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Myocyte-specific enhancer factor 2C

 MEF2C_PONAB             Reviewed;         473 AA.
01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
21-DEC-2004, sequence version 1.
16-JAN-2019, entry version 81.
RecName: Full=Myocyte-specific enhancer factor 2C {ECO:0000305};
Name=MEF2C {ECO:0000250|UniProtKB:Q06413};
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Pongo.
TISSUE=Brain cortex;
The German cDNA consortium;
Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
-!- FUNCTION: Transcription activator which binds specifically to the
MEF2 element present in the regulatory regions of many muscle-
specific genes. Controls cardiac morphogenesis and myogenesis, and
is also involved in vascular development. Plays an essential role
in hippocampal-dependent learning and memory by suppressing the
number of excitatory synapses and thus regulating basal and evoked
synaptic transmission. Crucial for normal neuronal development,
distribution, and electrical activity in the neocortex. Necessary
for proper development of megakaryocytes and platelets and for
bone marrow B-lymphopoiesis. Required for B-cell survival and
proliferation in response to BCR stimulation, efficient IgG1
antibody responses to T-cell-dependent antigens and for normal
induction of germinal center B-cells. May also be involved in
neurogenesis and in the development of cortical architecture (By
similarity). {ECO:0000250|UniProtKB:Q06413,
-!- SUBUNIT: Forms a complex with class II HDACs in undifferentiating
cells. On myogenic differentiation, HDACs are released into the
cytoplasm allowing MEF2s to interact with other proteins for
activation. Interacts with EP300 in differentiating cells; the
interaction acetylates MEF2C leading to increased DNA binding and
activation. Interacts with HDAC7 and CARM1. Interacts with HDAC4
and HDAC9; the interaction with HDACs represses transcriptional
activity. Interacts with LPIN1. Interacts with MYOCD. Interacts
with AKAP13. Interacts with FOXK1; the interaction inhibits MEF2C
transactivation activity. Interacts (via N-terminus) with HABP4;
this interaction decreases DNA-binding activity of MEF2C in
myocardial cells in response to mechanical stress.
{ECO:0000250|UniProtKB:A0A096MJY4, ECO:0000250|UniProtKB:Q06413,
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:A0A096MJY4}.
Cytoplasm, sarcoplasm {ECO:0000250|UniProtKB:A0A096MJY4}.
-!- DOMAIN: The beta domain is required for enhancement of
transcriptional activity. {ECO:0000250}.
-!- PTM: Phosphorylated on Ser-59; which enhances DNA binding
activity. Phosphorylated on Ser-396; which is required for Lys-391
sumoylation and inhibits transcriptional activity. {ECO:0000250}.
-!- PTM: Acetylated by p300 on several sites in diffentiating
myocytes. Acetylation on Lys-4 increases DNA binding and
transactivation (By similarity). {ECO:0000250}.
-!- PTM: Sumoylated on Lys-391 with SUMO2 but not SUMO1; which
represses transcriptional activity. {ECO:0000250}.
-!- PTM: Proteolytically cleaved in cerebellar granule neurons on
several sites by caspase 3 and caspase 7 following neurotoxicity.
Preferentially cleaves the CDK5-mediated hyperphosphorylated form
which leads to neuron apoptosis and transcriptional inactivation
(By similarity). {ECO:0000250}.
-!- SIMILARITY: Belongs to the MEF2 family. {ECO:0000305}.
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
Distributed under the Creative Commons Attribution (CC BY 4.0) License
EMBL; CR861416; CAH93472.1; -; mRNA.
RefSeq; NP_001127669.1; NM_001134197.1.
RefSeq; XP_009239150.1; XM_009240875.1.
UniGene; Pab.19580; -.
ProteinModelPortal; Q5R444; -.
SMR; Q5R444; -.
PRIDE; Q5R444; -.
GeneID; 100174751; -.
KEGG; pon:100174751; -.
CTD; 4208; -.
HOVERGEN; HBG053944; -.
InParanoid; Q5R444; -.
KO; K04454; -.
OrthoDB; 729387at2759; -.
Proteomes; UP000001595; Unplaced.
GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
GO; GO:0005634; C:nucleus; ISS:UniProtKB.
GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
GO; GO:0016528; C:sarcoplasm; IEA:UniProtKB-SubCell.
GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
GO; GO:0016251; F:RNA polymerase II general transcription initiation factor activity; ISS:UniProtKB.
GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; ISS:UniProtKB.
GO; GO:0044212; F:transcription regulatory region DNA binding; ISS:UniProtKB.
GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO; GO:0001782; P:B cell homeostasis; ISS:UniProtKB.
GO; GO:0042100; P:B cell proliferation; ISS:UniProtKB.
GO; GO:0050853; P:B cell receptor signaling pathway; ISS:UniProtKB.
GO; GO:0001568; P:blood vessel development; ISS:UniProtKB.
GO; GO:0001974; P:blood vessel remodeling; ISS:UniProtKB.
GO; GO:0003211; P:cardiac ventricle formation; ISS:UniProtKB.
GO; GO:0035051; P:cardiocyte differentiation; ISS:UniProtKB.
GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
GO; GO:0035690; P:cellular response to drug; ISS:UniProtKB.
GO; GO:0071498; P:cellular response to fluid shear stress; ISS:UniProtKB.
GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; ISS:UniProtKB.
GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISS:UniProtKB.
GO; GO:0035984; P:cellular response to trichostatin A; ISS:UniProtKB.
GO; GO:0002062; P:chondrocyte differentiation; ISS:UniProtKB.
GO; GO:0001958; P:endochondral ossification; ISS:UniProtKB.
GO; GO:2001013; P:epithelial cell proliferation involved in renal tubule morphogenesis; ISS:UniProtKB.
GO; GO:0002467; P:germinal center formation; ISS:UniProtKB.
GO; GO:0072102; P:glomerulus morphogenesis; ISS:UniProtKB.
GO; GO:0007507; P:heart development; ISS:UniProtKB.
GO; GO:0001947; P:heart looping; ISS:UniProtKB.
GO; GO:0006959; P:humoral immune response; ISS:UniProtKB.
GO; GO:0007611; P:learning or memory; ISS:UniProtKB.
GO; GO:0000165; P:MAPK cascade; ISS:UniProtKB.
GO; GO:0030318; P:melanocyte differentiation; ISS:UniProtKB.
GO; GO:0007521; P:muscle cell fate determination; ISS:UniProtKB.
GO; GO:0010629; P:negative regulation of gene expression; ISS:UniProtKB.
GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
GO; GO:0030279; P:negative regulation of ossification; ISS:UniProtKB.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
GO; GO:0072160; P:nephron tubule epithelial cell differentiation; ISS:UniProtKB.
GO; GO:0014033; P:neural crest cell differentiation; ISS:UniProtKB.
GO; GO:0048666; P:neuron development; ISS:UniProtKB.
GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
GO; GO:0003151; P:outflow tract morphogenesis; ISS:UniProtKB.
GO; GO:0030220; P:platelet formation; ISS:UniProtKB.
GO; GO:0010694; P:positive regulation of alkaline phosphatase activity; ISS:UniProtKB.
GO; GO:0030890; P:positive regulation of B cell proliferation; ISS:UniProtKB.
GO; GO:2000987; P:positive regulation of behavioral fear response; ISS:UniProtKB.
GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB.
GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; ISS:UniProtKB.
GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISS:UniProtKB.
GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
GO; GO:2000111; P:positive regulation of macrophage apoptotic process; ISS:UniProtKB.
GO; GO:0045663; P:positive regulation of myoblast differentiation; ISS:UniProtKB.
GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB.
GO; GO:0090073; P:positive regulation of protein homodimerization activity; ISS:UniProtKB.
GO; GO:2001016; P:positive regulation of skeletal muscle cell differentiation; ISS:UniProtKB.
GO; GO:0048643; P:positive regulation of skeletal muscle tissue development; ISS:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
GO; GO:0003138; P:primary heart field specification; ISS:UniProtKB.
GO; GO:0002634; P:regulation of germinal center formation; ISS:UniProtKB.
GO; GO:0045652; P:regulation of megakaryocyte differentiation; ISS:UniProtKB.
GO; GO:0060025; P:regulation of synaptic activity; ISS:UniProtKB.
GO; GO:0061333; P:renal tubule morphogenesis; ISS:UniProtKB.
GO; GO:0003139; P:secondary heart field specification; ISS:UniProtKB.
GO; GO:0003185; P:sinoatrial valve morphogenesis; ISS:UniProtKB.
GO; GO:0007519; P:skeletal muscle tissue development; ISS:UniProtKB.
GO; GO:0051145; P:smooth muscle cell differentiation; ISS:UniProtKB.
GO; GO:0055012; P:ventricular cardiac muscle cell differentiation; ISS:UniProtKB.
CDD; cd00265; MADS_MEF2_like; 1.
Gene3D; 3.40.1810.10; -; 1.
InterPro; IPR022102; HJURP_C.
InterPro; IPR033896; MADS_MEF2-like.
InterPro; IPR002100; TF_MADSbox.
InterPro; IPR036879; TF_MADSbox_sf.
Pfam; PF12347; HJURP_C; 1.
Pfam; PF00319; SRF-TF; 1.
SMART; SM00432; MADS; 1.
SUPFAM; SSF55455; SSF55455; 1.
PROSITE; PS00350; MADS_BOX_1; 1.
PROSITE; PS50066; MADS_BOX_2; 1.
2: Evidence at transcript level;
Acetylation; Activator; Apoptosis; Complete proteome; Cytoplasm;
Developmental protein; Differentiation; DNA-binding; Isopeptide bond;
Neurogenesis; Nucleus; Phosphoprotein; Reference proteome;
Transcription; Transcription regulation; Ubl conjugation.
CHAIN 1 473 Myocyte-specific enhancer factor 2C.
DOMAIN 3 57 MADS-box. {ECO:0000255|PROSITE-
DNA_BIND 58 86 Mef2-type. {ECO:0000255}.
REGION 271 278 Beta domain. {ECO:0000250}.
REGION 368 399 Transcription repressor. {ECO:0000250}.
COMPBIAS 4 31 Lys-rich (basic).
COMPBIAS 146 183 Ser-rich.
SITE 432 433 Cleavage. {ECO:0000305}.
MOD_RES 4 4 N6-acetyllysine.
MOD_RES 59 59 Phosphoserine; by CK2.
MOD_RES 98 98 Phosphoserine.
MOD_RES 106 106 Phosphoserine.
MOD_RES 110 110 Phosphoserine.
MOD_RES 116 116 N6-acetyllysine.
MOD_RES 119 119 N6-acetyllysine.
MOD_RES 222 222 Phosphoserine.
MOD_RES 228 228 Phosphoserine.
MOD_RES 234 234 N6-acetyllysine.
MOD_RES 239 239 N6-acetyllysine.
MOD_RES 240 240 Phosphoserine.
MOD_RES 252 252 N6-acetyllysine.
MOD_RES 264 264 N6-acetyllysine.
MOD_RES 293 293 Phosphothreonine; by MAPK14.
MOD_RES 300 300 Phosphothreonine; by MAPK14.
MOD_RES 396 396 Phosphoserine; by CDK5.
MOD_RES 419 419 Phosphoserine; by MAPK7.
MOD_RES 445 445 Phosphoserine.
CROSSLNK 391 391 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO).
SEQUENCE 473 AA; 51221 MW; A7982020BB8C8949 CRC64;

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