BIR7A_XENLA
ID BIR7A_XENLA Reviewed; 401 AA.
AC Q8JHV9; B7ZR06;
DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Baculoviral IAP repeat-containing protein 7-A;
DE EC=2.3.2.27 {ECO:0000269|PubMed:17008917};
DE AltName: Full=E3 ubiquitin-protein ligase EIAP-A;
DE AltName: Full=Embryonic/Egg IAP {ECO:0000303|PubMed:15853809};
DE Short=xEIAP/XLX {ECO:0000303|PubMed:15853809, ECO:0000303|PubMed:17425806};
DE AltName: Full=Inhibitor of apoptosis-like protein {ECO:0000303|PubMed:15853809};
DE Short=IAP-like protein {ECO:0000312|EMBL:AAM88215.1};
DE AltName: Full=RING-type E3 ubiquitin transferase EIAP-A {ECO:0000305};
DE AltName: Full=XIAP homolog XLX {ECO:0000303|PubMed:12021770};
DE Short=XLX {ECO:0000303|PubMed:12021770, ECO:0000303|PubMed:17008917};
GN Name=birc7-a;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN DEGRADATION.
RC TISSUE=Gastrula {ECO:0000269|PubMed:12021770};
RX PubMed=12021770; DOI=10.1038/ncb798;
RA Holley C.L., Olson M.R., Colon-Ramos D.A., Kornbluth S.;
RT "Reaper eliminates IAP proteins through stimulated IAP degradation and
RT generalized translational inhibition.";
RL Nat. Cell Biol. 4:439-444(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, RING FINGER
RP DOMAIN FUNCTION, AND PROTEIN DEGRADATION.
RC TISSUE=Oocyte {ECO:0000269|PubMed:15853809};
RX PubMed=15853809; DOI=10.1111/j.1742-4658.2005.04648.x;
RA Tsuchiya Y., Murai S., Yamashita S.;
RT "Apoptosis-inhibiting activities of BIR family proteins in Xenopus egg
RT extracts.";
RL FEBS J. 272:2237-2250(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Gastrula {ECO:0000312|EMBL:AAI69996.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PHOSPHORYLATION AT SER-235; SER-251 AND SER-254, AND MUTAGENESIS OF
RP SER-235; SER-251 AND SER-254.
RX PubMed=17425806; DOI=10.1186/1471-2091-8-5;
RA Tsuchiya Y., Yamashita S.;
RT "p42MAPK-mediated phosphorylation of xEIAP/XLX in Xenopus cytostatic
RT factor-arrested egg extracts.";
RL BMC Biochem. 8:5-5(2007).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, DEVELOPMENTAL STAGE, BIR DOMAIN,
RP AUTOUBIQUITINATION, PHOSPHORYLATION AT SER-231; SER-235; SER-247; SER-251
RP AND SER-254, AND MUTAGENESIS OF SER-231; SER-235; SER-247; SER-251 AND
RP SER-254.
RX PubMed=17008917; DOI=10.1038/sj.cdd.4402031;
RA Greenwood J., Gautier J.;
RT "XLX is an IAP family member regulated by phosphorylation during meiosis.";
RL Cell Death Differ. 14:559-567(2007).
CC -!- FUNCTION: Weak apoptotic suppressor. Has E3 ubiquitin-protein ligase
CC activity. Weak inhibitor of caspase activity.
CC {ECO:0000269|PubMed:15853809, ECO:0000269|PubMed:17008917}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:17008917};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P98170}.
CC -!- DEVELOPMENTAL STAGE: Expressed maternally in the unfertilized egg and
CC early embryo. In the embryo, expressed through cleavage stages (stage
CC 2-8), becoming nearly undetectable following gastrulation (stage 10.5).
CC {ECO:0000269|PubMed:15853809, ECO:0000269|PubMed:17008917}.
CC -!- DOMAIN: The BIR2 domain is required for caspase-inhibition.
CC {ECO:0000269|PubMed:17008917}.
CC -!- DOMAIN: The C-terminal region containing the RING finger domain is
CC required for the initial degradation step, and the final digestion of
CC cleavage fragments. {ECO:0000269|PubMed:15853809}.
CC -!- PTM: Auto-ubiquitinated, and degraded in a 2-step mechanism; a caspase-
CC independent first step and a caspase-dependent second step.
CC {ECO:0000269|PubMed:17008917}.
CC -!- PTM: Phosphorylated via MAPK-dependent and CDK-dependent pathways
CC during oocyte maturation. Phosphorylation does not appear to affect
CC caspase inhibition or autoubiquitination activity.
CC {ECO:0000269|PubMed:17008917, ECO:0000269|PubMed:17425806}.
CC -!- SIMILARITY: Belongs to the IAP family. {ECO:0000255}.
CC -!- CAUTION: PubMed:17425806 show that the phosphorylation state does not
CC affect protein stability, whereas PubMed:17008917 show that
CC phosphorylation may play a role in caspase-dependent cleavage.
CC {ECO:0000305}.
CC -!- CAUTION: Although originally named XLX for its homology to mammalian
CC XIAP, a more similar Xenopus XIAP homolog (xiap) has since been
CC identified. {ECO:0000305}.
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DR EMBL; AF468029; AAM88215.1; -; mRNA.
DR EMBL; AB197251; BAD98267.1; -; mRNA.
DR EMBL; BC169996; AAI69996.1; -; mRNA.
DR RefSeq; NP_001082290.1; NM_001088821.1.
DR AlphaFoldDB; Q8JHV9; -.
DR SMR; Q8JHV9; -.
DR BioGRID; 99719; 1.
DR iPTMnet; Q8JHV9; -.
DR GeneID; 398387; -.
DR KEGG; xla:398387; -.
DR CTD; 398387; -.
DR Xenbase; XB-GENE-5914085; birc7.S.
DR OrthoDB; 1340284at2759; -.
DR Proteomes; UP000186698; Chromosome 9_10S.
DR Bgee; 398387; Expressed in oocyte and 8 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR CDD; cd00022; BIR; 2.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001370; BIR_rpt.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF00653; BIR; 2.
DR SMART; SM00238; BIR; 2.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS01282; BIR_REPEAT_1; 2.
DR PROSITE; PS50143; BIR_REPEAT_2; 2.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cytoplasm; Developmental protein; Metal-binding; Phosphoprotein;
KW Protease inhibitor; Reference proteome; Repeat; Thiol protease inhibitor;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..401
FT /note="Baculoviral IAP repeat-containing protein 7-A"
FT /id="PRO_0000379959"
FT REPEAT 43..109
FT /note="BIR 1"
FT /evidence="ECO:0000255"
FT REPEAT 148..213
FT /note="BIR 2"
FT /evidence="ECO:0000255"
FT ZN_FING 354..389
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 110..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 219..269
FT /note="Self-inhibits the anti-apoptotic function"
FT /evidence="ECO:0000269|PubMed:15853809"
FT REGION 231..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 312..343
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 110..127
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O15392,
FT ECO:0000255|PROSITE-ProRule:PRU00029"
FT BINDING 185
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O15392,
FT ECO:0000255|PROSITE-ProRule:PRU00029"
FT BINDING 202
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O15392,
FT ECO:0000255|PROSITE-ProRule:PRU00029"
FT BINDING 209
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O15392,
FT ECO:0000255|PROSITE-ProRule:PRU00029"
FT MOD_RES 231
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17008917"
FT MOD_RES 235
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:17008917,
FT ECO:0000269|PubMed:17425806"
FT MOD_RES 247
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17008917"
FT MOD_RES 251
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:17008917,
FT ECO:0000269|PubMed:17425806"
FT MOD_RES 254
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:17008917,
FT ECO:0000269|PubMed:17425806"
FT MUTAGEN 231
FT /note="S->A: Abolishes phosphorylation, but no effect on
FT caspase inhibitory activity; when associated with A-235; A-
FT 247; A-251 and A-254."
FT /evidence="ECO:0000269|PubMed:17008917"
FT MUTAGEN 231
FT /note="S->D: No effect on caspase inhibitory activity or
FT auto-ubiquitination activity; when associated with D-235;
FT D-247; D-251 and D-254. No effect on protein stability or
FT anti-apoptotic activity; when associated with D-235 and D-
FT 251."
FT /evidence="ECO:0000269|PubMed:17008917"
FT MUTAGEN 235
FT /note="S->A: Abolishes phosphorylation, but no effect on
FT caspase inhibitory activity; when associated with A-231; A-
FT 247; A-251 and A-254. No effect on protein stability or
FT anti-apoptotic activity; when associated with A-251 and A-
FT 254."
FT /evidence="ECO:0000269|PubMed:17008917,
FT ECO:0000269|PubMed:17425806"
FT MUTAGEN 235
FT /note="S->D: No effect on caspase inhibitory activity or
FT auto-ubiquitination activity; when associated with D-231;
FT D-247; D-251 and D-254."
FT /evidence="ECO:0000269|PubMed:17008917,
FT ECO:0000269|PubMed:17425806"
FT MUTAGEN 247
FT /note="S->A: Abolishes phosphorylation, but no effect on
FT caspase inhibitory activity; when associated with A-231; A-
FT 235; A-251 and A-254."
FT /evidence="ECO:0000269|PubMed:17008917"
FT MUTAGEN 247
FT /note="S->D: No effect on caspase inhibitory activity or
FT auto-ubiquitination activity; when associated with D-231;
FT D-235; D-251 and D-254."
FT /evidence="ECO:0000269|PubMed:17008917"
FT MUTAGEN 251
FT /note="S->A: Abolishes phosphorylation, but no effect on
FT caspase inhibitory activity; when associated with A-231; A-
FT 235; A-247 and A-254. No effect on protein stability or
FT anti-apoptotic activity; when associated with A-235 and A-
FT 254."
FT /evidence="ECO:0000269|PubMed:17008917,
FT ECO:0000269|PubMed:17425806"
FT MUTAGEN 251
FT /note="S->D: No effect on caspase inhibitory activity or
FT auto-ubiquitination activity; when associated with D-231;
FT D-235; D-247 and D-254. No effect on protein stability or
FT anti-apoptotic activity; when associated with D-235 and D-
FT 254."
FT /evidence="ECO:0000269|PubMed:17008917,
FT ECO:0000269|PubMed:17425806"
FT MUTAGEN 254
FT /note="S->A: Abolishes phosphorylation, but no effect on
FT caspase inhibitory activity; when associated with A-231; A-
FT 235; A-247 and A-251. No effect on protein stability or
FT anti-apoptotic activity; when associated with A-235 and A-
FT 251."
FT /evidence="ECO:0000269|PubMed:17008917,
FT ECO:0000269|PubMed:17425806"
FT MUTAGEN 254
FT /note="S->D: No effect on caspase inhibitory activity or
FT auto-ubiquitination activity; when associated with D-231;
FT D-235; D-247 and D-251. No effect on protein stability or
FT anti-apoptotic activity; when associated with D-235 and D-
FT 251."
FT /evidence="ECO:0000269|PubMed:17008917,
FT ECO:0000269|PubMed:17425806"
FT CONFLICT 197
FT /note="D -> E (in Ref. 3; AAI69996)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 401 AA; 45287 MW; F8FDD31AFFBFD146 CRC64;
MSRWSVSQGC GNSHKALTMA GHGEQLFRGW GMVRPSMRSE AERLRSFSAW PRTCPQPSPV
EMARSGFYYL GPGDRVQCFS CGGVLRSWEP GDRPDTEHRK FFPSCTFLQQ QQRDPGATDS
QILGQHSGEE PDRTWESVYP EMAEERDRLD SFRNWPMYAH GNPEHLAGSG FFYTGHRDNV
KCFHCDGGLR NWEQGDDPWT EHAKWFPMCD FLLHVKGEAF IRRVQESLFR SPESSPDSLG
SYIYDRSPAS SPGSPESWRY LQSSVAQDAL QMGFKQSLVA SLIQSKFLLT GSSYSSVSDL
VTDLLVAEEE THSTESVSVS RAPTRMERSE PPKESAPPLS TEEQLRRLKE ERMCKVCMDK
DVSMLFVPCG HLVVCTECAP NLRHCPICRA AIRGSVRAFM S
