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Protein

Induced myeloid leukemia cell differentiation protein Mcl-1 homolog

Gene

Mcl1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Apoptosis, Differentiation

Names & Taxonomyi

Protein namesi
Recommended name:
Induced myeloid leukemia cell differentiation protein Mcl-1 homolog
Alternative name(s):
Bcl-2-related protein EAT/mcl1
Gene namesi
Name:Mcl1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:101769. Mcl1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei308 – 330HelicalSequence analysisAdd BLAST23

GO - Cellular componenti

  • Bcl-2 family protein complex Source: MGI
  • cytoplasm Source: MGI
  • cytosol Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: UniProtKB
  • mitochondrial matrix Source: MGI
  • mitochondrial outer membrane Source: GO_Central
  • mitochondrion Source: ParkinsonsUK-UCL
  • nucleoplasm Source: UniProtKB-SubCell
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL5768.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001430811 – 331Induced myeloid leukemia cell differentiation protein Mcl-1 homologAdd BLAST331

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei102PhosphoserineBy similarity1
Cross-linki117Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei140Phosphoserine; by GSK3-alpha and GSK3-beta1 Publication1
Modified residuei143PhosphoserineBy similarity1
Modified residuei144Phosphothreonine; by MAPKBy similarity1
Cross-linki175Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki178Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

Post-translational modificationi

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 Ser-140, by GSK3, in response to IL3/interleukin-3 withdrawal. Phosphorylation at Ser-140 induces ubiquitination and proteasomal degradation, abrogating the anti-apoptotic activity. Treatment with taxol or okadaic acid induces phosphorylation on additional sites.1 Publication
Ubiquitinated. Ubiquitination is induced by phosphorylation at Ser-140 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei108 – 109Cleavage; by caspase-3By similarity2
Sitei138 – 139Cleavage; by caspase-3By similarity2

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP97287.
MaxQBiP97287.
PaxDbiP97287.
PeptideAtlasiP97287.
PRIDEiP97287.

PTM databases

iPTMnetiP97287.
PhosphoSitePlusiP97287.

Expressioni

Inductioni

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.2 Publications

Gene expression databases

BgeeiENSMUSG00000038612.
CleanExiMM_MCL1.
GenevisibleiP97287. MM.

Interactioni

Subunit structurei

Interacts with HIF3A isoform 2 (via C-terminus domain) (PubMed:21546903). Interacts with BAD, BOK, BIK, BAX, BAK1, and TPT1. Interacts with BBC3, BMF and PMAIP1 (PubMed:15550399, PubMed:18589438). Interacts with BOP. Interacts with BCL2L11; this interaction may sequester BCL2L11 and prevent its pro-apoptotic activity (PubMed:16543145, PubMed:27013495, PubMed:15550399).5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BAK1Q166113EBI-707292,EBI-519866From a different organism.
BAXQ078122EBI-707292,EBI-516580From a different organism.
BBC3Q9BXH15EBI-707292,EBI-519884From a different organism.
BCL2L11O435217EBI-707292,EBI-526406From a different organism.
Bcl2l11O549184EBI-707292,EBI-526067
Pmaip1Q9JM544EBI-707292,EBI-709183

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201344. 14 interactors.
DIPiDIP-33343N.
IntActiP97287. 14 interactors.
MINTiMINT-209660.
STRINGi10090.ENSMUSP00000044048.

Chemistry databases

BindingDBiP97287.

Structurei

Secondary structure

1331
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi154 – 172Combined sources19
Turni181 – 183Combined sources3
Helixi185 – 189Combined sources5
Helixi206 – 213Combined sources8
Turni221 – 223Combined sources3
Helixi227 – 234Combined sources8
Turni235 – 237Combined sources3
Helixi242 – 261Combined sources20
Helixi265 – 267Combined sources3
Helixi268 – 289Combined sources22
Helixi292 – 300Combined sources9
Turni301 – 303Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WSXNMR-A152-308[»]
2JM6NMR-B152-308[»]
2NL9X-ray1.55A152-189[»]
2NLAX-ray2.80A152-189[»]
2ROCNMR-A152-308[»]
2RODNMR-A152-308[»]
3D7VX-ray2.03A152-189[»]
3IO9X-ray2.40A152-189[»]
4BPIX-ray1.98A152-189[»]
4BPJX-ray1.60A152-189[»]
4G35X-ray2.00A152-308[»]
ProteinModelPortaliP97287.
SMRiP97287.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP97287.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni85 – 156PEST-likeBy similarityAdd BLAST72

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi190 – 204BH3Add BLAST15
Motifi234 – 253BH1Add BLAST20
Motifi285 – 300BH2Add BLAST16

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi149 – 152Poly-Glu4

Sequence similaritiesi

Belongs to the Bcl-2 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4728. Eukaryota.
ENOG41123S0. LUCA.
GeneTreeiENSGT00510000048923.
HOGENOMiHOG000232116.
HOVERGENiHBG003527.
InParanoidiP97287.
KOiK02539.
OMAiAKDTKPM.
OrthoDBiEOG091G0E6Q.
PhylomeDBiP97287.
TreeFamiTF315834.

Family and domain databases

InterProiIPR013281. 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]
PANTHERiPTHR11256. PTHR11256. 1 hit.
PfamiPF00452. Bcl-2. 1 hit.
[Graphical view]
PRINTSiPR01866. APOPREGMCL1.
PR01862. BCL2FAMILY.
PROSITEiPS50062. BCL2_FAMILY. 1 hit.
PS01080. BH1. 1 hit.
PS01258. BH2. 1 hit.
PS01259. BH3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P97287-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MFGLRRNAVI GLNLYCGGAS LGAGGGSPAG ARLVAEEAKA RREGGGEAAL
60 70 80 90 100
LPGARVVARP PPVGAEDPDV TASAERRLHK SPGLLAVPPE EMAASAAAAI
110 120 130 140 150
VSPEEELDGC EPEAIGKRPA VLPLLERVSE AAKSSGADGS LPSTPPPPEE
160 170 180 190 200
EEDDLYRQSL EIISRYLREQ ATGSKDSKPL GEAGAAGRRA LETLRRVGDG
210 220 230 240 250
VQRNHETAFQ GMLRKLDIKN EGDVKSFSRV MVHVFKDGVT NWGRIVTLIS
260 270 280 290 300
FGAFVAKHLK SVNQESFIEP LAETITDVLV RTKRDWLVKQ RGWDGFVEFF
310 320 330
HVQDLEGGIR NVLLAFAGVA GVGAGLAYLI R
Length:331
Mass (Da):35,217
Last modified:November 1, 1998 - v3
Checksum:iE4FD369DB0EC6723
GO
Isoform 2 (identifier: P97287-2) [UniParc]FASTAAdd to basket
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.
Show »
Length:285
Mass (Da):30,930
Checksum:i73643EE7EE849B27
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04644318 – 63Missing in isoform 2. 1 PublicationAdd BLAST46

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS57236.1. [P97287-1]
RefSeqiNP_032588.1. NM_008562.3. [P97287-1]
UniGeneiMm.1639.

Genome annotation databases

EnsembliENSMUST00000037947; ENSMUSP00000044048; ENSMUSG00000038612. [P97287-1]
ENSMUST00000178686; ENSMUSP00000135915; ENSMUSG00000038612. [P97287-2]
GeneIDi17210.
KEGGimmu:17210.
UCSCiuc029unp.1. mouse. [P97287-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS57236.1. [P97287-1]
RefSeqiNP_032588.1. NM_008562.3. [P97287-1]
UniGeneiMm.1639.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WSXNMR-A152-308[»]
2JM6NMR-B152-308[»]
2NL9X-ray1.55A152-189[»]
2NLAX-ray2.80A152-189[»]
2ROCNMR-A152-308[»]
2RODNMR-A152-308[»]
3D7VX-ray2.03A152-189[»]
3IO9X-ray2.40A152-189[»]
4BPIX-ray1.98A152-189[»]
4BPJX-ray1.60A152-189[»]
4G35X-ray2.00A152-308[»]
ProteinModelPortaliP97287.
SMRiP97287.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201344. 14 interactors.
DIPiDIP-33343N.
IntActiP97287. 14 interactors.
MINTiMINT-209660.
STRINGi10090.ENSMUSP00000044048.

Chemistry databases

BindingDBiP97287.
ChEMBLiCHEMBL5768.

PTM databases

iPTMnetiP97287.
PhosphoSitePlusiP97287.

Proteomic databases

EPDiP97287.
MaxQBiP97287.
PaxDbiP97287.
PeptideAtlasiP97287.
PRIDEiP97287.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000037947; ENSMUSP00000044048; ENSMUSG00000038612. [P97287-1]
ENSMUST00000178686; ENSMUSP00000135915; ENSMUSG00000038612. [P97287-2]
GeneIDi17210.
KEGGimmu:17210.
UCSCiuc029unp.1. mouse. [P97287-1]

Organism-specific databases

CTDi4170.
MGIiMGI:101769. Mcl1.

Phylogenomic databases

eggNOGiKOG4728. Eukaryota.
ENOG41123S0. LUCA.
GeneTreeiENSGT00510000048923.
HOGENOMiHOG000232116.
HOVERGENiHBG003527.
InParanoidiP97287.
KOiK02539.
OMAiAKDTKPM.
OrthoDBiEOG091G0E6Q.
PhylomeDBiP97287.
TreeFamiTF315834.

Miscellaneous databases

ChiTaRSiMcl1. mouse.
EvolutionaryTraceiP97287.
PROiP97287.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038612.
CleanExiMM_MCL1.
GenevisibleiP97287. MM.

Family and domain databases

InterProiIPR013281. 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]
PANTHERiPTHR11256. PTHR11256. 1 hit.
PfamiPF00452. Bcl-2. 1 hit.
[Graphical view]
PRINTSiPR01866. APOPREGMCL1.
PR01862. BCL2FAMILY.
PROSITEiPS50062. BCL2_FAMILY. 1 hit.
PS01080. BH1. 1 hit.
PS01258. BH2. 1 hit.
PS01259. BH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMCL1_MOUSE
AccessioniPrimary (citable) accession number: P97287
Secondary accession number(s): D2K6L9
, Q3TUS0, Q792P0, Q9CRI4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: November 1, 1998
Last modified: November 30, 2016
This is version 147 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.