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Protein

MKL/myocardin-like protein 1

Gene

MKL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • actin monomer binding Source: UniProtKB
  • leucine zipper domain binding Source: BHF-UCL
  • RNA polymerase II transcription coactivator activity Source: GO_Central
  • transcription coactivator activity Source: UniProtKB

GO - Biological processi

  • positive regulation of transcription by RNA polymerase II Source: BHF-UCL
  • positive regulation of transcription via serum response element binding Source: UniProtKB
  • smooth muscle cell differentiation Source: BHF-UCL

Keywordsi

Molecular functionActin-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-5663220 RHO GTPases Activate Formins
SIGNORiQ969V6

Names & Taxonomyi

Protein namesi
Recommended name:
MKL/myocardin-like protein 1
Alternative name(s):
Megakaryoblastic leukemia 1 protein
Megakaryocytic acute leukemia protein
Myocardin-related transcription factor A
Short name:
MRTF-A
Gene namesi
Name:MKL1
Synonyms:KIAA1438, MAL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000196588.14
HGNCiHGNC:14334 MKL1
MIMi606078 gene
neXtProtiNX_Q969V6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei3 – 4Breakpoint for translocation to form RBM15-MKL12

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi57591
MalaCardsiMKL1
OpenTargetsiENSG00000196588
Orphaneti402023 'Megakaryoblastic acute myeloid leukemia with t(1;22)(p13;q13)'
PharmGKBiPA30827

Chemistry databases

DrugBankiDB08080 LATRUNCULIN B

Polymorphism and mutation databases

BioMutaiMKL1
DMDMi32363202

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001266251 – 931MKL/myocardin-like protein 1Add BLAST931

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei6PhosphoserineCombined sources1
Modified residuei156PhosphoserineCombined sources1
Modified residuei305PhosphothreonineCombined sources1
Modified residuei333PhosphoserineCombined sources1
Modified residuei385PhosphoserineCombined sources1
Modified residuei450PhosphothreonineCombined sources1
Modified residuei454PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ969V6
MaxQBiQ969V6
PaxDbiQ969V6
PeptideAtlasiQ969V6
PRIDEiQ969V6

PTM databases

iPTMnetiQ969V6
PhosphoSitePlusiQ969V6

Expressioni

Tissue specificityi

Ubiquitously expressed, has been detected in lung, placenta, small intestine, liver, kidney, spleen, thymus, colon, muscle, heart and brain.

Gene expression databases

BgeeiENSG00000196588
CleanExiHS_MAL
HS_MKL1
ExpressionAtlasiQ969V6 baseline and differential
GenevisibleiQ969V6 HS

Organism-specific databases

HPAiHPA030782

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
SRFP118312EBI-493122,EBI-493034

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • actin monomer binding Source: UniProtKB
  • leucine zipper domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi121642, 24 interactors
IntActiQ969V6, 12 interactors
MINTiQ969V6
STRINGi9606.ENSP00000347847

Structurei

Secondary structure

1931
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni345 – 349Combined sources5
Helixi352 – 361Combined sources10
Helixi370 – 382Combined sources13
Beta strandi388 – 390Combined sources3
Beta strandi392 – 394Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KVUNMR-A336-396[»]
2KW9NMR-A336-396[»]
ProteinModelPortaliQ969V6
SMRiQ969V6
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ969V6

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati24 – 49RPEL 1Add BLAST26
Repeati68 – 93RPEL 2Add BLAST26
Domaini347 – 381SAPPROSITE-ProRule annotationAdd BLAST35

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 256Mediates interaction with SCAI and ACTBBy similarityAdd BLAST256

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili515 – 563Sequence analysisAdd BLAST49

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi264 – 286Gln-richAdd BLAST23
Compositional biasi564 – 811Pro-richAdd BLAST248

Domaini

The N-terminal region is required for nuclear localization and the C-terminal region mediates transcriptional activity.By similarity
The RPEL repeats mediate binding to globular actin.By similarity

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiENOG410IFJX Eukaryota
ENOG41101AM LUCA
GeneTreeiENSGT00530000063195
HOGENOMiHOG000038001
HOVERGENiHBG036493
InParanoidiQ969V6
KOiK22525
PhylomeDBiQ969V6
TreeFamiTF326024

Family and domain databases

Gene3Di1.10.720.30, 1 hit
InterProiView protein in InterPro
IPR029992 MRTF-A
IPR004018 RPEL_repeat
IPR003034 SAP_dom
IPR036361 SAP_dom_sf
PANTHERiPTHR22793:SF6 PTHR22793:SF6, 2 hits
PfamiView protein in Pfam
PF02755 RPEL, 2 hits
PF02037 SAP, 1 hit
SMARTiView protein in SMART
SM00707 RPEL, 2 hits
SM00513 SAP, 1 hit
SUPFAMiSSF68906 SSF68906, 1 hit
PROSITEiView protein in PROSITE
PS51073 RPEL, 2 hits
PS50800 SAP, 1 hit

Sequencei

Sequence statusi: Complete.

Q969V6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPPLKSPAAF HEQRRSLERA RTEDYLKRKI RSRPERSELV RMHILEETSA
60 70 80 90 100
EPSLQAKQLK LKRARLADDL NEKIAQRPGP MELVEKNILP VESSLKEAII
110 120 130 140 150
VGQVNYPKVA DSSSFDEDSS DALSPEQPAS HESQGSVPSP LEARVSEPLL
160 170 180 190 200
SATSASPTQV VSQLPMGRDS REMLFLAEQP PLPPPPLLPP SLTNGTTIPT
210 220 230 240 250
AKSTPTLIKQ SQPKSASEKS QRSKKAKELK PKVKKLKYHQ YIPPDQKQDR
260 270 280 290 300
GAPPMDSSYA KILQQQQLFL QLQILNQQQQ QHHNYQAILP APPKSAGEAL
310 320 330 340 350
GSSGTPPVRS LSTTNSSSSS GAPGPCGLAR QNSTSLTGKP GALPANLDDM
360 370 380 390 400
KVAELKQELK LRSLPVSGTK TELIERLRAY QDQISPVPGA PKAPAATSIL
410 420 430 440 450
HKAGEVVVAF PAARLSTGPA LVAAGLAPAE VVVATVASSG VVKFGSTGST
460 470 480 490 500
PPVSPTPSER SLLSTGDENS TPGDTFGEMV TSPLTQLTLQ ASPLQILVKE
510 520 530 540 550
EGPRAGSCCL SPGGRAELEG RDKDQMLQEK DKQIEALTRM LRQKQQLVER
560 570 580 590 600
LKLQLEQEKR AQQPAPAPAP LGTPVKQENS FSSCQLSQQP LGPAHPFNPS
610 620 630 640 650
LAAPATNHID PCAVAPGPPS VVVKQEALQP EPEPVPAPQL LLGPQGPSLI
660 670 680 690 700
KGVAPPTLIT DSTGTHLVLT VTNKNADSPG LSSGSPQQPS SQPGSPAPAP
710 720 730 740 750
SAQMDLEHPL QPLFGTPTSL LKKEPPGYEE AMSQQPKQQE NGSSSQQMDD
760 770 780 790 800
LFDILIQSGE ISADFKEPPS LPGKEKPSPK TVCGSPLAAQ PSPSAELPQA
810 820 830 840 850
APPPPGSPSL PGRLEDFLES STGLPLLTSG HDGPEPLSLI DDLHSQMLSS
860 870 880 890 900
TAILDHPPSP MDTSELHFVP EPSSTMGLDL ADGHLDSMDW LELSSGGPVL
910 920 930
SLAPLSTTAP SLFSTDFLDG HDLQLHWDSC L
Length:931
Mass (Da):98,919
Last modified:December 1, 2001 - v1
Checksum:i6EDE5E2C56D89609
GO

Sequence cautioni

The sequence AAK56920 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAA92676 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAC38828 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAC38829 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021409648S → G2 PublicationsCorresponds to variant dbSNP:rs878756Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ297257 mRNA Translation: CAC38826.1
AF364035 mRNA Translation: AAK56920.1 Different initiation.
CR456522 mRNA Translation: CAG30408.1
AJ297258 mRNA Translation: CAC38827.1
AF368061 mRNA Translation: AAK54721.1
AJ303089 mRNA Translation: CAC38828.1 Different initiation.
AJ303090 mRNA Translation: CAC38829.1 Different initiation.
AB037859 mRNA Translation: BAA92676.2 Different initiation.
AL022238 Genomic DNA No translation available.
AL713710 mRNA Translation: CAD28507.2
CCDSiCCDS14003.1
RefSeqiNP_001269589.1, NM_001282660.1
NP_001269590.1, NM_001282661.1
NP_065882.1, NM_020831.4
XP_005261751.1, XM_005261694.1
UniGeneiHs.654688

Genome annotation databases

EnsembliENST00000355630; ENSP00000347847; ENSG00000196588
ENST00000407029; ENSP00000385835; ENSG00000196588
GeneIDi57591
KEGGihsa:57591
UCSCiuc003ayv.3 human

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMKL1_HUMAN
AccessioniPrimary (citable) accession number: Q969V6
Secondary accession number(s): Q8TCL1
, Q96SC5, Q96SC6, Q9P2B0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 27, 2003
Last sequence update: December 1, 2001
Last modified: May 23, 2018
This is version 162 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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