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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
Complete GO annotation...

Keywords - Biological processi

Apoptosis, Host-virus interaction

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:G66-32367-MONOMER.
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)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

MaxQBiO15304.
PaxDbiO15304.
PeptideAtlasiO15304.
PRIDEiO15304.

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.
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. 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. 28 interactors.
IntActiO15304. 11 interactors.
MINTiMINT-237554.
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.
OMAiRALCGQC.
OrthoDBiEOG091G163Z.
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 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

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.
IntActiO15304. 11 interactors.
MINTiMINT-237554.
STRINGi9606.ENSP00000329213.

PTM databases

iPTMnetiO15304.
PhosphoSitePlusiO15304.

Polymorphism and mutation databases

BioMutaiSIVA1.

Proteomic databases

MaxQBiO15304.
PaxDbiO15304.
PeptideAtlasiO15304.
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.
DisGeNETi10572.
GeneCardsiSIVA1.
HGNCiHGNC:17712. SIVA1.
HPAiHPA065398.
HPA066693.
MIMi605567. gene.
neXtProtiNX_O15304.
OpenTargetsiENSG00000184990.
PharmGKBiPA162403351.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IZ95. Eukaryota.
ENOG4112463. LUCA.
GeneTreeiENSGT00390000004842.
HOGENOMiHOG000253914.
HOVERGENiHBG044526.
InParanoidiO15304.
OMAiRALCGQC.
OrthoDBiEOG091G163Z.
PhylomeDBiO15304.
TreeFamiTF332962.

Enzyme and pathway databases

BioCyciZFISH:G66-32367-MONOMER.
SIGNORiO15304.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000184990.
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...

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: November 30, 2016
This is version 141 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.