B2CL1_PIG
ID B2CL1_PIG Reviewed; 233 AA.
AC O77737;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Bcl-2-like protein 1;
DE Short=Bcl2-L-1;
DE AltName: Full=Apoptosis regulator Bcl-X;
GN Name=BCL2L1; Synonyms=BCLX, BLC2L;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10072723; DOI=10.1006/jmcc.1998.0855;
RA Bartling B., Hoffmann J., Holtz J., Schulz R., Heusch G., Darmer D.;
RT "Quantification of cardioprotective gene expression in porcine short-term
RT hibernating myocardium.";
RL J. Mol. Cell. Cardiol. 31:147-158(1999).
CC -!- FUNCTION: Potent inhibitor of cell death. Inhibits activation of
CC caspases. Appears to regulate cell death by blocking the voltage-
CC dependent anion channel (VDAC) by binding to it and preventing the
CC release of the caspase activator, CYC1, from the mitochondrial
CC membrane. Also acts as a regulator of G2 checkpoint and progression to
CC cytokinesis during mitosis. Regulates presynaptic plasticity, including
CC neurotransmitter release and recovery, number of axonal mitochondria as
CC well as size and number of synaptic vesicle clusters. During synaptic
CC stimulation, increases ATP availability from mitochondria through
CC regulation of mitochondrial membrane ATP synthase F(1)F(0) activity and
CC regulates endocytic vesicle retrieval in hippocampal neurons through
CC association with DMN1L and stimulation of its GTPase activity in
CC synaptic vesicles. May attenuate inflammation impairing NLRP1-
CC inflammasome activation, hence CASP1 activation and IL1B release (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q07817}.
CC -!- SUBUNIT: Homodimer. Heterodimers with BAX, BAK or BCL2.
CC Heterodimerization with BAX does not seem to be required for anti-
CC apoptotic activity. Interacts with BCL2L11. Interacts with BAD.
CC Interacts with SIVA1 isoform 1; the interaction inhibits the anti-
CC apoptotic activity. Interacts with BECN1 and PGAM5. Interacts with
CC IKZF3. Interacts with HEBP2. Interacts with BOP. Interacts with
CC p53/TP53 and BBC3; interaction with BBC3 disrupts the interaction with
CC p53/TP53. Interacts with DNM1L and CLTA; DNM1L and BCL2L1 may form a
CC complex in synaptic vesicles that also contains clathrin and MFF.
CC Interacts with ATP5F1A and ATP5F1B; the interactions mediate the
CC association of BCL2L1 with the mitochondrial membrane ATP synthase
CC F(1)F(0) ATP synthase. Interacts with VDAC1. Interacts (via the loop
CC between motifs BH4 and BH3) with NLRP1 (via LRR repeats), but not with
CC NLRP2, NLRP3, NLRP4, PYCARD, nor MEFV. Interacts with BCL2L11 (via BH3)
CC (By similarity). Interacts with RNF183 (By similarity). Interacts with
CC GIMAP3/IAN4 (By similarity). Interacts with GIMAP5 and HSPA8/HSC70; the
CC interaction between HSPA8 and BCL2L1 is impaired in the absence of
CC GIMAP5 (By similarity). Interacts with CLU (isoform 4); this
CC interaction releases and activates BAX and promotes cell death (By
CC similarity). {ECO:0000250|UniProtKB:P53563,
CC ECO:0000250|UniProtKB:Q07817, ECO:0000250|UniProtKB:Q64373}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane {ECO:0000250}; Single-pass
CC membrane protein {ECO:0000250}. Nucleus membrane {ECO:0000250}; Single-
CC pass membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}.
CC Mitochondrion matrix {ECO:0000250}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome {ECO:0000250}. Cytoplasm,
CC cytosol {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000250}. Note=After neuronal stimulation,
CC translocates from cytosol to synaptic vesicle and mitochondrion
CC membrane in a calmodulin-dependent manner. Localizes to the centrosome
CC when phosphorylated at Ser-49 (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The BH4 motif is required for anti-apoptotic activity. The BH1
CC and BH2 motifs are required for both heterodimerization with other Bcl-
CC 2 family members and for repression of cell death.
CC -!- DOMAIN: The loop between motifs BH4 and BH3 is required for the
CC interaction with NLRP1. {ECO:0000250|UniProtKB:Q07817}.
CC -!- PTM: Proteolytically cleaved by caspases during apoptosis. The cleaved
CC protein, lacking the BH4 motif, has pro-apoptotic activity.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated on Ser-62 by CDK1. This phosphorylation is partial
CC in normal mitotic cells, but complete in G2-arrested cells upon DNA-
CC damage, thus promoting subsequent apoptosis probably by triggering
CC caspases-mediated proteolysis. Phosphorylated by PLK3, leading to
CC regulate the G2 checkpoint and progression to cytokinesis during
CC mitosis. Phosphorylation at Ser-49 appears during the S phase and G2,
CC disappears rapidly in early mitosis during prometaphase, metaphase and
CC early anaphase, and re-appears during telophase and cytokinesis (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated by RNF183 during prolonged ER stress, leading to
CC degradation by the proteosome. {ECO:0000250|UniProtKB:Q07817}.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
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DR EMBL; AJ001203; CAA04597.1; -; mRNA.
DR RefSeq; NP_999450.1; NM_214285.1.
DR AlphaFoldDB; O77737; -.
DR BMRB; O77737; -.
DR SMR; O77737; -.
DR STRING; 9823.ENSSSCP00000007697; -.
DR PaxDb; O77737; -.
DR PeptideAtlas; O77737; -.
DR PRIDE; O77737; -.
DR GeneID; 397536; -.
DR KEGG; ssc:397536; -.
DR CTD; 598; -.
DR eggNOG; KOG4728; Eukaryota.
DR InParanoid; O77737; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; IBA:GO_Central.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046982; F:protein heterodimerization activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IBA:GO_Central.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; ISS:UniProtKB.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0032465; P:regulation of cytokinesis; ISS:UniProtKB.
DR CDD; cd06845; Bcl-2_like; 1.
DR Gene3D; 1.10.437.10; -; 1.
DR InterPro; IPR013279; Apop_reg_BclX.
DR InterPro; IPR036834; Bcl-2-like_sf.
DR InterPro; IPR046371; Bcl-2_BH1-3.
DR InterPro; IPR026298; Bcl-2_fam.
DR InterPro; IPR002475; Bcl2-like.
DR InterPro; IPR004725; Bcl2/BclX.
DR InterPro; IPR020717; Bcl2_BH1_motif_CS.
DR InterPro; IPR020726; Bcl2_BH2_motif_CS.
DR InterPro; IPR020728; Bcl2_BH3_motif_CS.
DR InterPro; IPR003093; Bcl2_BH4.
DR InterPro; IPR020731; Bcl2_BH4_motif_CS.
DR PANTHER; PTHR11256; PTHR11256; 1.
DR PANTHER; PTHR11256:SF12; PTHR11256:SF12; 1.
DR Pfam; PF00452; Bcl-2; 1.
DR Pfam; PF02180; BH4; 1.
DR PRINTS; PR01864; APOPREGBCLX.
DR PRINTS; PR01862; BCL2FAMILY.
DR SMART; SM00337; BCL; 1.
DR SMART; SM00265; BH4; 1.
DR SUPFAM; SSF56854; SSF56854; 1.
DR TIGRFAMs; TIGR00865; bcl-2; 1.
DR PROSITE; PS50062; BCL2_FAMILY; 1.
DR PROSITE; PS01080; BH1; 1.
DR PROSITE; PS01258; BH2; 1.
DR PROSITE; PS01259; BH3; 1.
DR PROSITE; PS01260; BH4_1; 1.
DR PROSITE; PS50063; BH4_2; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Endocytosis;
KW Membrane; Mitochondrion; Nucleus; Phosphoprotein; Reference proteome;
KW Synapse; Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..233
FT /note="Bcl-2-like protein 1"
FT /id="PRO_0000143064"
FT TRANSMEM 210..226
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 29..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 4..24
FT /note="BH4"
FT MOTIF 86..100
FT /note="BH3"
FT MOTIF 129..148
FT /note="BH1"
FT MOTIF 180..195
FT /note="BH2"
FT MOD_RES 49
FT /note="Phosphoserine; by PLK3"
FT /evidence="ECO:0000250|UniProtKB:Q07817"
FT MOD_RES 62
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q07817"
SQ SEQUENCE 233 AA; 26061 MW; 18BF6FA0441912B2 CRC64;
MSQSNRELVV DFLSYKLSQK GYSWSQFTDV EENRTEAPEG TESEAETPSA INGNPSWHLA
DSPAVNGATG HSSSLDAREV IPMAAVKQAL REAGDEFELR YRRAFSDLTS QLHITPGTAY
QSFEQVLNEL FRDGVNWGRI VAFFSFGGAL CVESVDKEMQ VLVSRIATWM ATYLNDHLEP
WIQENGGWDT FVELYGNNAA AESRKGQERF NRWFLTGMTL AGVVLLGSLF SRK
