P97287 (MCL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Induced myeloid leukemia cell differentiation protein Mcl-1 homolog

Alternative name(s):
Bcl-2-related protein EAT/mcl1

Gene names

Name:

Mcl1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	331 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 2 has antiapoptotic activity. Ref.2
Subunit structure	Interacts with BAD, BOK, BIK, BAX, BAK1, and TPT1 By similarity. Interacts with BBC3, BCL2L11, BFM and PMAIP1. Interacts with BOP By similarity. Ref.7
Subcellular location	Membrane; Single-pass membrane protein By similarity. Cytoplasm By similarity. Mitochondrion. Nucleus › nucleoplasm By similarity. Note: Cytoplasmic, associated with mitochondria.
Induction	Up-regulated by IL3 and CSF2. Up-regulated in murine embryonal carcinoma cells in response to retinoic acid treatment. Levels reach a maximum after 4 hours, are decreased after 8 hours and are back to maximum after 12 hours. Levels are decreased after 24 hours and back to basal levels after 48 hours. Expression remains constant in retinoic acid-treated embryonic stem cells. Ref.1 Ref.6
Post-translational modification	Cleaved by CASP3 during apoptosis, yielding a pro-apoptotic C-terminal fragment By similarity. Rapidly degraded in the absence of phosphorylation in the PEST region By similarity. Phosphorylated on several Ser and Thr residues By similarity.
Sequence similarities	Belongs to the Bcl-2 family.

Ontologies

Keywords
Biological process	Apoptosis Differentiation
Cellular component	Cytoplasm Membrane Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Molecular function	Developmental protein
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of anoikis Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from direct assay Ref.2. Source: MGI negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Inferred from electronic annotation. Source: Compara response to cytokine stimulus Inferred from electronic annotation. Source: Compara
Cellular_component	Bcl-2 family protein complex Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane Inferred from sequence orthology PubMed 7896880. Source: MGI mitochondrial matrix Inferred from direct assay PubMed 20627101. Source: MGI mitochondrion Inferred from sequence orthology PubMed 7896880. Source: MGI nucleoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay PubMed 20467439. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BAK1	Q16611	3	EBI-707292,EBI-519866	From a different organism.
BAX	Q07812	2	EBI-707292,EBI-516580	From a different organism.
BBC3	Q9BXH1	3	EBI-707292,EBI-519884	From a different organism.
BCL2L11	O43521	5	EBI-707292,EBI-526406	From a different organism.
Bcl2l11	O54918	3	EBI-707292,EBI-526067
Pmaip1	Q9JM54	2	EBI-707292,EBI-709183

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P97287-1)

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 2 (identifier: P97287-2)

Also known as: Mck-1V;

The sequence of this isoform differs from the canonical sequence as follows:
     18-63: Missing.

Note: This isoform is more stable than isoform 1 in cells undergoing apoptosis.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 331

331

Induced myeloid leukemia cell differentiation protein Mcl-1 homolog

PRO_0000143081

Regions

Transmembrane

308 – 330

23

Helical; Potential

Region

85 – 156

72

PEST-like By similarity

Motif

190 – 204

15

BH3

Motif

234 – 253

20

BH1

Motif

285 – 300

16

BH2

Compositional bias

149 – 152

4

Poly-Glu

Sites

Site

108 – 109

2

Cleavage; by caspase-3 By similarity

Site

138 – 139

2

Cleavage; by caspase-3 By similarity

Amino acid modifications

Modified residue

102

1

Phosphoserine By similarity

Modified residue

143

1

Phosphoserine By similarity

Modified residue

144

1

Phosphothreonine; by MAPK By similarity

Cross-link

117

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Cross-link

175

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Cross-link

178

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence

18 – 63

46

Missing in isoform 2.

VSP_046443

Secondary structure

1

.

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.

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.

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.

.

.

.

331

Helix Strand Turn

Details...

Helix

154 – 172

19

Beta strand

181 – 183

3

Helix

185 – 189

5

Helix

206 – 213

8

Turn

221 – 223

3

Helix

227 – 234

8

Turn

235 – 237

3

Helix

242 – 261

20

Helix

265 – 267

3

Helix

268 – 289

22

Helix

292 – 300

9

Turn

301 – 303

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 3. Checksum: E4FD369DB0EC6723	FASTA	331	35,217
	10 20 30 40 50 60 MFGLRRNAVI GLNLYCGGAS LGAGGGSPAG ARLVAEEAKA RREGGGEAAL LPGARVVARP 70 80 90 100 110 120 PPVGAEDPDV TASAERRLHK SPGLLAVPPE EMAASAAAAI VSPEEELDGC EPEAIGKRPA 130 140 150 160 170 180 VLPLLERVSE AAKSSGADGS LPSTPPPPEE EEDDLYRQSL EIISRYLREQ ATGSKDSKPL 190 200 210 220 230 240 GEAGAAGRRA LETLRRVGDG VQRNHETAFQ GMLRKLDIKN EGDVKSFSRV MVHVFKDGVT 250 260 270 280 290 300 NWGRIVTLIS FGAFVAKHLK SVNQESFIEP LAETITDVLV RTKRDWLVKQ RGWDGFVEFF 310 320 330 HVQDLEGGIR NVLLAFAGVA GVGAGLAYLI R
	Isoform 2 (Mck-1V) [UniParc]. Checksum: 73643EE7EE849B27	FASTA	285	30,930
	10 20 30 40 50 60 MFGLRRNAVI GLNLYCGGAE DPDVTASAER RLHKSPGLLA VPPEEMAASA AAAIVSPEEE 70 80 90 100 110 120 LDGCEPEAIG KRPAVLPLLE RVSEAAKSSG ADGSLPSTPP PPEEEEDDLY RQSLEIISRY 130 140 150 160 170 180 LREQATGSKD SKPLGEAGAA GRRALETLRR VGDGVQRNHE TAFQGMLRKL DIKNEGDVKS 190 200 210 220 230 240 FSRVMVHVFK DGVTNWGRIV TLISFGAFVA KHLKSVNQES FIEPLAETIT DVLVRTKRDW 250 260 270 280 LVKQRGWDGF VEFFHVQDLE GGIRNVLLAF AGVAGVGAGL AYLIR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Up-regulated expression of murine Mcl1/EAT, a bcl-2 related gene, in the early stage of differentiation of murine embryonal carcinoma cells and embryonic stem cells." Okita H., Umezawa A., Suzuki A., Hata J. Biochim. Biophys. Acta 1398:335-341(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION. Tissue: Fetus.
[2]	"MCL-1V, a novel mouse antiapoptotic MCL-1 variant, generated by RNA splicing at a non-canonical splicing pair." Kojima S., Hyakutake A., Koshikawa N., Nakagawara A., Takenaga K. Biochem. Biophys. Res. Commun. 391:492-497(2010) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCALIZATION. Strain: C57BL/6.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Embryo and Embryonic stem cell.
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[5]	"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] (ISOFORM 1). Strain: Czech II and FVB/N. Tissue: Mammary tumor and Salivary gland.
[6]	"Mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway and is one component of the GM-CSF viability response." Chao J.-R., Wang J.-M., Lee S.-F., Peng H.-W., Lin Y.-H., Chou C.-H., Li J.-C., Huang H.-M., Chou C.-K., Kuo M.-L., Yen J.J.-Y., Yang-Yen H.-F. Mol. Cell. Biol. 18:4883-4898(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-65, INDUCTION. Strain: 129/SvJ.
[7]	"Solution structure of prosurvival Mcl-1 and characterization of its binding by proapoptotic BH3-only ligands." Day C.L., Chen L., Richardson S.J., Harrison P.J., Huang D.C.S., Hinds M.G. J. Biol. Chem. 280:4738-4744(2005) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 152-308, INTERACTION WITH BCL2L11; BMF AND PMAIP.
[8]	"Structure of the BH3 domains from the p53-inducible BH3-only proteins Noxa and Puma in complex with Mcl-1." Day C.L., Smits C., Fan F.C., Lee E.F., Fairlie W.D., Hinds M.G. J. Mol. Biol. 380:958-971(2008) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 148-308 IN COMPLEXES WITH WITH BBC3 AND PMAIP1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U35623 mRNA. Translation: AAC31790.1.
GU182318 mRNA. Translation: ACZ54910.1.
AK010424 mRNA. Translation: BAB26927.1.
AK159504 mRNA. Translation: BAE35137.1.
AK160594 mRNA. Translation: BAE35901.1.
AC092479 Genomic DNA. No translation available.
FO082281 Genomic DNA. No translation available.
BC003839 mRNA. Translation: AAH03839.1.
BC005427 mRNA. Translation: AAH05427.1.
BC021638 mRNA. Translation: AAH21638.1.
AF063886 Genomic DNA. Translation: AAC27929.1.

IPI

IPI00122958.
IPI00955164.

RefSeq

NP_032588.1. NM_008562.3.

UniGene

Mm.1639.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WSX	NMR	-	A	152-308	[»]
2JM6	NMR	-	B	152-308	[»]
2NL9	X-ray	1.55	A	152-189	[»]
2NLA	X-ray	2.80	A	152-189	[»]
2ROC	NMR	-	A	152-308	[»]
2ROD	NMR	-	A	152-308	[»]
3IO9	X-ray	2.40	A	152-189	[»]
4G35	X-ray	2.00	A	152-308	[»]

ProteinModelPortal

P97287.

SMR

P97287. Positions 137-331.

ModBase

Search...

Protein-protein interaction databases

IntAct

P97287. 8 interactions.

PTM databases

PhosphoSite

P97287.

Proteomic databases

PaxDb

P97287.

PRIDE

P97287.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000037947; ENSMUSP00000044048; ENSMUSG00000038612.

GeneID

17210.

KEGG

mmu:17210.

UCSC

uc008qkl.1. mouse.

Organism-specific databases

CTD

4170.

MGI

MGI:101769. Mcl1.

Phylogenomic databases

eggNOG

NOG282183.

GeneTree

ENSGT00510000048923.

HOGENOM

HOG000232116.

HOVERGEN

HBG003527.

InParanoid

P97287.

KO

K02539.

OMA

KDTKPMG.

OrthoDB

EOG4M65K0.

Gene expression databases

ArrayExpress

P97287.

Bgee

P97287.

CleanEx

MM_MCL1.

Genevestigator

P97287.

GermOnline

ENSMUSG00000038612. Mus musculus.

Family and domain databases

InterPro

IPR013281. Apop_reg_Mc1.
IPR002475. Bcl2-like.
IPR020717. Bcl2_BH1_motif_CS.
IPR020726. Bcl2_BH2_motif_CS.
IPR020728. Bcl2_BH3_motif_CS.
IPR026298. Blc2_fam.
[Graphical view]

PANTHER

PTHR11256. PTHR11256. 1 hit.
PTHR11256:SF6. PTHR11256:SF6. 1 hit.

Pfam

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

PRINTS

PR01866. APOPREGMCL1.
PR01862. BCL2FAMILY.

PROSITE

PS50062. BCL2_FAMILY. 1 hit.
PS01080. BH1. 1 hit.
PS01258. BH2. 1 hit.
PS01259. BH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P97287.

ChEMBL

CHEMBL5768.

ChiTaRS

MCL1. mouse.

EvolutionaryTrace

P97287.

NextBio

291598.

SOURCE

Search...

Entry information

Entry name

MCL1_MOUSE

Accession

Primary (citable) accession number: P97287
Secondary accession number(s): D2K6L9 , Q3TUS0, Q792P0, Q9CRI4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2005
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 112 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program