B2LA1_HUMAN
ID B2LA1_HUMAN Reviewed; 175 AA.
AC Q16548; Q6FGZ4; Q6FH19; Q86W13; Q99524;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Bcl-2-related protein A1;
DE AltName: Full=Bcl-2-like protein 5;
DE Short=Bcl2-L-5;
DE AltName: Full=Hemopoietic-specific early response protein;
DE AltName: Full=Protein BFL-1;
DE AltName: Full=Protein GRS;
GN Name=BCL2A1; Synonyms=BCL2L5, BFL1, GRS, HBPA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=7478596;
RA Choi S.S., Park I.-C., Yun J.W., Sung Y.C., Hong S.-I., Shin H.-S.;
RT "A novel Bcl-2 related gene, Bfl-1, is overexpressed in stomach cancer and
RT preferentially expressed in bone marrow.";
RL Oncogene 11:1693-1698(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Umbilical vein;
RX PubMed=8605321;
RA Karsan A., Yee E., Kaushansky K., Harlan J.M.;
RT "Cloning of human Bcl-2 homologue: inflammatory cytokines induce human A1
RT in cultured endothelial cells.";
RL Blood 87:3089-3096(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=T-cell;
RX PubMed=9050999; DOI=10.1038/sj.onc.1200898;
RA Kenny J.J., Knobloch T.J., Augustus M., Carter K.C., Rosen C.A., Lang J.C.;
RT "GRS, a novel member of the Bcl-2 gene family, is highly expressed in
RT multiple cancer cell lines and in normal leukocytes.";
RL Oncogene 14:997-1001(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Barnes F.A., Rowe S.J., Whyte M.K.B., Bingle C.D.;
RT "A widely expressed pro-apoptotic splice variant of the human A1 gene is
RT specifically targeted to the nucleus.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS TYR-19;
RP LYS-39 AND ASP-82.
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [10]
RP INTERACTION WITH BAX.
RX PubMed=10772918; DOI=10.1006/bbrc.2000.2537;
RA Schmitt E., Paquet C., Beauchemin M., Dever-Bertrand J., Bertrand R.;
RT "Characterization of Bax-sigma, a cell death-inducing isoform of Bax.";
RL Biochem. Biophys. Res. Commun. 270:868-879(2000).
RN [11]
RP INTERACTION WITH RTL10/BOP.
RX PubMed=23055042; DOI=10.1007/s13238-012-2069-7;
RA Zhang X., Weng C., Li Y., Wang X., Jiang C., Li X., Xu Y., Chen Q., Pan L.,
RA Tang H.;
RT "Human Bop is a novel BH3-only member of the Bcl-2 protein family.";
RL Protein Cell 3:790-801(2012).
RN [12]
RP INTERACTION WITH UBQLN4, AND SUBCELLULAR LOCATION.
RX PubMed=34245648; DOI=10.1002/1878-0261.13058;
RA Liu F., Pan R., Ding H., Gu L., Yang Y., Li C., Xu Y., Hu R., Chen H.,
RA Zhang X., Nie Y.;
RT "UBQLN4 is an ATM substrate that stabilizes the anti-apoptotic proteins
RT BCL2A1 and BCL2L10 in mesothelioma.";
RL Mol. Oncol. 15:3738-3752(2021).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-149 IN COMPLEX WITH BCL2L11/BIM.
RX PubMed=18812174; DOI=10.1016/j.febslet.2008.09.028;
RA Herman M.D., Nyman T., Welin M., Lehtio L., Flodin S., Tresaugues L.,
RA Kotenyova T., Flores A., Nordlund P.;
RT "Completing the family portrait of the anti-apoptotic Bcl-2 proteins:
RT crystal structure of human Bfl-1 in complex with Bim.";
RL FEBS Lett. 582:3590-3594(2008).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 149-608 IN COMPLEX WITH BCL2L11.
RG Structural genomics consortium (SGC);
RT "Human BCL-2A1 in complex with BIM.";
RL Submitted (FEB-2008) to the PDB data bank.
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 1-151 IN COMPLEX WITH PMAIP1.
RG Northeast structural genomics consortium (NESG);
RT "Crystal structure of human bfl-1 in complex with noxa bh3 peptide.";
RL Submitted (JUL-2010) to the PDB data bank.
CC -!- FUNCTION: Retards apoptosis induced by IL-3 deprivation. May function
CC in the response of hemopoietic cells to external signals and in
CC maintaining endothelial survival during infection (By similarity). Can
CC inhibit apoptosis induced by serum starvation in the mammary epithelial
CC cell line HC11 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q07440}.
CC -!- SUBUNIT: Interacts directly with BAK1, BID, BMF and BBC3 (By
CC similarity). Interacts directly with BCL2L11/BIM. Interacts with BAX
CC isoform Sigma. Interacts directly with PMAIP1. Interacts with
CC RTL10/BOP. Interacts with ING4 (By similarity). Interacts with UBQLN4
CC (PubMed:34245648). {ECO:0000250|UniProtKB:Q07440,
CC ECO:0000269|PubMed:10772918, ECO:0000269|PubMed:18812174,
CC ECO:0000269|PubMed:23055042, ECO:0000269|PubMed:34245648,
CC ECO:0000269|Ref.14, ECO:0000269|Ref.15}.
CC -!- INTERACTION:
CC Q16548; Q16611: BAK1; NbExp=6; IntAct=EBI-1003550, EBI-519866;
CC Q16548; O43521: BCL2L11; NbExp=4; IntAct=EBI-1003550, EBI-526406;
CC Q16548; Q13323: BIK; NbExp=10; IntAct=EBI-1003550, EBI-700794;
CC Q16548; Q5HYN5: CT45A1; NbExp=3; IntAct=EBI-1003550, EBI-12051833;
CC Q16548; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-1003550, EBI-10175124;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:34245648}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q16548-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16548-2; Sequence=VSP_043106;
CC -!- TISSUE SPECIFICITY: Seems to be restricted to the hematopoietic
CC compartment. Expressed in peripheral blood, spleen, and bone marrow, at
CC moderate levels in lung, small intestine and testis, at a minimal
CC levels in other tissues. Also found in vascular smooth muscle cells and
CC hematopoietic malignancies.
CC -!- INDUCTION: By phorbol ester and inflammatory cytokines, such as TNF or
CC IL1B/interleukin-1 beta, but not by growth factors.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
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DR EMBL; U27467; AAC50288.1; -; mRNA.
DR EMBL; U29680; AAC50438.1; -; mRNA.
DR EMBL; Y09397; CAA70566.1; -; mRNA.
DR EMBL; AY234180; AAO89009.1; -; mRNA.
DR EMBL; BT007103; AAP35767.1; -; mRNA.
DR EMBL; CR541937; CAG46735.1; -; mRNA.
DR EMBL; CR541962; CAG46760.1; -; mRNA.
DR EMBL; AC015871; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471136; EAW99129.1; -; Genomic_DNA.
DR EMBL; BC016281; AAH16281.1; -; mRNA.
DR CCDS; CCDS10312.1; -. [Q16548-1]
DR CCDS; CCDS45322.1; -. [Q16548-2]
DR PIR; I39055; I39055.
DR RefSeq; NP_001108207.1; NM_001114735.1. [Q16548-2]
DR RefSeq; NP_004040.1; NM_004049.3. [Q16548-1]
DR PDB; 2VM6; X-ray; 2.20 A; A=1-149.
DR PDB; 3I1H; X-ray; 2.20 A; A=1-151.
DR PDB; 3MQP; X-ray; 2.24 A; A=1-151.
DR PDB; 4ZEQ; X-ray; 1.80 A; A=1-151.
DR PDB; 5UUK; X-ray; 1.20 A; A=1-151.
DR PDB; 5UUL; X-ray; 1.33 A; A=1-151.
DR PDB; 5UUP; X-ray; 1.73 A; A=1-151.
DR PDB; 5WHH; X-ray; 2.38 A; A=1-151.
DR PDB; 5WHI; X-ray; 1.69 A; A=1-151.
DR PDB; 6E3I; X-ray; 1.48 A; A=1-151.
DR PDB; 6E3J; X-ray; 1.48 A; A=1-151.
DR PDB; 6MBB; X-ray; 1.59 A; A=1-151.
DR PDB; 6MBC; X-ray; 1.75 A; A=1-151.
DR PDB; 6RJP; X-ray; 2.57 A; A/B=1-149.
DR PDB; 6VO4; X-ray; 1.74 A; A=1-151.
DR PDBsum; 2VM6; -.
DR PDBsum; 3I1H; -.
DR PDBsum; 3MQP; -.
DR PDBsum; 4ZEQ; -.
DR PDBsum; 5UUK; -.
DR PDBsum; 5UUL; -.
DR PDBsum; 5UUP; -.
DR PDBsum; 5WHH; -.
DR PDBsum; 5WHI; -.
DR PDBsum; 6E3I; -.
DR PDBsum; 6E3J; -.
DR PDBsum; 6MBB; -.
DR PDBsum; 6MBC; -.
DR PDBsum; 6RJP; -.
DR PDBsum; 6VO4; -.
DR AlphaFoldDB; Q16548; -.
DR SMR; Q16548; -.
DR BioGRID; 107069; 22.
DR IntAct; Q16548; 12.
DR STRING; 9606.ENSP00000267953; -.
DR BindingDB; Q16548; -.
DR ChEMBL; CHEMBL6044; -.
DR iPTMnet; Q16548; -.
DR PhosphoSitePlus; Q16548; -.
DR BioMuta; BCL2A1; -.
DR DMDM; 2493280; -.
DR MassIVE; Q16548; -.
DR MaxQB; Q16548; -.
DR PaxDb; Q16548; -.
DR PeptideAtlas; Q16548; -.
DR PRIDE; Q16548; -.
DR ProteomicsDB; 60907; -. [Q16548-1]
DR ProteomicsDB; 60908; -. [Q16548-2]
DR Antibodypedia; 4163; 426 antibodies from 40 providers.
DR DNASU; 597; -.
DR Ensembl; ENST00000267953.4; ENSP00000267953.3; ENSG00000140379.9. [Q16548-1]
DR Ensembl; ENST00000335661.6; ENSP00000335250.6; ENSG00000140379.9. [Q16548-2]
DR GeneID; 597; -.
DR KEGG; hsa:597; -.
DR MANE-Select; ENST00000267953.4; ENSP00000267953.3; NM_004049.4; NP_004040.1.
DR UCSC; uc002bfc.5; human. [Q16548-1]
DR CTD; 597; -.
DR DisGeNET; 597; -.
DR GeneCards; BCL2A1; -.
DR HGNC; HGNC:991; BCL2A1.
DR HPA; ENSG00000140379; Tissue enriched (bone).
DR MIM; 601056; gene.
DR neXtProt; NX_Q16548; -.
DR OpenTargets; ENSG00000140379; -.
DR PharmGKB; PA25303; -.
DR VEuPathDB; HostDB:ENSG00000140379; -.
DR eggNOG; KOG4728; Eukaryota.
DR GeneTree; ENSGT01050000244872; -.
DR HOGENOM; CLU_1554763_0_0_1; -.
DR InParanoid; Q16548; -.
DR OMA; IMDAFSF; -.
DR OrthoDB; 1218929at2759; -.
DR PhylomeDB; Q16548; -.
DR TreeFam; TF315834; -.
DR PathwayCommons; Q16548; -.
DR Reactome; R-HSA-9725371; Nuclear events stimulated by ALK signaling in cancer.
DR SignaLink; Q16548; -.
DR SIGNOR; Q16548; -.
DR BioGRID-ORCS; 597; 22 hits in 1062 CRISPR screens.
DR ChiTaRS; BCL2A1; human.
DR EvolutionaryTrace; Q16548; -.
DR GeneWiki; BCL2-related_protein_A1; -.
DR GenomeRNAi; 597; -.
DR Pharos; Q16548; Tchem.
DR PRO; PR:Q16548; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q16548; protein.
DR Bgee; ENSG00000140379; Expressed in periodontal ligament and 127 other tissues.
DR ExpressionAtlas; Q16548; baseline and differential.
DR Genevisible; Q16548; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005741; C:mitochondrial outer membrane; IBA:GO_Central.
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: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:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR CDD; cd06845; Bcl-2_like; 1.
DR Gene3D; 1.10.437.10; -; 1.
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; IPR020717; Bcl2_BH1_motif_CS.
DR InterPro; IPR020726; Bcl2_BH2_motif_CS.
DR InterPro; IPR013282; Bcl2A1.
DR PANTHER; PTHR11256; PTHR11256; 1.
DR PANTHER; PTHR11256:SF10; PTHR11256:SF10; 1.
DR Pfam; PF00452; Bcl-2; 1.
DR PRINTS; PR01862; BCL2FAMILY.
DR PRINTS; PR01867; BCL2RLATEDA1.
DR SMART; SM00337; BCL; 1.
DR SUPFAM; SSF56854; SSF56854; 1.
DR PROSITE; PS50062; BCL2_FAMILY; 1.
DR PROSITE; PS01080; BH1; 1.
DR PROSITE; PS01258; BH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cytoplasm;
KW Reference proteome.
FT CHAIN 1..175
FT /note="Bcl-2-related protein A1"
FT /id="PRO_0000143094"
FT MOTIF 77..97
FT /note="BH1"
FT MOTIF 132..147
FT /note="BH2"
FT VAR_SEQ 141..175
FT /note="ENGFVKKFEPKSGWMTFLEVTGKICEMLSLLKQYC -> GKWHNHTPMLVES
FT VAHKKRKMAL (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_043106"
FT VARIANT 19
FT /note="C -> Y (in dbSNP:rs1138357)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_020342"
FT VARIANT 39
FT /note="N -> K (in dbSNP:rs1138358)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_020343"
FT VARIANT 82
FT /note="G -> D (in dbSNP:rs3826007)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_020344"
FT VARIANT 117
FT /note="E -> D (in dbSNP:rs34080999)"
FT /id="VAR_044059"
FT CONFLICT 72
FT /note="N -> T (in Ref. 3; CAA70566)"
FT /evidence="ECO:0000305"
FT CONFLICT 107
FT /note="Q -> H (in Ref. 3; CAA70566)"
FT /evidence="ECO:0000305"
FT HELIX 1..4
FT /evidence="ECO:0007829|PDB:5UUK"
FT HELIX 6..21
FT /evidence="ECO:0007829|PDB:5UUK"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:6E3I"
FT HELIX 32..51
FT /evidence="ECO:0007829|PDB:5UUK"
FT HELIX 53..56
FT /evidence="ECO:0007829|PDB:5UUK"
FT HELIX 64..78
FT /evidence="ECO:0007829|PDB:5UUK"
FT TURN 79..81
FT /evidence="ECO:0007829|PDB:5UUK"
FT HELIX 86..106
FT /evidence="ECO:0007829|PDB:5UUK"
FT HELIX 114..136
FT /evidence="ECO:0007829|PDB:5UUK"
FT HELIX 139..142
FT /evidence="ECO:0007829|PDB:5UUK"
FT HELIX 144..148
FT /evidence="ECO:0007829|PDB:5UUK"
SQ SEQUENCE 175 AA; 20132 MW; 329D98AF2BE07A0D CRC64;
MTDCEFGYIY RLAQDYLQCV LQIPQPGSGP SKTSRVLQNV AFSVQKEVEK NLKSCLDNVN
VVSVDTARTL FNQVMEKEFE DGIINWGRIV TIFAFEGILI KKLLRQQIAP DVDTYKEISY
FVAEFIMNNT GEWIRQNGGW ENGFVKKFEP KSGWMTFLEV TGKICEMLSL LKQYC
