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SIVA_MOUSE
ID   SIVA_MOUSE              Reviewed;         175 AA.
AC   O54926; Q3U6J2; Q921I8; Q9CWL1; Q9R1Q0; Q9R1Q1;
DT   23-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1998, sequence version 1.
DT   03-AUG-2022, entry version 148.
DE   RecName: Full=Apoptosis regulatory protein Siva;
DE   AltName: Full=CD27-binding protein;
DE            Short=CD27BP;
GN   Name=Siva1; Synonyms=Siva;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6J; TISSUE=Embryonic stem cell;
RX   PubMed=10597319; DOI=10.1038/sj.onc.1203144;
RA   Yoon Y., Ao Z., Cheng Y., Schlossman S.F., Prasad K.V.S.;
RT   "Murine Siva-1 and Siva-2, alternate splice forms of the mouse Siva gene,
RT   both bind to CD27 but differentially transduce apoptosis.";
RL   Oncogene 18:7174-7179(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Bone marrow, and Embryonic stem cell;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   FUNCTION.
RX   PubMed=9177220; DOI=10.1073/pnas.94.12.6346;
RA   Prasad K.V.S., Ao Z., Yoon Y., Wu M.X., Rizk M., Jacquot S.,
RA   Schlossman S.F.;
RT   "CD27, a member of the tumor necrosis factor receptor family, induces
RT   apoptosis and binds to Siva, a proapoptotic protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:6346-6351(1997).
RN   [5]
RP   INDUCTION.
RX   PubMed=10756043; DOI=10.1128/jvi.74.9.4284-4290.2000;
RA   Henke A., Launhardt H., Klement K., Stelzner A., Zell R., Munder T.;
RT   "Apoptosis in coxsackievirus B3-caused diseases: interaction between the
RT   capsid protein VP2 and the proapoptotic protein siva.";
RL   J. Virol. 74:4284-4290(2000).
RN   [6]
RP   INTERACTION WITH TNFRSF18.
RX   PubMed=12478477; DOI=10.1038/sj.cdd.4401140;
RA   Spinicelli S., Nocentini G., Ronchetti S., Krausz L.T., Bianchini R.,
RA   Riccardi C.;
RT   "GITR interacts with the pro-apoptotic protein Siva and induces
RT   apoptosis.";
RL   Cell Death Differ. 9:1382-1384(2002).
RN   [7]
RP   INDUCTION.
RX   PubMed=15105421; DOI=10.1074/jbc.m400376200;
RA   Fortin A., MacLaurin J.G., Arbour N., Cregan S.P., Kushwaha N.,
RA   Callaghan S.M., Park D.S., Albert P.R., Slack R.S.;
RT   "The proapoptotic gene SIVA is a direct transcriptional target for the
RT   tumor suppressors p53 and E2F1.";
RL   J. Biol. Chem. 279:28706-28714(2004).
CC   -!- FUNCTION: Induces CD27-mediated apoptosis. Inhibits BCL2L1 isoform Bcl-
CC       x(L) anti-apoptotic activity. Inhibits activation of NF-kappa-B and
CC       promotes T-cell receptor-mediated apoptosis (By similarity).
CC       {ECO:0000250, ECO:0000269|PubMed:9177220}.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Isoform 1 binds 3 zinc ions. Isoform 2 binds 2 zinc ions.
CC       {ECO:0000250};
CC   -!- SUBUNIT: Binds through its N-terminal region to the C-terminus of CD27
CC       and to PXMP2/PMP22. Binds to the C-terminus of TNFRSF18/GITR. Isoform 1
CC       binds to BCL2L1/BCLX isoform Bcl-x(L) but not to BAX.
CC       {ECO:0000269|PubMed:12478477}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000250}. Note=In the
CC       nucleus, accumulates in dot-like structures. {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=Siva-1;
CC         IsoId=O54926-1; Sequence=Displayed;
CC       Name=2; Synonyms=Siva-2;
CC         IsoId=O54926-2; Sequence=VSP_007526;
CC   -!- TISSUE SPECIFICITY: Highly expressed in testis, heart, liver, lung, and
CC       muscle, and less in kidney, spleen and brain.
CC   -!- INDUCTION: By p53, camptothecin, stroke injury and infection with
CC       coxsackievirus B3. This up-regulation is sufficient to induce apoptosis
CC       in neural tissue. {ECO:0000269|PubMed:10756043,
CC       ECO:0000269|PubMed:15105421}.
CC   -!- PTM: Phosphorylated by ABL2/ARG in response to oxidative stress.
CC       {ECO:0000250}.
CC   -!- MISCELLANEOUS: [Isoform 2]: Mouse isoform 2 has been shown to have no
CC       pro-apoptotic activity. {ECO:0000305|PubMed:9177220}.
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DR   EMBL; AF033115; AAC04706.1; -; Genomic_DNA.
DR   EMBL; AF033113; AAD50059.1; -; mRNA.
DR   EMBL; AF033112; AAD50058.1; -; mRNA.
DR   EMBL; AF033114; AAD50060.1; -; mRNA.
DR   EMBL; AK010562; BAB27029.1; -; mRNA.
DR   EMBL; AK017570; BAB30811.1; -; mRNA.
DR   EMBL; AK153115; BAE31732.1; -; mRNA.
DR   EMBL; BC012279; AAH12279.1; -; mRNA.
DR   CCDS; CCDS26193.1; -. [O54926-1]
DR   CCDS; CCDS49189.1; -. [O54926-2]
DR   RefSeq; NP_001155209.1; NM_001161737.1. [O54926-2]
DR   RefSeq; NP_038957.2; NM_013929.2. [O54926-1]
DR   AlphaFoldDB; O54926; -.
DR   BioGRID; 206030; 2.
DR   IntAct; O54926; 1.
DR   STRING; 10090.ENSMUSP00000021728; -.
DR   PhosphoSitePlus; O54926; -.
DR   EPD; O54926; -.
DR   MaxQB; O54926; -.
DR   PaxDb; O54926; -.
DR   PeptideAtlas; O54926; -.
DR   PRIDE; O54926; -.
DR   ProteomicsDB; 261241; -. [O54926-1]
DR   ProteomicsDB; 261242; -. [O54926-2]
DR   Antibodypedia; 28226; 324 antibodies from 28 providers.
DR   DNASU; 30954; -.
DR   Ensembl; ENSMUST00000021728; ENSMUSP00000021728; ENSMUSG00000064326. [O54926-1]
DR   Ensembl; ENSMUST00000109755; ENSMUSP00000105377; ENSMUSG00000064326. [O54926-2]
DR   GeneID; 30954; -.
DR   KEGG; mmu:30954; -.
DR   UCSC; uc007pev.2; mouse. [O54926-1]
DR   UCSC; uc007pew.2; mouse. [O54926-2]
DR   CTD; 10572; -.
DR   MGI; MGI:1353606; Siva1.
DR   VEuPathDB; HostDB:ENSMUSG00000064326; -.
DR   eggNOG; ENOG502S2B7; Eukaryota.
DR   GeneTree; ENSGT00390000004842; -.
DR   HOGENOM; CLU_127299_0_0_1; -.
DR   InParanoid; O54926; -.
DR   OMA; FRGAQAC; -.
DR   OrthoDB; 1386185at2759; -.
DR   PhylomeDB; O54926; -.
DR   TreeFam; TF332962; -.
DR   BioGRID-ORCS; 30954; 11 hits in 71 CRISPR screens.
DR   ChiTaRS; Siva1; mouse.
DR   PRO; PR:O54926; -.
DR   Proteomes; UP000000589; Chromosome 12.
DR   RNAct; O54926; protein.
DR   Bgee; ENSMUSG00000064326; Expressed in floor plate of midbrain and 252 other tissues.
DR   Genevisible; O54926; MM.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005175; F:CD27 receptor binding; IPI:HGNC-UCL.
DR   GO; GO:0005164; F:tumor necrosis factor receptor binding; IPI:HGNC-UCL.
DR   GO; GO:0001618; F:virus receptor activity; IDA:HGNC-UCL.
DR   GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR   GO; GO:0006924; P:activation-induced cell death of T cells; ISO:MGI.
DR   GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:MGI.
DR   GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR   GO; GO:1901030; P:positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; ISO:MGI.
DR   InterPro; IPR022773; Siva.
DR   PANTHER; PTHR14365; PTHR14365; 1.
DR   Pfam; PF05458; Siva; 1.
DR   PIRSF; PIRSF038096; Siva_cd27_bd; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Apoptosis; Cytoplasm; Metal-binding; Nucleus;
KW   Phosphoprotein; Reference proteome; Zinc.
FT   CHAIN           1..175
FT                   /note="Apoptosis regulatory protein Siva"
FT                   /id="PRO_0000097775"
FT   REGION          36..55
FT                   /note="Interaction with BCL2L1 isoform Bcl-x(L) and
FT                   inhibition of BCL2L1 anti-apoptotic activity"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         34
FT                   /note="Phosphotyrosine; by ABL2"
FT                   /evidence="ECO:0000250|UniProtKB:O15304"
FT   MOD_RES         70
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O15304"
FT   VAR_SEQ         40..104
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10597319"
FT                   /id="VSP_007526"
FT   CONFLICT        1..15
FT                   /note="MPKRSCPFADAAPLQ -> MAKGRWRLAEAGAVE (in Ref. 2;
FT                   BAB27029)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        126
FT                   /note="V -> A (in Ref. 3; AAH12279)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        142
FT                   /note="C -> S (in Ref. 1; AAD50060)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   175 AA;  18770 MW;  1E132C1580ABE3F2 CRC64;
     MPKRSCPFAD AAPLQLKVHV GLKELSHGVF AERYSREVFE RTKQLLFQGA RAYRDHISSE
     DCSVNHLQES LKSGVVGAPQ PARGQMLIGP DGRLTRCQAQ ASEGGLPRTA PIACSSCMRS
     VDGKAVCSQC ERALCGQCVY TCWGCGALAC VLCGLADYAD DGEKTLCTSC AMFEA
 
 
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