O15392 (BIRC5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Baculoviral IAP repeat-containing protein 5

Alternative name(s):
Apoptosis inhibitor 4
Apoptosis inhibitor survivin

Gene names

Name:	BIRC5
Synonyms:	API4, IAP4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	142 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis. Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis. Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules. The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. May counteract a default induction of apoptosis in G2/M phase. The acetylated form represses STAT3 transactivation of target gene promoters. May play a role in neoplasia. Inhibitor of CASP3 and CASP7. Isoform 2 and isoform 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.16 Ref.18 Ref.23 Ref.28 Ref.33 Ref.34 Ref.37
Subunit structure	Monomer or homodimer. Exists as a homodimer in the apo state and as a monomer in the CPC-bound state. The monomer protects cells against apoptosis more efficiently than the dimer. Only the dimeric form is capable of enhancing tubulin stability in cells. When phosphorylated, interacts with HBXIP; the resulting complex binds pro-CASP9, as well as active CASP9, but much less efficiently. Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB and AURKC. Interacts with JTB. Interacts with CDCA8 and INCENP; interaction is direct. Interacts with EVI5. Interacts with GTP-bound RAN in both the S and M phases of the cell cycle. Interacts with USP9X. Interacts with tubulin. Interacts with BIRC2/c-IAP1. The acetylated form at Lys-129 interacts with STAT3. The monomeric form deacetylated at Lys-129 interacts with XPO1/CRM1. The monomeric form interacts with XIAP/BIRC4. Both the dimeric and monomeric form can interact with DIABLO/SMAC. Interacts with BIRC6/bruce. Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.33 Ref.34 Ref.36 Ref.37 Ref.40
Subcellular location	Cytoplasm. Nucleus. Chromosome. Chromosome › centromere. Cytoplasm › cytoskeleton › spindle. Chromosome › centromere › kinetochore. Midbody. Note: Localizes on chromosome arms and inner centromeres from prophase through metaphase. Localizes to kinetochores in metaphase, distributes to the midzone microtubules in anaphase and at telophase, localizes exclusively to the midbody. Colocalizes with AURKB at mitotic chromosomes. Acetylation at Lys-129 directs its localization to the nucleus by enhancing homodimerization and thereby inhibiting XPO1/CRM1-mediated nuclear export. Ref.3 Ref.18 Ref.19 Ref.21 Ref.23 Ref.33 Ref.34
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
Developmental stage	Expression is cell cycle-dependent and peaks at mitosis. Ref.33
Induction	Up-regulated by COMP. Ref.31
Domain	The BIR repeat is necessary and sufficient for HBXIP binding.
Post-translational modification	Ubiquitination is required for centrosomal targeting. In vitro phosphorylation at Thr-117 by AURKB prevents interaction with INCENP and localization to mitotic chromosomes. Phosphorylation at Thr-48 by CK2 is critical for its mitotic and anti-apoptotic activities. Acetylation at Lys-129 by CBP results in its homodimerization, while deacetylation promotes the formation of monomers which heterodimerize with XPO1/CRM1 which facilitates its nuclear export. The acetylated form represses STAT3 transactivation. The dynamic equilibrium between its acetylation and deacetylation at Lys-129 determines its interaction with XPO1/CRM1, its subsequent subcellular localization, and its ability to inhibit STAT3 transactivation.
Sequence similarities	Belongs to the IAP family. Contains 1 BIR repeat.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Cell division Chromosome partition Mitosis Transcription Transcription regulation
Cellular component	Centromere Chromosome Cytoplasm Cytoskeleton Kinetochore Microtubule Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Metal-binding Zinc
Molecular function	Protease inhibitor Repressor Thiol protease inhibitor
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G2/M transition of mitotic cell cycle Inferred from direct assay Ref.16. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW chromosome segregation Inferred from electronic annotation. Source: UniProtKB-KW cytokinesis Inferred from mutant phenotype PubMed 12805209. Source: UniProtKB establishment of chromosome localization Inferred from mutant phenotype PubMed 12805209. Source: UniProtKB mitosis Traceable author statement Ref.28. Source: UniProtKB mitotic prometaphase Traceable author statement. Source: Reactome negative regulation of apoptotic process Inferred from direct assay Ref.2Ref.18Ref.1Ref.16. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from mutant phenotype Ref.34. Source: UniProtKB positive regulation of cell proliferation Traceable author statement Ref.22. Source: UniProtKB positive regulation of exit from mitosis Inferred from mutant phenotype PubMed 12805209. Source: UniProtKB positive regulation of mitotic cell cycle Inferred from mutant phenotype Ref.28. Source: UniProtKB protein complex localization Inferred from mutant phenotype Ref.25. Source: UniProtKB protein phosphorylation Inferred from direct assay Ref.35. Source: UniProtKB regulation of apoptotic process Inferred from mutant phenotype Ref.37. Source: UniProtKB spindle checkpoint Inferred from mutant phenotype PubMed 12805209. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	centriole Inferred from direct assay Ref.16. Source: UniProtKB chromosome passenger complex Inferred from physical interaction PubMed 15260989Ref.33. Source: UniProtKB chromosome, centromeric region Inferred from direct assay PubMed 11516652Ref.28. Source: UniProtKB condensed chromosome kinetochore Inferred from direct assay Ref.21. Source: UniProtKB cytoplasm Inferred from direct assay Ref.28. Source: UniProtKB cytoplasmic microtubule Inferred from direct assay Ref.16. Source: UniProtKB cytosol Inferred from direct assay Ref.33Ref.18. Source: UniProtKB interphase microtubule organizing center Inferred from direct assay Ref.16. Source: UniProtKB microtubule Inferred from electronic annotation. Source: UniProtKB-KW midbody Inferred from direct assay Ref.21Ref.17Ref.28Ref.16. Source: UniProtKB nuclear chromosome Inferred from direct assay Ref.23. Source: UniProtKB spindle Inferred from electronic annotation. Source: UniProtKB-SubCell spindle microtubule Inferred from direct assay Ref.17Ref.16. Source: UniProtKB
Molecular_function	cobalt ion binding Non-traceable author statement Ref.38. Source: UniProtKB cofactor binding Inferred from direct assay Ref.18. Source: UniProtKB cysteine-type endopeptidase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW cysteine-type endopeptidase inhibitor activity involved in apoptotic process Inferred from mutant phenotype Ref.16. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW microtubule binding Inferred from direct assay Ref.16. Source: UniProtKB protein heterodimerization activity Inferred from direct assay Ref.28. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.39Ref.38. Source: UniProtKB zinc ion binding Inferred from direct assay Ref.39. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AURKB	Q96GD4	2	EBI-518838,EBI-624291
CDCA8	Q53HL2	10	EBI-518823,EBI-979174
CDK1	P06493	6	EBI-518823,EBI-444308

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: AKETNNKKKEFEETAKKVRRAIEQLAAMD → ERALLAE

Isoform 5 (identifier: O15392-5)

Also known as: SI;

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

23

1

N6-acetyllysine Ref.34

Modified residue

34

1

Phosphothreonine; by CDK1 Ref.17 Ref.32

Modified residue

48

1

Phosphothreonine; by CK2; in vitro Ref.35

Modified residue

90

1

N6-acetyllysine Ref.34

Modified residue

110

1

N6-acetyllysine Ref.34

Modified residue

112

1

N6-acetyllysine Ref.34

Modified residue

115

1

N6-acetyllysine Ref.34

Modified residue

117

1

Phosphothreonine; by AURKB Ref.19

Modified residue

121

1

N6-acetyllysine Ref.34

Modified residue

129

1

N6-acetyllysine Ref.34

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

K → E Loss of acetylation; localization primarily within the cytoplasm; increased likelihood of existing as monomer; stronger binding to XPO1/CRM1. Ref.13 Ref.34
Corresponds to variant rs2071214 [ dbSNP | Ensembl ].

VAR_021071

Experimental info

Mutagenesis

23

1

K → R: Increases ubiquitination and blocks dissociation from centromeres; when associated with R-62; R-78 and R-79. Ref.23

Mutagenesis

34

1

T → A: Loss of HBXIP binding. Ref.18

Mutagenesis

34

1

T → E: Higher affinity for HBXIP binding. Ref.18

Mutagenesis

48

1

T → A or E: Localizes normally during mitosis but cannot support cell proliferation. Increased affinity for CDCA8/borealin. Ref.35

Mutagenesis

62

1

K → R: Increases ubiquitination and blocks dissociation from centromeres; when associated with R-23; R-78 and R-79. Ref.23

Mutagenesis

65

1

E → A: Almost abolishes RAN-binding. Does not disrupt binding to AURKB or CDCA8. Disrupts mitotic spindle assembly. Does not disrupt nuclear export. Ref.33

Mutagenesis

70

1

D → A: No change. Loss of interaction with AURKB; when associated with A-71. Ref.24

Mutagenesis

71

1

D → A: No change. Loss of interaction with AURKB; when associated with A-70. Ref.24

Mutagenesis

78

1

K → R: Increases ubiquitination and blocks dissociation from centromeres; when associated with R-23; R-62 and R-79. Ref.23

Mutagenesis

79

1

K → R: Increases ubiquitination and blocks dissociation from centromeres; when associated with R-23; R-62 and R-78. Ref.23

Mutagenesis

84

1

C → A: Loss of cytoprotection.

Mutagenesis

117

1

T → A: Prevents phosphorylation by AURKB. Still able to localize correctly but prevents interaction with INCENP. Ref.19

Mutagenesis

117

1

T → E: Mimics phosphorylation. Disrupts subcellular localization during mitosis and prevents interaction with INCENP. Ref.19

Mutagenesis

129

1

K → A or Q: Mimics acetylation. Localization primarily within the nucleus. Ref.34

Mutagenesis

129

1

K → R: Loss of acetylation. Localization primarily within the cytoplasm. Ref.34

Sequence conflict

57 – 58

2

CF → WV in AAW22624. Ref.5

Sequence conflict

58

1

F → L in BAD97148. Ref.11

Sequence conflict

128

1

A → V in CAG46540. Ref.9

Secondary structure

1

.

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142

Helix Strand Turn

Details...

Turn

8 – 10

3

Helix

11 – 13

3

Helix

15 – 20

6

Beta strand

31 – 33

3

Helix

35 – 40

6

Beta strand

43 – 45

3

Beta strand

49 – 51

3

Beta strand

55 – 57

3

Turn

58 – 60

3

Beta strand

63 – 65

3

Helix

73 – 80

8

Turn

81 – 83

3

Helix

85 – 88

4

Helix

93 – 95

3

Helix

98 – 139

42

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) [UniParc]. Last modified March 21, 2012. Version 3. Checksum: 9E7CADCDF2822286	FASTA	142	16,389
	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 KKEFEETAKK VRRAIEQLAA MD
	Isoform 2 (2B) (Beta) [UniParc]. Checksum: D1E961E51ADDD01E	FASTA	165	18,636
	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 AKKVRRAIEQ LAAMD
	Isoform 3 (DeltaEx3) [UniParc]. Checksum: 38C82D22E46BFF7C	FASTA	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) [UniParc]. Checksum: 3904E8C8AF6945F7	FASTA	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) [UniParc]. Checksum: 82FC6A9B55F06876	FASTA	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) [UniParc]. Checksum: D06E2937DCAC8283	FASTA	78	8,991
	10 20 30 40 50 60 MGAPTLPPAW QPFLKDHRIS TFKNWPFLEG CACTPERMAE AGFIHCPTEN EPDLAQCFFC 70 FKELEGWEPD DDPMRELC
	Isoform 7 (2 alpha) [UniParc]. Checksum: 8CAC8283CD371FD9	FASTA	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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), FUNCTION, TISSUE SPECIFICITY.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), TISSUE SPECIFICITY. 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), 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). 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).
[10]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[11]	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).
[12]	NIEHS SNPs program Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[13]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-129.
[14]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[15]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung, Mammary gland and Muscle.
[16]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[17]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-34.
[18]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN APOPTOSIS SUPPRESSION, INTERACTION WITH HBXIP, MUTAGENESIS OF THR-34, SUBCELLULAR LOCATION.
[19]	"Aurora-B phosphorylation in vitro identifies a residue of survivin that is essential for its localization and binding to inner centromere protein (INCENP) in vivo." Wheatley S.P., Henzing A.J., Dodson H., Khaled W., Earnshaw W.C. J. Biol. Chem. 279:5655-5660(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INCENP, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-117, MUTAGENESIS OF THR-117.
[20]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDCA8.
[21]	"cIAP1 Localizes to the nuclear compartment and modulates the cell cycle." Samuel T., Okada K., Hyer M., Welsh K., Zapata J.M., Reed J.C. Cancer Res. 65:210-218(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH BIRC2/C-IAP1.
[22]	"Survivin: a protein with dual roles in mitosis and apoptosis." Wheatley S.P., McNeish I.A. Int. Rev. Cytol. 247:35-88(2005) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[23]	"Chromosome alignment and segregation regulated by ubiquitination of survivin." Vong Q.P., Cao K., Li H.Y., Iglesias P.A., Zheng Y. Science 310:1499-1504(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH USP9X, SUBCELLULAR LOCATION, UBIQUITINATION, MUTAGENESIS OF LYS-23; LYS-62; LYS-78 AND LYS-79.
[24]	"Survivin mutant (Surv-DD70, 71AA) disrupts the interaction of Survivin with Aurora B and causes multinucleation in HeLa cells." Cao L., Yan X., Wu Y., Hu H., Li Q., Zhou T., Jiang S., Yu L. Biochem. Biophys. Res. Commun. 346:400-407(2006) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASP-70; ASP-71 AND 70-ASP--ASP-71.
[25]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDCA8.
[26]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDCA8.
[27]	"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., Ranalli T.A., Cowell J.K. Exp. Cell Res. 312:2325-2335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EVI5.
[28]	"Molecular analysis of survivin isoforms: evidence that alternatively spliced variants do not play a role in mitosis." Noton E.A., Colnaghi R., Tate S., Starck C., Carvalho A., Ko Ferrigno P., Wheatley S.P. J. Biol. Chem. 281:1286-1295(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CDCA8.
[29]	"Uncoupling the central spindle-associated function of the chromosomal passenger complex from its role at centromeres." Lens S.M.A., Rodriguez J.A., Vader G., Span S.W., Giaccone G., Medema R.H. Mol. Biol. Cell 17:1897-1909(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDCA8.
[30]	"Final stages of cytokinesis and midbody ring formation are controlled by BRUCE." Pohl C., Jentsch S. Cell 132:832-845(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BIRC6/BRUCE.
[31]	"Cartilage oligomeric matrix protein protects cells against death by elevating members of the IAP family of survival proteins." Gagarina V., Carlberg A.L., Pereira-Mouries L., Hall D.J. J. Biol. Chem. 283:648-659(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[32]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-34, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[33]	"A survivin-ran complex regulates spindle formation in tumor cells." Xia F., Canovas P.M., Guadagno T.M., Altieri D.C. Mol. Cell. Biol. 28:5299-5311(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RAN; AURKB AND CDCA8, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, MUTAGENESIS OF GLU-65.
[34]	"Acetylation directs survivin nuclear localization to repress STAT3 oncogenic activity." Wang H., Holloway M.P., Ma L., Cooper Z.A., Riolo M., Samkari A., Elenitoba-Johnson K.S., Chin Y.E., Altura R.A. J. Biol. Chem. 285:36129-36137(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STAT3 AND XPO1/CRM1, ACETYLATION AT LYS-23; LYS-90; LYS-110; LYS-112; LYS-115; LYS-121 AND LYS-129, MUTAGENESIS OF LYS-129, CHARACTERIZATION OF VARIANT GLU-129.
[35]	"Threonine 48 in the BIR domain of survivin is critical to its mitotic and anti-apoptotic activities and can be phosphorylated by CK2 in vitro." Barrett R.M., Colnaghi R., Wheatley S.P. Cell Cycle 10:538-548(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-48, MUTAGENESIS OF THR-48.
[36]	"PAR, a protein involved in the cell cycle, is functionally related to chromosomal passenger proteins." Platica M., Ionescu A., Ivan E., Holland J.F., Mandeli J., Platica O. Int. J. Oncol. 38:777-785(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH JTB.
[37]	"Survivin monomer plays an essential role in apoptosis regulation." Pavlyukov M.S., Antipova N.V., Balashova M.V., Vinogradova T.V., Kopantzev E.P., Shakhparonov M.I. J. Biol. Chem. 286:23296-23307(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, INTERACTION WITH XIAP/BIRC4 AND DIABLO/SMAC.
[38]	"Crystal structure of human survivin reveals a bow tie-shaped dimer with two unusual alpha-helical extensions." Chantalat L., Skoufias D.A., Kleman J.P., Jung B., Dideberg O., Margolis R.L. Mol. Cell 6:183-189(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) OF ISOFORM 1.
[39]	"Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement." Verdecia M.A., Huang H., Dutil E., Kaiser D.A., Hunter T., Noel J.P. Nat. Struct. Biol. 7:602-608(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS) OF ISOFORM 1.
[40]	"Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together." Jeyaprakash A.A., Klein U.R., Lindner D., Ebert J., Nigg E.A., Conti E. Cell 131:271-285(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH ZINC IONS, SUBUNIT, INTERACTION WITH CDCA8 AND INCENP.
[41]	"Phosphorylation of a borealin dimerization domain is required for proper chromosome segregation." Bourhis E., Lingel A., Phung Q., Fairbrother W.J., Cochran A.G. Biochemistry 48:6783-6793(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U75285 Genomic DNA. Translation: AAC51660.1.
AF077350 mRNA. Translation: AAD34226.1.
AB154416 mRNA. Translation: BAD11155.1.
AY830084 mRNA. Translation: AAW22624.1.
AB028869 mRNA. Translation: BAA93676.1.
AY927772 mRNA. Translation: AAY15202.1.
DQ227257 mRNA. Translation: ABB76601.1.
DQ310375 mRNA. Translation: ABC42341.1.
DQ310376 mRNA. Translation: ABC42342.1.
DQ310377 mRNA. Translation: ABC42343.1.
DQ310378 mRNA. Translation: ABC42344.1.
DQ310379 mRNA. Translation: ABC42345.1.
CR541740 mRNA. Translation: CAG46540.1.
AK223428 mRNA. Translation: BAD97148.1.
AK311917 mRNA. Translation: BAG34858.1.
AY795969 Genomic DNA. Translation: AAV40840.1.
AC087645 Genomic DNA. No translation available.
CH471099 Genomic DNA. Translation: EAW89514.1.
BC008718 mRNA. Translation: AAH08718.1.
BC034148 mRNA. Translation: AAH34148.1.
BC065497 mRNA. Translation: AAH65497.1.

IPI

IPI00006210.
IPI00218095.
IPI00735946.
IPI00784873.
IPI00784916.
IPI00784964.
IPI00785191.

RefSeq

NP_001012270.1. NM_001012270.1.
NP_001012271.1. NM_001012271.1.
NP_001159.2. NM_001168.2.

UniGene

Hs.514527.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E31	X-ray	2.71	A/B	1-142	[»]
1F3H	X-ray	2.58	A/B	1-142	[»]
1XOX	NMR	-	A/B	1-117	[»]
2QFA	X-ray	1.40	A	1-142	[»]
2RAW	X-ray	2.40	A	1-142	[»]
2RAX	X-ray	3.30	A/E/X	1-120	[»]
3UEC	X-ray	2.18	A	1-142	[»]
3UED	X-ray	2.70	A/C	1-142	[»]
3UEE	X-ray	2.61	A/C	1-142	[»]
3UEF	X-ray	2.45	A/C	1-142	[»]
3UEG	X-ray	2.80	A/B	1-142	[»]
3UEH	X-ray	2.60	A/B	1-142	[»]
3UEI	X-ray	2.70	A/B	1-142	[»]
3UIG	X-ray	2.40	A/B	1-142	[»]
3UIH	X-ray	2.40	A/B	1-142	[»]
3UII	X-ray	2.60	A/B	1-142	[»]
3UIJ	X-ray	2.70	A/B	1-142	[»]
3UIK	X-ray	2.70	A/B	1-142	[»]
4A0I	X-ray	2.60	A/B	1-142	[»]
4A0J	X-ray	2.80	A/B	1-142	[»]
4A0N	X-ray	2.74	A	1-142	[»]

ProteinModelPortal

O15392.

SMR

O15392. Positions 5-142.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34662N.

IntAct

O15392. 10 interactions.

MINT

MINT-147138.

STRING

9606.ENSP00000301633.

Protein family/group databases

MEROPS

I32.005.

PTM databases

PhosphoSite

O15392.

Proteomic databases

PaxDb

O15392.

PRIDE

O15392.

Protocols and materials databases

DNASU

332.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000374948; ENSP00000364086; ENSG00000089685.
ENST00000590449; ENSP00000465868; ENSG00000089685.
ENST00000590925; ENSP00000467336; ENSG00000089685.
ENST00000590946; ENSP00000465671; ENSG00000089685.
ENST00000592734; ENSP00000466617; ENSG00000089685.

GeneID

332.

KEGG

hsa:332.

UCSC

uc002jvd.1. human.
uc002jvg.3. human.
uc002jvh.3. human.

Organism-specific databases

CTD

332.

GeneCards

GC17P076210.

HGNC

HGNC:593. BIRC5.

HPA

CAB004270.
HPA002830.

MIM

603352. gene.

neXtProt

NX_O15392.

PharmGKB

PA25362.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG271140.

HOVERGEN

HBG050690.

KO

K08731.

Enzyme and pathway databases

Pathway_Interaction_DB

aurora_a_pathway. Aurora A signaling.
aurora_b_pathway. Aurora B signaling.
foxm1pathway. FOXM1 transcription factor network.

Reactome

REACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.

Gene expression databases

ArrayExpress

O15392.

Bgee

O15392.

CleanEx

HS_BIRC5.

Genevestigator

O15392.

GermOnline

ENSG00000089685. Homo sapiens.

Family and domain databases

Gene3D

1.10.1170.10. 1 hit.

InterPro

IPR001370. BIR.
[Graphical view]

Pfam

PF00653. BIR. 1 hit.
[Graphical view]

SMART

SM00238. BIR. 1 hit.
[Graphical view]

PROSITE

PS01282. BIR_REPEAT_1. False negative.
PS50143. BIR_REPEAT_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O15392.

ChEMBL

CHEMBL5989.

ChiTaRS

BIRC5. human.

EvolutionaryTrace

O15392.

GenomeRNAi

332.

NextBio

1369.

SOURCE

Search...

Entry information

Entry name

BIRC5_HUMAN

Accession

Primary (citable) accession number: O15392
Secondary accession number(s): A2SUH6 , B2R4R1, Q2I3N8, Q4VGX0, Q53F61, Q5MGC6, Q6FHL2, Q75SP2, Q9P2W8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	March 21, 2012
Last modified:	May 1, 2013
This is version 157 of the entry and version 3 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.