Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Apoptosis regulatory protein Siva

Gene

SIVA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.5 Publications

Cofactori (for Isoform 1)

Zn2+1 PublicationNote: Isoform 1 binds 3 Zn2+ ions.1 Publication

Cofactori (for Isoform 2)

Zn2+1 PublicationNote: Isoform 2 binds 2 Zn2+ ions.1 Publication

GO - Molecular functioni

  • CD27 receptor binding Source: HGNC
  • metal ion binding Source: UniProtKB-KW
  • virus receptor activity Source: HGNC
  • zinc ion binding Source: HGNC

GO - Biological processi

  • activation-induced cell death of T cells Source: HGNC
  • extrinsic apoptotic signaling pathway Source: BHF-UCL
  • intrinsic apoptotic signaling pathway Source: BHF-UCL
  • negative regulation of NF-kappaB transcription factor activity Source: HGNC
  • positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: BHF-UCL
  • viral entry into host cell Source: GOC
Complete GO annotation...

Keywords - Biological processi

Apoptosis, Host-virus interaction

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

SIGNORiO15304.

Names & Taxonomyi

Protein namesi
Recommended name:
Apoptosis regulatory protein Siva
Alternative name(s):
CD27-binding protein
Short name:
CD27BP
Gene namesi
Name:SIVA1
Synonyms:SIVA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:17712. SIVA1.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

  • Note: In the nucleus, accumulates in dot-like structures.

GO - Cellular componenti

  • cytoplasm Source: HGNC
  • mitochondrion Source: HGNC
  • nucleoplasm Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Pharmaceutical usei

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.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi34 – 341Y → F: Abolishes phosphorylation and apoptotic activity. 1 Publication
Mutagenesisi53 – 531Y → F: No effect on phosphorylation or apoptotic activity. 1 Publication

Organism-specific databases

PharmGKBiPA162403351.

Polymorphism and mutation databases

BioMutaiSIVA1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 175175Apoptosis regulatory protein SivaPRO_0000097774Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei34 – 341Phosphotyrosine; by ABL21 Publication
Modified residuei70 – 701PhosphoserineCombined sources

Post-translational modificationi

Phosphorylated by ABL2/ARG in response to oxidative stress.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO15304.
PaxDbiO15304.
PRIDEiO15304.

PTM databases

iPTMnetiO15304.
PhosphoSiteiO15304.

Expressioni

Tissue specificityi

Ubiquitous. Mostly expressed in thymus, testis, ovary, prostate, small intestine and spleen and less in colon.

Gene expression databases

BgeeiO15304.
CleanExiHS_SIVA1.
ExpressionAtlasiO15304. baseline and differential.
GenevisibleiO15304. HS.

Interactioni

Subunit structurei

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 VP2.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BCL2P104152EBI-520756,EBI-77694
BCL2L1Q078172EBI-520756,EBI-78035
BCL2L1Q07817-15EBI-520766,EBI-287195
CD27P268423EBI-520756,EBI-520729
E7P031294EBI-520756,EBI-866453From a different organism.
PXMP2Q9NR773EBI-520756,EBI-1392944

GO - Molecular functioni

  • CD27 receptor binding Source: HGNC

Protein-protein interaction databases

BioGridi115823. 27 interactions.
IntActiO15304. 10 interactions.
MINTiMINT-237554.
STRINGi9606.ENSP00000329213.

Structurei

3D structure databases

ProteinModelPortaliO15304.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni36 – 5520Interaction with BCL2L1 isoform Bcl-x(L) and inhibition of BCL2L1 anti-apoptotic activityAdd
BLAST
Regioni105 – 12319Interaction with coxsackievirus B3 VP2Add
BLAST

Phylogenomic databases

eggNOGiENOG410IZ95. Eukaryota.
ENOG4112463. LUCA.
GeneTreeiENSGT00390000004842.
HOGENOMiHOG000253914.
HOVERGENiHBG044526.
InParanoidiO15304.
OMAiRALCGQC.
PhylomeDBiO15304.
TreeFamiTF332962.

Family and domain databases

InterProiIPR022773. Siva_cd27-bd.
[Graphical view]
PANTHERiPTHR14365. PTHR14365. 1 hit.
PfamiPF05458. Siva. 1 hit.
[Graphical view]
PIRSFiPIRSF038096. Siva_cd27_bd. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O15304-1) [UniParc]FASTAAdd to basket

Also known as: Siva-1

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.

« Hide

        10         20         30         40         50
MPKRSCPFAD VAPLQLKVRV SQRELSRGVC AERYSQEVFE KTKRLLFLGA
60 70 80 90 100
QAYLDHVWDE GCAVVHLPES PKPGPTGAPR AARGQMLIGP DGRLIRSLGQ
110 120 130 140 150
ASEADPSGVA SIACSSCVRA VDGKAVCGQC ERALCGQCVR TCWGCGSVAC
160 170
TLCGLVDCSD MYEKVLCTSC AMFET
Length:175
Mass (Da):18,695
Last modified:May 23, 2003 - v2
Checksum:iDB62B7DF4E6B39B3
GO
Isoform 2 (identifier: O15304-2) [UniParc]FASTAAdd to basket

Also known as: Siva-2

The sequence of this isoform differs from the canonical sequence as follows:
     40-104: Missing.

Note: 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).2 Publications
Show »
Length:110
Mass (Da):11,778
Checksum:i6A802C0D5B5CE41E
GO

Sequence cautioni

The sequence AAC51372.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence AAD50057.1 differs from that shown. Reason: Erroneous initiation. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei40 – 10465Missing in isoform 2. 2 PublicationsVSP_007525Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82938 mRNA. Translation: AAC51372.1. Different initiation.
AF033111 mRNA. Translation: AAD50057.1. Different initiation.
BC034562 mRNA. Translation: AAH34562.1.
AF401214 mRNA. Translation: AAL02171.1.
BK000018 Genomic DNA. Translation: DAA01049.1.
CCDSiCCDS9992.1. [O15304-1]
CCDS9993.1. [O15304-2]
RefSeqiNP_006418.2. NM_006427.3. [O15304-1]
NP_068355.1. NM_021709.2. [O15304-2]
UniGeneiHs.112058.

Genome annotation databases

EnsembliENST00000329967; ENSP00000329213; ENSG00000184990. [O15304-1]
ENST00000347067; ENSP00000329447; ENSG00000184990. [O15304-2]
GeneIDi10572.
KEGGihsa:10572.
UCSCiuc001yph.4. human. [O15304-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82938 mRNA. Translation: AAC51372.1. Different initiation.
AF033111 mRNA. Translation: AAD50057.1. Different initiation.
BC034562 mRNA. Translation: AAH34562.1.
AF401214 mRNA. Translation: AAL02171.1.
BK000018 Genomic DNA. Translation: DAA01049.1.
CCDSiCCDS9992.1. [O15304-1]
CCDS9993.1. [O15304-2]
RefSeqiNP_006418.2. NM_006427.3. [O15304-1]
NP_068355.1. NM_021709.2. [O15304-2]
UniGeneiHs.112058.

3D structure databases

ProteinModelPortaliO15304.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115823. 27 interactions.
IntActiO15304. 10 interactions.
MINTiMINT-237554.
STRINGi9606.ENSP00000329213.

PTM databases

iPTMnetiO15304.
PhosphoSiteiO15304.

Polymorphism and mutation databases

BioMutaiSIVA1.

Proteomic databases

MaxQBiO15304.
PaxDbiO15304.
PRIDEiO15304.

Protocols and materials databases

DNASUi10572.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000329967; ENSP00000329213; ENSG00000184990. [O15304-1]
ENST00000347067; ENSP00000329447; ENSG00000184990. [O15304-2]
GeneIDi10572.
KEGGihsa:10572.
UCSCiuc001yph.4. human. [O15304-1]

Organism-specific databases

CTDi10572.
GeneCardsiSIVA1.
HGNCiHGNC:17712. SIVA1.
MIMi605567. gene.
neXtProtiNX_O15304.
PharmGKBiPA162403351.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IZ95. Eukaryota.
ENOG4112463. LUCA.
GeneTreeiENSGT00390000004842.
HOGENOMiHOG000253914.
HOVERGENiHBG044526.
InParanoidiO15304.
OMAiRALCGQC.
PhylomeDBiO15304.
TreeFamiTF332962.

Enzyme and pathway databases

SIGNORiO15304.

Miscellaneous databases

ChiTaRSiSIVA1. human.
GeneWikiiSIVA1.
GenomeRNAii10572.
PROiO15304.
SOURCEiSearch...

Gene expression databases

BgeeiO15304.
CleanExiHS_SIVA1.
ExpressionAtlasiO15304. baseline and differential.
GenevisibleiO15304. HS.

Family and domain databases

InterProiIPR022773. Siva_cd27-bd.
[Graphical view]
PANTHERiPTHR14365. PTHR14365. 1 hit.
PfamiPF05458. Siva. 1 hit.
[Graphical view]
PIRSFiPIRSF038096. Siva_cd27_bd. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "CD27, a member of the tumor necrosis factor receptor family, induces apoptosis and binds to Siva, a proapoptotic protein."
    Prasad K.V.S., Ao Z., Yoon Y., Wu M.X., Rizk M., Jacquot S., Schlossman S.F.
    Proc. Natl. Acad. Sci. U.S.A. 94:6346-6351(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH CD27.
    Tissue: Cervix carcinoma and Thymus.
  2. "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 2).
    Tissue: Ovary.
  3. "Characterization of TPA-responsive genes in U937 cells using ordered differential display PCR."
    Kang H.S., Park Y.J., Jung H.M., Jun D.Y., Huh T.L., Kim Y.H.
    Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 164-175.
    Tissue: Monocytic leukemia.
  4. "Apoptosis in coxsackievirus B3-caused diseases: interaction between the capsid protein VP2 and the proapoptotic protein siva."
    Henke A., Launhardt H., Klement K., Stelzner A., Zell R., Munder T.
    J. Virol. 74:4284-4290(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH COXSACKIEVIRUS B3 VP2.
  5. "The ARG tyrosine kinase interacts with Siva-1 in the apoptotic response to oxidative stress."
    Cao C., Ren X., Kharbanda S., Koleske A., Prasad K.V.S., Kufe D.
    J. Biol. Chem. 276:11465-11468(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-34, MUTAGENESIS OF TYR-34 AND TYR-53.
  6. "The apoptotic capability of coxsackievirus B3 is influenced by the efficient interaction between the capsid protein VP2 and the proapoptotic host protein Siva."
    Henke A., Nestler M., Strunze S., Saluz H.-P., Hortschansky P., Menzel B., Martin U., Zell R., Stelzner A., Munder T.
    Virology 289:15-22(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH COXSACKIEVIRUS B3 VP2.
  7. "Siva-1 binds to and inhibits BCL-X(L)-mediated protection against UV radiation-induced apoptosis."
    Xue L., Chu F., Cheng Y., Sun X., Borthakur A., Ramarao M., Pandey P., Wu M., Schlossman S.F., Prasad K.V.S.
    Proc. Natl. Acad. Sci. U.S.A. 99:6925-6930(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH BCL2L1.
  8. "The Siva-1 putative amphipathic helical region (SAH) is sufficient to bind to BCL-XL and sensitize cells to UV radiation induced apoptosis."
    Chu F., Borthakur A., Sun X., Barkinge J., Gudi R., Hawkins S., Prasad K.V.S.
    Apoptosis 9:83-95(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH BCL2L1.
  9. "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."
    Py B., Slomianny C., Auberger P., Petit P.X., Benichou S.
    J. Immunol. 172:4008-4017(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  10. "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."
    Chu F., Barkinge J., Hawkins S., Gudi R., Salgia R., Kanteti P.V.S.
    Cancer Res. 65:5301-5309(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, POSSIBLE PHARMACEUTICAL USE.
  11. "The zinc containing pro-apoptotic protein siva interacts with the peroxisomal membrane protein pmp22."
    Nestler M., Martin U., Hortschansky P., Saluz H.-P., Henke A., Munder T.
    Mol. Cell. Biochem. 287:147-155(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: ZINC-BINDING, INTERACTION WITH CD27 AND PXMP2.
  12. "Siva-1 negatively regulates NF-kappaB activity: effect on T-cell receptor-mediated activation-induced cell death (AICD)."
    Gudi R., Barkinge J., Hawkins S., Chu F., Manicassamy S., Sun Z., Duke-Cohan J.S., Prasad K.V.S.
    Oncogene 25:3458-3462(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiSIVA_HUMAN
AccessioniPrimary (citable) accession number: O15304
Secondary accession number(s): Q96P98, Q9UPD6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 23, 2003
Last sequence update: May 23, 2003
Last modified: June 8, 2016
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Pharmaceutical, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.