MEF2A_PIG
ID MEF2A_PIG Reviewed; 507 AA.
AC A2ICN5; A5JUQ6; A5JUQ7;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 2.
DT 25-MAY-2022, entry version 85.
DE RecName: Full=Myocyte-specific enhancer factor 2A;
GN Name=MEF2A;
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; 2 AND 3).
RA Yang L., Gao Z., Liu D.;
RT "Cloning and expression roles of the MEF2A gene in pig.";
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Transcriptional activator which binds specifically to the
CC MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific
CC genes. Also involved in the activation of numerous growth factor- and
CC stress-induced genes. Mediates cellular functions not only in skeletal
CC and cardiac muscle development, but also in neuronal differentiation
CC and survival. Plays diverse roles in the control of cell growth,
CC survival and apoptosis via p38 MAPK signaling in muscle-specific and/or
CC growth factor-related transcription. In cerebellar granule neurons,
CC phosphorylated and sumoylated MEF2A represses transcription of NUR77
CC promoting synaptic differentiation. Associates with chromatin to the
CC ZNF16 promoter (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Binds DNA as a homo- or heterodimer (By similarity). Dimerizes
CC with MEF2D. Interacts with HDAC7. Interacts with PIAS1; the interaction
CC enhances sumoylation. Interacts with HDAC4, HDAC9 and SLC2A4RG.
CC Interacts (via the N-terminal) with MAPK7; the interaction results in
CC the phosphorylation and transcriptional activity of MEF2A (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00251}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A2ICN5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A2ICN5-2; Sequence=VSP_036599;
CC Name=3;
CC IsoId=A2ICN5-3; Sequence=VSP_036598, VSP_036599;
CC -!- DOMAIN: The beta domain, missing in a number of isoforms, is required
CC for enhancement of transcriptional activity. {ECO:0000250}.
CC -!- PTM: Constitutive phosphorylation on Ser-408 promotes Lys-403
CC sumoylation thus preventing acetylation at this site. Dephosphorylation
CC on Ser-408 by PPP3CA upon neuron depolarization promotes a switch from
CC sumoylation to acetylation on residue Lys-403 leading to inhibition of
CC dendrite claw differentiation. Phosphorylation on Thr-312 and Thr-319
CC are the main sites involved in p38 MAPK signaling and activate
CC transcription. Phosphorylated on these sites by MAPK14/p38alpha and
CC MAPK11/p38beta, but not by MAPK13/p38delta nor by MAPK12/p38gamma.
CC Phosphorylation on Ser-408 by CDK5 induced by neurotoxicity inhibits
CC MEF2A transcriptional activation leading to apoptosis of cortical
CC neurons. Phosphorylation on Thr-312, Thr-319 and Ser-355 can be induced
CC by EGF (By similarity). {ECO:0000250}.
CC -!- PTM: Sumoylation on Lys-403 is enhanced by PIAS1 and represses
CC transcriptional activity. Phosphorylation on Ser-408 is required for
CC sumoylation. Has no effect on nuclear location nor on DNA binding.
CC Sumoylated with SUMO1 and, to a lesser extent with SUMO2 and SUMO3.
CC PIASx facilitates sumoylation in postsynaptic dendrites in the
CC cerebellar cortex and promotes their morphogenesis (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Acetylation on Lys-403 activates transcriptional activity.
CC Acetylated by p300 on several sites in diffentiating myocytes.
CC Acetylation on Lys-4 increases DNA binding and transactivation (By
CC similarity). Hyperacetylation by p300 leads to enhanced cardiac myocyte
CC growth and heart failure (By similarity). {ECO:0000250}.
CC -!- PTM: Proteolytically cleaved on several sites by caspase 3 and caspase
CC 7 following neurotoxicity. Preferentially cleaves the CDK5-mediated
CC hyperphosphorylated form which leads to cortical neuron apoptosis and
CC transcriptional inactivation (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the MEF2 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; EF194143; ABM68043.1; -; mRNA.
DR EMBL; EF576922; ABQ53159.1; -; mRNA.
DR EMBL; EF576923; ABQ53160.1; -; mRNA.
DR RefSeq; NP_001090890.1; NM_001097421.1.
DR RefSeq; NP_001093168.1; NM_001099698.1. [A2ICN5-1]
DR AlphaFoldDB; A2ICN5; -.
DR SMR; A2ICN5; -.
DR STRING; 9823.ENSSSCP00000026217; -.
DR PaxDb; A2ICN5; -.
DR GeneID; 100037273; -.
DR KEGG; ssc:100037273; -.
DR CTD; 4205; -.
DR eggNOG; KOG0014; Eukaryota.
DR InParanoid; A2ICN5; -.
DR OrthoDB; 729387at2759; -.
DR ChiTaRS; MEF2A; pig.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISS:UniProtKB.
DR GO; GO:0035035; F:histone acetyltransferase binding; ISS:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; 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:0046332; F:SMAD binding; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0061337; P:cardiac conduction; ISS:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0048813; P:dendrite morphogenesis; ISS:UniProtKB.
DR GO; GO:0070375; P:ERK5 cascade; ISS:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; ISS:UniProtKB.
DR GO; GO:0000002; P:mitochondrial genome maintenance; ISS:UniProtKB.
DR GO; GO:0048311; P:mitochondrion distribution; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0055005; P:ventricular cardiac myofibril assembly; 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; Apoptosis;
KW Developmental protein; Differentiation; DNA-binding; Isopeptide bond;
KW Neurogenesis; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..507
FT /note="Myocyte-specific enhancer factor 2A"
FT /id="PRO_0000366968"
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 175..269
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 266..283
FT /note="Required for interaction with MAPKs"
FT /evidence="ECO:0000250"
FT REGION 289..296
FT /note="Beta domain"
FT /evidence="ECO:0000250"
FT REGION 390..507
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..249
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 390..405
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 420..443
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 444..466
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 176..177
FT /note="Cleavage"
FT /evidence="ECO:0000305"
FT SITE 213..214
FT /note="Cleavage"
FT /evidence="ECO:0000305"
FT SITE 466..467
FT /note="Cleavage"
FT /evidence="ECO:0000305"
FT MOD_RES 59
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 235
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 249
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 312
FT /note="Phosphothreonine; by MAPK7 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 319
FT /note="Phosphothreonine; by MAPK7 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 355
FT /note="Phosphoserine; by MAPK7"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 403
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q2MJT0"
FT MOD_RES 408
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 415
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60929"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT CROSSLNK 403
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT VAR_SEQ 87..132
FT /note="ALNKKEHRGCDSPDPDTSYVLTPHTEEKYKKINEEFDNMMRNHKIA -> TL
FT RKKGLNGCESPDADDYFEHSPLSEDRFSKLNEDSDFIFKRGP (in isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_036598"
FT VAR_SEQ 227..260
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_036599"
FT CONFLICT 51
FT /note="S -> T (in Ref. 1; ABM68043)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="M -> I (in Ref. 1; ABM68043)"
FT /evidence="ECO:0000305"
FT CONFLICT 79
FT /note="G -> R (in Ref. 1; ABQ53160)"
FT /evidence="ECO:0000305"
FT CONFLICT 179
FT /note="M -> T (in Ref. 1; ABQ53159)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 507 AA; 54482 MW; 0D84E0AB59A6C017 CRC64;
MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS SNKLFQYAST
DMDKVLLKYT EYNEPHESGT NSDIVEALNK KEHRGCDSPD PDTSYVLTPH TEEKYKKINE
EFDNMMRNHK IAPGLPPQNF SMSVTVPVTS PNALSYTNPG SSLVSPSLAA SSTLADSSML
SPPQATLHRN VSPGAPQRPP STGSAGGMLS TSDLTVPNGA GSSPVGNGFV NSRASPNLVG
TTGANSLGKV MPTESPPPPG GGNLGMNSRK PDLRVVIPPS SKGMMPPLSE EEELELNTQR
ISSSQAPQPL ATPVVSVTTP SLPQQGLVYS AMPTAYNTDY SLTSADLSAL QGFNSPGMLS
LGQVSAWQQH HLGQAALSSL VAGGQLSQGS NLSINTNQNI NIKSEPISPP RDRMTPSGFQ
QQQPPPPSQA PQPQPPQPQP QPQPQARQEM GRSPVDSLSS SSSSYDGSDR EDPRGDFHSP
VVLGRPPNTE DRESPSVKRM RMDAWVT
