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    SIVA1 SIVA1 apoptosis inducing factor [ Homo sapiens (human) ]

    Gene ID: 10572, updated on 2-Nov-2024

    Summary

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    Official Symbol
    SIVA1provided by HGNC
    Official Full Name
    SIVA1 apoptosis inducing factorprovided by HGNC
    Primary source
    HGNC:HGNC:17712
    See related
    Ensembl:ENSG00000184990 MIM:605567; AllianceGenome:HGNC:17712
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SIVA; CD27BP; Siva-1; Siva-2
    Summary
    This gene encodes an E3 ubiquitin ligase that regulates cell cycle progression, cell proliferation and apoptosis. The N-terminus of this protein binds to the cytoplasmic tail of the CD27 antigen, a member of the tumor necrosis factor receptor (TNFR) superfamily. In response to UV radiation-induced DNA damage, this protein has been shown to mediate the ubiquitination of proliferating cell nuclear antigen (PCNA), an important step in translesion DNA synthesis. [provided by RefSeq, Sep 2018]
    Expression
    Ubiquitous expression in bone marrow (RPKM 15.7), fat (RPKM 10.9) and 25 other tissues See more
    Orthologs
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    Genomic context

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    See SIVA1 in Genome Data Viewer
    Location:
    14q32.33
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (104753147..104759654)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (98996033..99002540)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (105219484..105225991)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene adenylosuccinate synthase 1 Neighboring gene uncharacterized LOC124903396 Neighboring gene uncharacterized LOC107984670 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:105209535-105210340 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:105212701-105213200 Neighboring gene uncharacterized LOC107987209 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9121 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6196 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:105219303-105219804 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:105225732-105226680 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:105226681-105227627 Neighboring gene uncharacterized LOC102723342 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:105233884-105234434 Neighboring gene Sharpr-MPRA regulatory region 15301 Neighboring gene AKT serine/threonine kinase 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:105257987-105258628 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:105259269-105259910 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:105259911-105260550 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:105260551-105261192 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6197 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6198 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6199 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:105263234-105264006 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:105264007-105264779 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6200 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6201 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6202 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:105270463-105270962 Neighboring gene zinc finger and BTB domain containing 42

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Mutation of SIVA, a candidate metastasis gene identified from clonally related bilateral breast cancers, promotes breast cancer cell spread in vitro and in vivo. Vermehren-Schmaedick A, et al. PLoS One, 2024. PMID 38722955, Free PMC Article
    2. Requirement for Siva-1 for replication of influenza A virus through apoptosis induction. Shiozaki T, et al. J Gen Virol, 2011 Feb. PMID 21048035
    3. Siva‑1 regulates multidrug resistance of gastric cancer by targeting MDR1 and MRP1 via the NF‑κB pathway. Kong FB, et al. Mol Med Rep, 2020 Aug. PMID 32626967, Free PMC Article
    4. The role of the pro-apoptotic protein Siva in the pathogenesis of Familial Mediterranean fever: A structural and functional analysis. Goulielmos GN, et al. Biochem Biophys Res Commun, 2010 Nov 5. PMID 20934406
    5. PM2.5 exposure induces alveolar epithelial cell apoptosis and causes emphysema through p53/Siva-1. Xu F, et al. Eur Rev Med Pharmacol Sci, 2020 Apr. PMID 32329870

    See all (61) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Mutation of SIVA, a candidate metastasis gene identified from clonally related bilateral breast cancers, promotes breast cancer cell spread in vitro and in vivo.
      Title: Mutation of SIVA, a candidate metastasis gene identified from clonally related bilateral breast cancers, promotes breast cancer cell spread in vitro and in vivo.
    2. Inhibition of apoptosis-regulatory protein Siva-1 reverses multidrug resistance in gastric cancer by targeting PCBP1.
      Title: Inhibition of apoptosis-regulatory protein Siva-1 reverses multidrug resistance in gastric cancer by targeting PCBP1.
    3. N6-methyladenosine demethylase FTO enhances chemo-resistance in colorectal cancer through SIVA1-mediated apoptosis.
      Title: N6-methyladenosine demethylase FTO enhances chemo-resistance in colorectal cancer through SIVA1-mediated apoptosis.
    4. Siva1 regulates multidrug resistance of gastric cancer by targeting MDR1 and MRP1 via the NFkappaB pathway.
      Title: Siva‑1 regulates multidrug resistance of gastric cancer by targeting MDR1 and MRP1 via the NF‑κB pathway.
    5. PM2.5 exposure induces alveolar epithelial cell apoptosis and causes emphysema through p53/Siva-1.
      Title: PM2.5 exposure induces alveolar epithelial cell apoptosis and causes emphysema through p53/Siva-1.
    6. SIVA1 enhances SSBP3 ubiquitination and promotes SSBP3 protein turnover
      Title: [SIVA1 Regulates the Stability of Single-Stranded DNA-Binding Protein 3 Isoforms].
    7. Loss of SIVA1 expression is associated with nasopharyngeal carcinoma.
      Title: Anticancer activity of recombinant Siva1 protein in human nasopharyngeal carcinoma cell line CNE-2.
    8. These findings collectively reveal a novel role for the p53 target gene SIVA both in regulating metabolism and in enabling tumorigenesis, independently of p53.
      Title: The p53 Target Gene SIVA Enables Non-Small Cell Lung Cancer Development.
    9. Functional test demonstrated that Siva1 significantly inhibited the invasion and migration of HCT116 cells.
      Title: Preliminary research on the expression, purification and function of the apoptotic fusion protein, Sival.
    10. electrical stimulation -inducible SIVA1 modulates p53 activities in proliferating keratinocytes, and exogenous electrical stimulation affects p53/HDM2/SIVA1 axis leading to increased proliferation during re-epithelialization
      Title: Electrical stimulation enhances epidermal proliferation in human cutaneous wounds by modulating p53-SIVA1 interaction.
    Submit: New GeneRIF Correction See all GeneRIFs (29)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of SIVA1, apoptosis-inducing factor (SIVA1) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9 PubMed
    Envelope transmembrane glycoprotein gp41 env Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9 PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables CD27 receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables CD27 receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables tumor necrosis factor receptor binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables virus receptor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in activation-induced cell death of T cells IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in extrinsic apoptotic signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in extrinsic apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT involved_in intrinsic apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in intrinsic apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in symbiont entry into host cell IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    apoptosis regulatory protein Siva
    Names
    CD27-binding (Siva) protein

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029449.1 RefSeqGene

      Range
      5015..11522
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_006427.4 → NP_006418.2  apoptosis regulatory protein Siva isoform 1

      See identical proteins and their annotated locations for NP_006418.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) is the predominant and longer transcript. It encodes isoform 1 and includes the apoptotic properties of Siva.
      Source sequence(s)
      BC034562, BU195069, CK001877
      Consensus CDS
      CCDS9992.1
      UniProtKB/Swiss-Prot
      O15304, Q96P98, Q9UPD6
      UniProtKB/TrEMBL
      Q53FF7
      Related
      ENSP00000329213.6, ENST00000329967.11
      Conserved Domains (1) summary
      pfam05458
      Location:1 → 175
      Siva; Cd27 binding protein (Siva)

    2. NM_021709.3 → NP_068355.1  apoptosis regulatory protein Siva isoform 2

      See identical proteins and their annotated locations for NP_068355.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame segment, compared to variant 1. It appears to lack the apoptotic properties of Siva. The resulting protein (isoform 2) is shorter when it is compared to isoform 1.
      Source sequence(s)
      BC034562, BU195069
      Consensus CDS
      CCDS9993.1
      UniProtKB/Swiss-Prot
      O15304
      Related
      ENSP00000329447.6, ENST00000347067.9
      Conserved Domains (1) summary
      pfam05458
      Location:1 → 110
      Siva; Cd27 binding protein (Siva)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      104753147..104759654
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011536360.3 → XP_011534662.1  apoptosis regulatory protein Siva isoform X1

      See identical proteins and their annotated locations for XP_011534662.1

      UniProtKB/TrEMBL
      B4DTY2
      Related
      ENSP00000485991.1, ENST00000535554.4
      Conserved Domains (1) summary
      pfam05458
      Location:1 → 157
      Siva; Cd27 binding protein (Siva)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      98996033..99002540
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054375275.1 → XP_054231250.1  apoptosis regulatory protein Siva isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O15304.2 GenPept UniProtKB/Swiss-Prot:O15304

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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