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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

SIVA1 Gene

protein-coding GIFtS: 51
GCID: GC14P105219

SIVA1, apoptosis-inducing factor

Explore 8 diseases affiliated with
SIVA1 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
SIVA1, Apoptosis-Inducing Factor¹ ²		Siva-2¹ ²
CD27BP¹ ² ³		Apoptosis Regulatory Protein Siva²
SIVA¹ ² ³		CD27-Binding (Siva) Protein²
Siva-1¹ ²		CD27-Binding Protein³

External Ids:	HGNC: 17712¹	Entrez Gene: 10572²	Ensembl: ENSG00000184990⁷	OMIM: 605567⁵	UniProtKB: O15304³

Export aliases for SIVA1 gene to outside databases

Previous GC identifers: GC14P104291 GC14P085416

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for SIVA1:

This gene encodes a protein with an important role in the apoptotic (programmed cell death) pathway induced by the CD27

antigen, a member of the tumor necrosis factor receptor (TFNR) superfamily. The CD27 antigen cytoplasmic tail binds to

the N-terminus of this protein. Two alternatively spliced transcript variants encoding distinct proteins have been

described. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: SIVA_HUMAN, O15304

Function: Induces CD27-mediated apoptosis. Inhibits BCL2L1 isoform Bcl-x(L) anti-apoptotic activity. Inhibits

activation of NF-kappa-B and promotes T-cell receptor-mediated apoptosis

Gene Wiki entry for SIVA1

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000014.8 NC_018925.1 NT_026437.12

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the SIVA1 gene promoter:
AhR Pax-5 Tal-1 ATF-2 GATA-2 YY1 Arnt E47 CREB c-Jun
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): SIVA1 promoter sequence

Search SABiosciences Chromatin IP Primers for SIVA1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat SIVA1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 14q32.33 Ensembl cytogenetic band: 14q32.33 HGNC cytogenetic band: 14q32.33

SIVA1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SIVA1 gene location

GeneLoc information about chromosome 14 GeneLoc Exon Structure

GeneLoc location for GC14P105219: view genomic region (about GC identifiers)

Start:	105,219,437 bp from pter	End:	105,234,831 bp from pter
Size:	15,395 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: SIVA_HUMAN, O15304 (See protein sequence)

Recommended Name: Apoptosis regulatory protein Siva

Size: 175 amino acids; 18695 Da

Cofactor: Isoform 1 binds 3 zinc ions. Isoform 2 binds 2 zinc ions

Subunit: Binds through its N-terminal region to the C-terminus of CD27 and to PXMP2/PMP22. Binds to the C-terminus of

TNFRSF18/GITR. Isoform 1 binds to BCL2L1/BCLX isoform Bcl-x(L) but not to BAX. Binds to capsid protein VP2 from

coxsackievirus B3. Binding of SIVA1 to CD27 can be blocked by VP2

Subcellular location: Cytoplasm. Nucleus. Note=In the nucleus, accumulates in dot-like structures

Sequence caution: Sequence=AAC51372.1; Type=Erroneous initiation; Sequence=AAD50057.1; Type=Erroneous initiation;

Secondary accessions: Q96P98 Q9UPD6

Alternative splicing: 2 isoforms: O15304-1 O15304-2 (Mouse isoform 2 has been shown (PubMed:9177220) to have no pro-apoptotic activity. However, human isoform 2 has been shown to be capable of inducing apoptosis (PubMed:15034012))

Explore the universe of human proteins at neXtProt for SIVA1: NX_O15304

Post-translational modifications:

Phosphorylated by ABL2/ARG in response to oxidative stress¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_O15304

SIVA1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_006418.2 NP_068355.1

ENSEMBL proteins:

ENSP00000329213 ENSP00000329447 ENSP00000451570 ENSP00000451427 ENSP00000451823

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	Uscn Proteins for SIVA1

Gene Ontology (GO): 4 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IEA	--
GO:0005654	nucleoplasm	IDA	15034012
GO:0005737	cytoplasm	IEA	--
GO:0005739	mitochondrion	IDA	12011449

SIVA1 for ontologies About GeneDecksing

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	Uscn ELISAs and CLIAs for SIVA1

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

SIVA1 for domains About GeneDecksing

1 InterPro domain/family:

IPR022773 Siva_cd27-bd

Graphical View of Domain Structure for InterPro Entry O15304

ProtoNet protein and cluster: O15304

1 Blocks protein family: IPB008842 Cd27 binding

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: SIVA_HUMAN, O15304

Function: Induces CD27-mediated apoptosis. Inhibits BCL2L1 isoform Bcl-x(L) anti-apoptotic activity. Inhibits

activation of NF-kappa-B and promotes T-cell receptor-mediated apoptosis

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		hsa-miR-142-5p hsa-miR-19b hsa-miR-19a hsa-miR-340
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In Situ Assay
Products:

Search Advanced Cell Diagnostics for RNAscope RNA in situ hybridization assays for SIVA1

Gene Ontology (GO): 5/6 molecular function terms (GO ID links to tree view) (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001618	viral receptor activity	ISS	--
GO:0005175	CD27 receptor binding	IPI	16683188
GO:0005515	protein binding	IPI	16683188
GO:0008270	zinc ion binding	IDA	16683188
GO:0008656	cysteine-type endopeptidase activator activity involved in apoptotic process	IDA	15034012

SIVA1 for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for SIVA1:

Decreased Hepatitis C virus re

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Apoptosis and survival_Apoptotic TNF-family pathways

Apoptosis and survival_Apoptotic TNF-family pathways

1.00

Apoptosis and survival Apoptotic TNF-family pathways

1.00

Pathway sources
See GeneCards unified pathways
Show all pathways

1 EMD Millipore Pathway for SIVA1

Apoptosis and survival Apoptotic TNF-family pathways

1 GeneGo (Thomson Reuters) Pathway for SIVA1

Apoptosis and survival Apoptotic TNF-family pathways

SIVA1 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for SIVA1

STRING Interaction Network Preview (showing 5 interactants - click image to see 17)

5/23 Interacting proteins for SIVA1 (O15304^{1, 2, 3} ENSP00000329213⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 23)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
GCOM1	P0CAP1²^,³	MINT-65204 I2D: score=3
MYZAP	P0CAP1²^,³	MINT-65204 I2D: score=3
BCL2	P10415¹^,³, ENSP00000329623⁴	EBI-520756,EBI-77694 I2D: score=1 STRING: ENSP00000329623
PXMP2	Q9NR77¹^,³	EBI-520756,EBI-1392944 I2D: score=2
BCL2L1	Q07817¹^,³, ENSP00000302564⁴	EBI-520756,EBI-78035 I2D: score=3 STRING: ENSP00000302564

About this table

Gene Ontology (GO): 5/9 biological process terms (GO ID links to tree view) (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006915	apoptotic process	IEA	--
GO:0006917	NOT induction of apoptosis	IDA	12011449
GO:0006924	activation-induced cell death of T cells	IDA	16491128
GO:0008635	activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c	IDA	15034012
GO:0009615	response to virus	ISS	--

SIVA1 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for SIVA1
UniProtKB/Swiss-Prot: SIVA_HUMAN, O15304

Pharmaceutical: Could be used as a potentiator of cisplatin-based chemotherapy. Enhances cisplatin-mediated apoptosis,

even under conditions where cisplatin resistance occurs due to elevated levels of BCL2 or BCL2L1

Search CenterWatch for drugs/clinical trials and news about SIVA1 / SIVA

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for SIVA1 gene (2 alternative transcripts):

NM_006427.3 NM_021709.2

Unigene Cluster for SIVA1:

SIVA1, apoptosis-inducing factor

Hs.112058 [show with all ESTs]

Unigene Representative Sequence: AK128704

8 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000329967(uc001yph.3 uc001ypi.3) ENST00000535554(uc010tyj.1)

ENST00000347067 ENST00000553810 ENST00000553819 ENST00000554013 ENST00000556431(uc001ypg.1)

ENST00000556195

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		hsa-miR-142-5p hsa-miR-19b hsa-miR-19a hsa-miR-340
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Additional cDNA sequence:

AF033111.1 AF401214.1 AK095949.1 AK124078.1 AK128704.1 AK223332.1 AK300415.1 AK316457.1

AK316550.1 BC034562.1

8 DOTS entries:

DT.217007 DT.101956883 DT.100792266 DT.101969811 DT.40121780 DT.40284918 DT.95279965 DT.95140185

24/268 AceView cDNA sequences (see all 268):

AI802676 BU845323 BQ433694 BQ778150 F26136 BM919839 AI560326 NM_006427

AA953323 AA029204 BQ013489 CD370667 BM043890 BF037110 BU162880 BG683095

CR593834 AW025365 AA628332 NM_021709 CA432072 BM310878 AA938516 BE792641

GeneLoc Exon Structure

4 Alternative Splicing Database (ASD) splice patterns (SP) for SIVA1 About this scheme

ExUns:	1a	·	1b	^	2	^	3	^	4	^	5	^	6a	·	6b
SP1:					-						-
SP2:					-
SP3:					-		-				-
SP4:

ECgene alternative splicing isoforms for SIVA1

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

SIVA1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TTCTATTTTG

About this image
See SIVA1 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for SIVA1

SOURCE GeneReport for Unigene cluster: Hs.112058

UniProtKB/Swiss-Prot: SIVA_HUMAN, O15304

Tissue specificity: Ubiquitous. Mostly expressed in thymus, testis, ovary, prostate, small intestine and spleen and

less in colon

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In Situ
Assay Products:

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for SIVA1 gene from 5/12 species (see all 12) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Siva1^{1 , 5}	SIVA1, apoptosis-inducing factor^{1, 5}	73.95(n)¹ 71.26(a)¹		12 (61.20 cM)⁵ 30954¹ NM_013929.2¹ NP_038957.2¹ 112644828⁵
chicken (Gallus gallus)	Aves	SIVA1¹	SIVA1, apoptosis-inducing factor	58.87(n) 52.05(a)		423493 XM_421397.3 XP_421397.2
lizard (Anolis carolinensis)	Reptilia	SIVA1⁶	--	47(a)	1 ↔ 1	1(3687148-3687661)
zebrafish (Danio rerio)	Actinopterygii	siva1¹	SIVA1, apoptosis-inducing factor	53.09(n) 43.83(a)		571845 XM_695476.5 XP_700568.5
honey bee (Apis mellifera)	Insecta	--	--	28(a)	1 ↔ 1	GroupUn.120(33944-34773)

ENSEMBL Gene Tree for SIVA1 (if available)
TreeFam Gene Tree for SIVA1 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 14 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs8011620^1,2	C,F,	--	85414903(+)	`ggggcC/Tgcgca`	2	--	us2k¹		1		WA	118
rs8012284^1,2	C,	--	85415098(+)	`cggtgG/Actccg`	2	--	us2k¹		2		WA	120
rs10134390^1,2	C,	--	85415172(+)	`agcccA/Gggttc`	2	--	us2k¹		0	--	--	--	--
rs8006932^1,2	C,A,	--	85415517(+)	`ACAGCA/GGCGCA`	2	--	us2k¹		0	--	--	--	--
rs59165659^1,2		--	85416168(+)	`CGCTTA/CGCGCC`	2	--	us2k¹		0	--	--	--	--
rs60829853^1,2	C,	--	85416298(+)	`TCGAGT/ACCAGT`	2	--	us2k¹		2		WA	120
rs61493636^1,2	F,	--	85416391(+)	`GCCCGC/TAGCCT`	2	--	us2k¹		1		WA	118
rs58368728^1,2	C,	--	85416932(+)	`TCGCCT/GCCCTG`	2	--	int¹		2		WA	120
rs78475567^1,2	F,	--	85417066(+)	`GTATTC/TATGGA`	2	--	int¹		1		NA	120
rs73362584^1,2	C,	--	85417274(+)	`TGAGCG/AGAATC`	2	--	int¹		2		WA	120

HapMap Linkage Disequilibrium report for SIVA1 (105219437 - 105234831 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 5 variations for SIVA1
5 CNVs: 29963 49291 29962 29964 59556

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing SIVA1

DNA2.0 Custom Variant and Variant Library Synthesis for SIVA1

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

SIVA1 for disorders           About GeneDecksing

OMIM gene information: 605567    OMIM disorders: --

8 diseases for SIVA1:    About MalaCards

familial mediterranean fever typhoid fever gastroenteritis influenza

breast cancer ischemia prostatitis neuronitis

Export disorders for SIVA1 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for SIVA1 gene, integrated from 9 sources (see all 47):
(articles sorted by number of sources associating them with SIVA1)

Utopia: connect your pdf to the dynamic
world of online information

CD27, a member of the tumor necrosis factor receptor family, induces apoptosis and binds to Siva, a proapoptotic protein. (PubMed id 9177220)^{1, 2, 3} Prasad K.V.S....Schlossman S.F. (1997)
The apoptotic capability of coxsackievirus B3 is influenced by the efficient interaction between the capsid protein VP2 and the proapoptotic host protein Siva. (PubMed id 11601913)^{1, 2, 9} Henke A.... Munder T. (2001)
Siva-1 and an alternative splice form lacking the death domain, Siva- 2, similarly induce apoptosis in T lymphocytes via a caspase-dependent mitochondrial pathway. (PubMed id 15034012)^{1, 2, 9} Py B.... Benichou S. (2004)
Apoptosis in coxsackievirus B3-caused diseases: interaction between the capsid protein VP2 and the proapoptotic protein siva. (PubMed id 10756043)^{1, 2, 9} Henke A.... Munder T. (2000)
The zinc containing pro-apoptotic protein siva interacts with the peroxisomal membrane protein pmp22. (PubMed id 16683188)^{1, 2} Nestler M....Munder T. (2006)
Siva-1 negatively regulates NF-kappaB activity: effect on T-cell receptor-mediated activation-induced cell death (AICD). (PubMed id 16491128)^{1, 2} Gudi R.... Prasad K.V.S. (2006)
Expression of Siva-1 protein or its putative amphipathic helical region enhances cisplatin-induced apoptosis in breast cancer cells: effect of elevated levels of BCL-2. (PubMed id 15958577)^{1, 2} Chu F.... Kanteti P.V.S. (2005)
The Siva-1 putative amphipathic helical region (SAH) is sufficient to bind to BCL-XL and sensitize cells to UV radiation induced apoptosis. (PubMed id 14739602)^{1, 2} Chu F....Prasad K.V.S. (2004)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S....Malek J. (2004)
Siva-1 binds to and inhibits BCL-X(L)-mediated protection against UV radiation-induced apoptosis. (PubMed id 12011449)^{1, 2} Xue L.... Prasad K.V.S. (2002)

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Entrez Gene: 10572	HGNC: 17712	AceView: SIVA	Ensembl:ENSG00000184990	euGenes: HUgn10572
ECgene: SIVA1	H-InvDB: SIVA1

(According to HUGE)
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