Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q92843 (B2CL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bcl-2-like protein 2

Short name=Bcl2-L-2
Alternative name(s):
Apoptosis regulator Bcl-W
Gene names
Name:BCL2L2
Synonyms:BCLW, KIAA0271
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length193 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX. Ref.1

Subunit structure

Interacts with BOP By similarity.

Subcellular location

Mitochondrion membrane; Peripheral membrane protein. Note: Loosely associated with the mitochondrial membrane in healthy cells. During apoptosis, tightly bound to the membrane. Ref.8 Ref.9

Tissue specificity

Expressed (at protein level) in a wide range of tissues with highest levels in brain, spinal cord, testis, pancreas, heart, spleen and mammary glands. Moderate levels found in thymus, ovary and small intestine. Not detected in salivary gland, muscle or liver. Also expressed in cell lines of myeloid, fibroblast and epithelial origin. Not detected in most lymphoid cell lines. Ref.8

Domain

The BH4 motif seems to be involved in the anti-apoptotic function.

The BH1 and BH2 motifs form a hydrophobic groove which acts as a docking site for the BH3 domain of some pro-apoptotic proteins. The C-terminal residues of BCL2L2 fold into the BH3-binding cleft and modulate pro-survival activity by regulating ligand access. When BH3 domain-containing proteins bind, they displace the C-terminus, allowing its insertion into the membrane and neutralizing the pro-survival activity of BCL2L2.

Sequence similarities

Belongs to the Bcl-2 family.

Sequence caution

The sequence BAA19666.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q92843-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 3 (identifier: Q92843-2)

Also known as: BCL2L2-PABPN1;

The sequence of this isoform differs from the canonical sequence as follows:
     145-193: AEFTALYGDG...VTVGAFFASK → ELEAIKARVR...ARATSWYSPY
Note: Based on a readthrough transcript which may produce a BCL2L2-PABPN1 fusion protein. No experimental confirmation available. Contains a phosphoserine at position 177.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.11
Chain2 – 193192Bcl-2-like protein 2
PRO_0000143066

Regions

Motif9 – 2921BH4
Motif85 – 10420BH1
Motif136 – 15116BH2

Amino acid modifications

Modified residue21N-acetylalanine Ref.11

Natural variations

Alternative sequence145 – 19349AEFTA…FFASK → ELEAIKARVREMEEEAEKLK ELQNEVEKQMNMSPPPGNAG PVIMSIEEKMEADARSIYVG NVDYGATAEELEAHFHGCGS VNRVTILCDKFSGHPKGFAY IEFSDKESVRTSLALDESLF RGRQIKVIPKRTNRPGISTT DRGFPRARYRARTTNYNSSR SRFYSGFNSRPRGRVYRGRA RATSWYSPY in isoform 3.
VSP_042064
Natural variant1331Q → R. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.7
Corresponds to variant rs910332 [ dbSNP | Ensembl ].
VAR_048418

Secondary structure

....................... 193
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: 3542243A532B1762

FASTA19320,746
        10         20         30         40         50         60 
MATPASAPDT RALVADFVGY KLRQKGYVCG AGPGEGPAAD PLHQAMRAAG DEFETRFRRT 

        70         80         90        100        110        120 
FSDLAAQLHV TPGSAQQRFT QVSDELFQGG PNWGRLVAFF VFGAALCAES VNKEMEPLVG 

       130        140        150        160        170        180 
QVQEWMVAYL ETQLADWIHS SGGWAEFTAL YGDGALEEAR RLREGNWASV RTVLTGAVAL 

       190 
GALVTVGAFF ASK 

« Hide

Isoform 3 (BCL2L2-PABPN1) [UniParc].

Checksum: F2C9A67BF3D38122
Show »

FASTA33337,171

References

« Hide 'large scale' references
[1]"Bcl-w, a novel member of the Bcl-2 family, promotes cell survival."
Gibson L., Holmgreen S.P., Huang D.C., Bernard O., Copeland N.G., Jenkins N.A., Sutherland G.R., Baker E., Adams J.M., Cory S.
Oncogene 13:665-675(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, VARIANT ARG-133.
[2]"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain."
Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N.
DNA Res. 3:321-329(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-133.
Tissue: Brain.
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-133.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-133.
Tissue: Cerebellum.
[5]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ARG-133.
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANT ARG-133.
Tissue: Brain, Lung and Rhabdomyosarcoma.
[8]"Tissue expression and subcellular localization of the pro-survival molecule Bcl-w."
O'Reilly L.A., Print C., Hausmann G., Moriishi K., Cory S., Huang D.C.S., Strasser A.
Cell Death Differ. 8:486-494(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]"Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity."
Wilson-Annan J., O'Reilly L.A., Crawford S.A., Hausmann G., Beaumont J.G., Parma L.P., Chen L., Lackmann M., Lithgow T., Hinds M.G., Day C.L., Adams J.M., Huang D.C.S.
J. Cell Biol. 162:877-887(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177 (ISOFORM 3), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[12]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177 (ISOFORM 3), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[13]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177 (ISOFORM 3), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177 (ISOFORM 3), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity."
Hinds M.G., Lackmann M., Skea G.L., Harrison P.J., Huang D.C.S., Day C.L.
EMBO J. 22:1497-1507(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-183.
[17]"Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix."
Denisov A.Y., Madiraju M.S.R., Chen G., Khadir A., Beauparlant P., Attardo G., Shore G.C., Gehring K.
J. Biol. Chem. 278:21124-21128(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 2-171.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U59747 mRNA. Translation: AAB09055.1.
D87461 mRNA. Translation: BAA19666.2. Different initiation.
BT019549 mRNA. Translation: AAV38356.1.
AK289519 mRNA. Translation: BAF82208.1.
AL049829 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW66169.1.
BC011637 mRNA. No translation available.
BC021198 mRNA. Translation: AAH21198.1.
BC104789 mRNA. Translation: AAI04790.1.
BC113522 mRNA. Translation: AAI13523.1.
RefSeqNP_001186768.1. NM_001199839.1.
NP_004041.1. NM_004050.4.
UniGeneHs.410026.
Hs.735863.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1MK3NMR-A2-171[»]
1O0LNMR-A1-183[»]
1ZY3NMR-A2-171[»]
2Y6WX-ray2.00A/B1-164[»]
ProteinModelPortalQ92843.
SMRQ92843. Positions 1-183.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107071. 13 interactions.
DIPDIP-33700N.
IntActQ92843. 13 interactions.
MINTMINT-206525.
STRING9606.ENSP00000250405.

Chemistry

ChEMBLCHEMBL4677.

Protein family/group databases

TCDB1.A.21.1.5. the bcl-2 (bcl-2) family.

PTM databases

PhosphoSiteQ92843.

Polymorphism databases

DMDM296434404.

Proteomic databases

PaxDbQ92843.
PRIDEQ92843.

Protocols and materials databases

DNASU599.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000250405; ENSP00000250405; ENSG00000129473. [Q92843-1]
ENST00000553781; ENSP00000451320; ENSG00000258643. [Q92843-2]
ENST00000557008; ENSP00000452479; ENSG00000258643. [Q92843-2]
GeneID599.
KEGGhsa:599.
UCSCuc001wjg.4. human. [Q92843-1]
uc001wjh.4. human. [Q92843-2]

Organism-specific databases

CTD599.
GeneCardsGC14P023776.
GC14P023777.
HGNCHGNC:995. BCL2L2.
HGNC:42959. BCL2L2-PABPN1.
HPACAB040539.
HPA000637.
MIM601931. gene.
neXtProtNX_Q92843.
PharmGKBPA25307.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG300479.
HOGENOMHOG000056452.
InParanoidQ92843.
KOK02163.
OMAWEEQHAT.
PhylomeDBQ92843.
TreeFamTF105907.
TF315834.

Gene expression databases

ArrayExpressQ92843.
BgeeQ92843.
CleanExHS_BCL2L2.
GenevestigatorQ92843.

Family and domain databases

InterProIPR013280. Apop_reg_BclW.
IPR002475. Bcl2-like.
IPR020717. Bcl2_BH1_motif_CS.
IPR020726. Bcl2_BH2_motif_CS.
IPR003093. Bcl2_BH4.
IPR020731. Bcl2_BH4_motif_CS.
IPR026298. Blc2_fam.
[Graphical view]
PANTHERPTHR11256. PTHR11256. 1 hit.
PTHR11256:SF13. PTHR11256:SF13. 1 hit.
PfamPF00452. Bcl-2. 1 hit.
PF02180. BH4. 1 hit.
[Graphical view]
PRINTSPR01865. APOPREGBCLW.
PR01862. BCL2FAMILY.
SMARTSM00265. BH4. 1 hit.
[Graphical view]
PROSITEPS50062. BCL2_FAMILY. 1 hit.
PS01080. BH1. 1 hit.
PS01258. BH2. 1 hit.
PS01260. BH4_1. 1 hit.
PS50063. BH4_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSBCL2L2. human.
EvolutionaryTraceQ92843.
GeneWikiBCL2L2.
GenomeRNAi599.
NextBio2439.
PROQ92843.
SOURCESearch...

Entry information

Entry nameB2CL2_HUMAN
AccessionPrimary (citable) accession number: Q92843
Secondary accession number(s): A8K0F4, Q2M3U0, Q5U0H4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 18, 2010
Last modified: April 16, 2014
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM