Reviewed, UniProtKB/Swiss-Prot O43521 (BIM_HUMAN)

Names and origin

Protein names

Recommended name:
    Bcl-2-like protein 11
Alternative name(s):
    Bcl2-interacting mediator of cell death

Gene names

Name:	BCL2L11
Synonyms:	BIM

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	198 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Induces apoptosis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than the isoforms BimEL, BimL and BimS. Isoform Bim-gamma induces apoptosis. Ref.1 Ref.2 Ref.3 Ref.4
Subunit structure	Forms heterodimers with a number of antiapoptotic Bcl-2 proteins including MCL1, BCL2, BCL2L1 isoform Bcl-X(L), BCL2A1/BFL-1, and BHRF1. Does not heterodimerize with proapoptotic proteins such as BAD, BOK, BAX or BAK By similarity.
Subcellular location	Intracytoplasmic membrane; Peripheral membrane proteinBy similarity. Note= Associated with intracytoplasmic membranes By similarity. Isoform BimEL: Mitochondrion. Ref.2 Ref.3 Isoform BimL: Mitochondrion. Ref.2 Ref.3 Isoform BimS: Mitochondrion. Ref.2 Ref.3 Isoform Bim-alpha1: Mitochondrion. Ref.2 Ref.3
Tissue specificity	Isoform BimEL, isoform BimL and isoform BimS are the predominant isoforms and are ubiquitously expressed with a tissue-specific variation. Isoform Bim-gamma is most abundantly expressed in small intestine and colon, and in lower levels in spleen, prostate, testis, heart, liver and kidney. Ref.3
Domain	The BH3 motif is required for Bcl-2 binding and cytotoxicity.
Sequence similarities	Belongs to the Bcl-2 family.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Membrane Mitochondrion
Coding sequence diversity	Alternative splicing
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	activation of pro-apoptotic gene products Inferred from Experiment. Source: Reactome induction of apoptosis Traceable author statement. Source: UniProtKB
Cellular component	cytosol Inferred from Experiment. Source: Reactome endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell membrane fraction Ref.1 Traceable author statement. Source: ProtInc mitochondrial outer membrane Inferred from Experiment. Source: Reactome plasma membrane Inferred from Experiment. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AKT1	P31749	1	EBI-526416,EBI-296087
BCL2	P10415	2	EBI-526406,EBI-77694
BCL2	P10415	1	EBI-526416,EBI-77694
BCL2	P10415	2	EBI-526420,EBI-77694
BCL2A1	Q16548	1	EBI-526406,EBI-1003550
Bcl2a1	Q07440	1	EBI-526406,EBI-707754	From a different organism.
BCL2L1	Q07817	1	EBI-526406,EBI-78035
BCL2L1	Q07817-1	4	EBI-526406,EBI-287195
BCL2L1	Q07817-1	1	EBI-526416,EBI-287195
BCL2L2	Q92843	2	EBI-526406,EBI-707714
DYNLRB1	Q9NP97	1	EBI-526406,EBI-372128
Mapk1	P63085	1	EBI-526416,EBI-397697	From a different organism.
MCL1	Q07820	1	EBI-526406,EBI-1003422
Mcl1	P97287	3	EBI-526406,EBI-707292	From a different organism.
YWHAB	P31946	1	EBI-526406,EBI-359815

Alternative products

This entry describes 17 isoforms produced by alternative splicing. [Align] [Select]

Isoform BimEL (identifier: O43521-1)

Also known as: Bim(EL);

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 BimL (identifier: O43521-2)

Also known as: Bim(L);

The sequence of this isoform differs from the canonical sequence as follows:
     42-101: Missing.

Isoform BimS (identifier: O43521-3)

Also known as: BCL2-like 11 transcript variant 9; Bim(S);

The sequence of this isoform differs from the canonical sequence as follows:
     42-131: Missing.

Isoform Bim-alpha1 (identifier: O43521-4)

The sequence of this isoform differs from the canonical sequence as follows:
     167-198: VFLNNYQAAEDHPRMVILRLLRYIVRLVWRMH → LEK

Isoform Bim-alpha2 (identifier: O43521-5)

The sequence of this isoform differs from the canonical sequence as follows:
     42-101: Missing.
     167-198: VFLNNYQAAEDHPRMVILRLLRYIVRLVWRMH → LEK

Isoform Bim-alpha3 (identifier: O43521-6)

Also known as: BCL2-like 11 transcript variant 10;

The sequence of this isoform differs from the canonical sequence as follows:
     42-131: Missing.
     167-198: VFLNNYQAAEDHPRMVILRLLRYIVRLVWRMH → LEK

Isoform Bim-alpha4 (identifier: O43521-7)

The sequence of this isoform differs from the canonical sequence as follows:
     42-131: Missing.
     167-198: VFLNNYQAAEDHPRMVILRLLRYIVRLVWRMH → LAKLLASST

Isoform Bim-alpha5 (identifier: O43521-8)

The sequence of this isoform differs from the canonical sequence as follows:
     167-198: VFLNNYQAAEDHPRMVILRLLRYIVRLVWRMH → MPLPPD

Isoform Bim-alpha6 (identifier: O43521-9)

The sequence of this isoform differs from the canonical sequence as follows:
     42-131: Missing.
     167-198: VFLNNYQAAEDHPRMVILRLLRYIVRLVWRMH → MPLPPD

Isoform Bim-beta1 (identifier: O43521-10)

The sequence of this isoform differs from the canonical sequence as follows:
     133-135: SMR → NWD
     136-198: Missing.

Isoform Bim-beta2 (identifier: O43521-11)

The sequence of this isoform differs from the canonical sequence as follows:
     132-135: ASMR → GIFE
     136-198: Missing.

Isoform Bim-beta3 (identifier: O43521-12)

The sequence of this isoform differs from the canonical sequence as follows:
     42-75: GNPEGNHGGEGDSCPHGSPQGPLAPPASPGPFAT → VSLCHPGWSALVRSWLTATSNSQVQAVLLPQPPK

Isoform Bim-beta4 (identifier: O43521-13)

The sequence of this isoform differs from the canonical sequence as follows:
     43-44: NP → IF
     45-198: Missing.

Isoform Bim-beta5 (identifier: O43521-14)

The sequence of this isoform differs from the canonical sequence as follows:
     132-140: ASMRQAEPA → VREIEEVVV
     141-198: Missing.

Isoform Bim-beta6 (identifier: O43521-15)

The sequence of this isoform differs from the canonical sequence as follows:
     42-101: Missing.
     132-135: ASMR → GIFE
     136-198: Missing.

Isoform Bim-beta7 (identifier: O43521-16)

The sequence of this isoform differs from the canonical sequence as follows:
     42-101: Missing.
     132-140: ASMRQAEPA → VREIEEVVV
     141-198: Missing.

Isoform Bim-gamma (identifier: O43521-17)

The sequence of this isoform differs from the canonical sequence as follows:
     42-101: Missing.
     132-198: ASMRQAEPAD...YIVRLVWRMH → VVILEDIGDL...TEQLNHKDFS

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 198

198

Bcl-2-like protein 11

PRO_0000143109

Regions

Motif

148 – 162

15

BH3

Amino acid modifications

Modified residue

77

1

Phosphoserine Ref.10 Ref.11

Natural variations

Alternative sequence

42 – 131

90

Missing in isoform BimS, isoform Bim-alpha3, isoform Bim-alpha6 and isoform Bim-alpha4.

VSP_035608

Alternative sequence

42 – 101

60

Missing in isoform BimL, isoform Bim-alpha2, isoform Bim-gamma, isoform Bim-beta6 and isoform Bim-beta7.

VSP_000535

Alternative sequence

42 – 75

34

GNPEG…GPFAT → VSLCHPGWSALVRSWLTATS NSQVQAVLLPQPPK in isoform Bim-beta3.

VSP_035609

Alternative sequence

43 – 44

2

NP → IF in isoform Bim-beta4.

VSP_035610

Alternative sequence

45 – 198

154

Missing in isoform Bim-beta4.

VSP_035611

Alternative sequence

132 – 198

67

ASMRQ…VWRMH → VVILEDIGDLSLCFGFIFTG LDLYGHHHSQDTEQLNHKDF S in isoform Bim-gamma.

VSP_035612

Alternative sequence

132 – 140

9

ASMRQAEPA → VREIEEVVV in isoform Bim-beta5 and isoform Bim-beta7.

VSP_035613

Alternative sequence

132 – 135

4

ASMR → GIFE in isoform Bim-beta2 and isoform Bim-beta6.

VSP_035614

Alternative sequence

133 – 135

3

SMR → NWD in isoform Bim-beta1.

VSP_035615

Alternative sequence

136 – 198

63

Missing in isoform Bim-beta1, isoform Bim-beta2 and isoform Bim-beta6.

VSP_035616

Alternative sequence

141 – 198

58

Missing in isoform Bim-beta5 and isoform Bim-beta7.

VSP_035617

Alternative sequence

167 – 198

32

VFLNN…VWRMH → LEK in isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3.

VSP_035620

Alternative sequence

167 – 198

32

VFLNN…VWRMH → LAKLLASST in isoform Bim-alpha4.

VSP_035618

Alternative sequence

167 – 198

32

VFLNN…VWRMH → MPLPPD in isoform Bim-alpha5 and isoform Bim-alpha6.

VSP_035619

Experimental info

Sequence conflict

33

1

P → L in BAF83066. Ref.6

Secondary structure

1

.

.

.

198

Helix Strand Turn

Details...

Helix

144 – 164

21

Sequences

	Sequence		Length	Mass (Da)
	Isoform BimEL (Bim(EL)) [UniParc]. Last modified June 1, 1998. Version 1. Checksum: D75735E469CA6997	FASTA	198	22,171
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QGNPEGNHGG EGDSCPHGSP 70 80 90 100 110 120 QGPLAPPASP GPFATRSPLF IFMRRSSLLS RSSSGYFSFD TDRSPAPMSC DKSTQTPSPP 130 140 150 160 170 180 CQAFNHYLSA MASMRQAEPA DMRPEIWIAQ ELRRIGDEFN AYYARRVFLN NYQAAEDHPR 190 MVILRLLRYI VRLVWRMH
	Isoform BimL (Bim(L)). Checksum: 8BB4AAE06CB080FA		138	15,967
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QDRSPAPMSC DKSTQTPSPP 70 80 90 100 110 120 CQAFNHYLSA MASMRQAEPA DMRPEIWIAQ ELRRIGDEFN AYYARRVFLN NYQAAEDHPR 130 MVILRLLRYI VRLVWRMH
	Isoform BimS (BCL2-like 11 transcript variant 9) (Bim(S)). Checksum: 60067208524D5BEA		108	12,717
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QASMRQAEPA DMRPEIWIAQ 70 80 90 100 ELRRIGDEFN AYYARRVFLN NYQAAEDHPR MVILRLLRYI VRLVWRMH
	Isoform Bim-alpha1. Checksum: E2E24D5697C955BA		169	18,536
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QGNPEGNHGG EGDSCPHGSP 70 80 90 100 110 120 QGPLAPPASP GPFATRSPLF IFMRRSSLLS RSSSGYFSFD TDRSPAPMSC DKSTQTPSPP 130 140 150 160 CQAFNHYLSA MASMRQAEPA DMRPEIWIAQ ELRRIGDEFN AYYARRLEK
	Isoform Bim-alpha2. Checksum: 4335FA21C13B49AD		109	12,332
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QDRSPAPMSC DKSTQTPSPP 70 80 90 100 CQAFNHYLSA MASMRQAEPA DMRPEIWIAQ ELRRIGDEFN AYYARRLEK
	Isoform Bim-alpha3 (BCL2-like 11 transcript variant 10). Checksum: 3E03CCF2154A242C		79	9,081
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QASMRQAEPA DMRPEIWIAQ 70 ELRRIGDEFN AYYARRLEK
	Isoform Bim-alpha4. Checksum: 7A6FD9AF07DA3E05		85	9,596
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QASMRQAEPA DMRPEIWIAQ 70 80 ELRRIGDEFN AYYARRLAKL LASST
	Isoform Bim-alpha5. Checksum: D2F7FC06EE3CE697		172	18,816
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QGNPEGNHGG EGDSCPHGSP 70 80 90 100 110 120 QGPLAPPASP GPFATRSPLF IFMRRSSLLS RSSSGYFSFD TDRSPAPMSC DKSTQTPSPP 130 140 150 160 170 CQAFNHYLSA MASMRQAEPA DMRPEIWIAQ ELRRIGDEFN AYYARRMPLP PD
	Isoform Bim-alpha6. Checksum: 08678A7A0FBD4215		82	9,362
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QASMRQAEPA DMRPEIWIAQ 70 80 ELRRIGDEFN AYYARRMPLP PD
	Isoform Bim-beta1. Checksum: D208F1CB6D324539		135	14,458
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QGNPEGNHGG EGDSCPHGSP 70 80 90 100 110 120 QGPLAPPASP GPFATRSPLF IFMRRSSLLS RSSSGYFSFD TDRSPAPMSC DKSTQTPSPP 130 CQAFNHYLSA MANWD
	Isoform Bim-beta2. Checksum: D3A245DECD324539		135	14,418
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QGNPEGNHGG EGDSCPHGSP 70 80 90 100 110 120 QGPLAPPASP GPFATRSPLF IFMRRSSLLS RSSSGYFSFD TDRSPAPMSC DKSTQTPSPP 130 CQAFNHYLSA MGIFE
	Isoform Bim-beta3. Checksum: A8FA866EBD5CF16E		198	22,649
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QVSLCHPGWS ALVRSWLTAT 70 80 90 100 110 120 SNSQVQAVLL PQPPKRSPLF IFMRRSSLLS RSSSGYFSFD TDRSPAPMSC DKSTQTPSPP 130 140 150 160 170 180 CQAFNHYLSA MASMRQAEPA DMRPEIWIAQ ELRRIGDEFN AYYARRVFLN NYQAAEDHPR 190 MVILRLLRYI VRLVWRMH
	Isoform Bim-beta4. Checksum: FA9541901CA32FD1		44	4,834
	10 20 30 40 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QGIF
	Isoform Bim-beta5. Checksum: B7590CC04A98E081		140	15,025
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QGNPEGNHGG EGDSCPHGSP 70 80 90 100 110 120 QGPLAPPASP GPFATRSPLF IFMRRSSLLS RSSSGYFSFD TDRSPAPMSC DKSTQTPSPP 130 140 CQAFNHYLSA MVREIEEVVV
	Isoform Bim-beta6. Checksum: 7CFE6B5A5ED671F3		75	8,214
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QDRSPAPMSC DKSTQTPSPP 70 CQAFNHYLSA MGIFE
	Isoform Bim-beta7. Checksum: 6958582B30D7BCAF		80	8,821
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QDRSPAPMSC DKSTQTPSPP 70 80 CQAFNHYLSA MVREIEEVVV
	Isoform Bim-gamma. Checksum: 15E21254C12C239B		112	12,412
	10 20 30 40 50 60 MAKQPSDVSS ECDREGRQLQ PAERPPQLRP GAPTSLQTEP QDRSPAPMSC DKSTQTPSPP 70 80 90 100 110 CQAFNHYLSA MVVILEDIGD LSLCFGFIFT GLDLYGHHHS QDTEQLNHKD FS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Bim: a novel member of the Bcl-2 family that promotes apoptosis." O'Connor L., Strasser A., O'Reilly L.A., Hausmann G., Adams J.M., Cory S., Huang D.C.S. EMBO J. 17:384-395(1998) [PubMed: 9430630] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BIMEL AND BIML), FUNCTION. Tissue: Peripheral blood and Spleen.
[2]	"Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bcl-2 family." Mami U., Miyashita T., Shikama Y., Tadokoro K., Yamada M. FEBS Lett. 509:135-141(2001) [PubMed: 11734221] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BIM-ALPHA1; BIM-ALPHA2; BIM-BETA1; BIM-BETA2; BIM-BETA3 AND BIM-BETA4), FUNCTION (ISOFORMS BIM-ALPHA1 AND BIM-ALPHA2), SUBCELLULAR LOCATION.
[3]	"Identification and characterization of Bimgamma, a novel proapoptotic BH3-only splice variant of Bim." Liu J.-W., Chandra D., Tang S.H., Chopra D., Tang D.G. Cancer Res. 62:2976-2981(2002) [PubMed: 12019181] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BIM-GAMMA), FUNCTION (ISOFORM BIM-GAMMA), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]	"Over-expression of Bim alpha3, a novel isoform of human Bim, result in cell apoptosis." Chen J.Z., Ji C.N., Gu S.H., Li J.X., Zhao E.P., Huang Y., Huang L., Ying K., Xie Y., Mao Y.M. Int. J. Biochem. Cell Biol. 36:1554-1561(2004) [PubMed: 15147734] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BIMS AND BIM-ALPHA3), FUNCTION (ISOFORM BIM-ALPHA3).
[5]	"Identification and characterization of BH3 domain protein Bim and its isoforms in human hepatocellular carcinomas." Miao J., Chen G.G., Yun J.P., Chun S.Y., Zheng Z.Z., Ho R.L.K., Chak E.C., Xia N.S., Lai P.B. Apoptosis 12:1691-1701(2007) [PubMed: 17503221] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] ((ISOFORMS BIM-ALPHA3; BIM-ALPHA4; BIM-ALPHA5; BIM-ALPHA6; BIM-BETA5; BIM-BETA6; BIM-BETA7).
[6]	"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.,