Reviewed, UniProtKB/Swiss-Prot P97287 (MCL1_MOUSE)

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)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	331 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
Subunit structure	Interacts with BAD, BOK, BIK, BAX, BAK1, and TPT1 By similarity. Interacts with BBC3, BCL2L11, BFM and PMAIP1.
Subcellular location	Membrane; Single-pass membrane proteinBy similarity. CytoplasmBy similarity. MitochondrionBy similarity. Nucleus › nucleoplasmBy 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.
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
Domain	Transmembrane
Molecular function	Developmental protein
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW regulation of apoptosis Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrion Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BAK1	Q16611	3	EBI-707292,EBI-519866	From a different organism.
BBC3	Q9BXH1	2	EBI-707292,EBI-519884	From a different organism.
BCL2L11	O43521	3	EBI-707292,EBI-526406	From a different organism.
Bcl2l11	O54918	1	EBI-707292,EBI-526067
PMAIP1	Q13794	1	EBI-707292,EBI-707392	From a different organism.
Pmaip1	Q9JM54	1	EBI-707292,EBI-709183

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

Potential

Region

85 – 156

72

PEST-like By similarity

Motif

190 – 204

15

BH3

Motif

233 – 253

21

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

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

Secondary structure

1

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331

Helix Strand Turn

Details...

Helix

154 – 172

19

Beta strand

181 – 183

3

Helix

185 – 215

31

Turn

221 – 223

3

Helix

224 – 234

11

Beta strand

237 – 239

3

Helix

242 – 261

20

Helix

265 – 282

18

Helix

284 – 289

6

Turn

290 – 292

3

Helix

293 – 299

7

Sequences

	Sequence		Length	Mass (Da)
	P97287-1 [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

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: 9655929] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION. Tissue: Fetus.
[2]	"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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Embryo and Embryonic stem cell.
[3]	"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]. Strain: Czech II and FVB/N. Tissue: Mammary tumor and Salivary gland.
[4]	"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: 9671497] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-65, INDUCTION. Strain: 129/SvJ.
[5]	"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: 15550399] [Abstract] Cited for: STRUCTURE BY NMR OF 152-308, INTERACTION WITH BCL2L11; BMF AND PMAIP.
[6]	"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: 18589438] [Abstract] Cited for: STRUCTURE BY NMR OF 148-308 IN COMPLEXES WITH WITH BBC3 AND PMAIP1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U35623 mRNA. Translation: AAC31790.1.
AK010424 mRNA. Translation: BAB26927.1.
AK159504 mRNA. Translation: BAE35137.1.
AK160594 mRNA. Translation: BAE35901.1.
BC003839 mRNA. Translation: AAH03839.1.
BC005427 mRNA. Translation: AAH05427.1.
BC021638 mRNA. Translation: AAH21638.1.
AF063886 Genomic DNA. Translation: AAC27929.1.

RefSeq

NP_032588.1.

UniGene

Mm.1639

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WSX	NMR	-	A	152-308	[»]
2JM6	NMR	-	B	148-308	[»]
2ROC	NMR	-	A	148-308	[»]
2ROD	NMR	-	A	148-308	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P97287.

PTM databases

PhosphoSite

P97287.

Genome annotation databases

Ensembl

ENSMUSG00000038612. Mus musculus. [Contig view]

GeneID

17210.

KEGG

mmu:17210.

Organism-specific databases

MGI

MGI:101769. Mcl1.

Phylogenomic databases

HOGENOM

P97287.

HOVERGEN

P97287.

Gene expression databases

ArrayExpress

P97287.

CleanEx

MM_MCL1.

GermOnline

ENSMUSG00000038612. Mus musculus.

Family and domain databases

InterPro

IPR013281. Apop_reg_Mc1.
IPR002475. BCL2_apoptsis.
IPR000712. Bcl2_BH.
[Graphical view]

Pfam

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

PRINTS

PR01866. APOPREGMCL1.
PR01862. BCL2FAMILY.

SMART

SM00337. BCL. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other Resources

NextBio

291598.

SOURCE

Search...

Entry information

Entry name

MCL1_MOUSE

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2005
Last sequence update:	November 1, 1998
Last modified:	November 25, 2008
This is version 74 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)