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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)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei308 – 33023HelicalSequence analysisAdd
BLAST

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

ChEMBLiCHEMBL5768.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 331331Induced myeloid leukemia cell differentiation protein Mcl-1 homologPRO_0000143081Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei102 – 1021PhosphoserineBy similarity
Cross-linki117 – 117Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei140 – 1401Phosphoserine; by GSK3-alpha and GSK3-beta1 Publication
Modified residuei143 – 1431PhosphoserineBy similarity
Modified residuei144 – 1441Phosphothreonine; by MAPKBy similarity
Cross-linki175 – 175Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki178 – 178Glycyl 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)LengthDescriptionGraphical viewFeature identifierActions
Sitei108 – 1092Cleavage; by caspase-3By similarity
Sitei138 – 1392Cleavage; by caspase-3By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP97287.
MaxQBiP97287.
PaxDbiP97287.
PeptideAtlasiP97287.
PRIDEiP97287.

PTM databases

iPTMnetiP97287.
PhosphoSiteiP97287.

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, BFM and PMAIP1. Interacts with BOP. Interacts with BCL2L11; may sequester BCL2L11 to prevent its pro-apoptotic activity.3 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 interactions.
DIPiDIP-33343N.
IntActiP97287. 14 interactions.
MINTiMINT-209660.
STRINGi10090.ENSMUSP00000044048.

Chemistry

BindingDBiP97287.

Structurei

Secondary structure

1
331
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi154 – 17219Combined sources
Turni181 – 1833Combined sources
Helixi185 – 1895Combined sources
Helixi206 – 2138Combined sources
Turni221 – 2233Combined sources
Helixi227 – 2348Combined sources
Turni235 – 2373Combined sources
Helixi242 – 26120Combined sources
Helixi265 – 2673Combined sources
Helixi268 – 28922Combined sources
Helixi292 – 3009Combined sources
Turni301 – 3033Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 115-308.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP97287.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni85 – 15672PEST-likeBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi190 – 20415BH3Add
BLAST
Motifi234 – 25320BH1Add
BLAST
Motifi285 – 30016BH2Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi149 – 1524Poly-Glu

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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei18 – 6346Missing in isoform 2. 1 PublicationVSP_046443Add
BLAST

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
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. Positions 115-308.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry

BindingDBiP97287.
ChEMBLiCHEMBL5768.

PTM databases

iPTMnetiP97287.
PhosphoSiteiP97287.

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: September 7, 2016
This is version 144 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.