIRSC.
PhylomeDBQ96CA5.

Gene expression databases

ArrayExpressQ96CA5.
BgeeQ96CA5.
CleanExHS_BIRC7.
GenevestigatorQ96CA5.
GermOnlineENSG00000101197. Homo sapiens.

Family and domain databases

InterProIPR001370. BIR.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
Gene3DG3DSA:1.10.1170.10. BIR. 2 hits.
G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.
PfamPF00653. BIR. 1 hit.
[Graphical view]
SMARTSM00238. BIR. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
PROSITEPS01282. 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]
ProtoNetSearch...

Other

NextBio68407.
PMAP-CutDBQ96CA5.
SOURCESearch...

Entry information

Entry nameBIRC7_HUMAN
AccessionPrimary (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: January 25, 2012
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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