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Protein

Induced myeloid leukemia cell differentiation protein Mcl-1

Gene

MCL1

Organism
Homo sapiens (Human)
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 1 inhibits apoptosis. Isoform 2 promotes apoptosis.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei127 – 1282Cleavage; by caspase-3
Sitei157 – 1582Cleavage; by caspase-3

GO - Molecular functioni

  1. BH3 domain binding Source: BHF-UCL
  2. protein channel activity Source: UniProtKB
  3. protein heterodimerization activity Source: UniProtKB
  4. protein homodimerization activity Source: GO_Central

GO - Biological processi

  1. apoptotic mitochondrial changes Source: Ensembl
  2. cell fate determination Source: UniProtKB
  3. cellular homeostasis Source: UniProtKB
  4. extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
  5. intrinsic apoptotic signaling pathway in response to DNA damage Source: GO_Central
  6. multicellular organismal development Source: UniProtKB-KW
  7. negative regulation of anoikis Source: UniProtKB
  8. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
  9. negative regulation of intrinsic apoptotic signaling pathway Source: GO_Central
  10. positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
  11. protein transmembrane transport Source: GOC
  12. regulation of response to DNA damage stimulus Source: MGI
  13. response to cytokine Source: MGI
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
Alternative name(s):
Bcl-2-like protein 3
Short name:
Bcl2-L-3
Bcl-2-related protein EAT/mcl1
mcl1/EAT
Gene namesi
Name:MCL1
Synonyms:BCL2L3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:6943. MCL1.

Subcellular locationi

  1. Membrane Curated; Single-pass membrane protein Curated
  2. Cytoplasm
  3. Mitochondrion
  4. Nucleusnucleoplasm

  5. Note: Cytoplasmic, associated with mitochondria.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei328 – 34821HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. Bcl-2 family protein complex Source: UniProtKB
  2. cytoplasm Source: UniProtKB
  3. cytosol Source: UniProtKB
  4. integral component of membrane Source: UniProtKB-KW
  5. membrane Source: UniProtKB
  6. mitochondrial matrix Source: Ensembl
  7. mitochondrial outer membrane Source: UniProtKB
  8. mitochondrion Source: MGI
  9. nucleoplasm Source: UniProtKB-SubCell
  10. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi5 – 51K → R: Reduced ubiquitination. 1 Publication
Mutagenesisi40 – 401K → R: Reduced ubiquitination. 1 Publication
Mutagenesisi127 – 1271D → A: Abolishes formation of 28 and 17 kDa cleavage products by CASP3. Abolishes cleavage by caspase-3; when associated with A-157. 1 Publication
Mutagenesisi136 – 1361K → R: Reduced ubiquitination. 1 Publication
Mutagenesisi157 – 1571D → A: Abolishes formation of 23 and 21 kDa cleavage products by CASP3. Abolishes cleavage by caspase-3; when associated with A-127. 1 Publication
Mutagenesisi159 – 1591S → A: Loss of phosphorylation by GSK3 and loss of ubiquitination increasing protein stability. 1 Publication
Mutagenesisi162 – 1621S → A: Abolishes mitochondrial localization and decreases stability. 2 Publications
Mutagenesisi162 – 1621S → A: No effect. 2 Publications
Mutagenesisi163 – 1631T → A or E: No effect on mitochondrial localization. 1 Publication
Mutagenesisi163 – 1631T → A: Abolishes phosphorylation by MAPK. No effect on phosphorylation induced by okadaic acid or taxol. 1 Publication
Mutagenesisi194 – 1941K → R: Reduced ubiquitination. 1 Publication
Mutagenesisi197 – 1971K → R: Reduced ubiquitination. 1 Publication
Mutagenesisi208 – 2081K → R: No effect on ubiquitination. 1 Publication
Mutagenesisi234 – 2341K → R: No effect on ubiquitination. 1 Publication

Organism-specific databases

PharmGKBiPA30688.

Polymorphism and mutation databases

BioMutaiMCL1.
DMDMi83304396.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 350350Induced myeloid leukemia cell differentiation protein Mcl-1PRO_0000143080Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki5 – 5Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-linki40 – 40Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residuei121 – 1211Phosphoserine1 Publication
Cross-linki136 – 136Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residuei159 – 1591Phosphoserine; by GSK3-alpha and GSK3-beta1 Publication
Modified residuei162 – 1621Phosphoserine1 Publication
Modified residuei163 – 1631Phosphothreonine; by MAPK3 Publications
Cross-linki194 – 194Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-linki197 – 197Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Post-translational modificationi

Cleaved by CASP3 during apoptosis. In intact cells cleavage occurs preferentially after Asp-127, yielding a pro-apoptotic 28 kDa C-terminal fragment.
Rapidly degraded in the absence of phosphorylation on Thr-163 in the PEST region.3 Publications
Phosphorylated on Ser-159, by GSK3, in response to IL3/interleukin-3 withdrawal. Phosphorylation at Ser-159 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-159.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ07820.
PaxDbiQ07820.
PRIDEiQ07820.

PTM databases

PhosphoSiteiQ07820.

Miscellaneous databases

PMAP-CutDBQ07820.

Expressioni

Inductioni

Expression increases early during phorbol ester-induced differentiation along the monocyte/macrophage pathway in myeloid leukemia cell line ML-1. Rapidly up-regulated by CSF2 in ML-1 cells. Up-regulated by heat shock-induced differentiation. Expression increases early during retinoic acid-induced differentiation.2 Publications

Gene expression databases

BgeeiQ07820.
CleanExiHS_MCL1.
ExpressionAtlasiQ07820. baseline and differential.
GenevestigatoriQ07820.

Organism-specific databases

HPAiCAB002781.
CAB068195.
HPA008455.
HPA031125.

Interactioni

Subunit structurei

Interacts with HIF3A (via C-terminus domain) (By similarity). Interacts with BAD, BOK, BIK and BFM. Interacts with PMAIP1. Isoform 1 interacts with BAX, BAK1, TPT1 and BCL2L11. Heterodimer of isoform 1 and isoform 2. Homodimers of isoform 1 or isoform 2 are not detected. Isoform 2 does not interact with pro-apoptotic BCL2-related proteins. Interacts with BOP. Interacts with BCL2L11; may sequester BCL2L11 to prevent its pro-apoptotic activity.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Q91AU02EBI-1003422,EBI-9657017From a different organism.
BAK1Q1661110EBI-1003422,EBI-519866
BAXQ078126EBI-1003422,EBI-516580
BBC3Q9BXH13EBI-1003422,EBI-519884
BCL2L11O4352111EBI-1003422,EBI-526406
BECN1Q144572EBI-1003422,EBI-949378
CAV1Q031353EBI-1003422,EBI-603614
Cav1P498173EBI-1003422,EBI-1161338From a different organism.
PMAIP1Q137945EBI-1003422,EBI-707392
Pmaip1Q9JM542EBI-1003422,EBI-709183From a different organism.

Protein-protein interaction databases

BioGridi110338. 58 interactions.
DIPiDIP-231N.
IntActiQ07820. 27 interactions.
MINTiMINT-89669.

Structurei

Secondary structure

1
350
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi173 – 19119Combined sources
Beta strandi200 – 2023Combined sources
Helixi203 – 22321Combined sources
Helixi225 – 23511Combined sources
Helixi240 – 25314Combined sources
Helixi254 – 2563Combined sources
Helixi261 – 28020Combined sources
Helixi284 – 2863Combined sources
Helixi287 – 29913Combined sources
Turni300 – 3023Combined sources
Helixi303 – 3086Combined sources
Helixi311 – 3199Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KBWNMR-A163-326[»]
2MHSNMR-A171-327[»]
2NL9X-ray1.55A209-327[»]
2NLAX-ray2.80A209-327[»]
2PQKX-ray2.00A172-327[»]
3D7VX-ray2.03A209-327[»]
3IO9X-ray2.40A209-327[»]
3KJ0X-ray1.70A172-327[»]
3KJ1X-ray1.94A172-327[»]
3KJ2X-ray2.35A172-327[»]
3KZ0X-ray2.35A/B172-327[»]
3MK8X-ray2.32A172-327[»]
B208-228[»]
3PK1X-ray2.49A/C174-326[»]
3TWUX-ray1.80B73-88[»]
3WIXX-ray1.90A/B/C/D172-327[»]
3WIYX-ray2.15A/B/C/D/E/F172-327[»]
4BPIX-ray1.98A209-327[»]
4BPJX-ray1.60A209-327[»]
4HW2X-ray2.80A/B/C/D/E/F172-323[»]
4HW3X-ray2.40A/B/C/D/E/F/G/H/I/J/K/L172-323[»]
4HW4X-ray1.53A/B172-327[»]
4OQ5X-ray2.86A/B/C/D/E/F174-326[»]
4OQ6X-ray1.81A/B174-326[»]
4WGIX-ray1.85A173-321[»]
ProteinModelPortaliQ07820.
SMRiQ07820. Positions 133-324.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ07820.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni104 – 17572PEST-likeAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi209 – 22315BH3Add
BLAST
Motifi252 – 27221BH1Add
BLAST
Motifi304 – 31916BH2Add
BLAST

Sequence similaritiesi

Belongs to the Bcl-2 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG282183.
GeneTreeiENSGT00510000048923.
HOVERGENiHBG003527.
InParanoidiQ07820.
KOiK02539.
OMAiKDTKPMG.
OrthoDBiEOG7S2209.
PhylomeDBiQ07820.
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.
PTHR11256:SF6. PTHR11256:SF6. 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: Q07820-1) [UniParc]FASTAAdd to basket

Also known as: MCL1L, MCL-1L

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
MFGLKRNAVI GLNLYCGGAG LGAGSGGATR PGGRLLATEK EASARREIGG
60 70 80 90 100
GEAGAVIGGS AGASPPSTLT PDSRRVARPP PIGAEVPDVT ATPARLLFFA
110 120 130 140 150
PTRRAAPLEE MEAPAADAIM SPEEELDGYE PEPLGKRPAV LPLLELVGES
160 170 180 190 200
GNNTSTDGSL PSTPPPAEEE EDELYRQSLE IISRYLREQA TGAKDTKPMG
210 220 230 240 250
RSGATSRKAL ETLRRVGDGV QRNHETAFQG MLRKLDIKNE DDVKSLSRVM
260 270 280 290 300
IHVFSDGVTN WGRIVTLISF GAFVAKHLKT INQESCIEPL AESITDVLVR
310 320 330 340 350
TKRDWLVKQR GWDGFVEFFH VEDLEGGIRN VLLAFAGVAG VGAGLAYLIR
Length:350
Mass (Da):37,337
Last modified:December 6, 2005 - v3
Checksum:iD85821AC59275F1F
GO
Isoform 2 (identifier: Q07820-2) [UniParc]FASTAAdd to basket

Also known as: Delta S, MCL-1S, TM

The sequence of this isoform differs from the canonical sequence as follows:
     231-271: MLRKLDIKNE...GRIVTLISFG → WVCGVLPCRG...FGISNKIALL
     272-350: Missing.

Show »
Length:271
Mass (Da):28,662
Checksum:iFAE0BF9E126523EF
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti173 – 1731E → D.2 Publications
Corresponds to variant rs2737820 [ dbSNP | Ensembl ].
VAR_024021
Natural varianti227 – 2271A → V.3 Publications
Corresponds to variant rs11580946 [ dbSNP | Ensembl ].
VAR_024022
Natural varianti231 – 2311M → L.1 Publication
VAR_054157

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei231 – 27141MLRKL…LISFG → WVCGVLPCRGPRRWHQECAA GFCRCCWSRSWFGISNKIAL L in isoform 2. 1 PublicationVSP_000532Add
BLAST
Alternative sequencei272 – 35079Missing in isoform 2. 1 PublicationVSP_000533Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L08246 mRNA. No translation available.
AF118124 mRNA. Translation: AAD13299.1.
AF147742 Genomic DNA. Translation: AAF74821.1.
AF198614 Genomic DNA. Translation: AAF64255.1.
AF198614 Genomic DNA. Translation: AAF64256.1.
AF162677, AF162676 Genomic DNA. Translation: AAG00896.1.
AF203373 mRNA. Translation: AAG00904.1.
BT006640 mRNA. Translation: AAP35286.1.
AK312508 mRNA. Translation: BAG35409.1.
DQ088966 Genomic DNA. Translation: AAY68220.1.
AL356356 Genomic DNA. Translation: CAI15503.1.
AL356356 Genomic DNA. Translation: CAI15504.1.
CH471121 Genomic DNA. Translation: EAW53538.1.
CH471121 Genomic DNA. Translation: EAW53539.1.
CH471121 Genomic DNA. Translation: EAW53540.1.
CH471121 Genomic DNA. Translation: EAW53541.1.
BC017197 mRNA. Translation: AAH17197.1.
BC071897 mRNA. Translation: AAH71897.1.
BC107735 mRNA. Translation: AAI07736.1.
AF118276 mRNA. Translation: AAF15309.1.
AF118277 mRNA. Translation: AAF15310.1.
AF118278 mRNA. Translation: AAF15311.1.
CCDSiCCDS956.1. [Q07820-2]
CCDS957.1. [Q07820-1]
PIRiA47476.
RefSeqiNP_001184249.1. NM_001197320.1.
NP_068779.1. NM_021960.4. [Q07820-1]
NP_877495.1. NM_182763.2. [Q07820-2]
UniGeneiHs.632486.

Genome annotation databases

EnsembliENST00000307940; ENSP00000309973; ENSG00000143384. [Q07820-2]
ENST00000369026; ENSP00000358022; ENSG00000143384. [Q07820-1]
GeneIDi4170.
KEGGihsa:4170.
UCSCiuc001euz.3. human. [Q07820-1]
uc001eva.3. human. [Q07820-2]

Polymorphism and mutation databases

BioMutaiMCL1.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L08246 mRNA. No translation available.
AF118124 mRNA. Translation: AAD13299.1.
AF147742 Genomic DNA. Translation: AAF74821.1.
AF198614 Genomic DNA. Translation: AAF64255.1.
AF198614 Genomic DNA. Translation: AAF64256.1.
AF162677, AF162676 Genomic DNA. Translation: AAG00896.1.
AF203373 mRNA. Translation: AAG00904.1.
BT006640 mRNA. Translation: AAP35286.1.
AK312508 mRNA. Translation: BAG35409.1.
DQ088966 Genomic DNA. Translation: AAY68220.1.
AL356356 Genomic DNA. Translation: CAI15503.1.
AL356356 Genomic DNA. Translation: CAI15504.1.
CH471121 Genomic DNA. Translation: EAW53538.1.
CH471121 Genomic DNA. Translation: EAW53539.1.
CH471121 Genomic DNA. Translation: EAW53540.1.
CH471121 Genomic DNA. Translation: EAW53541.1.
BC017197 mRNA. Translation: AAH17197.1.
BC071897 mRNA. Translation: AAH71897.1.
BC107735 mRNA. Translation: AAI07736.1.
AF118276 mRNA. Translation: AAF15309.1.
AF118277 mRNA. Translation: AAF15310.1.
AF118278 mRNA. Translation: AAF15311.1.
CCDSiCCDS956.1. [Q07820-2]
CCDS957.1. [Q07820-1]
PIRiA47476.
RefSeqiNP_001184249.1. NM_001197320.1.
NP_068779.1. NM_021960.4. [Q07820-1]
NP_877495.1. NM_182763.2. [Q07820-2]
UniGeneiHs.632486.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KBWNMR-A163-326[»]
2MHSNMR-A171-327[»]
2NL9X-ray1.55A209-327[»]
2NLAX-ray2.80A209-327[»]
2PQKX-ray2.00A172-327[»]
3D7VX-ray2.03A209-327[»]
3IO9X-ray2.40A209-327[»]
3KJ0X-ray1.70A172-327[»]
3KJ1X-ray1.94A172-327[»]
3KJ2X-ray2.35A172-327[»]
3KZ0X-ray2.35A/B172-327[»]
3MK8X-ray2.32A172-327[»]
B208-228[»]
3PK1X-ray2.49A/C174-326[»]
3TWUX-ray1.80B73-88[»]
3WIXX-ray1.90A/B/C/D172-327[»]
3WIYX-ray2.15A/B/C/D/E/F172-327[»]
4BPIX-ray1.98A209-327[»]
4BPJX-ray1.60A209-327[»]
4HW2X-ray2.80A/B/C/D/E/F172-323[»]
4HW3X-ray2.40A/B/C/D/E/F/G/H/I/J/K/L172-323[»]
4HW4X-ray1.53A/B172-327[»]
4OQ5X-ray2.86A/B/C/D/E/F174-326[»]
4OQ6X-ray1.81A/B174-326[»]
4WGIX-ray1.85A173-321[»]
ProteinModelPortaliQ07820.
SMRiQ07820. Positions 133-324.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110338. 58 interactions.
DIPiDIP-231N.
IntActiQ07820. 27 interactions.
MINTiMINT-89669.

Chemistry

BindingDBiQ07820.
ChEMBLiCHEMBL4361.

PTM databases

PhosphoSiteiQ07820.

Polymorphism and mutation databases

BioMutaiMCL1.
DMDMi83304396.

Proteomic databases

MaxQBiQ07820.
PaxDbiQ07820.
PRIDEiQ07820.

Protocols and materials databases

DNASUi4170.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000307940; ENSP00000309973; ENSG00000143384. [Q07820-2]
ENST00000369026; ENSP00000358022; ENSG00000143384. [Q07820-1]
GeneIDi4170.
KEGGihsa:4170.
UCSCiuc001euz.3. human. [Q07820-1]
uc001eva.3. human. [Q07820-2]

Organism-specific databases

CTDi4170.
GeneCardsiGC01M150547.
HGNCiHGNC:6943. MCL1.
HPAiCAB002781.
CAB068195.
HPA008455.
HPA031125.
MIMi159552. gene.
neXtProtiNX_Q07820.
PharmGKBiPA30688.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG282183.
GeneTreeiENSGT00510000048923.
HOVERGENiHBG003527.
InParanoidiQ07820.
KOiK02539.
OMAiKDTKPMG.
OrthoDBiEOG7S2209.
PhylomeDBiQ07820.
TreeFamiTF315834.

Miscellaneous databases

ChiTaRSiMCL1. human.
EvolutionaryTraceiQ07820.
GeneWikiiMCL1.
GenomeRNAii4170.
NextBioi16422.
PMAP-CutDBQ07820.
PROiQ07820.
SOURCEiSearch...

Gene expression databases

BgeeiQ07820.
CleanExiHS_MCL1.
ExpressionAtlasiQ07820. baseline and differential.
GenevestigatoriQ07820.

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.
PTHR11256:SF6. PTHR11256:SF6. 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...

Publicationsi

« Hide 'large scale' publications
  1. "MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2."
    Kozopas K.M., Yang T., Buchan H.L., Zhou P., Craig R.W.
    Proc. Natl. Acad. Sci. U.S.A. 90:3516-3520(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASP-173.
    Tissue: Myeloid leukemia cell.
  2. "Induction of mcl1/EAT, Bcl-2 related gene, by retinoic acid or heat shock in the human embryonal carcinoma cells, NCR-G3."
    Umezawa A., Maruyama T., Inazawa J., Imai S., Takano T., Hata J.
    Cell Struct. Funct. 21:143-150(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION.
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  4. "Exon skipping in Mcl-1 results in a Bcl-2 homology domain 3 only gene product that promotes cell death."
    Bingle C.D., Craig R.W., Swales B.M., Singleton V., Zhou P., Whyte M.K.B.
    J. Biol. Chem. 275:22136-22146(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), VARIANT ASP-173, FUNCTION.
    Tissue: Myeloid leukemia cell and Neuroblastoma.
  5. "MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain."
    Bae J., Leo C.P., Hsu S.Y., Hsueh A.J.W.
    J. Biol. Chem. 275:25255-25261(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH BAX; BAK1; BCL2L11 AND BETWEEN ISOFORMS 1 AND 2.
  6. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  7. "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., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-227.
    Tissue: Thalamus.
  8. NIEHS SNPs program
    Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-227.
  9. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  10. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  11. "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).
    Tissue: Mammary gland and Placenta.
  12. "Acute myeloid leukemia possessing jumping translocation is related to highly elevated levels of EAT/mcl-1, a Bcl-2 related gene with anti-apoptotic functions."
    Okita H., Umezawa A., Fukuma M., Hata J.
    Leuk. Res. 24:73-77(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 182-289 (ISOFORM 1), VARIANT VAL-227.
    Tissue: Ewing sarcoma.
  13. "Mcl-1 is required for Akata6 B-lymphoma cell survival and is converted to a cell death molecule by efficient caspase-mediated cleavage."
    Michels J., O'Neill J.W., Dallman C.L., Mouzakiti A., Habens F., Brimmell M., Zhang K.Y.J., Craig R.W., Marcusson E.G., Johnson P.W.M., Packham G.
    Oncogene 23:4818-4827(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF N-TERMINUS OF FRAGMENTS OBTAINED BY CASPASE CLEAVAGE, MUTAGENESIS OF ASP-127 AND ASP-157.
  14. "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: INDUCTION.
  15. "Physical and functional interaction between myeloid cell leukemia 1 protein (MCL1) and fortilin. The potential role of MCL1 as a fortilin chaperone."
    Zhang D., Li F., Weidner D., Mnjoyan Z.H., Fujise K.
    J. Biol. Chem. 277:37430-37438(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TPT1, SUBCELLULAR LOCATION.
  16. "Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stress."
    Inoshita S., Takeda K., Hatai T., Terada Y., Sano M., Hata J., Umezawa A., Ichijo H.
    J. Biol. Chem. 277:43730-43734(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-121 AND THR-163.
  17. "Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex."
    Leu J.I.-J., Dumont P., Hafey M., Murphy M.E., George D.L.
    Nat. Cell Biol. 6:443-450(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH BAK, SUBCELLULAR LOCATION.
  18. "MCL1 is phosphorylated in the PEST region and stabilized upon ERK activation in viable cells, and at additional sites with cytotoxic okadaic acid or taxol."
    Domina A.M., Vrana J.A., Gregory M.A., Hann S.R., Craig R.W.
    Oncogene 23:5301-5315(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-163, MUTAGENESIS OF SER-162 AND THR-163.
  19. "Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis."
    Zhong Q., Gao W., Du F., Wang X.
    Cell 121:1085-1095(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION, MUTAGENESIS OF LYS-5; LYS-40; LYS-136; LYS-194; LYS-197; LYS-208 AND LYS-234.
  20. "Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1."
    Maurer U., Charvet C., Wagman A.S., Dejardin E., Green D.R.
    Mol. Cell 21:749-760(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS INHIBITOR OF APOPTOSIS, PHOSPHORYLATION AT SER-159 BY GSK3-ALPHA AND GSK3-BETA, UBIQUITINATION, MUTAGENESIS OF SER-159.
  21. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  22. "Serine 162, an essential residue for the mitochondrial localization, stability and anti-apoptotic function of Mcl-1."
    Thomas L.W., Lam C., Clark R.E., White M.R., Spiller D.G., Moots R.J., Edwards S.W.
    PLoS ONE 7:E45088-E45088(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-162 AND THR-163, MUTAGENESIS OF SER-162.
  23. "Human Bop is a novel BH3-only member of the Bcl-2 protein family."
    Zhang X., Weng C., Li Y., Wang X., Jiang C., Li X., Xu Y., Chen Q., Pan L., Tang H.
    Protein Cell 3:790-801(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH BOP/C22ORF29.
  24. Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 151-307 IN COMPLEXES WITH PMAIP1 AND BCL2L11.
  25. "The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer."
    Stewart M.L., Fire E., Keating A.E., Walensky L.D.
    Nat. Chem. Biol. 6:595-601(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 172-327 IN COMPLEX WITH BCL2L11.
  26. Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-231.

Entry informationi

Entry nameiMCL1_HUMAN
AccessioniPrimary (citable) accession number: Q07820
Secondary accession number(s): B2R6B2
, D3DV03, D3DV04, Q9HD91, Q9NRQ3, Q9NRQ4, Q9UHR7, Q9UHR8, Q9UHR9, Q9UNJ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: December 6, 2005
Last modified: April 29, 2015
This is version 164 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.