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Protein

Apoptosis regulatory protein Siva

Gene

SIVA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • tumor necrosis factor receptor binding Source: Ensembl
  • virus receptor activity Source: HGNC
  • zinc ion binding Source: HGNC

GO - Biological processi

Keywordsi

Biological processApoptosis, Host-virus interaction
LigandMetal-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

EuPathDBiHostDB:ENSG00000184990.12
HGNCiHGNC:17712 SIVA1
MIMi605567 gene
neXtProtiNX_O15304

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Mutagenesisi34Y → F: Abolishes phosphorylation and apoptotic activity. 1 Publication1
Mutagenesisi53Y → F: No effect on phosphorylation or apoptotic activity. 1 Publication1

Organism-specific databases

DisGeNETi10572
OpenTargetsiENSG00000184990
PharmGKBiPA162403351

Polymorphism and mutation databases

BioMutaiSIVA1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000977741 – 175Apoptosis regulatory protein SivaAdd BLAST175

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei34Phosphotyrosine; by ABL21 Publication1
Modified residuei70PhosphoserineCombined sources1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO15304
MaxQBiO15304
PaxDbiO15304
PeptideAtlasiO15304
PRIDEiO15304
ProteomicsDBi48572
48573 [O15304-2]

PTM databases

iPTMnetiO15304
PhosphoSitePlusiO15304

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000184990 Expressed in 218 organ(s), highest expression level in tibial artery
CleanExiHS_SIVA1
ExpressionAtlasiO15304 baseline and differential
GenevisibleiO15304 HS

Organism-specific databases

HPAiHPA065398
HPA066693

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.6 Publications
(Microbial infection) Interacts with coxsackievirus B3 capsid protein VP2; this interaction inhibits the binding of SIVA1 to CD27.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115823, 28 interactors
CORUMiO15304
IntActiO15304, 21 interactors
MINTiO15304
STRINGi9606.ENSP00000329213

Structurei

3D structure databases

ProteinModelPortaliO15304
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni36 – 55Interaction with BCL2L1 isoform Bcl-x(L) and inhibition of BCL2L1 anti-apoptotic activityAdd BLAST20
Regioni105 – 123Interaction with coxsackievirus B3 VP2Add BLAST19

Phylogenomic databases

eggNOGiENOG410IZ95 Eukaryota
ENOG4112463 LUCA
GeneTreeiENSGT00390000004842
HOGENOMiHOG000253914
HOVERGENiHBG044526
InParanoidiO15304
KOiK22744
OMAiFRGAQAC
OrthoDBiEOG091G163Z
PhylomeDBiO15304
TreeFamiTF332962

Family and domain databases

InterProiView protein in InterPro
IPR022773 Siva_cd27-bd
PANTHERiPTHR14365 PTHR14365, 1 hit
PfamiView protein in Pfam
PF05458 Siva, 1 hit
PIRSFiPIRSF038096 Siva_cd27_bd, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YJN1H0YJN1_HUMAN
Apoptosis regulatory protein Siva
SIVA1
90Annotation score:
G3V439G3V439_HUMAN
Apoptosis regulatory protein Siva
SIVA1
169Annotation score:
B4DTY2B4DTY2_HUMAN
cDNA, FLJ79449, highly similar to A...
SIVA1
157Annotation score:
G3V3U1G3V3U1_HUMAN
Apoptosis regulatory protein Siva
SIVA1
169Annotation score:

Sequence cautioni

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

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00752540 – 104Missing in isoform 2. 2 PublicationsAdd BLAST65

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

Similar proteinsi

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, 28 interactors
CORUMiO15304
IntActiO15304, 21 interactors
MINTiO15304
STRINGi9606.ENSP00000329213

PTM databases

iPTMnetiO15304
PhosphoSitePlusiO15304

Polymorphism and mutation databases

BioMutaiSIVA1

Proteomic databases

EPDiO15304
MaxQBiO15304
PaxDbiO15304
PeptideAtlasiO15304
PRIDEiO15304
ProteomicsDBi48572
48573 [O15304-2]

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
DisGeNETi10572
EuPathDBiHostDB:ENSG00000184990.12
GeneCardsiSIVA1
HGNCiHGNC:17712 SIVA1
HPAiHPA065398
HPA066693
MIMi605567 gene
neXtProtiNX_O15304
OpenTargetsiENSG00000184990
PharmGKBiPA162403351
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IZ95 Eukaryota
ENOG4112463 LUCA
GeneTreeiENSGT00390000004842
HOGENOMiHOG000253914
HOVERGENiHBG044526
InParanoidiO15304
KOiK22744
OMAiFRGAQAC
OrthoDBiEOG091G163Z
PhylomeDBiO15304
TreeFamiTF332962

Enzyme and pathway databases

SIGNORiO15304

Miscellaneous databases

ChiTaRSiSIVA1 human
GeneWikiiSIVA1
GenomeRNAii10572
PROiPR:O15304
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000184990 Expressed in 218 organ(s), highest expression level in tibial artery
CleanExiHS_SIVA1
ExpressionAtlasiO15304 baseline and differential
GenevisibleiO15304 HS

Family and domain databases

InterProiView protein in InterPro
IPR022773 Siva_cd27-bd
PANTHERiPTHR14365 PTHR14365, 1 hit
PfamiView protein in Pfam
PF05458 Siva, 1 hit
PIRSFiPIRSF038096 Siva_cd27_bd, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSIVA_HUMAN
AccessioniPrimary (citable) accession number: O15304
Secondary accession number(s): Q96P98, Q9UPD6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 23, 2003
Last sequence update: May 23, 2003
Last modified: November 7, 2018
This is version 151 of the entry and version 2 of the sequence. See 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  2. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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