SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00000441 
UniProt Accession
Theoretical PI
5.85  
Molecular Weight
16389 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
BIRC5 
Gene Synonyms/Alias
API4, IAP4 
Protein Name
Baculoviral IAP repeat-containing protein 5 
Protein Synonyms/Alias
Apoptosis inhibitor 4; Apoptosis inhibitor survivin; 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:17;76210277-76221715;1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
Deregulated apoptosis of germ cells may contribute to male infertility as well as malignant transformation. survivin is expressed in human germ cells and might be involved in apoptosis control during spermatogenesis.  
The information of related literatures
1. S. Weikert, M. Schrader, F. Christoph, W. Schulze, H. Krause, M. Muller and K. Miller (2005) Quantification of survivin mRNA in testes of infertile patients and in testicular germ cell tumours. Int J Androl 28(4): 224-9. 

Abstract
Deregulated apoptosis of germ cells may contribute to male infertility as well as malignant transformation. Survivin, an inhibitor of apoptosis (IAP), is overexpressed in all the most common human malignancies, but barely detectable in normal tissues. We used real-time polymerase chain reaction (PCR) to quantify survivin mRNA expression in normal testes (n = 22), testes with defective spermatogenesis (n = 26) and testicular germ cell tumours (TGCTs; n = 16). Survivin was expressed at high levels in normal testes. Testicular survivin levels in infertile patients were related inversely to the severity of spermatogenic failure (p < 0.001), with a lack of expression in most specimens with pre-meiotic spermatogenic arrest and in all those with germ cell aplasia. Lower levels of expression were observed in TGCTs than in normal testes. While survivin expression was detected in most TGCTs with undifferentiated components (12 of 13), it was absent in all mature teratomas (n = 3). These data show that survivin is expressed in normal and transformed germ cells. Its downregulation in spermatogenic disorders indicates that survivin may contribute to the normal balance between germ cell proliferation and apoptosis. In TGCTs, survivin expression appears to be lost with somatic differentiation. PMID: [16048634] 

2. S. Weikert, F. Christoph, W. Schulze, H. Krause, C. Kempkensteffen, M. Schostak, K. Miller and M. Schrader (2006) Testicular expression of survivin and human telomerase reverse transcriptase (hTERT) associated with spermatogenic function in infertile patients. Asian J Androl 8(1): 95-100. 

Abstract
AIM PMID: [16372125] 

3. S. Weikert, M. Schrader, M. Muller, H. Krause and K. Miller (2004) Expression of the apoptosis inhibitor survivin in testicular tissue of infertile patients. Int J Androl 27(3): 161-5. 

Abstract
Summary Apoptosis is a common phenomenon during spermatogenesis, and its dysregulation has been associated with male infertility. Survivin is an inhibitor of apoptosis protein that regulates apoptosis at cell division and is overexpressed in common human cancers. We investigated whether survivin mRNA expression is detectable in testicular biopsies from patients with infertility of varying aetiology. The aim of this study was to examine the testicular survivin expression in azoospermic men with normal spermatogenesis and in those with specific spermatogenic disorders. Survivin mRNA expression was detected by reverse transcriptase-polymerase chain reaction in histologically classified testicular biopsy specimens from 30 azoospermic men. Survivin was found to be expressed in normal spermatogenesis (n = 10), in post-meiotic spermatogenic arrest (n = 6), and in specimens showing a mixed picture of pre-meiotic maturation arrest with sparse islands of post-meiotic arrest (n = 2). In contrast, a lack of survivin expression was seen in specimens without haploid germ cells (pre-meiotic maturation arrest, n = 2) and in those with Sertoli-cell-only syndrome (SCOS, n = 10). These data indicate for the first time that survivin is expressed in human testis. Moreover, its expression seems to correlate with the stage of maturation arrest in patients presenting with spermatogenic disorders. Survivin mRNA expression was not found in SCOS specimens, possibly indicating germ-cell-specific expression in human testicular tissue. Thus, survivin is a potential molecular marker of spermatogenesis, whose expression is altered in specific spermatogenic disorders. PMID: [15139971] 

4. S. Weikert, M. Schrader, M. Muller, W. Schulze, H. Krause and K. Miller (2005) Expression levels of the inhibitor of apoptosis survivin in testes of patients with normal spermatogenesis and spermatogenic failure. Fertil Steril 83 Suppl 1(): 1100-5. 

Abstract
OBJECTIVE PMID: [15831281] 

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Figures for illustrating the function of this protein/gene
Function
Multitasking protein that has dual roles in promotingcell proliferation and preventing apoptosis. Component of achromosome passage protein complex (CPC) which is essential forchromosome alignment and segregation during mitosis andcytokinesis. Acts as an important regulator of the localization ofthis complex; directs CPC movement to different locations from theinner centromere during prometaphase to midbody during cytokinesisand participates in the organization of the center spindle byassociating with polymerized microtubules. The complex with RANplays a role in mitotic spindle formation by serving as a physicalscaffold to help deliver the RAN effector molecule TPX2 tomicrotubules. May counteract a default induction of apoptosis inG2/M phase. The acetylated form represses STAT3 transactivation oftarget gene promoters. May play a role in neoplasia. Inhibitor ofCASP3 and CASP7. Isoform 2 and isoform 3 do not appear to playvital roles in mitosis. Isoform 3 shows a marked reduction in itsanti-apoptotic effects when compared with the displayed wild-typeisoform. 
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Subcellular Location
Cytoplasm. Nucleus. Chromosome. Chromosome,centromere. Cytoplasm, cytoskeleton, spindle. Chromosome,centromere, kinetochore. Midbody. Note=Localizes on chromosomearms and inner centromeres from prophase through metaphase.Localizes to kinetochores in metaphase, distributes to the midzonemicrotubules in anaphase and at telophase, localizes exclusivelyto the midbody. Colocalizes with AURKB at mitotic chromosomes.Acetylation at Lys-129 directs its localization to the nucleus byenhancing homodimerization and thereby inhibiting XPO1/CRM1-mediated nuclear export. 
Tissue Specificity
Expressed only in fetal kidney and liver, andto lesser extent, lung and brain. Abundantly expressed inadenocarcinoma (lung, pancreas, colon, breast, and prostate) andin high-grade lymphomas. Also expressed in various renal cellcarcinoma cell lines. 
Gene Ontology
GO IDGO termEvidence
GO:0005814 C:centriole IDA:UniProtKB.
GO:0032133 C:chromosome passenger complex IPI:UniProtKB.
GO:0000775 C:chromosome, centromeric region IDA:UniProtKB.
GO:0000777 C:condensed chromosome kinetochore IDA:UniProtKB.
GO:0005737 C:cytoplasm IDA:UniProtKB.
GO:0005881 C:cytoplasmic microtubule IDA:UniProtKB.
GO:0005829 C:cytosol IDA:UniProtKB.
GO:0031021 C:interphase microtubule organizing center IDA:UniProtKB.
GO:0005874 C:microtubule IEA:UniProtKB-KW.
GO:0030496 C:midbody IDA:UniProtKB.
GO:0000228 C:nuclear chromosome IDA:UniProtKB.
GO:0005819 C:spindle IEA:UniProtKB-SubCell.
GO:0005876 C:spindle microtubule IDA:UniProtKB.
GO:0050897 F:cobalt ion binding NAS:UniProtKB.
GO:0048037 F:cofactor binding IDA:UniProtKB.
GO:0004869 F:cysteine-type endopeptidase inhibitor activity IEA:UniProtKB-KW.
GO:0043027 F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process IMP:UniProtKB.
GO:0046872 F:metal ion binding IEA:UniProtKB-KW.
GO:0008270 F:zinc ion binding IDA:UniProtKB.
GO:0006916 P:anti-apoptosis IDA:UniProtKB.
GO:0006915 P:apoptotic process IEA:UniProtKB-KW.
GO:0051301 P:cell division IEA:UniProtKB-KW.
GO:0007059 P:chromosome segregation IEA:UniProtKB-KW.
GO:0000910 P:cytokinesis IMP:UniProtKB.
GO:0051303 P:establishment of chromosome localization IMP:UniProtKB.
GO:0000086 P:G2/M transition of mitotic cell cycle IDA:UniProtKB.
GO:0007067 P:mitosis TAS:UniProtKB.
GO:0000236 P:mitotic prometaphase TAS:Reactome.
GO:0045892 P:negative regulation of transcription, DNA-dependent IMP:UniProtKB.
GO:0008284 P:positive regulation of cell proliferation TAS:UniProtKB.
GO:0031536 P:positive regulation of exit from mitosis IMP:UniProtKB.
GO:0045931 P:positive regulation of mitotic cell cycle IMP:UniProtKB.
GO:0031503 P:protein complex localization IMP:UniProtKB.
GO:0006468 P:protein phosphorylation IDA:UniProtKB.
GO:0042981 P:regulation of apoptotic process IMP:UniProtKB.
GO:0031577 P:spindle checkpoint IMP:UniProtKB.
GO:0006351 P:transcription, DNA-dependent IEA:UniProtKB-KW.
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Interpro
Pfam
PF00653;    BIR;    1.
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SMART
SM00238;    BIR;    1.
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PROSITE
PS01282;    BIR_REPEAT_1;    FALSE_NEG.
PS50143;    BIR_REPEAT_2;    1.
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PRINTS
Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
CHAIN         1    142       Baculoviral IAP repeat-containing protein
                             5.
                             /FTId=PRO_0000122356.
REPEAT       18     88       BIR.
METAL        57     57       Zinc.
METAL        60     60       Zinc.
METAL        77     77       Zinc.
METAL        84     84       Zinc.
MOD_RES      23     23       N6-acetyllysine.
MOD_RES      34     34       Phosphothreonine; by CDK1.
MOD_RES      48     48       Phosphothreonine; by CK2; in vitro.
MOD_RES      90     90       N6-acetyllysine.
MOD_RES     110    110       N6-acetyllysine.
MOD_RES     112    112       N6-acetyllysine.
MOD_RES     115    115       N6-acetyllysine.
MOD_RES     117    117       Phosphothreonine; by AURKB.
MOD_RES     121    121       N6-acetyllysine.
MOD_RES     129    129       N6-acetyllysine.
VAR_SEQ      74    142       IEEHKKHSSGCAFLSVKKQFEELTLGEFLKLDRERAKNKIA
                             KETNNKKKEFEETAKKVRRAIEQLAAMD -> MQRKPTIRR
                             KNLRKLRRKCAVPSSSWLPWIEASGRSCLVPEWLHHFQGLF
                             PGATSLPVGPLAMS (in isoform 3).
                             /FTId=VSP_020338.
VAR_SEQ      74    142       IEEHKKHSSGCAFLSVKKQFEELTLGEFLKLDRERAKNKIA
                             KETNNKKKEFEETAKKVRRAIEQLAAMD -> MRELC (in
                             isoform 6).
                             /FTId=VSP_020339.
VAR_SEQ      74    142       IEEHKKHSSGCAFLSVKKQFEELTLGEFLKLDRERAKNKIA
                             KETNNKKKEFEETAKKVRRAIEQLAAMD -> M (in
                             isoform 7).
                             /FTId=VSP_020340.
VAR_SEQ      74     74       I -> IGPGTVAYACNTSTLGGRGGRITR (in isoform
                             2).
                             /FTId=VSP_002454.
VAR_SEQ     105    142       DRERAKNKIAKETNNKKKEFEETAKKVRRAIEQLAAMD ->
                             VRETLPPPRSFIR (in isoform 5).
                             /FTId=VSP_020341.
VAR_SEQ     114    142       AKETNNKKKEFEETAKKVRRAIEQLAAMD -> ERALLAE
                             (in isoform 4).
                             /FTId=VSP_020342.
VARIANT     129    129       K -> E (loss of acetylation; localization
                             primarily within the cytoplasm; increased
                             likelihood of existing as monomer;
                             stronger binding to XPO1/CRM1;
                             dbSNP:rs2071214).
                             /FTId=VAR_021071.
MUTAGEN      23     23       K->R: Increases ubiquitination and blocks
                             dissociation from centromeres; when
                             associated with R-62; R-78 and R-79.
MUTAGEN      34     34       T->A: Loss of HBXIP binding.
MUTAGEN      34     34       T->E: Higher affinity for HBXIP binding.
MUTAGEN      48     48       T->A,E: Localizes normally during mitosis
                             but cannot support cell proliferation.
                             Increased affinity for CDCA8/borealin.
MUTAGEN      62     62       K->R: Increases ubiquitination and blocks
                             dissociation from centromeres; when
                             associated with R-23; R-78 and R-79.
MUTAGEN      65     65       E->A: Almost abolishes RAN-binding. Does
                             not disrupt binding to AURKB or CDCA8.
                             Disrupts mitotic spindle assembly. Does
                             not disrupt nuclear export.
MUTAGEN      70     70       D->A: No change. Loss of interaction with
                             AURKB; when associated with A-71.
MUTAGEN      71     71       D->A: No change. Loss of interaction with
                             AURKB; when associated with A-70.
MUTAGEN      78     78       K->R: Increases ubiquitination and blocks
                             dissociation from centromeres; when
                             associated with R-23; R-62 and R-79.
MUTAGEN      79     79       K->R: Increases ubiquitination and blocks
                             dissociation from centromeres; when
                             associated with R-23; R-62 and R-78.
MUTAGEN      84     84       C->A: Loss of cytoprotection.
MUTAGEN     117    117       T->A: Prevents phosphorylation by AURKB.
                             Still able to localize correctly but
                             prevents interaction with INCENP.
MUTAGEN     117    117       T->E: Mimics phosphorylation. Disrupts
                             subcellular localization during mitosis
                             and prevents interaction with INCENP.
MUTAGEN     129    129       K->A,Q: Mimics acetylation. Localization
                             primarily within the nucleus.
MUTAGEN     129    129       K->R: Loss of acetylation. Localization
                             primarily within the cytoplasm.
CONFLICT     57     58       CF -> WV (in Ref. 5; AAW22624).
CONFLICT     58     58       F -> L (in Ref. 11; BAD97148).
CONFLICT    128    128       A -> V (in Ref. 9; CAG46540).
TURN          8     10
HELIX        11     13
HELIX        15     20
STRAND       31     33
HELIX        35     40
STRAND       43     45
STRAND       49     51
STRAND       55     57
TURN         58     60
STRAND       63     65
HELIX        73     80
TURN         81     83
HELIX        85     88
HELIX        93     95
HELIX        98    139
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Nucleotide Sequence
Length: 14796 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 142 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
UFD1LBioGRID 
AURKBHPRD 
_BioGRID 
BECN1MINT 
BIRC2BioGRID 
BIRC3BioGRID 
UFD1LBioGRID 
AURKADIP 
AURKBBioGRID 
_BioGRID 
_HPRD 
_BioGRID 
BECN1MINT 
BIRC5HPRD 
BIRC5HPRD 
CDCA8IntAct 
aurkbBioGRID 
CASP3HPRD 
CASP7HPRD 
CASP9HPRD 
CDK1IntAct 
CDK2BioGRID 
CDK4HPRD 
INCENPBioGRID 
INCENPBioGRID 
_IntAct 
CDK2deltaTBioGRID 
_IntAct 
UFD1LBioGRID 
_HPRD 
USP9XBioGRID 
USP9XBioGRID 
RASA1HPRD 
UFD1LBioGRID 
USF2IntAct 
USP9XBioGRID 
XIAPBioGRID 
XPO1HPRD 
BIRC6HPRD 
CDCA8HPRD 
aurkbHPRD 
CASP9IntAct 
CDK1HPRD 
DIABLOHPRD 
EVI5BioGRID 
HSP90AA1HPRD 
INCENPHPRD 
IncenpIntAct 
KCNJ6BioGRID 
Birc6IntAct 
UFD1LBioGRID 
_BioGRID 
_BioGRID 
_HPRD 
UFD1LBioGRID 
USF2BioGRID 
XIAPHPRD 
Other Protein-Protein interaction resources
String database  
View Microarray data
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