MRTFA_HUMAN
ID MRTFA_HUMAN Reviewed; 931 AA.
AC Q969V6; Q8TCL1; Q96SC5; Q96SC6; Q9P2B0;
DT 27-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Myocardin-related transcription factor A {ECO:0000305};
DE Short=MRTF-A {ECO:0000305};
DE AltName: Full=MKL/myocardin-like protein 1 {ECO:0000303|PubMed:11431691};
DE AltName: Full=Megakaryoblastic leukemia 1 protein {ECO:0000303|PubMed:11431691};
DE AltName: Full=Megakaryocytic acute leukemia protein {ECO:0000250|UniProtKB:Q8K4J6};
GN Name=MRTFA {ECO:0000312|HGNC:HGNC:14334};
GN Synonyms=KIAA1438 {ECO:0000303|PubMed:10718198},
GN MAL {ECO:0000250|UniProtKB:Q8K4J6}, MKL1 {ECO:0000303|PubMed:11431691};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHROMOSOMAL TRANSLOCATION WITH RBM15.
RX PubMed=11431691; DOI=10.1038/90054;
RA Ma Z., Morris S.W., Valentine V., Li M., Herbrick J.-A., Cui X., Bouman D.,
RA Li Y., Mehta P.K., Nizetic D., Kaneko Y., Chan G.C.F., Chan L.C.,
RA Squire J., Scherer S.W., Hitzler J.K.;
RT "Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of
RT acute megakaryoblastic leukemia.";
RL Nat. Genet. 28:220-221(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION WITH RBM15, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Blood;
RX PubMed=11344311; DOI=10.1073/pnas.101001498;
RA Mercher T., Coniat M.B.-L., Monni R., Mauchauffe M., Khac F.N., Gressin L.,
RA Mugneret F., Leblanc T., Dastugue N., Berger R., Bernard O.A.;
RT "Involvement of a human gene related to the Drosophila spen gene in the
RT recurrent t(1;22) translocation of acute megakaryocytic leukemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:5776-5779(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [4]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-648.
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 195-931, AND VARIANT GLY-648.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP INTERACTION WITH MRTFB AND SRF.
RC TISSUE=Cervix carcinoma;
RX PubMed=14565952; DOI=10.1074/jbc.m305679200;
RA Selvaraj A., Prywes R.;
RT "Megakaryoblastic leukemia-1/2, a transcriptional co-activator of serum
RT response factor, is required for skeletal myogenic differentiation.";
RL J. Biol. Chem. 278:41977-41987(2003).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-305 AND THR-450, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP INTERACTION WITH SCAI AND SRF, AND SUBCELLULAR LOCATION.
RX PubMed=19350017; DOI=10.1038/ncb1862;
RA Brandt D.T., Baarlink C., Kitzing T.M., Kremmer E., Ivaska J., Nollau P.,
RA Grosse R.;
RT "SCAI acts as a suppressor of cancer cell invasion through the
RT transcriptional control of beta1-integrin.";
RL Nat. Cell Biol. 11:557-568(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-450 AND SER-454, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6; THR-450 AND SER-454, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156; SER-333; SER-385 AND
RP THR-450, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP SUBCELLULAR LOCATION.
RX PubMed=24440334; DOI=10.1016/j.cell.2013.12.035;
RA Lundquist M.R., Storaska A.J., Liu T.C., Larsen S.D., Evans T.,
RA Neubig R.R., Jaffrey S.R.;
RT "Redox modification of nuclear actin by MICAL-2 regulates SRF signaling.";
RL Cell 156:563-576(2014).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP STRUCTURE BY NMR OF 336-396.
RG Northeast structural genomics consortium (NESG);
RT "Northeast structural genomics consortium target HR4547E.";
RL Submitted (JUN-2010) to the PDB data bank.
RN [20]
RP FUNCTION, INVOLVEMENT IN IMD66, VARIANT IMD66 723-LYS--LEU-931 DEL,
RP CHARACTERIZATION OF VARIANT IMD66 723-LYS--LEU-931 DEL, AND TISSUE
RP SPECIFICITY.
RX PubMed=26224645; DOI=10.1182/blood-2014-12-611012;
RA Record J., Malinova D., Zenner H.L., Plagnol V., Nowak K., Syed F.,
RA Bouma G., Curtis J., Gilmour K., Cale C., Hackett S., Charras G.,
RA Moulding D., Nejentsev S., Thrasher A.J., Burns S.O.;
RT "Immunodeficiency and severe susceptibility to bacterial infection
RT associated with a loss-of-function homozygous mutation of MKL1.";
RL Blood 126:1527-1535(2015).
CC -!- FUNCTION: Transcription coactivator that associates with the serum
CC response factor (SRF) transcription factor to control expression of
CC genes regulating the cytoskeleton during development, morphogenesis and
CC cell migration (PubMed:26224645). The SRF-MRTFA complex activity
CC responds to Rho GTPase-induced changes in cellular globular actin (G-
CC actin) concentration, thereby coupling cytoskeletal gene expression to
CC cytoskeletal dynamics. MRTFA binds G-actin via its RPEL repeats,
CC regulating activity of the MRTFA-SRF complex. Activity is also
CC regulated by filamentous actin (F-actin) in the nucleus.
CC {ECO:0000250|UniProtKB:Q8K4J6, ECO:0000269|PubMed:26224645}.
CC -!- SUBUNIT: Interacts with SRF, forming the SRF-MRTFA nuclear complex
CC which binds the 5'-CArG-3' consensus motif (CArG box) on DNA via SRF
CC (PubMed:14565952, PubMed:19350017). Interacts (via RPEL repeats) with
CC globular actin (G-actin), thereby regulating its subcellular location
CC and activity of the complex formed with SRF (PubMed:19350017). Either
CC forms a trivalent (by binding three G-actin monomers) or pentavalent
CC (by binding five G-actin monomers) complex with G-actin (By
CC similarity). Forms a nuclear ternary complex with SCAI and SRF, leading
CC to suppress MRTFA-induced SRF transcriptional activity
CC (PubMed:19350017). Interacts with beta-actin (ACTB); interaction with
CC ACTB prevents interaction with SCAI (By similarity). Interacts with
CC MRTFB (PubMed:14565952). {ECO:0000250|UniProtKB:Q8K4J6,
CC ECO:0000269|PubMed:14565952, ECO:0000269|PubMed:19350017}.
CC -!- INTERACTION:
CC Q969V6; P11831: SRF; NbExp=2; IntAct=EBI-493122, EBI-493034;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24440334}. Nucleus
CC {ECO:0000269|PubMed:19350017, ECO:0000269|PubMed:24440334}.
CC Note=Subcellular location is tightly regulated by actin both in
CC cytoplasm and nucleus: high levels of G-actin in the nucleus observed
CC during serum deprivation lead to low levels of nuclear MRTFA, while
CC reduced levels of nuclear G-actin result in accumulation of MRTFA in
CC the nucleus (By similarity). G-actin-binding in the cytoplasm inhibits
CC nuclear import by masking the nuclear localization signal (NLS) (By
CC similarity). In contrast, binding to nuclear globular actin (G-actin)
CC promotes nuclear export to the cytoplasm (By similarity). Nuclear
CC localization is regulated by MICAL2, which mediates depolymerization of
CC nuclear actin, which decreases nuclear G-actin pool, thereby promoting
CC retention of MRTFA in the nucleus and subsequent formation of an active
CC complex with SRF (PubMed:24440334). {ECO:0000250|UniProtKB:Q8K4J6,
CC ECO:0000269|PubMed:24440334}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, has been detected in lung,
CC placenta, small intestine, liver, kidney, spleen, thymus, colon,
CC muscle, heart and brain (PubMed:11344311). Expressed in peripheral
CC blood mononuclear cells (at protein level) (PubMed:26224645).
CC {ECO:0000269|PubMed:11344311, ECO:0000269|PubMed:26224645}.
CC -!- DOMAIN: The N-terminal region is required for nuclear localization and
CC the C-terminal region mediates transcriptional activity.
CC {ECO:0000250|UniProtKB:Q8K4J6}.
CC -!- DOMAIN: The RPEL repeats mediate binding to globular actin (G-actin);
CC each RPEL repeat-binding to one G-actin monomer. In addition, each
CC intervening spacer sequence region can bind one G-actin monomer, to
CC reach a pentavalent complex. {ECO:0000250|UniProtKB:Q8K4J6}.
CC -!- PTM: Phosphorylation at Ser-6 by Erk inhibits binding of globular actin
CC (G-actin), unmasking the nuclear localization signal (NLS) and
CC promoting nuclear import. {ECO:0000250|UniProtKB:Q8K4J6}.
CC -!- DISEASE: Note=A chromosomal aberration involving MRTFA may be a cause
CC of acute megakaryoblastic leukemia. Translocation t(1;22)(p13;q13) with
CC RBM15 (PubMed:11431691, PubMed:11344311). Although both reciprocal
CC fusion transcripts are detected in acute megakaryoblastic leukemia
CC (AMKL, FAB-M7), the RBM15-MRTFA chimeric protein has all the putative
CC functional domains encoded by each gene and is the candidate oncogene
CC (PubMed:11431691, PubMed:11344311). {ECO:0000269|PubMed:11344311,
CC ECO:0000269|PubMed:11431691}.
CC -!- DISEASE: Immunodeficiency 66 (IMD66) [MIM:618847]: An autosomal
CC recessive primary immunologic disorder characterized by recurrent viral
CC infections from infancy, associated with impaired neutrophil migration
CC due to defects in cytoskeletal actin dynamics.
CC {ECO:0000269|PubMed:26224645}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK56920.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA92676.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAC38828.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAC38829.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MALID352.html";
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DR EMBL; AJ297257; CAC38826.1; -; mRNA.
DR EMBL; AF364035; AAK56920.1; ALT_INIT; mRNA.
DR EMBL; CR456522; CAG30408.1; -; mRNA.
DR EMBL; AJ297258; CAC38827.1; -; mRNA.
DR EMBL; AF368061; AAK54721.1; -; mRNA.
DR EMBL; AJ303089; CAC38828.1; ALT_INIT; mRNA.
DR EMBL; AJ303090; CAC38829.1; ALT_INIT; mRNA.
DR EMBL; AB037859; BAA92676.2; ALT_INIT; mRNA.
DR EMBL; AL022238; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL713710; CAD28507.2; -; mRNA.
DR CCDS; CCDS14003.1; -.
DR RefSeq; NP_001269589.1; NM_001282660.1.
DR RefSeq; NP_001269590.1; NM_001282661.1.
DR RefSeq; NP_065882.1; NM_020831.4.
DR RefSeq; XP_005261751.1; XM_005261694.1.
DR PDB; 2KVU; NMR; -; A=336-396.
DR PDB; 2KW9; NMR; -; A=336-396.
DR PDBsum; 2KVU; -.
DR PDBsum; 2KW9; -.
DR AlphaFoldDB; Q969V6; -.
DR BMRB; Q969V6; -.
DR SMR; Q969V6; -.
DR BioGRID; 121642; 44.
DR IntAct; Q969V6; 18.
DR MINT; Q969V6; -.
DR STRING; 9606.ENSP00000347847; -.
DR DrugBank; DB08080; Latrunculin B.
DR GlyGen; Q969V6; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q969V6; -.
DR PhosphoSitePlus; Q969V6; -.
DR BioMuta; MKL1; -.
DR DMDM; 32363202; -.
DR EPD; Q969V6; -.
DR jPOST; Q969V6; -.
DR MassIVE; Q969V6; -.
DR MaxQB; Q969V6; -.
DR PaxDb; Q969V6; -.
DR PeptideAtlas; Q969V6; -.
DR PRIDE; Q969V6; -.
DR ProteomicsDB; 75854; -.
DR Antibodypedia; 26780; 362 antibodies from 33 providers.
DR DNASU; 57591; -.
DR Ensembl; ENST00000407029.7; ENSP00000385835.1; ENSG00000196588.21.
DR GeneID; 57591; -.
DR KEGG; hsa:57591; -.
DR UCSC; uc003ayv.3; human.
DR CTD; 57591; -.
DR DisGeNET; 57591; -.
DR GeneCards; MRTFA; -.
DR HGNC; HGNC:14334; MRTFA.
DR HPA; ENSG00000196588; Low tissue specificity.
DR MalaCards; MRTFA; -.
DR MIM; 606078; gene.
DR MIM; 618847; phenotype.
DR neXtProt; NX_Q969V6; -.
DR OpenTargets; ENSG00000196588; -.
DR Orphanet; 402023; Megakaryoblastic acute myeloid leukemia with t(1;22)(p13;q13).
DR PharmGKB; PA30827; -.
DR VEuPathDB; HostDB:ENSG00000196588; -.
DR eggNOG; ENOG502R5FB; Eukaryota.
DR GeneTree; ENSGT00950000182979; -.
DR InParanoid; Q969V6; -.
DR PhylomeDB; Q969V6; -.
DR TreeFam; TF326024; -.
DR PathwayCommons; Q969V6; -.
DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR SignaLink; Q969V6; -.
DR SIGNOR; Q969V6; -.
DR BioGRID-ORCS; 57591; 27 hits in 1084 CRISPR screens.
DR ChiTaRS; SMARCA4; human.
DR EvolutionaryTrace; Q969V6; -.
DR GeneWiki; MKL1; -.
DR GenomeRNAi; 57591; -.
DR Pharos; Q969V6; Tbio.
DR PRO; PR:Q969V6; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q969V6; protein.
DR Bgee; ENSG00000196588; Expressed in monocyte and 182 other tissues.
DR ExpressionAtlas; Q969V6; baseline and differential.
DR Genevisible; Q969V6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0003785; F:actin monomer binding; ISS:UniProtKB.
DR GO; GO:0043522; F:leucine zipper domain binding; IPI:BHF-UCL.
DR GO; GO:0003713; F:transcription coactivator activity; IGI:ARUK-UCL.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IGI:ARUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0010735; P:positive regulation of transcription via serum response element binding; IDA:UniProtKB.
DR GO; GO:0051145; P:smooth muscle cell differentiation; IMP:BHF-UCL.
DR GO; GO:0044319; P:wound healing, spreading of cells; IDA:CACAO.
DR Gene3D; 1.10.720.30; -; 1.
DR IDEAL; IID00493; -.
DR InterPro; IPR029992; MRTF-A.
DR InterPro; IPR043451; Myocardin-like.
DR InterPro; IPR004018; RPEL_repeat.
DR InterPro; IPR003034; SAP_dom.
DR InterPro; IPR036361; SAP_dom_sf.
DR PANTHER; PTHR22793; PTHR22793; 1.
DR PANTHER; PTHR22793:SF6; PTHR22793:SF6; 1.
DR Pfam; PF02755; RPEL; 2.
DR Pfam; PF02037; SAP; 1.
DR SMART; SM00707; RPEL; 2.
DR SMART; SM00513; SAP; 1.
DR SUPFAM; SSF68906; SSF68906; 1.
DR PROSITE; PS51073; RPEL; 2.
DR PROSITE; PS50800; SAP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Chromosomal rearrangement; Coiled coil;
KW Cytoplasm; Disease variant; Nucleus; Phosphoprotein; Proto-oncogene;
KW Reference proteome; Repeat; Transcription; Transcription regulation.
FT CHAIN 1..931
FT /note="Myocardin-related transcription factor A"
FT /id="PRO_0000126625"
FT REPEAT 24..49
FT /note="RPEL 1"
FT REPEAT 68..93
FT /note="RPEL 2"
FT DOMAIN 347..381
FT /note="SAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00186"
FT REGION 1..256
FT /note="Mediates interaction with SCAI and ACTB"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT REGION 6..23
FT /note="Intervening spacer sequence 1"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT REGION 50..67
FT /note="Intervening spacer sequence 2"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT REGION 110..256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 290..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 444..476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 558..577
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 674..746
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 763..816
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 515..563
FT /evidence="ECO:0000255"
FT COMPBIAS 110..140
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 149..165
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 178..192
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 193..217
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 305..340
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 674..690
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 732..746
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 796..810
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 3..4
FT /note="Breakpoint for translocation to form RBM15-MRTFA"
FT /evidence="ECO:0000269|PubMed:11431691"
FT MOD_RES 6
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 124
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 305
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 310
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 313
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 317
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 385
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 447
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 450
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 454
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 456
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 482
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 511
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 685
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 691
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 695
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 792
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 807
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT MOD_RES 859
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4J6"
FT VARIANT 648
FT /note="S -> G (in dbSNP:rs878756)"
FT /evidence="ECO:0000269|PubMed:15461802,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_021409"
FT VARIANT 723..931
FT /note="Missing (in IMD66; probable loss-of-function;
FT patient's dendritic cells are morphologically distinct from
FT control dendritic cells and show reduced spreading on
FT fibronectin-coated coverslips, a marked reduction in total
FT F-actin staining and a complete absence of podosomes, a
FT similar phenotype to that of THP1 cells in which MRTFA was
FT silenced)"
FT /evidence="ECO:0000269|PubMed:26224645"
FT /id="VAR_084011"
FT TURN 345..349
FT /evidence="ECO:0007829|PDB:2KVU"
FT HELIX 352..361
FT /evidence="ECO:0007829|PDB:2KVU"
FT HELIX 370..382
FT /evidence="ECO:0007829|PDB:2KVU"
FT STRAND 388..390
FT /evidence="ECO:0007829|PDB:2KVU"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:2KW9"
SQ SEQUENCE 931 AA; 98919 MW; 6EDE5E2C56D89609 CRC64;
MPPLKSPAAF HEQRRSLERA RTEDYLKRKI RSRPERSELV RMHILEETSA EPSLQAKQLK
LKRARLADDL NEKIAQRPGP MELVEKNILP VESSLKEAII VGQVNYPKVA DSSSFDEDSS
DALSPEQPAS HESQGSVPSP LEARVSEPLL SATSASPTQV VSQLPMGRDS REMLFLAEQP
PLPPPPLLPP SLTNGTTIPT AKSTPTLIKQ SQPKSASEKS QRSKKAKELK PKVKKLKYHQ
YIPPDQKQDR GAPPMDSSYA KILQQQQLFL QLQILNQQQQ QHHNYQAILP APPKSAGEAL
GSSGTPPVRS LSTTNSSSSS GAPGPCGLAR QNSTSLTGKP GALPANLDDM KVAELKQELK
LRSLPVSGTK TELIERLRAY QDQISPVPGA PKAPAATSIL HKAGEVVVAF PAARLSTGPA
LVAAGLAPAE VVVATVASSG VVKFGSTGST PPVSPTPSER SLLSTGDENS TPGDTFGEMV
TSPLTQLTLQ ASPLQILVKE EGPRAGSCCL SPGGRAELEG RDKDQMLQEK DKQIEALTRM
LRQKQQLVER LKLQLEQEKR AQQPAPAPAP LGTPVKQENS FSSCQLSQQP LGPAHPFNPS
LAAPATNHID PCAVAPGPPS VVVKQEALQP EPEPVPAPQL LLGPQGPSLI KGVAPPTLIT
DSTGTHLVLT VTNKNADSPG LSSGSPQQPS SQPGSPAPAP SAQMDLEHPL QPLFGTPTSL
LKKEPPGYEE AMSQQPKQQE NGSSSQQMDD LFDILIQSGE ISADFKEPPS LPGKEKPSPK
TVCGSPLAAQ PSPSAELPQA APPPPGSPSL PGRLEDFLES STGLPLLTSG HDGPEPLSLI
DDLHSQMLSS TAILDHPPSP MDTSELHFVP EPSSTMGLDL ADGHLDSMDW LELSSGGPVL
SLAPLSTTAP SLFSTDFLDG HDLQLHWDSC L
