Human Gene MKL1 (uc003ayw.1) Description and Page Index
  Description: Homo sapiens megakaryoblastic leukemia (translocation) 1 (MKL1), mRNA.
RefSeq Summary (NM_020831): The protein encoded by this gene interacts with the transcription factor myocardin, a key regulator of smooth muscle cell differentiation. The encoded protein is predominantly nuclear and may help transduce signals from the cytoskeleton to the nucleus. This gene is involved in a specific translocation event that creates a fusion of this gene and the RNA-binding motif protein-15 gene. This translocation has been associated with acute megakaryocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013].
Transcript (Including UTRs)
   Position: hg19 chr22:40,806,292-41,032,690 Size: 226,399 Total Exon Count: 15 Strand: -
Coding Region
   Position: hg19 chr22:40,807,394-40,859,231 Size: 51,838 Coding Exon Count: 12 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr22:40,806,292-41,032,690)mRNA (may differ from genome)Protein (931 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=MKL/myocardin-like protein 1; AltName: Full=Megakaryoblastic leukemia 1 protein; AltName: Full=Megakaryocytic acute leukemia protein; AltName: Full=Myocardin-related transcription factor A; Short=MRTF-A;
FUNCTION: Transcriptional coactivator of serum response factor (SRF) with the potential to modulate SRF target genes. Suppresses TNF-induced cell death by inhibiting activation of caspases; its transcriptional activity is indispensable for the antiapoptotic function. It may up-regulate antiapoptotic molecules, which in turn inhibit caspase activation (By similarity).
SUBUNIT: Forms with SCAI and SRF a nuclear ternary complex which binds the CArG consensus motif (CArG box) on DNA via SRF. Interacts with ACTB; interaction with ACTB prevents interaction with SCAI. Interacts with MKL2 (By similarity).
INTERACTION: P11831:SRF; NbExp=2; IntAct=EBI-493122, EBI-493034;
SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). Note=Binding to globular actin is required to maintain cytoplasmic localization (By similarity).
TISSUE SPECIFICITY: Ubiquitously expressed, has been detected in lung, placenta, small intestine, liver, kidney, spleen, thymus, colon, muscle, heart and brain.
DOMAIN: The N-terminal region is required for nuclear localization and the C-terminal region mediates transcriptional activity (By similarity).
DOMAIN: The RPEL repeats mediate binding to globular actin (By similarity).
DISEASE: Note=A chromosomal aberration involving MKL1 may be a cause of acute megakaryoblastic leukemia. Translocation t(1;22)(p13;q13) with RBM15. Although both reciprocal fusion transcripts are detected in acute megakaryoblastic leukemia (AMKL, FAB-M7), the RBM15-MKL1 chimeric protein has all the putative functional domains encoded by each gene and is the candidate oncogene.
SIMILARITY: Contains 2 RPEL repeats.
SIMILARITY: Contains 1 SAP domain.
SEQUENCE CAUTION: Sequence=AAK56920.1; Type=Erroneous initiation; Sequence=BAA92676.2; Type=Erroneous initiation; Sequence=CAC38828.1; Type=Erroneous initiation; Sequence=CAC38829.1; Type=Erroneous initiation;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): MKL1
CDC HuGE Published Literature: MKL1
Positive Disease Associations: Body Height , Coronary Artery Disease , height
Related Studies:
  1. Body Height
    Karol Estrada et al. Human molecular genetics 2009, A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation., Human molecular genetics. [PubMed 19570815]
  2. Coronary Artery Disease
    , , . [PubMed 0]
  3. height
    Estrada ,et al. 2009, A genome-wide association study of northwestern Europeans involves the CNP signaling pathway in the etiology of human height variation, Human molecular genetics 2009 18- 18 : 3516-24. [PubMed 19570815]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: MKL1
Diseases sorted by gene-association score: megakaryoblastic acute myeloid leukemia with t(1;22)(p13;q13)* (247), megakaryocytic leukemia (22), leukemia (11), endocardium disease (7)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 19.99 RPKM in Testis
Total median expression: 414.85 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -249.10592-0.421 Picture PostScript Text
3' UTR -480.791102-0.436 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR004018 - RPEL_repeat
IPR003034 - SAP_DNA-bd

Pfam Domains:
PF02037 - SAP domain
PF02755 - RPEL repeat

SCOP Domains:
68906 - SAP domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help



ModBase Predicted Comparative 3D Structure on Q969V6
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001105 RNA polymerase II transcription coactivator activity
GO:0003713 transcription coactivator activity
GO:0003779 actin binding
GO:0003785 actin monomer binding
GO:0005515 protein binding
GO:0043522 leucine zipper domain binding

Biological Process:
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006366 transcription from RNA polymerase II promoter
GO:0010735 positive regulation of transcription via serum response element binding
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0051145 smooth muscle cell differentiation

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol

-  Descriptions from all associated GenBank mRNAs
  BC115039 - Homo sapiens megakaryoblastic leukemia (translocation) 1, mRNA (cDNA clone MGC:131756 IMAGE:5551767), complete cds.
HG764171 - Homo sapiens mRNA for MKL1 variant 1 MKL1_S.
AF368061 - Homo sapiens megakaryoblastic leukemia-1 protein (MKL1) mRNA, complete cds.
AB037859 - Homo sapiens KIAA1438 mRNA for KIAA1438 protein.
BC064620 - Homo sapiens megakaryoblastic leukemia (translocation) 1, mRNA (cDNA clone IMAGE:5591634), partial cds.
AJ297258 - Homo sapiens mRNA for megacaryocytic acute leukemia protein (MAL gene), isoform I.
BC139730 - Homo sapiens megakaryoblastic leukemia (translocation) 1, mRNA (cDNA clone IMAGE:40028619).
BC114364 - Homo sapiens megakaryoblastic leukemia (translocation) 1, mRNA (cDNA clone IMAGE:40028620), complete cds.
AF364036 - Homo sapiens megakaryoblastic leukemia-1 protein/RNA-binding motif protein 15s fusion protein (MKL1/RBM15 fusion) mRNA, complete cds.
AF364037 - Homo sapiens megakaryoblastic leukemia-1 protein/RNA-binding motif protein 15s + ae fusion protein (MKL1/RBM15 fusion) mRNA, complete cds.
AF448806 - Homo sapiens MKL1 mRNA, 5' untranslated region, partial sequence; alternatively spliced.
AL713710 - Homo sapiens mRNA; cDNA DKFZp434N1322 (from clone DKFZp434N1322).
BC021586 - Homo sapiens megakaryoblastic leukemia (translocation) 1, mRNA (cDNA clone IMAGE:4890439), with apparent retained intron.
AK096572 - Homo sapiens cDNA FLJ39253 fis, clone OCBBF2008768.
AJ303090 - Homo sapiens mRNA for OTT-MAL protein resulting from common (1;22) translocation breakpoint.
AJ303089 - Homo sapiens mRNA for OTT-MAL protein resulting from variant (1;22) translocation breakpoint.
AJ297257 - Homo sapiens mRNA for megacaryocytic acute leukemia (MAL gene).
JD385241 - Sequence 366265 from Patent EP1572962.
JD385240 - Sequence 366264 from Patent EP1572962.
JD320110 - Sequence 301134 from Patent EP1572962.
JD036763 - Sequence 17787 from Patent EP1572962.
JD206063 - Sequence 187087 from Patent EP1572962.
JD117481 - Sequence 98505 from Patent EP1572962.
JD406071 - Sequence 387095 from Patent EP1572962.
JD129029 - Sequence 110053 from Patent EP1572962.
JD520772 - Sequence 501796 from Patent EP1572962.
JD470902 - Sequence 451926 from Patent EP1572962.
JD402501 - Sequence 383525 from Patent EP1572962.
JD079098 - Sequence 60122 from Patent EP1572962.
JD521381 - Sequence 502405 from Patent EP1572962.
JD281718 - Sequence 262742 from Patent EP1572962.
JD046085 - Sequence 27109 from Patent EP1572962.
JD512935 - Sequence 493959 from Patent EP1572962.
JD151411 - Sequence 132435 from Patent EP1572962.
JD495166 - Sequence 476190 from Patent EP1572962.
JD290461 - Sequence 271485 from Patent EP1572962.
JD078397 - Sequence 59421 from Patent EP1572962.
JD336293 - Sequence 317317 from Patent EP1572962.
CR456522 - Homo sapiens MKL1 full length open reading frame (ORF) cDNA clone (cDNA clone C22ORF:pGEM.MKL1).
JD336332 - Sequence 317356 from Patent EP1572962.
JD483697 - Sequence 464721 from Patent EP1572962.
JD409094 - Sequence 390118 from Patent EP1572962.
JD173634 - Sequence 154658 from Patent EP1572962.
JD152663 - Sequence 133687 from Patent EP1572962.
BC141653 - Synthetic construct Homo sapiens clone IMAGE:100000379, MGC:164688 megakaryoblastic leukemia (translocation) 1 (MKL1) mRNA, encodes complete protein.
CU013122 - Homo sapiens MKL1, mRNA (cDNA clone IMAGE:100000379), complete cds, with stop codon, in Gateway system.
AB384209 - Synthetic construct DNA, clone: pF1KSDA1438, Homo sapiens MKL1 gene for MKL/myocardin-like protein 1, complete cds, without stop codon, in Flexi system.
BC141655 - Synthetic construct Homo sapiens clone IMAGE:100000283, MGC:164695 megakaryoblastic leukemia (translocation) 1 (MKL1) mRNA, encodes complete protein.
CU013410 - Homo sapiens MKL1, mRNA (cDNA clone IMAGE:100000283), complete cds, without stop codon, in Gateway system.
AF364035 - Homo sapiens RNA-binding motif protein 15/megakaryoblastic leukemia-1 fusion protein (RBM15/MKL1 fusion) mRNA, partial cds.
JD435957 - Sequence 416981 from Patent EP1572962.
JD461634 - Sequence 442658 from Patent EP1572962.
JD451792 - Sequence 432816 from Patent EP1572962.
JD171996 - Sequence 153020 from Patent EP1572962.
JD408644 - Sequence 389668 from Patent EP1572962.
JD377207 - Sequence 358231 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q969V6 (Reactome details) participates in the following event(s):

R-HSA-5665998 MKL1 binds SRF
R-HSA-5665999 MKL1 translocates from cytosol to the nucleus
R-HSA-5666001 Profilin:G-actin binds MKL1
R-HSA-5665982 RHOA:GTP:DIAPH1 binds EVL and sequesters profilin:G-actin from MKL1
R-HSA-5666008 SCAI binds SRF:MKL1
R-HSA-5666046 SRF:MKL1 binds ITGB1 Gene
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-195258 RHO GTPase Effectors
R-HSA-194315 Signaling by Rho GTPases
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: KIAA1438, MAL, MKL1_HUMAN, NM_020831, NP_065882, Q8TCL1, Q969V6, Q96SC5, Q96SC6, Q9P2B0
UCSC ID: uc003ayw.1
RefSeq Accession: NM_020831
Protein: Q969V6 (aka MKL1_HUMAN)
CCDS: CCDS14003.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_020831.3
exon count: 15CDS single in 3' UTR: no RNA size: 4507
ORF size: 2796CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 5000.00frame shift in genome: no % Coverage: 99.62
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.