Reviewed, UniProtKB/Swiss-Prot Q92843 (B2CL2_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	193 AA.
Sequence status	Complete.
Protein existence	Evidence 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
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.7 Ref.8
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.7
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.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Membrane Mitochondrion
Coding sequence diversity	Polymorphism
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	anti-apoptosis Traceable author statement. Source: ProtInc apoptosis Inferred from electronic annotation. Source: UniProtKB-KW spermatogenesis Ref.1 Traceable author statement. Source: ProtInc
Cellular component	extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BAD	Q92934	1	EBI-707714,EBI-700771
Bad	Q61337	1	EBI-707714,EBI-400328	From a different organism.
BBC3	Q9BXH1	2	EBI-707714,EBI-519884
BCL2L11	O43521	2	EBI-707714,EBI-526406
Bcl2l11	O54918	1	EBI-707714,EBI-526067	From a different organism.
BID	P55957	2	EBI-707714,EBI-519672
Bid	P70444	1	EBI-707714,EBI-783400	From a different organism.
BIK	Q13323	2	EBI-707714,EBI-700794
Bmf	Q91ZE9	2	EBI-707714,EBI-708032	From a different organism.
HRK	O00198	1	EBI-707714,EBI-701322

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 193

193

Bcl-2-like protein 2

PRO_0000143066

Regions

Motif

9 – 29

21

BH4

Motif

85 – 104

20

BH1

Motif

136 – 151

16

BH2

Amino acid modifications

Modified residue

192

1

Phosphoserine Ref.9

Natural variations

Natural variant

133

1

R → Q: dbSNP rs910332.

VAR_048418

Secondary structure

1

.

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.

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193

Helix Strand Turn

Details...

Helix

10 – 23

14

Helix

42 – 56

15

Helix

60 – 70

11

Helix

76 – 87

12

Helix

94 – 112

19

Helix

116 – 132

17

Helix

135 – 141

7

Helix

144 – 148

5

Beta strand

151 – 154

4

Helix

156 – 168

13

Sequences

	Sequence		Length	Mass (Da)
	Q92843-1 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: 3792243A50281761	FASTA	193	20,774
	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 ETRLADWIHS SGGWAEFTAL YGDGALEEAR RLREGNWASV RTVLTGAVAL 190 GALVTVGAFF ASK

References

	« Hide 'large scale' referencesShow '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: 8761287] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
[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: 9039502] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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].
[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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[5]	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. , 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].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Lung.
[7]	"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: 11423909] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]	"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: 12952938] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-192, MASS SPECTROMETRY.
[10]	"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: 12660157] [Abstract] Cited for: STRUCTURE BY NMR OF 1-183.
[11]	"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: 12651847] [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.
CH471078 Genomic DNA. Translation: EAW66169.1.
BC021198 mRNA. Translation: AAH21198.1.
BC104789 mRNA. Translation: AAI04790.1.
BC113522 mRNA. Translation: AAI13523.1.

IPI

IPI00023787.

RefSeq

NP_004041.1.

UniGene

Hs.410026

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MK3	NMR	-	A	2-171	[»]
1O0L	NMR	-	A	1-183	[»]
1ZY3	NMR	-	A	2-171	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33700N.

IntAct

Q92843. 11 interactions.

STRING

Q92843.

PTM databases

PhosphoSite

Q92843.

Proteomic databases

PRIDE

Q92843.

Genome annotation databases

Ensembl

ENST00000250405; ENSP00000250405; ENSG00000129473; Homo sapiens. [Genome view]

GeneID

599.

KEGG

hsa:599.

UCSC

uc001wjg.2. human.

Organism-specific databases

CTD

599.

GeneCards

GC14P022845.

HGNC

HGNC:995. BCL2L2.

HPA

CAB002048.

MIM

601931. gene.

PharmGKB

PA25307.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12634.

HOGENOM

HBG717457.

HOVERGEN

Q92843.

InParanoid

Q92843.

OrthoDB

EOG99GP2S.

Gene expression databases

ArrayExpress

Q92843.

Bgee

Q92843.

CleanEx

HS_BCL2L2.

Genevestigator

Q92843.

GermOnline

ENSG00000129473. Homo sapiens.

Family and domain databases

InterPro

IPR013280. Apop_reg_BclW.
IPR002475. BCL2_apoptsis.
IPR000712. Bcl2_BH.
IPR020717. Bcl2_BH1_motif_CS.
IPR020726. Bcl2_BH2_motif_CS.
IPR003093. Bcl2_BH4.
IPR020731. Bcl2_BH4_motif_CS.
[Graphical view]

Pfam

PF00452. Bcl-2. 1 hit.
PF02180. BH4. 1 hit.
[Graphical view]

PRINTS

PR01865. APOPREGBCLW.
PR01862. BCL2FAMILY.

SMART

SM00337. BCL. 1 hit.
SM00265. BH4. 1 hit.
[Graphical view]

PROSITE

PS50062. BCL2_FAMILY. 1 hit.
PS01080. BH1. 1 hit.
PS01258. BH2. 1 hit.
PS01260. BH4_1. 1 hit.
PS50063. BH4_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

2439.

SOURCE

Search...

Entry information

Entry name

B2CL2_HUMAN

Accession

Primary (citable) accession number: Q92843
Secondary accession number(s): A8K0F4, Q2M3U0, Q5U0H4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 1, 1997
Last modified:	January 19, 2010
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.