MCL1_RAT
ID MCL1_RAT Reviewed; 330 AA.
AC Q9Z1P3; Q6AYY5; Q9R289;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Induced myeloid leukemia cell differentiation protein Mcl-1 homolog;
GN Name=Mcl1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH BAD; BAX; BOK; BIK AND
RP BCL2L11, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Ovary;
RX PubMed=10579309; DOI=10.1210/endo.140.12.7171;
RA Leo C.P., Hsu S.Y., Chun S.-Y., Bae H.-W., Hsueh A.J.W.;
RT "Characterization of the antiapoptotic Bcl-2 family member myeloid cell
RT leukemia-1 (Mcl-1) and the stimulation of its message by gonadotropins in
RT the rat ovary.";
RL Endocrinology 140:5469-5477(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 227-330.
RC STRAIN=Wistar; TISSUE=Ovary;
RA Murray J.F., Dong Y.B., Leigh A.J., Scaramuzzi R.J., Carter N.D.;
RT "Mcl-1 in the rat ovary.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
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.
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 (PubMed:10579309). 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) (PubMed:10579309). Interacts with GIMAP5 and
CC HSPA8/HSC70; the interaction between HSPA8 and MCL1 is impaired in the
CC absence of GIMAP5 (By similarity). {ECO:0000250|UniProtKB:P97287,
CC ECO:0000250|UniProtKB:Q07820, ECO:0000269|PubMed:10579309}.
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: Ubiquitous. Highly expressed in heart, spleen,
CC lung, liver, skeletal muscle and kidney. Detected at lower levels in
CC brain, ovary, oviduct and testis. {ECO:0000269|PubMed:10579309}.
CC -!- DEVELOPMENTAL STAGE: Detected in neonate ovaries and expressed at
CC constant levels in 3 to 6 day old animals. Levels are increased in at
CC day 12 and thereafter.
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-139, by GSK3, in response to
CC IL3/interleukin-3 withdrawal. Phosphorylation at Ser-139 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-139 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
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DR EMBL; AF115380; AAD13295.1; -; mRNA.
DR EMBL; BC078835; AAH78835.1; -; mRNA.
DR EMBL; AF144096; AAD31519.1; -; mRNA.
DR RefSeq; NP_068618.2; NM_021846.2.
DR AlphaFoldDB; Q9Z1P3; -.
DR SMR; Q9Z1P3; -.
DR ComplexPortal; CPX-306; MCL1:PMAIP1 complex.
DR ELM; Q9Z1P3; -.
DR IntAct; Q9Z1P3; 2.
DR iPTMnet; Q9Z1P3; -.
DR PhosphoSitePlus; Q9Z1P3; -.
DR jPOST; Q9Z1P3; -.
DR Ensembl; ENSRNOT00000109758; ENSRNOP00000097988; ENSRNOG00000063678.
DR GeneID; 60430; -.
DR KEGG; rno:60430; -.
DR CTD; 4170; -.
DR RGD; 620525; Mcl1.
DR GeneTree; ENSGT01050000244872; -.
DR InParanoid; Q9Z1P3; -.
DR OrthoDB; 1218929at2759; -.
DR PhylomeDB; Q9Z1P3; -.
DR PRO; PR:Q9Z1P3; -.
DR Proteomes; UP000002494; Chromosome 2.
DR GO; GO:0097136; C:Bcl-2 family protein complex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
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:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0051400; F:BH domain binding; IPI:RGD.
DR GO; GO:0051434; F:BH3 domain binding; ISO:RGD.
DR GO; GO:0046983; F:protein dimerization activity; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; ISO:RGD.
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; ISO:RGD.
DR GO; GO:2000811; P:negative regulation of anoikis; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:RGD.
DR GO; GO:0010507; P:negative regulation of autophagy; ISO:RGD.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:1903378; P:positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:2001020; P:regulation of response to DNA damage stimulus; ISO:RGD.
DR GO; GO:0034097; P:response to cytokine; ISO:RGD.
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 1: Evidence at protein 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..330
FT /note="Induced myeloid leukemia cell differentiation
FT protein Mcl-1 homolog"
FT /id="PRO_0000143082"
FT TRANSMEM 307..329
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 85..155
FT /note="PEST-like"
FT /evidence="ECO:0000250"
FT REGION 129..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 189..203
FT /note="BH3"
FT MOTIF 232..252
FT /note="BH1"
FT MOTIF 284..299
FT /note="BH2"
FT SITE 107..108
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT SITE 137..138
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT MOD_RES 139
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT MOD_RES 143
FT /note="Phosphothreonine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT CROSSLNK 116
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT CROSSLNK 174
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT CROSSLNK 177
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q07820"
FT CONFLICT 156
FT /note="R -> H (in Ref. 1; AAD13295)"
FT /evidence="ECO:0000305"
FT CONFLICT 231
FT /note="T -> I (in Ref. 3; AAD31519)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="A -> V (in Ref. 3; AAD31519)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 330 AA; 35214 MW; C4A9DEB41897258E CRC64;
MFGLRRNAVI GLNLYCGGAS LGAGGGSPAG TRLAAEEAKA RREGGGEAAL LPGARVVARP
PPVGAEDPDV TASAERRLLK SPGLLAVPPE EMAASAAAIM SPEEELDGCE PEVLSKRPAV
LPLLERVSEA AKSSGADGSL PSTPPPPEEE DDELYRQSLE IISRYLREQA TGSKDAKPLG
EAGAAGRRAL ETLRRVGDGV QRNHETAFQG MLRKLDIKNE DDVKSFSRVM THVFKDGVTN
WGRIVTLISF GAFVAKHLKS INQESCIEPL AESITDVLVR TKRDWLVKQR GWDGFVEFFH
VQDLEGGIRN VLLAFAGVAG VGAGLAYLIR
