ID   B2L12_HUMAN             Reviewed;         334 AA.
AC   Q9HB09; Q3SY11; Q3SY13; Q96I96; Q9HB08;
DT   19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   27-MAR-2024, entry version 165.
DE   RecName: Full=Bcl-2-like protein 12;
DE            Short=Bcl2-L-12;
DE   AltName: Full=Bcl-2-related proline-rich protein;
GN   Name=BCL2L12; Synonyms=BPR;
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 [GENOMIC DNA] (ISOFORMS 1 AND 2).
RX   PubMed=11401436; DOI=10.1006/geno.2000.6455;
RA   Scorilas A., Kyriakopoulou L., Yousef G.M., Ashworth L.K., Kwamie A.,
RA   Diamandis E.P.;
RT   "Molecular cloning, physical mapping, and expression analysis of a novel
RT   gene, BCL2L12, encoding a proline-rich protein with a highly conserved BH2
RT   domain of the Bcl-2 family.";
RL   Genomics 72:217-221(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA   Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA   Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA   Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA   Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA   Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA   Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA   Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA   Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA   McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA   Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA   Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA   She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA   Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC   TISSUE=Uterus;
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   SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX   PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA   Hillman R.T., Green R.E., Brenner S.E.;
RT   "An unappreciated role for RNA surveillance.";
RL   Genome Biol. 5:R8.1-R8.16(2004).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113; THR-117; SER-121 AND
RP   SER-242, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-242, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-242 AND SER-243, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-195; SER-245 AND SER-273, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [11]
RP   METHYLATION [LARGE SCALE ANALYSIS] AT ARG-144, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Colon carcinoma;
RX   PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA   Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA   Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA   Bedford M.T., Comb M.J.;
RT   "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT   methylation.";
RL   Mol. Cell. Proteomics 13:372-387(2014).
CC   -!- INTERACTION:
CC       Q9HB09-1; P0CG48: UBC; NbExp=3; IntAct=EBI-6968951, EBI-3390054;
CC       Q9HB09-2; P08107: HSPA1B; NbExp=2; IntAct=EBI-6969019, EBI-629985;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q9HB09-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9HB09-2; Sequence=VSP_000522, VSP_000523;
CC       Name=3;
CC         IsoId=Q9HB09-3; Sequence=VSP_043269;
CC   -!- TISSUE SPECIFICITY: Expressed mainly in breast, thymus, prostate, fetal
CC       liver, colon, placenta, pancreas, small intestine, spinal cord, kidney,
CC       and bone marrow and to a lesser extent in many other tissues. Isoform 2
CC       is primarily expressed in skeletal muscle.
CC   -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/773/BCL2L12";
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DR   EMBL; AF289220; AAG29495.1; -; Genomic_DNA.
DR   EMBL; AF289220; AAG29496.1; -; Genomic_DNA.
DR   EMBL; AC011495; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC007724; AAH07724.2; -; mRNA.
DR   EMBL; BC104004; AAI04005.1; -; mRNA.
DR   EMBL; BC104005; AAI04006.1; -; mRNA.
DR   EMBL; BC104006; AAI04007.1; -; mRNA.
DR   RefSeq; NP_001035758.1; NM_001040668.1.
DR   RefSeq; NP_001269445.1; NM_001282516.1.
DR   RefSeq; NP_001269446.1; NM_001282517.1.
DR   RefSeq; NP_001269448.1; NM_001282519.1.
DR   RefSeq; NP_001269449.1; NM_001282520.1.
DR   RefSeq; NP_001269450.1; NM_001282521.1.
DR   RefSeq; NP_619580.1; NM_138639.1.
DR   RefSeq; XP_016882835.1; XM_017027346.1.
DR   AlphaFoldDB; Q9HB09; -.
DR   BioGRID; 123692; 56.
DR   IntAct; Q9HB09; 9.
DR   MINT; Q9HB09; -.
DR   STRING; 9606.ENSP00000482218; -.
DR   GlyGen; Q9HB09; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9HB09; -.
DR   PhosphoSitePlus; Q9HB09; -.
DR   SwissPalm; Q9HB09; -.
DR   BioMuta; BCL2L12; -.
DR   DMDM; 23396468; -.
DR   EPD; Q9HB09; -.
DR   jPOST; Q9HB09; -.
DR   MassIVE; Q9HB09; -.
DR   MaxQB; Q9HB09; -.
DR   PaxDb; 9606-ENSP00000482218; -.
DR   PeptideAtlas; Q9HB09; -.
DR   ProteomicsDB; 81467; -. [Q9HB09-1]
DR   ProteomicsDB; 81468; -. [Q9HB09-2]
DR   ProteomicsDB; 81469; -. [Q9HB09-3]
DR   Pumba; Q9HB09; -.
DR   Antibodypedia; 18662; 237 antibodies from 31 providers.
DR   DNASU; 83596; -.
DR   Ensembl; ENST00000246785.7; ENSP00000246785.3; ENSG00000126453.11.
DR   Ensembl; ENST00000441864.6; ENSP00000393803.2; ENSG00000126453.11.
DR   GeneID; 83596; -.
DR   KEGG; hsa:83596; -.
DR   UCSC; uc002ppa.4; human. [Q9HB09-1]
DR   AGR; HGNC:13787; -.
DR   CTD; 83596; -.
DR   DisGeNET; 83596; -.
DR   GeneCards; BCL2L12; -.
DR   HGNC; HGNC:13787; BCL2L12.
DR   HPA; ENSG00000126453; Low tissue specificity.
DR   MIM; 610837; gene.
DR   neXtProt; NX_Q9HB09; -.
DR   PharmGKB; PA25306; -.
DR   VEuPathDB; HostDB:ENSG00000126453; -.
DR   eggNOG; ENOG502RYM6; Eukaryota.
DR   InParanoid; Q9HB09; -.
DR   OMA; FCSREDR; -.
DR   OrthoDB; 3876075at2759; -.
DR   PhylomeDB; Q9HB09; -.
DR   TreeFam; TF338350; -.
DR   PathwayCommons; Q9HB09; -.
DR   SignaLink; Q9HB09; -.
DR   SIGNOR; Q9HB09; -.
DR   BioGRID-ORCS; 83596; 49 hits in 1156 CRISPR screens.
DR   ChiTaRS; BCL2L12; human.
DR   GeneWiki; BCL2L12; -.
DR   GenomeRNAi; 83596; -.
DR   Pharos; Q9HB09; Tbio.
DR   PRO; PR:Q9HB09; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q9HB09; Protein.
DR   Bgee; ENSG00000126453; Expressed in primordial germ cell in gonad and 132 other cell types or tissues.
DR   ExpressionAtlas; Q9HB09; baseline and differential.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:1990001; P:inhibition of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:2001236; P:regulation of extrinsic apoptotic signaling pathway; IBA:GO_Central.
DR   InterPro; IPR036834; Bcl-2-like_sf.
DR   PANTHER; PTHR14965:SF2; BCL-2-LIKE PROTEIN 12; 1.
DR   PANTHER; PTHR14965; SI:CH73-248E21.1; 1.
DR   SUPFAM; SSF56854; Bcl-2 inhibitors of programmed cell death; 1.
DR   Genevisible; Q9HB09; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Apoptosis; Methylation; Phosphoprotein;
KW   Reference proteome.
FT   CHAIN           1..334
FT                   /note="Bcl-2-like protein 12"
FT                   /id="PRO_0000143072"
FT   REGION          109..128
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           311..322
FT                   /note="BH2"
FT   MOD_RES         113
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         117
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         121
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         144
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0007744|PubMed:24129315"
FT   MOD_RES         195
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         242
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT   MOD_RES         243
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21406692"
FT   MOD_RES         245
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         273
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         120
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_043269"
FT   VAR_SEQ         121..176
FT                   /note="SPAQEEPTDFLSRLRRCLPCSLGRGAAPSESPRPCSLPIRPCYGLEPGPATP
FT                   DFYA -> PSYSRLLCFGGPAAGTAGPRAAEISAQPRITGSPIDREGSHTAEAGGPAGG
FT                   GGRSH (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_000522"
FT   VAR_SEQ         177..334
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_000523"
FT   VARIANT         47
FT                   /note="G -> V (in dbSNP:rs2060263)"
FT                   /id="VAR_048419"
FT   CONFLICT        270
FT                   /note="P -> S (in Ref. 3; AAH07724)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   334 AA;  36821 MW;  5398E54C83E7CAB7 CRC64;
     MGRPAGLFPP LCPFLGFRPE ACWERHMQIE RAPSVPPFLR WAGYRPGPVR RRGKVELIKF
     VRVQWRRPQV EWRRRRWGPG PGASMAGSEE LGLREDTLRV LAAFLRRGEA AGSPVPTPPR
     SPAQEEPTDF LSRLRRCLPC SLGRGAAPSE SPRPCSLPIR PCYGLEPGPA TPDFYALVAQ
     RLEQLVQEQL KSPPSPELQG PPSTEKEAIL RRLVALLEEE AEVINQKLAS DPALRSKLVR
     LSSDSFARLV ELFCSRDDSS RPSRACPGPP PPSPEPLARL ALAMELSRRV AGLGGTLAGL
     SVEHVHSFTP WIQAHGGWEG ILAVSPVDLN LPLD
//