MEF2A_PONAB
ID MEF2A_PONAB Reviewed; 494 AA.
AC Q5REW7;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 25-MAY-2022, entry version 82.
DE RecName: Full=Myocyte-specific enhancer factor 2A;
GN Name=MEF2A;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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 -!- PTM: Constitutive phosphorylation on Ser-398 promotes Lys-393
CC sumoylation thus preventing acetylation at this site. Dephosphorylation
CC on Ser-398 by PPP3CA upon neuron depolarization promotes a switch from
CC sumoylation to acetylation on residue Lys-393 leading to inhibition of
CC dendrite claw differentiation. Phosphorylation on Thr-302 and Thr-309
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-398 by CDK5 induced by neurotoxicity inhibits
CC MEF2A transcriptional activation leading to apoptosis of cortical
CC neurons. Phosphorylation on Thr-302, Thr-309 and Ser-345 can be induced
CC by EGF (By similarity). {ECO:0000250}.
CC -!- PTM: Sumoylation on Lys-393 is enhanced by PIAS1 and represses
CC transcriptional activity. Phosphorylation on Ser-398 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-393 activates transcriptional activity.
CC Acetylated by p300 on several sites in diffentiating myocytes.
CC Acetylation on Lys-4 increases DNA binding and transactivation.
CC Hyperacetylation by p300 leads to enhanced cardiac myocyte growth and
CC heart failure (By similarity). {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}.
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; CR857398; CAH89690.1; -; mRNA.
DR RefSeq; NP_001124766.1; NM_001131294.1.
DR AlphaFoldDB; Q5REW7; -.
DR SMR; Q5REW7; -.
DR STRING; 9601.ENSPPYP00000007730; -.
DR GeneID; 100171617; -.
DR KEGG; pon:100171617; -.
DR CTD; 4205; -.
DR eggNOG; KOG0014; Eukaryota.
DR InParanoid; Q5REW7; -.
DR OrthoDB; 729387at2759; -.
DR Proteomes; UP000001595; 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: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: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; Apoptosis; Developmental protein; Differentiation;
KW DNA-binding; Isopeptide bond; Neurogenesis; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..494
FT /note="Myocyte-specific enhancer factor 2A"
FT /id="PRO_0000366969"
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 171..218
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 238..268
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..281
FT /note="Required for interaction with MAPKs"
FT /evidence="ECO:0000250"
FT REGION 380..494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 380..395
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 416..435
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 437..453
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 174..175
FT /note="Cleavage"
FT /evidence="ECO:0000305"
FT SITE 211..212
FT /note="Cleavage"
FT /evidence="ECO:0000305"
FT SITE 453..454
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 108
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60929"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 247
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 253
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 302
FT /note="Phosphothreonine; by MAPK7 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 309
FT /note="Phosphothreonine; by MAPK7 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 345
FT /note="Phosphoserine; by MAPK7"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 393
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q2MJT0"
FT MOD_RES 398
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT MOD_RES 405
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60929"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02078"
FT CROSSLNK 393
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 494 AA; 53138 MW; 859D8C71C9B1BEB0 CRC64;
MGRKKIQITR IMDERNRQVT FTKRKFGLMK KAYELSVLCD CEIALIIFNS SNKLFQYAST
DMDKVLLKYT EYNEPHESRT NSDIVETLRK KGLNGCESPD ADDYFEHSPL SEDRFSKLNE
DSDFIFKRGP PGLPPQNFSM SVTVPVTSPN ALSYTNPGSS LVSPSLAASS TLTDSSMLSP
PQTTLHRNVS PGAPQRPPST GNAGGMLSTT DLIVPNGAGS SPVGNGFVNS RASPNLIGAT
GANSLGKVMP TKSPPPPGGG NLGMNSRKPD LRVVIPPSSK GMMPPLNTQR ISSSQATQPL
ATPVVSVTTP SLPPQGLVYS AMPTAYNTDY SLTSADLSAL QGFNSPGMLS LGQVSAWQQH
HLGQAALSSL VAGGQLSQGS NLSINTNQNI NIKSEPISPP RDRMTPSGFQ QQQQQQQQPP
PPPPQPQPPQ PQPRQEMGRS PVDSLSSSSS SYDGSDREDP RGDFHSPIVL GRPPNTEDRE
SPSVKRMRMD AWVT
