Human Gene BCL2L1 (uc002wwn.3)
  Description: Homo sapiens BCL2-like 1 (BCL2L1), nuclear gene encoding mitochondrial protein, transcript variant 1, mRNA.
RefSeq Summary (NM_138578): The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The proteins encoded by this gene are located at the outer mitochondrial membrane, and have been shown to regulate outer mitochondrial membrane channel (VDAC) opening. VDAC regulates mitochondrial membrane potential, and thus controls the production of reactive oxygen species and release of cytochrome C by mitochondria, both of which are the potent inducers of cell apoptosis. Alternative splicing results in multiple transcript variants encoding two different isoforms. The longer isoform acts as an apoptotic inhibitor and the shorter isoform acts as an apoptotic activator. [provided by RefSeq, Dec 2015].
Transcript (Including UTRs)
   Position: hg19 chr20:30,252,261-30,310,656 Size: 58,396 Total Exon Count: 3 Strand: -
Coding Region
   Position: hg19 chr20:30,253,752-30,310,021 Size: 56,270 Coding Exon Count: 2 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr20:30,252,261-30,310,656)mRNA (may differ from genome)Protein (233 aa)
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-  Comments and Description Text from UniProtKB
  ID: B2CL1_HUMAN
DESCRIPTION: RecName: Full=Bcl-2-like protein 1; Short=Bcl2-L-1; AltName: Full=Apoptosis regulator Bcl-X;
FUNCTION: Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.
FUNCTION: Isoform Bcl-X(S) promotes apoptosis.
SUBUNIT: Homodimer. Isoform Bcl-X(L) forms heterodimers with BAX, BAK or BCL2. Heterodimerization with BAX does not seem to be required for anti-apoptotic activity. Interacts with BCL2L11. Interacts with DMN1L; the interaction stimulates the GTPase activity of DMN1L in synapses and increases the number of axonal mitochondria and the size and number of synaptic vesicle clusters (By similarity). Interacts with BAD and BBC3. Interacts (isoform Bcl-X(L)) with SIVA1 (isoform 1); the interaction inhibits the anti-apoptotic activity. Interacts with BECN1 and PGAM5. Interacts (isoform Bcl-X(L)) with BAX (isoform Sigma). Isoform Bcl-X(L) interacts with IKZF3. Interacts with HEBP2.
INTERACTION: Q92934:BAD; NbExp=6; IntAct=EBI-287195, EBI-700771; Q61337:Bad (xeno); NbExp=2; IntAct=EBI-287195, EBI-400328; Q16611:BAK1; NbExp=8; IntAct=EBI-287195, EBI-519866; Q07812:BAX; NbExp=13; IntAct=EBI-287195, EBI-516580; Q9BXH1:BBC3; NbExp=7; IntAct=EBI-287195, EBI-519884; Q99ML1:Bbc3 (xeno); NbExp=3; IntAct=EBI-287195, EBI-727801; O43521:BCL2L11; NbExp=8; IntAct=EBI-287195, EBI-526406; O43521-1:BCL2L11; NbExp=2; IntAct=EBI-287195, EBI-526416; Q14457:BECN1; NbExp=4; IntAct=EBI-287195, EBI-949378; P55957:BID; NbExp=6; IntAct=EBI-287195, EBI-519672; Q13323:BIK; NbExp=3; IntAct=EBI-287195, EBI-700794; P30429:ced-4 (xeno); NbExp=3; IntAct=EBI-78035, EBI-494118; P10909-4:CLU; NbExp=6; IntAct=EBI-287195, EBI-4322678; O00198:HRK; NbExp=2; IntAct=EBI-287195, EBI-701322; Q9C000:NLRP1; NbExp=9; IntAct=EBI-78035, EBI-1220518; O15304:SIVA1; NbExp=2; IntAct=EBI-287195, EBI-520756; O15304-1:SIVA1; NbExp=5; IntAct=EBI-287195, EBI-520766; Q9H2V7:SPNS1; NbExp=3; IntAct=EBI-78035, EBI-1386527; P04637:TP53; NbExp=18; IntAct=EBI-287195, EBI-366083; P02340:Tp53 (xeno); NbExp=3; IntAct=EBI-287195, EBI-474016;
SUBCELLULAR LOCATION: Mitochondrion membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein; Cytoplasmic side (By similarity). Cytoplasm, cytoskeleton, centrosome. Note=Mitochondrial membranes and perinuclear envelope (By similarity). Localizes to the centrosome when phosphorylated at Ser-49.
TISSUE SPECIFICITY: Bcl-X(S) is expressed at high levels in cells that undergo a high rate of turnover, such as developing lymphocytes. In contrast, Bcl-X(L) is found in tissues containing long-lived postmitotic cells, such as adult brain.
DOMAIN: The BH4 motif is required for anti-apoptotic activity. The BH1 and BH2 motifs are required for both heterodimerization with other Bcl-2 family members and for repression of cell death.
PTM: Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity.
PTM: Phosphorylated on Ser-62 by CDK1. This phosphorylation is partial in normal mitotic cells, but complete in G2-arrested cells upon DNA-damage, thus promoting subsequent apoptosis probably by triggering caspases-mediated proteolysis. Phosphorylated by PLK3, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Phosphorylation at Ser-49 appears during the S phase and G2, disappears rapidly in early mitosis during prometaphase, metaphase and early anaphase, and re-appears during telophase and cytokinesis.
SIMILARITY: Belongs to the Bcl-2 family.

-  Primer design for this transcript
 

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-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): BCL2L1
CDC HuGE Published Literature: BCL2L1

-  MalaCards Disease Associations
  MalaCards Gene Search: BCL2L1
Diseases sorted by gene-association score: lung cancer (8), hepatocellular carcinoma (7), pancreatic cancer (7), colorectal cancer (7), myeloid leukemia (5), b-cell lymphomas (5), follicular lymphoma (5), hepatoblastoma (4), malignant glioma (4), ovarian cancer, somatic (3), multiple myeloma (3), her2-receptor negative breast cancer (3), essential thrombocythemia (3), prostate cancer (3), adult t-cell leukemia (3), nasopharyngeal carcinoma (3), mantle cell lymphoma (3), chronic lymphocytic leukemia (3), squamous cell carcinoma, head and neck (2), alk-negative anaplastic large cell lymphoma (2), leukemia, chronic myeloid, somatic (2), nutmeg liver (2), lymphoma, non-hodgkin (2), medulloblastoma (2), esophageal cancer (2), breast cancer (2), lung cancer susceptibility 3 (2), apical myocardial infarction (1), myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency (1), gastrointestinal system cancer (1), lymphoproliferative syndrome 2 (1), valproate embryopathy, susceptibility to (1), carbuncle (1), leukemia, acute myeloid (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 68.57 RPKM in Whole Blood
Total median expression: 1601.97 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -127.90348-0.368 Picture PostScript Text
3' UTR -599.701491-0.402 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013279 - Apop_reg_BclX
IPR002475 - Bcl2-like
IPR004725 - Bcl2/BclX
IPR020717 - Bcl2_BH1_motif_CS
IPR020726 - Bcl2_BH2_motif_CS
IPR020728 - Bcl2_BH3_motif_CS
IPR003093 - Bcl2_BH4
IPR020731 - Bcl2_BH4_motif_CS
IPR026298 - Blc2_fam

Pfam Domains:
PF00452 - Apoptosis regulator proteins, Bcl-2 family
PF02180 - Bcl-2 homology region 4

SCOP Domains:
56854 - Bcl-2 inhibitors of programmed cell death

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1BXL - NMR 1G5J - NMR MuPIT 1LXL - NMR MuPIT 1MAZ - X-ray MuPIT 1R2D - X-ray MuPIT 1R2E - X-ray MuPIT 1R2G - X-ray MuPIT 1R2H - X-ray MuPIT 1R2I - X-ray MuPIT 1YSG - NMR MuPIT 1YSI - NMR MuPIT 1YSN - NMR MuPIT 2B48 - X-ray MuPIT 2LP8 - NMR MuPIT 2LPC - NMR MuPIT 2O1Y - NMR MuPIT 2O2M - NMR MuPIT 2O2N - NMR MuPIT 2P1L - X-ray MuPIT 2PON - NMR MuPIT 2YJ1 - X-ray MuPIT 2YXJ - X-ray MuPIT 3CVA - X-ray MuPIT 3FDL - X-ray MuPIT 3FDM - X-ray MuPIT 3INQ - X-ray MuPIT 3IO8 - X-ray MuPIT 3PL7 - X-ray MuPIT 3QKD - X-ray MuPIT 3R85 - X-ray 3SP7 - X-ray MuPIT 3SPF - X-ray MuPIT 4A1U - X-ray MuPIT 4A1W - X-ray MuPIT 4AQ3 - X-ray MuPIT 4EHR - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q07817
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
 Gene Details    
 Gene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0019901 protein kinase binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0046982 protein heterodimerization activity
GO:0051434 BH3 domain binding

Biological Process:
GO:0001541 ovarian follicle development
GO:0001701 in utero embryonic development
GO:0001836 release of cytochrome c from mitochondria
GO:0006897 endocytosis
GO:0006915 apoptotic process
GO:0007093 mitotic cell cycle checkpoint
GO:0007281 germ cell development
GO:0007283 spermatogenesis
GO:0008283 cell proliferation
GO:0008284 positive regulation of cell proliferation
GO:0008584 male gonad development
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0008637 apoptotic mitochondrial changes
GO:0009314 response to radiation
GO:0009566 fertilization
GO:0009615 response to virus
GO:0010507 negative regulation of autophagy
GO:0019050 suppression by virus of host apoptotic process
GO:0019221 cytokine-mediated signaling pathway
GO:0032465 regulation of cytokinesis
GO:0034097 response to cytokine
GO:0040007 growth
GO:0042981 regulation of apoptotic process
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043524 negative regulation of neuron apoptotic process
GO:0046898 response to cycloheximide
GO:0046902 regulation of mitochondrial membrane permeability
GO:0051402 neuron apoptotic process
GO:0051881 regulation of mitochondrial membrane potential
GO:0060154 cellular process regulating host cell cycle in response to virus
GO:0070584 mitochondrion morphogenesis
GO:0071230 cellular response to amino acid stimulus
GO:0071312 cellular response to alkaloid
GO:0071480 cellular response to gamma radiation
GO:0071839 apoptotic process in bone marrow
GO:0090201 negative regulation of release of cytochrome c from mitochondria
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
GO:0097284 hepatocyte apoptotic process
GO:1900118 negative regulation of execution phase of apoptosis
GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:1902230 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
GO:1903077 negative regulation of protein localization to plasma membrane
GO:2000811 negative regulation of anoikis
GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway

Cellular Component:
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005741 mitochondrial outer membrane
GO:0005743 mitochondrial inner membrane
GO:0005759 mitochondrial matrix
GO:0005783 endoplasmic reticulum
GO:0005813 centrosome
GO:0005815 microtubule organizing center
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030054 cell junction
GO:0030672 synaptic vesicle membrane
GO:0031410 cytoplasmic vesicle
GO:0031965 nuclear membrane
GO:0031966 mitochondrial membrane
GO:0045202 synapse
GO:0097136 Bcl-2 family protein complex


-  Descriptions from all associated GenBank mRNAs
  KJ890762 - Synthetic construct Homo sapiens clone ccsbBroadEn_00156 BCL2L1 gene, encodes complete protein.
BC019307 - Homo sapiens BCL2-like 1, mRNA (cDNA clone MGC:4204 IMAGE:2823498), complete cds.
CR936637 - Homo sapiens mRNA; cDNA DKFZp781P2092 (from clone DKFZp781P2092).
BX647525 - Homo sapiens mRNA; cDNA DKFZp686C01267 (from clone DKFZp686C01267).
Z23115 - H.sapiens bcl-xL mRNA.
Z23116 - H.sapiens bcl-xS mRNA.
AK290968 - Homo sapiens cDNA FLJ77105 complete cds, highly similar to Homo sapiens BCL2-like 1 (BCL2L1), nuclear gene encoding mitochondrial protein, transcript variant 2, mRNA.
BT007208 - Homo sapiens BCL2-like 1 mRNA, complete cds.
DQ893461 - Synthetic construct clone IMAGE:100006091; FLH193174.01X; RZPDo839D0678D BCL2-like 1 (BCL2L1) gene, encodes complete protein.
DQ896311 - Synthetic construct Homo sapiens clone IMAGE:100010771; FLH193170.01L; RZPDo839D0668D BCL2-like 1 (BCL2L1) gene, encodes complete protein.
AB464466 - Synthetic construct DNA, clone: pF1KB8901, Homo sapiens BCL2L1 gene for BCL2-like 1, without stop codon, in Flexi system.
KU177938 - Homo sapiens BCL2-like 1 isoform 1 (BCL2L1) mRNA, partial cds.
KU177939 - Homo sapiens BCL2-like 1 isoform 2 (BCL2L1) mRNA, partial cds.
KU177940 - Homo sapiens BCL2-like 1 isoform 3 (BCL2L1) mRNA, complete cds, alternatively spliced.
JD427771 - Sequence 408795 from Patent EP1572962.
JD121633 - Sequence 102657 from Patent EP1572962.
JD191453 - Sequence 172477 from Patent EP1572962.
JD108288 - Sequence 89312 from Patent EP1572962.
JD416124 - Sequence 397148 from Patent EP1572962.
JD283860 - Sequence 264884 from Patent EP1572962.
JD090658 - Sequence 71682 from Patent EP1572962.
JD259880 - Sequence 240904 from Patent EP1572962.
JD515159 - Sequence 496183 from Patent EP1572962.
JD537450 - Sequence 518474 from Patent EP1572962.
JD124198 - Sequence 105222 from Patent EP1572962.
JD190849 - Sequence 171873 from Patent EP1572962.
JD270710 - Sequence 251734 from Patent EP1572962.
JD230384 - Sequence 211408 from Patent EP1572962.
JD162385 - Sequence 143409 from Patent EP1572962.
JD527886 - Sequence 508910 from Patent EP1572962.
JD255228 - Sequence 236252 from Patent EP1572962.
JD079886 - Sequence 60910 from Patent EP1572962.
JD385044 - Sequence 366068 from Patent EP1572962.
JD062724 - Sequence 43748 from Patent EP1572962.
JD485992 - Sequence 467016 from Patent EP1572962.
JD073925 - Sequence 54949 from Patent EP1572962.
JD372564 - Sequence 353588 from Patent EP1572962.
JD170539 - Sequence 151563 from Patent EP1572962.
JD321579 - Sequence 302603 from Patent EP1572962.
JD122093 - Sequence 103117 from Patent EP1572962.
JD510151 - Sequence 491175 from Patent EP1572962.
JD515401 - Sequence 496425 from Patent EP1572962.
JD489378 - Sequence 470402 from Patent EP1572962.
JD096176 - Sequence 77200 from Patent EP1572962.
JD049542 - Sequence 30566 from Patent EP1572962.
JD130213 - Sequence 111237 from Patent EP1572962.
JD243812 - Sequence 224836 from Patent EP1572962.
JD444700 - Sequence 425724 from Patent EP1572962.
JD456429 - Sequence 437453 from Patent EP1572962.
JD421755 - Sequence 402779 from Patent EP1572962.
JD415691 - Sequence 396715 from Patent EP1572962.
JD310680 - Sequence 291704 from Patent EP1572962.
JD190287 - Sequence 171311 from Patent EP1572962.
JD324935 - Sequence 305959 from Patent EP1572962.
JD163420 - Sequence 144444 from Patent EP1572962.
JD545275 - Sequence 526299 from Patent EP1572962.
JD306575 - Sequence 287599 from Patent EP1572962.
JD452820 - Sequence 433844 from Patent EP1572962.
JD426322 - Sequence 407346 from Patent EP1572962.
JD122483 - Sequence 103507 from Patent EP1572962.
JD261210 - Sequence 242234 from Patent EP1572962.
JD290379 - Sequence 271403 from Patent EP1572962.
JD252072 - Sequence 233096 from Patent EP1572962.
JD115876 - Sequence 96900 from Patent EP1572962.
JD303040 - Sequence 284064 from Patent EP1572962.
AY263337 - Homo sapiens BCL2L1 mRNA, partial cds, alternatively spliced.
AY263336 - Homo sapiens BCL2L1 mRNA, partial cds, alternatively spliced.
AY263335 - Homo sapiens BCL2L1 mRNA, partial cds, alternatively spliced.
JD324579 - Sequence 305603 from Patent EP1572962.
JD155716 - Sequence 136740 from Patent EP1572962.
JD485702 - Sequence 466726 from Patent EP1572962.
JD555291 - Sequence 536315 from Patent EP1572962.
JD523305 - Sequence 504329 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04210 - Apoptosis
hsa04630 - Jak-STAT signaling pathway
hsa05014 - Amyotrophic lateral sclerosis (ALS)
hsa05200 - Pathways in cancer
hsa05212 - Pancreatic cancer
hsa05220 - Chronic myeloid leukemia
hsa05222 - Small cell lung cancer

Reactome (by CSHL, EBI, and GO)

Protein Q07817 (Reactome details) participates in the following event(s):

R-HSA-508162 BH3 only proteins associate with and inactivate anti-apoptotic BCL-XL
R-HSA-879201 Bcl-2 and Bcl-XL bind NLRP1
R-HSA-111453 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
R-HSA-844455 The NLRP1 inflammasome
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-109606 Intrinsic Pathway for Apoptosis
R-HSA-622312 Inflammasomes
R-HSA-449147 Signaling by Interleukins
R-HSA-109581 Apoptosis
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-5357801 Programmed Cell Death
R-HSA-168249 Innate Immune System
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: B2CL1_HUMAN, BCL2L, BCLX, CR936637, E1P5L6, NM_138578, NP_612815, Q07817, Q5CZ89, Q5TE65, Q92976
UCSC ID: uc002wwn.3
RefSeq Accession: NM_138578
Protein: Q07817 (aka B2CL1_HUMAN)
CCDS: CCDS13189.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: CR936637.1
exon count: 3CDS single in 3' UTR: no RNA size: 2604
ORF size: 702CDS single in intron: no Alignment % ID: 99.81
txCdsPredict score: 1547.00frame shift in genome: no % Coverage: 97.58
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.