Q969V6 (MKL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	MKL1
Synonyms:	KIAA1438, MAL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	931 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 structure	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. Ref.10
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Binding to globular actin is required to maintain cytoplasmic localization By similarity. Ref.10
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. The RPEL repeats mediate binding to globular actin By similarity.
Involvement in disease	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.
Sequence similarities	Contains 2 RPEL repeats. Contains 1 SAP domain.
Sequence caution	The sequence AAK56920.1 differs from that shown. Reason: Erroneous initiation. The sequence BAA92676.2 differs from that shown. Reason: Erroneous initiation. The sequence CAC38828.1 differs from that shown. Reason: Erroneous initiation. The sequence CAC38829.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Domain	Coiled coil Repeat
Ligand	Actin-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 14970199. Source: BHF-UCL smooth muscle cell differentiation Inferred from mutant phenotype PubMed 14970199. Source: BHF-UCL transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay PubMed 14970199. Source: BHF-UCL nucleus Inferred from direct assay PubMed 14970199. Source: BHF-UCL
Molecular_function	actin monomer binding Inferred from sequence or structural similarity. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara transcription coactivator activity Inferred from sequence or structural similarity. Source: UniProtKB transcription regulatory region sequence-specific DNA binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SRF	P11831	2	EBI-493122,EBI-493034

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 931

931

MKL/myocardin-like protein 1

PRO_0000126625

Regions

Repeat

24 – 49

26

RPEL 1

Repeat

68 – 93

26

RPEL 2

Domain

347 – 381

35

SAP

Region

1 – 256

256

Mediates interaction with SCAI and ACTB By similarity

Coiled coil

515 – 563

49

Potential

Compositional bias

264 – 286

23

Gln-rich

Compositional bias

564 – 811

248

Pro-rich

Sites

Site

3 – 4

2

Breakpoint for translocation to form RBM15-MKL1

Amino acid modifications

Modified residue

6

1

Phosphoserine Ref.8 Ref.13

Modified residue

305

1

Phosphothreonine Ref.9

Modified residue

450

1

Phosphothreonine Ref.9 Ref.12 Ref.13

Modified residue

454

1

Phosphoserine Ref.12 Ref.13

Natural variations

Natural variant

648

1

S → G. Ref.5 Ref.7
Corresponds to variant rs878756 [ dbSNP | Ensembl ].

VAR_021409

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

931

Helix Strand Turn

Details...

Turn

345 – 349

5

Helix

352 – 361

10

Helix

370 – 382

13

Beta strand

388 – 390

3

Beta strand

392 – 394

3

Sequences

	Sequence		Length	Mass (Da)
	Q969V6 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 6EDE5E2C56D89609	FASTA	931	98,919
	10 20 30 40 50 60 MPPLKSPAAF HEQRRSLERA RTEDYLKRKI RSRPERSELV RMHILEETSA EPSLQAKQLK 70 80 90 100 110 120 LKRARLADDL NEKIAQRPGP MELVEKNILP VESSLKEAII VGQVNYPKVA DSSSFDEDSS 130 140 150 160 170 180 DALSPEQPAS HESQGSVPSP LEARVSEPLL SATSASPTQV VSQLPMGRDS REMLFLAEQP 190 200 210 220 230 240 PLPPPPLLPP SLTNGTTIPT AKSTPTLIKQ SQPKSASEKS QRSKKAKELK PKVKKLKYHQ 250 260 270 280 290 300 YIPPDQKQDR GAPPMDSSYA KILQQQQLFL QLQILNQQQQ QHHNYQAILP APPKSAGEAL 310 320 330 340 350 360 GSSGTPPVRS LSTTNSSSSS GAPGPCGLAR QNSTSLTGKP GALPANLDDM KVAELKQELK 370 380 390 400 410 420 LRSLPVSGTK TELIERLRAY QDQISPVPGA PKAPAATSIL HKAGEVVVAF PAARLSTGPA 430 440 450 460 470 480 LVAAGLAPAE VVVATVASSG VVKFGSTGST PPVSPTPSER SLLSTGDENS TPGDTFGEMV 490 500 510 520 530 540 TSPLTQLTLQ ASPLQILVKE EGPRAGSCCL SPGGRAELEG RDKDQMLQEK DKQIEALTRM 550 560 570 580 590 600 LRQKQQLVER LKLQLEQEKR AQQPAPAPAP LGTPVKQENS FSSCQLSQQP LGPAHPFNPS 610 620 630 640 650 660 LAAPATNHID PCAVAPGPPS VVVKQEALQP EPEPVPAPQL LLGPQGPSLI KGVAPPTLIT 670 680 690 700 710 720 DSTGTHLVLT VTNKNADSPG LSSGSPQQPS SQPGSPAPAP SAQMDLEHPL QPLFGTPTSL 730 740 750 760 770 780 LKKEPPGYEE AMSQQPKQQE NGSSSQQMDD LFDILIQSGE ISADFKEPPS LPGKEKPSPK 790 800 810 820 830 840 TVCGSPLAAQ PSPSAELPQA APPPPGSPSL PGRLEDFLES STGLPLLTSG HDGPEPLSLI 850 860 870 880 890 900 DDLHSQMLSS TAILDHPPSP MDTSELHFVP EPSSTMGLDL ADGHLDSMDW LELSSGGPVL 910 920 930 SLAPLSTTAP SLFSTDFLDG HDLQLHWDSC L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia." Ma Z., Morris S.W., Valentine V., Li M., Herbrick J.-A., Cui X., Bouman D., Li Y., Mehta P.K., Nizetic D., Kaneko Y., Chan G.C.F., Chan L.C., Squire J., Scherer S.W., Hitzler J.K. Nat. Genet. 28:220-221(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION WITH RBM15.
[2]	"Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia." Mercher T., Coniat M.B.-L., Monni R., Mauchauffe M., Khac F.N., Gressin L., Mugneret F., Leblanc T., Dastugue N., Berger R., Bernard O.A. Proc. Natl. Acad. Sci. U.S.A. 98:5776-5779(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION WITH RBM15. Tissue: Blood.
[3]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[5]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-648.
[6]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 195-931, VARIANT GLY-648. Tissue: Testis.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-305 AND THR-450, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of beta1-integrin." Brandt D.T., Baarlink C., Kitzing T.M., Kremmer E., Ivaska J., Nollau P., Grosse R. Nat. Cell Biol. 11:557-568(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SCAI AND SRF, SUBCELLULAR LOCATION.
[11]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-450 AND SER-454, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6; THR-450 AND SER-454, MASS SPECTROMETRY.
[14]	"Northeast structural genomics consortium target HR4547E." Northeast structural genomics consortium (NESG) Submitted (JUN-2010) to the PDB data bank Cited for: STRUCTURE BY NMR OF 336-396.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. Translation: CAI18985.1.
AL713710 mRNA. Translation: CAD28507.2.

IPI

IPI00872937.

RefSeq

NP_065882.1. NM_020831.3.

UniGene

Hs.654688.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KVU	NMR	-	A	333-396	[»]
2KW9	NMR	-	A	336-396	[»]

ProteinModelPortal

Q969V6.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q969V6. 4 interactions.

STRING

9606.ENSP00000347847.

PTM databases

PhosphoSite

Q969V6.

Polymorphism databases

DMDM

32363202.

Proteomic databases

PaxDb

Q969V6.

PRIDE

Q969V6.

Protocols and materials databases

DNASU

57591.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355630; ENSP00000347847; ENSG00000196588.
ENST00000407029; ENSP00000385835; ENSG00000196588.

GeneID

57591.

KEGG

hsa:57591.

UCSC

uc003ayv.1. human.

Organism-specific databases

CTD

57591.

GeneCards

GC22M040807.

HGNC

HGNC:14334. MKL1.

HPA

HPA030782.

MIM

606078. gene.

neXtProt

NX_Q969V6.

PharmGKB

PA30827.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG82832.

HOGENOM

HOG000038001.

HOVERGEN

HBG036493.

InParanoid

Q969V6.

OMA

SADFKEP.

OrthoDB

EOG4T1HMH.

Gene expression databases

ArrayExpress

Q969V6.

Bgee

Q969V6.

CleanEx

HS_MAL.
HS_MKL1.

Genevestigator

Q969V6.

GermOnline

ENSG00000196588. Homo sapiens.

Family and domain databases

Gene3D

1.10.720.30. 1 hit.

InterPro

IPR004018. RPEL_repeat.
IPR003034. SAP_dom.
[Graphical view]

Pfam

PF02755. RPEL. 2 hits.
PF02037. SAP. 1 hit.
[Graphical view]

SMART

SM00707. RPEL. 2 hits.
SM00513. SAP. 1 hit.
[Graphical view]

PROSITE

PS51073. RPEL. 2 hits.
PS50800. SAP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

MKL1. human.

EvolutionaryTrace

Q969V6.

GenomeRNAi

57591.

NextBio

64178.

SOURCE

Search...

Entry information

Entry name

MKL1_HUMAN

Accession

Primary (citable) accession number: Q969V6
Secondary accession number(s): Q8TCL1 , Q96SC5, Q96SC6, Q9P2B0

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 27, 2003
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.