MCL1_CANLF
ID MCL1_CANLF Reviewed; 350 AA.
AC Q8HYS5;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 25-MAY-2022, entry version 107.
DE RecName: Full=Induced myeloid leukemia cell differentiation protein Mcl-1 homolog;
GN Name=MCL1;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Blood;
RX PubMed=15240948; DOI=10.1292/jvms.66.709;
RA Sano J., Oguma K., Kano R., Hasegawa A.;
RT "Molecular cloning of canine Mcl-1 gene and its expression in tumor cell
RT lines.";
RL J. Vet. Med. Sci. 66:709-712(2004).
CC -!- FUNCTION: Involved in the regulation of apoptosis versus cell survival,
CC and in the maintenance of viability but not of proliferation. Mediates
CC its effects by interactions with a number of other regulators of
CC apoptosis (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with HIF3A (via C-terminus domain) (By similarity).
CC Interacts with BOK, BIK, BAX, BAK1, and TPT1. Interacts with
CC unphosphorylated BAD (By similarity). Interacts with BMF, BBC3 and
CC PMAIP1 (By similarity). Interacts with BOP (By similarity). Interacts
CC with BCL2L11; may sequester BCL2L11 to prevent its pro-apoptotic
CC activity (By similarity). Interacts with GIMAP5 and HSPA8/HSC70; the
CC interaction between HSPA8 and MCL1 is impaired in the absence of GIMAP5
CC (By similarity). {ECO:0000250|UniProtKB:P97287,
CC ECO:0000250|UniProtKB:Q07820, ECO:0000250|UniProtKB:Q9Z1P3}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass membrane
CC protein {ECO:0000250}. Cytoplasm {ECO:0000250}. Mitochondrion
CC {ECO:0000250}. Nucleus, nucleoplasm {ECO:0000250}. Note=Cytoplasmic,
CC associated with mitochondria.
CC -!- TISSUE SPECIFICITY: Detected in peripheral blood mononuclear cells and
CC bone marrow. {ECO:0000269|PubMed:15240948}.
CC -!- PTM: Cleaved by CASP3 during apoptosis, yielding a pro-apoptotic C-
CC terminal fragment. {ECO:0000250}.
CC -!- PTM: Rapidly degraded in the absence of phosphorylation in the PEST
CC region. {ECO:0000250}.
CC -!- PTM: Phosphorylated on Ser-159, by GSK3, in response to
CC IL3/interleukin-3 withdrawal. Phosphorylation at Ser-159 induces
CC ubiquitination and proteasomal degradation, abrogating the anti-
CC apoptotic activity. Treatment with taxol or okadaic acid induces
CC phosphorylation on additional sites (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated. Ubiquitination is induced by phosphorylation at
CC Ser-159 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
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DR EMBL; AB093582; BAC21258.1; -; mRNA.
DR AlphaFoldDB; Q8HYS5; -.
DR SMR; Q8HYS5; -.
DR STRING; 9612.ENSCAFP00000043103; -.
DR eggNOG; KOG4728; Eukaryota.
DR InParanoid; Q8HYS5; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; ISS:UniProtKB.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IBA:GO_Central.
DR CDD; cd06845; Bcl-2_like; 1.
DR Gene3D; 1.10.437.10; -; 1.
DR InterPro; IPR013281; Apop_reg_Mc1.
DR InterPro; IPR036834; Bcl-2-like_sf.
DR InterPro; IPR046371; Bcl-2_BH1-3.
DR InterPro; IPR026298; Bcl-2_fam.
DR InterPro; IPR002475; Bcl2-like.
DR InterPro; IPR020717; Bcl2_BH1_motif_CS.
DR InterPro; IPR020726; Bcl2_BH2_motif_CS.
DR InterPro; IPR020728; Bcl2_BH3_motif_CS.
DR PANTHER; PTHR11256; PTHR11256; 1.
DR PANTHER; PTHR11256:SF46; PTHR11256:SF46; 1.
DR Pfam; PF00452; Bcl-2; 1.
DR PRINTS; PR01866; APOPREGMCL1.
DR PRINTS; PR01862; BCL2FAMILY.
DR SMART; SM00337; BCL; 1.
DR SUPFAM; SSF56854; SSF56854; 1.
DR PROSITE; PS50062; BCL2_FAMILY; 1.
DR PROSITE; PS01080; BH1; 1.
DR PROSITE; PS01258; BH2; 1.
DR PROSITE; PS01259; BH3; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; Cytoplasm; Developmental protein; Differentiation;
KW Isopeptide bond; Membrane; Mitochondrion; Nucleus; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..350
FT /note="Induced myeloid leukemia cell differentiation
FT protein Mcl-1 homolog"
FT /id="PRO_0000143078"
FT TRANSMEM 327..349
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 23..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 104..175
FT /note="PEST-like"
FT /evidence="ECO:0000250"
FT REGION 150..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 209..223
FT /note="BH3"
FT MOTIF 252..272
FT /note="BH1"
FT MOTIF 304..319
FT /note="BH2"
FT SITE 127..128
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT SITE 157..158
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT MOD_RES 159
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT MOD_RES 163
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT CROSSLNK 5
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT CROSSLNK 136
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT CROSSLNK 194
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT CROSSLNK 197
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
SQ SEQUENCE 350 AA; 36837 MW; 6E17DED8F55A9278 CRC64;
MFGLKRNAVI RTQLYCGGAG LGAGSGGASS SGGRLLASGR EATTRREGGG GEAGAVIGGS
AGASPPTTLA PDARRVARPS PIGAEGPNVS ATPPRLLLLA PPCRASPPEE MEGPAADAIM
SPEEELDGYE PEPLGKRPAV LPLLELVGEA SSGPGMDGSL PSTPPPAEEE EDELYRQSLE
IISRYLREQA TGAKDAKPLG GSRAASRKAL ETLQRVGDGV QRNHETAFQG MLRKLDIKNE
DDVKSLSRVI VHVFSDGVTN WGRIVTLISF GAFVAKHLKS INQESCIEPL AESITDVLVR
TKRDWLVKQR GWDGFVEFFH VEDLEGGIRN VLLAFAGVAG VGAGLAYLIR
