MEF2C_PIG
ID MEF2C_PIG Reviewed; 463 AA.
AC A4UTP7; Q2L9Y8;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 1.
DT 25-MAY-2022, entry version 90.
DE RecName: Full=Myocyte-specific enhancer factor 2C {ECO:0000305};
GN Name=MEF2C {ECO:0000250|UniProtKB:Q06413};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Liu M., Jiang S.W.;
RT "Molecular cloning and characterization of the porcine MEF2C gene.";
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Transcription activator which binds specifically to the MEF2
CC element present in the regulatory regions of many muscle-specific
CC genes. Controls cardiac morphogenesis and myogenesis, and is also
CC involved in vascular development. Enhances transcriptional activation
CC mediated by SOX18. Plays an essential role in hippocampal-dependent
CC learning and memory by suppressing the number of excitatory synapses
CC and thus regulating basal and evoked synaptic transmission. Crucial for
CC normal neuronal development, distribution, and electrical activity in
CC the neocortex. Necessary for proper development of megakaryocytes and
CC platelets and for bone marrow B-lymphopoiesis. Required for B-cell
CC survival and proliferation in response to BCR stimulation, efficient
CC IgG1 antibody responses to T-cell-dependent antigens and for normal
CC induction of germinal center B-cells. May also be involved in
CC neurogenesis and in the development of cortical architecture (By
CC similarity). {ECO:0000250|UniProtKB:Q06413,
CC ECO:0000250|UniProtKB:Q8CFN5}.
CC -!- SUBUNIT: Forms a complex with class II HDACs in undifferentiating
CC cells. On myogenic differentiation, HDACs are released into the
CC cytoplasm allowing MEF2s to interact with other proteins for
CC activation. Interacts with EP300 in differentiating cells; the
CC interaction acetylates MEF2C leading to increased DNA binding and
CC activation (By similarity). Interacts with HDAC7 and CARM1 (By
CC similarity). Interacts with HDAC4, HDAC7 AND HDAC9; the interaction
CC with HDACs represses transcriptional activity (By similarity).
CC Interacts with LPIN1. Interacts with MYOCD. Interacts with AKAP13.
CC Interacts with FOXK1; the interaction inhibits MEF2C transactivation
CC activity (By similarity). Interacts (via N-terminus) with HABP4; this
CC interaction decreases DNA-binding activity of MEF2C in myocardial cells
CC in response to mechanical stress (By similarity). Interacts with JPH2;
CC interaction specifically takes place with the Junctophilin-2 N-terminal
CC fragment cleavage product of JPH2 (By similarity). Interacts (via MADS
CC box) with SOX18 (By similarity). {ECO:0000250|UniProtKB:A0A096MJY4,
CC ECO:0000250|UniProtKB:Q06413, ECO:0000250|UniProtKB:Q8CFN5}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:A0A096MJY4}.
CC Cytoplasm, sarcoplasm {ECO:0000250|UniProtKB:A0A096MJY4}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A4UTP7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A4UTP7-2; Sequence=VSP_036600, VSP_036601;
CC -!- DOMAIN: The beta domain is required for enhancement of transcriptional
CC activity. {ECO:0000250}.
CC -!- PTM: Phosphorylated on Ser-59; which enhances DNA binding activity.
CC Phosphorylated on Ser-386; which is required for Lys-381 sumoylation
CC and inhibits transcriptional activity. {ECO:0000250}.
CC -!- PTM: Acetylated by p300 on several sites in diffentiating myocytes.
CC Acetylation on Lys-4 increases DNA binding and transactivation (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Sumoylated on Lys-381 with SUMO2 but not SUMO1; which represses
CC transcriptional activity. {ECO:0000250}.
CC -!- PTM: Proteolytically cleaved in cerebellar granule neurons on several
CC sites by caspase 3 and caspase 7 following neurotoxicity.
CC Preferentially cleaves the CDK5-mediated hyperphosphorylated form which
CC leads to neuron apoptosis and transcriptional inactivation (By
CC similarity). {ECO:0000250}.
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DR EMBL; DQ343149; ABC68473.1; -; mRNA.
DR EMBL; EF486522; ABO77944.1; -; mRNA.
DR RefSeq; NP_001038005.1; NM_001044540.1.
DR AlphaFoldDB; A4UTP7; -.
DR SMR; A4UTP7; -.
DR STRING; 9823.ENSSSCP00000015044; -.
DR PaxDb; A4UTP7; -.
DR PRIDE; A4UTP7; -.
DR GeneID; 733590; -.
DR KEGG; ssc:733590; -.
DR CTD; 4208; -.
DR eggNOG; KOG0014; Eukaryota.
DR InParanoid; A4UTP7; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0016528; C:sarcoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0001782; P:B cell homeostasis; ISS:UniProtKB.
DR GO; GO:0042100; P:B cell proliferation; ISS:UniProtKB.
DR GO; GO:0050853; P:B cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0001568; P:blood vessel development; ISS:UniProtKB.
DR GO; GO:0001974; P:blood vessel remodeling; ISS:UniProtKB.
DR GO; GO:0003211; P:cardiac ventricle formation; ISS:UniProtKB.
DR GO; GO:0035051; P:cardiocyte differentiation; ISS:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0071498; P:cellular response to fluid shear stress; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; ISS:UniProtKB.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISS:UniProtKB.
DR GO; GO:0035984; P:cellular response to trichostatin A; ISS:UniProtKB.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISS:UniProtKB.
DR GO; GO:0002062; P:chondrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0001958; P:endochondral ossification; ISS:UniProtKB.
DR GO; GO:2001013; P:epithelial cell proliferation involved in renal tubule morphogenesis; ISS:UniProtKB.
DR GO; GO:0002467; P:germinal center formation; ISS:UniProtKB.
DR GO; GO:0072102; P:glomerulus morphogenesis; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0001947; P:heart looping; ISS:UniProtKB.
DR GO; GO:0006959; P:humoral immune response; ISS:UniProtKB.
DR GO; GO:0007611; P:learning or memory; ISS:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; ISS:UniProtKB.
DR GO; GO:0030318; P:melanocyte differentiation; ISS:UniProtKB.
DR GO; GO:0007521; P:muscle cell fate determination; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0030279; P:negative regulation of ossification; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0072160; P:nephron tubule epithelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0014033; P:neural crest cell differentiation; ISS:UniProtKB.
DR GO; GO:0048666; P:neuron development; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:UniProtKB.
DR GO; GO:0030220; P:platelet formation; ISS:UniProtKB.
DR GO; GO:0010694; P:positive regulation of alkaline phosphatase activity; ISS:UniProtKB.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISS:UniProtKB.
DR GO; GO:2000987; P:positive regulation of behavioral fear response; ISS:UniProtKB.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB.
DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:2000111; P:positive regulation of macrophage apoptotic process; ISS:UniProtKB.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; ISS:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:2001016; P:positive regulation of skeletal muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0048643; P:positive regulation of skeletal muscle tissue development; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0003138; P:primary heart field specification; ISS:UniProtKB.
DR GO; GO:0002634; P:regulation of germinal center formation; ISS:UniProtKB.
DR GO; GO:0045652; P:regulation of megakaryocyte differentiation; ISS:UniProtKB.
DR GO; GO:0060025; P:regulation of synaptic activity; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0061333; P:renal tubule morphogenesis; ISS:UniProtKB.
DR GO; GO:0003139; P:secondary heart field specification; ISS:UniProtKB.
DR GO; GO:0003185; P:sinoatrial valve morphogenesis; ISS:UniProtKB.
DR GO; GO:0007519; P:skeletal muscle tissue development; ISS:UniProtKB.
DR GO; GO:0051145; P:smooth muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0055012; P:ventricular cardiac muscle cell differentiation; ISS:UniProtKB.
DR CDD; cd00265; MADS_MEF2_like; 1.
DR Gene3D; 3.40.1810.10; -; 1.
DR InterPro; IPR022102; HJURP_C.
DR InterPro; IPR033896; MADS_MEF2-like.
DR InterPro; IPR002100; TF_MADSbox.
DR InterPro; IPR036879; TF_MADSbox_sf.
DR Pfam; PF12347; HJURP_C; 1.
DR Pfam; PF00319; SRF-TF; 1.
DR PRINTS; PR00404; MADSDOMAIN.
DR SMART; SM00432; MADS; 1.
DR SUPFAM; SSF55455; SSF55455; 1.
DR PROSITE; PS00350; MADS_BOX_1; 1.
DR PROSITE; PS50066; MADS_BOX_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Activator; Alternative splicing; Cytoplasm;
KW Developmental protein; Differentiation; DNA-binding; Isopeptide bond;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..463
FT /note="Myocyte-specific enhancer factor 2C"
FT /id="PRO_0000366973"
FT DOMAIN 3..57
FT /note="MADS-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00251"
FT DNA_BIND 58..86
FT /note="Mef2-type"
FT /evidence="ECO:0000255"
FT REGION 178..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 358..389
FT /note="Transcription repressor"
FT /evidence="ECO:0000250"
FT REGION 365..463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 365..395
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 422..423
FT /note="Cleavage"
FT /evidence="ECO:0000305"
FT MOD_RES 4
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CFN5"
FT MOD_RES 59
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q8CFN5"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CFN5"
FT MOD_RES 104
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CFN5"
FT MOD_RES 114
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT MOD_RES 117
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT MOD_RES 232
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT MOD_RES 237
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT MOD_RES 238
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT MOD_RES 250
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT MOD_RES 262
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT MOD_RES 283
FT /note="Phosphothreonine; by MAPK7 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT MOD_RES 290
FT /note="Phosphothreonine; by MAPK7 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT MOD_RES 386
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT MOD_RES 409
FT /note="Phosphoserine; by MAPK7"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT MOD_RES 435
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06413"
FT CROSSLNK 381
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 87..132
FT /note="ALNKKENKGCESPDPDSSYALTPRTEEKYKKINEEFDNMIKSHKIP -> TL
FT RKKGLNGCDSPDPDADDSVGHSPESEDKYRKINEDLDLMISRQRLC (in isoform
FT 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_036600"
FT VAR_SEQ 358..389
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_036601"
FT CONFLICT 167
FT /note="F -> L (in Ref. 1; ABC68473)"
FT /evidence="ECO:0000305"
FT CONFLICT 269
FT /note="S -> N (in Ref. 1; ABC68473)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 463 AA; 50249 MW; 76BA0222D9996114 CRC64;
MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS TNKLFQYAST
DMDKVLLKYT EYNEPHESRT NSDIVEALNK KENKGCESPD PDSSYALTPR TEEKYKKINE
EFDNMIKSHK IPAVPPPNFE MPVSIPVSSH NSLVYSNPVS SLGNPNFLPL AHPSLQRNSM
SPGVTHRPPS AGNTGGLMGG DLTSGAGTSA GNGYGNPRNS PGLLVSPGNL NKNMQAKSPP
PMNLGMNNRK PDLRVLIPPG SKNTMPSVSQ RINNSQSAQS LATPVVSVAT PTLPGQGMGG
YPSAISTTYG TEYSLSSADL SSLSGFNTAS ALHLGSVTGW QQQHLHNMPP SALSQLGACT
STHLSQSSNL SLPSTQSLNI KSEPVSPPRD RTTTPSRYPQ HTRHEAGRSP VDSLSSCSSS
YDGSDREDHR NEFHSPIGLT RPSPDERESP SVKRMRLSEG WAT
