Reviewed, UniProtKB/Swiss-Prot O15392 (BIRC5_HUMAN)

Names and origin

Protein names

Recommended name:
    Baculoviral IAP repeat-containing protein 5
Alternative name(s):
    Apoptosis inhibitor survivin
    Apoptosis inhibitor 4

Gene names

Name:	BIRC5
Synonyms:	API4, IAP4

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

General annotation (Comments)

Function	May play a role in neoplasia. May counteract a default induction of apoptosis in G2/M phase. Interacts with tubulin. Inhibitor of caspase-3 and caspase-7. Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Isoforms 2 and 3 do not appear to play vital roles in mitosis. Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform. Ref.2 Ref.14 Ref.16 Ref.21
Subunit structure	Homodimer. When phosphorylated, interacts with HBXIP; the resulting complex binds pro-caspase-9, as well as active caspase-9, but much less efficiently. Component of the CPC at least composed of BIRC5/survivin, CDCA8/borealin, INCENP and AURKB/Aurora-B. Interacts with EVI5. Ref.16 Ref.21 Ref.17 Ref.18 Ref.19 Ref.20 Ref.22
Subcellular location	Cytoplasm. Nucleus. Centromere. Note= Localizes on chromosome arms and inner centromeres from prophase through metaphase and then transferring to the spindle midzone and midbody from anaphase through cytokinesis. Colocalizes with AURKB at mitotic chromosomes. Ref.16 Ref.3
Tissue specificity	Expressed only in fetal kidney and liver, and to lesser extent, lung and brain. Abundantly expressed in adenocarcinoma (lung, pancreas, colon, breast, and prostate) and in high-grade lymphomas. Also expressed in various renal cell carcinoma cell lines. Ref.2 Ref.4 Ref.5
Domain	The BIR repeat is necessary and sufficient for HBXIP binding.
Sequence similarities	Belongs to the IAP family. Contains 1 BIR repeat.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Cell division Mitosis
Cellular component	Centromere Chromosomal protein Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Metal-binding Zinc
Molecular function	Protease inhibitor Thiol protease inhibitor
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	G2/M transition of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB anti-apoptosis Inferred from sequence or structural similarity. Source: UniProtKB cytokinesis Inferred from sequence or structural similarity. Source: UniProtKB establishment of chromosome localization Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of caspase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of exit from mitosis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB protein complex localization Ref.18 Inferred from mutant phenotype. Source: UniProtKB spindle checkpoint Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	centriole Inferred from sequence or structural similarity. Source: UniProtKB chromosome, centromeric region Ref.3 Inferred from sequence or structural similarity. Source: UniProtKB cytoplasmic microtubule Inferred from sequence or structural similarity. Source: UniProtKB cytosol Inferred from sequence or structural similarity. Source: UniProtKB interphase microtubule organizing center Inferred from sequence or structural similarity. Source: UniProtKB midbody Ref.3 Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-KW protein complex Ref.18 Inferred from direct assay. Source: UniProtKB spindle microtubule Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	caspase inhibitor activity Inferred from sequence or structural similarity. Source: UniProtKB chaperone binding Inferred from physical interaction. Source: UniProtKB cofactor binding Inferred from sequence or structural similarity. Source: UniProtKB cysteine protease inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW microtubule binding Inferred from sequence or structural similarity. Source: UniProtKB protein heterodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-518838,EBI-518838
AURKB	Q96GD4	1	EBI-518823,EBI-624291
AURKB	Q96GD4	2	EBI-518838,EBI-624291
AURKB	Q96GD4	2	EBI-518842,EBI-624291
BIRC5	O15392-1	2	EBI-518842,EBI-518838
BIRC5	O15392-2	2	EBI-518838,EBI-518842
Birc6	O88738	1	EBI-518823,EBI-912068	From a different organism.
CASP9	P55211	1	EBI-518823,EBI-516799
CDC2	P06493	1	EBI-518823,EBI-444308
CDCA8	Q53HL2	2	EBI-518823,EBI-979174
CDCA8	Q53HL2	2	EBI-518838,EBI-979174
CDCA8	Q53HL2	2	EBI-518842,EBI-979174
PPP1CC	P36873-1	1	EBI-518823,EBI-356289
USF2	Q15853	1	EBI-518823,EBI-1055994

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O15392-1)

Also known as: 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 2 (identifier: O15392-2)

Also known as: 2B; Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     74-74: I → IGPGTVAYACNTSTLGGRGGRITR

Isoform 3 (identifier: O15392-3)

Also known as: DeltaEx3;

The sequence of this isoform differs from the canonical sequence as follows:
     74-142: IEEHKKHSSG...RAIEQLAAMD → MQRKPTIRRK...SLPVGPLAMS

Isoform 4 (identifier: O15392-4)

Also known as: 3B;

The sequence of this isoform differs from the canonical sequence as follows:
     114-142: AKETNNKKKEFEETAEKVRRAIEQLAAMD → ERALLAE

Isoform 5 (identifier: O15392-5)

Also known as: SI;

The sequence of this isoform differs from the canonical sequence as follows:
     105-142: DRERAKNKIAKETNNKKKEFEETAEKVRRAIEQLAAMD → VRETLPPPRSFIR

Isoform 6 (identifier: O15392-6)

Also known as: 3 alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     74-142: IEEHKKHSSGCAFLSVKKQFEELTLGEFLKLDRERAKNKIAKETNNKKKEFEETAEKVRRAIEQLAAMD → MRELC

Isoform 7 (identifier: O15392-7)

Also known as: 2 alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     74-142: IEEHKKHSSGCAFLSVKKQFEELTLGEFLKLDRERAKNKIAKETNNKKKEFEETAEKVRRAIEQLAAMD → M

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 142

142

Baculoviral IAP repeat-containing protein 5

PRO_0000122356

Regions

Repeat

18 – 88

71

BIR

Sites

Metal binding

57

1

Zinc

Metal binding

60

1

Zinc

Metal binding

77

1

Zinc

Metal binding

84

1

Zinc

Amino acid modifications

Modified residue

34

1

Phosphothreonine; by CDC2 Ref.15 Ref.23 Ref.24

Natural variations

Alternative sequence

74 – 142

69

IEEHK…LAAMD → MQRKPTIRRKNLRKLRRKCA VPSSSWLPWIEASGRSCLVP EWLHHFQGLFPGATSLPVGP LAMS in isoform 3.

VSP_020338

Alternative sequence

74 – 142

69

IEEHK…LAAMD → MRELC in isoform 6.

VSP_020339

Alternative sequence

74 – 142

69

IEEHK…LAAMD → M in isoform 7.

VSP_020340

Alternative sequence

74

1

I → IGPGTVAYACNTSTLGGRGG RITR in isoform 2.

VSP_002454

Alternative sequence

105 – 142

38

DRERA…LAAMD → VRETLPPPRSFIR in isoform 5.

VSP_020341

Alternative sequence

114 – 142

29

AKETN…LAAMD → ERALLAE in isoform 4.

VSP_020342

Natural variant

129

1

E → K: dbSNP rs2071214.

VAR_021071

Experimental info

Mutagenesis

34

1

T → A: Loss of HBXIP binding Ref.16

Mutagenesis

34

1

T → E: Higher affinity for HBXIP binding Ref.16

Mutagenesis

84

1

C → A: Loss of cytoprotection

Sequence conflict

57 – 58

2

CF → WV in AAW22624. Ref.5

Sequence conflict

58

1

F → L in BAD97148. Ref.10

Sequence conflict

128

1

A → V in CAG46540. Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

142

Helix Strand Turn

Details...

Turn

8 – 10

3

Helix

11 – 13

3

Helix

15 – 20

6

Helix

35 – 40

6

Beta strand

43 – 45

3

Beta strand

55 – 57

3

Turn

58 – 60

3

Helix

73 – 80

8

Helix

85 – 88

4

Helix

93 – 95

3

Helix

98 – 139

42

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) [UniParc]. Last modified October 23, 2007. Version 2. Checksum: 9E7CADCDF28F9486	FASTA	142	16,390
	10 20 30 40 50 60 MGAPTLPPAW QPFLKDHRIS TFKNWPFLEG CACTPERMAE AGFIHCPTEN EPDLAQCFFC 70 80 90 100 110 120 FKELEGWEPD DDPIEEHKKH SSGCAFLSVK KQFEELTLGE FLKLDRERAK NKIAKETNNK 130 140 KKEFEETAEK VRRAIEQLAA MD
	Isoform 2 (2B) (Beta). Checksum: D1E961E51AD0661E		165	18,637
	10 20 30 40 50 60 MGAPTLPPAW QPFLKDHRIS TFKNWPFLEG CACTPERMAE AGFIHCPTEN EPDLAQCFFC 70 80 90 100 110 120 FKELEGWEPD DDPIGPGTVA YACNTSTLGG RGGRITREEH KKHSSGCAFL SVKKQFEELT 130 140 150 160 LGEFLKLDRE RAKNKIAKET NNKKKEFEET AEKVRRAIEQ LAAMD
	Isoform 3 (DeltaEx3). Checksum: 38C82D22E46BFF7C		137	15,622
	10 20 30 40 50 60 MGAPTLPPAW QPFLKDHRIS TFKNWPFLEG CACTPERMAE AGFIHCPTEN EPDLAQCFFC 70 80 90 100 110 120 FKELEGWEPD DDPMQRKPTI RRKNLRKLRR KCAVPSSSWL PWIEASGRSC LVPEWLHHFQ 130 GLFPGATSLP VGPLAMS
	Isoform 4 (3B). Checksum: 3904E8C8AF6945F7		120	13,812
	10 20 30 40 50 60 MGAPTLPPAW QPFLKDHRIS TFKNWPFLEG CACTPERMAE AGFIHCPTEN EPDLAQCFFC 70 80 90 100 110 120 FKELEGWEPD DDPIEEHKKH SSGCAFLSVK KQFEELTLGE FLKLDRERAK NKIERALLAE
	Isoform 5 (SI). Checksum: 82FC6A9B55F06876		117	13,467
	10 20 30 40 50 60 MGAPTLPPAW QPFLKDHRIS TFKNWPFLEG CACTPERMAE AGFIHCPTEN EPDLAQCFFC 70 80 90 100 110 FKELEGWEPD DDPIEEHKKH SSGCAFLSVK KQFEELTLGE FLKLVRETLP PPRSFIR
	Isoform 6 (3 alpha). Checksum: D06E2937DCAC8283		78	8,991
	10 20 30 40 50 60 MGAPTLPPAW QPFLKDHRIS TFKNWPFLEG CACTPERMAE AGFIHCPTEN EPDLAQCFFC 70 FKELEGWEPD DDPMRELC
	Isoform 7 (2 alpha). Checksum: 8CAC8283CD371FD9		74	8,490
	10 20 30 40 50 60 MGAPTLPPAW QPFLKDHRIS TFKNWPFLEG CACTPERMAE AGFIHCPTEN EPDLAQCFFC 70 FKELEGWEPD DDPM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma." Ambrosini G., Adida C., Altieri D.C. Nat. Med. 3:917-921(1997) [PubMed: 9256286] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[2]	"Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties." Mahotka C., Wenzel M., Springer E., Gabbert H.E., Gerharz C.D. Cancer Res. 59:6097-6102(1999) [PubMed: 10626797] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), FUNCTION, TISSUE SPECIFICITY, VARIANT LYS-129.
[3]	"Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype." Uren A.G., Wong L., Pakusch M., Fowler K.J., Burrows F.J., Vaux D.L., Choo K.H. Curr. Biol. 10:1319-1328(2000) [PubMed: 11084331] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, VARIANT LYS-129.
[4]	"Identification of a novel splice variant of the human anti-apoptosis gene survivin." Badran A., Yoshida A., Ishikawa K., Goi T., Yamaguchi A., Ueda T., Inuzuka M. Biochem. Biophys. Res. Commun. 314:902-907(2004) [PubMed: 14741722] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), TISSUE SPECIFICITY, VARIANT LYS-129. Tissue: Myeloid leukemia cell.
[5]	"Molecular cloning and bioinformatics analysis of a novel spliced variant of survivin from human breast cancer cells." Zheng W., Ma X., Wei D., Wang T., Ma Y., Yang S. DNA Seq. 16:321-328(2005) [PubMed: 16329164] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), VARIANT LYS-129, TISSUE SPECIFICITY. Tissue: Mammary cancer.
[6]	"An isoform of survivin (survivin-beta) which has 23 amino acids insertion into the BIR domain." Kageyama H., Islam A., Takayasu H., Nakagawara A. Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT LYS-129. Tissue: Neuroblastoma.
[7]	"Survivin 2 alpha: a novel survivin splice variant expressed in human malignancies." Caldas H., Honsey L.E., Altura R.A. Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7).
[8]	"Identification of a novel survivin splicing variant 3alpha in acute myeloid leukemia." Vietri M.T., Cioffi M., Sessa M., Sica V., Molinari A.M. Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6). Tissue: Myeloid leukemia cell.
[9]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LYS-129.
[10]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LYS-129.
[11]	NIEHS SNPs program Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[12]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed: 16625196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[13]	"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 1), VARIANT LYS-129. Tissue: Lung, Mammary gland and Muscle.
[14]	"Control of apoptosis and mitotic spindle checkpoint by survivin." Li F., Ambrosini G., Chu E.Y., Plescia J., Tognin S., Marchisio P.C., Altieri D.C. Nature 396:580-584(1998) [PubMed: 9859993] [Abstract] Cited for: FUNCTION.
[15]	"Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin." O'Connor D.S., Grossman D., Plescia J., Li F., Zhang H., Villa A., Tognin S., Marchisio P.C., Altieri D.C. Proc. Natl. Acad. Sci. U.S.A. 97:13103-13107(2000) [PubMed: 11069302] [Abstract] Cited for: PHOSPHORYLATION AT THR-34.
[16]	"HBXIP functions as a cofactor of survivin in apoptosis suppression." Marusawa H., Matsuzawa S., Welsh K., Zou H., Armstrong R., Tamm I., Reed J.C. EMBO J. 22:2729-2740(2003) [PubMed: 12773388] [Abstract] Cited for: FUNCTION IN APOPTOSIS SUPPRESSION, INTERACTION WITH HBXIP, MUTAGENESIS OF THR-34, SUBCELLULAR LOCATION.
[17]	"Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle." Gassmann R., Carvalho A., Henzing A.J., Ruchaud S., Hudson D.F., Honda R., Nigg E.A., Gerloff D.L., Earnshaw W.C. J. Cell Biol. 166:179-191(2004) [PubMed: 15249581] [Abstract] Cited for: INTERACTION WITH CDCA8.
[18]	"Survivin mediates targeting of the chromosomal passenger complex to the centromere and midbody." Vader G., Kauw J.J.W., Medema R.H., Lens S.M.A. EMBO Rep. 7:85-92(2006) [PubMed: 16239925] [Abstract] Cited for: INTERACTION WITH CDCA8.
[19]	"Borealin/Dasra B is a cell cycle-regulated chromosomal passenger protein and its nuclear accumulation is linked to poor prognosis for human gastric cancer." Chang J.-L., Chen T.-H., Wang C.-F., Chiang Y.-H., Huang Y.-L., Wong F.-H., Chou C.-K., Chen C.-M. Exp. Cell Res. 312:962-973(2006) [PubMed: 16427043] [Abstract] Cited for: INTERACTION WITH CDCA8.
[20]	"EVI5 protein associates with the INCENP-aurora B kinase-survivin chromosomal passenger complex and is involved in the completion of cytokinesis." Faitar S.L., Sossey-Alaoui K