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Q9H1R3 (MYLK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Myosin light chain kinase 2, skeletal/cardiac muscle

Short name=MLCK2
EC=2.7.11.18
Gene names
Name:MYLK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length596 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Implicated in the level of global muscle contraction and cardiac function. Phosphorylates a specific serine in the N-terminus of a myosin light chain. Ref.1

Catalytic activity

ATP + [myosin light-chain] = ADP + [myosin light-chain] phosphate.

Subunit structure

May interact with centrin. Ref.5

Subcellular location

Cytoplasm. Note: Colocalizes with phosphorylated myosin light chain (RLCP) at filaments of the myofibrils.

Tissue specificity

Heart and skeletal muscles. Increased expression in the apical tissue compared to the interventricular septal tissue.

Involvement in disease

Cardiomyopathy, familial hypertrophic (CMH) [MIM:192600]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DiseaseCardiomyopathy
Disease mutation
   LigandATP-binding
Calmodulin-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcardiac muscle contraction

Inferred by curator PubMed 16448786. Source: BHF-UCL

cardiac muscle tissue morphogenesis

Inferred from mutant phenotype PubMed 16448786. Source: BHF-UCL

neuromuscular synaptic transmission

Inferred from electronic annotation. Source: Ensembl

peptidyl-threonine phosphorylation

Inferred from direct assay PubMed 21556048. Source: UniProtKB

positive regulation of gene expression

Inferred from direct assay PubMed 21556048. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay PubMed 21556048. Source: UniProtKB

regulation of muscle filament sliding

Inferred from direct assay PubMed 16448786. Source: BHF-UCL

satellite cell differentiation

Inferred from electronic annotation. Source: Ensembl

skeletal muscle cell differentiation

Inferred from direct assay PubMed 21556048. Source: UniProtKB

striated muscle contraction

Inferred from direct assay PubMed 16448786. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 21556048. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 21556048. Source: UniProtKB

sarcomere

Inferred by curator PubMed 16448786. Source: BHF-UCL

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calmodulin binding

Inferred from sequence or structural similarity. Source: BHF-UCL

calmodulin-dependent protein kinase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

myosin light chain kinase activity

Inferred from direct assay PubMed 16448786. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 21556048. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MEF2CQ064132EBI-356910,EBI-2684075

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 596595Myosin light chain kinase 2, skeletal/cardiac muscle
PRO_0000086408

Regions

Domain285 – 540256Protein kinase
Nucleotide binding291 – 2999ATP By similarity
Region574 – 58613Calmodulin-binding By similarity
Compositional bias261 – 2688Poly-Pro

Sites

Active site4061Proton acceptor By similarity
Binding site3141ATP By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity

Natural variations

Natural variant871A → V in CMH. Ref.1
Corresponds to variant rs121908107 [ dbSNP | Ensembl ].
VAR_014197
Natural variant951A → E in CMH. Ref.1
Corresponds to variant rs121908108 [ dbSNP | Ensembl ].
VAR_014198
Natural variant1171A → V in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.6
VAR_040860
Natural variant1421G → V. Ref.6
Corresponds to variant rs56385445 [ dbSNP | Ensembl ].
VAR_040861
Natural variant1441P → A. Ref.6
Corresponds to variant rs34396614 [ dbSNP | Ensembl ].
VAR_040862
Natural variant3241K → N. Ref.6
Corresponds to variant rs34146416 [ dbSNP | Ensembl ].
VAR_040863

Experimental info

Sequence conflict355 – 3617IVLFMEY → GGVCAHS in AAH07753. Ref.4

Secondary structure

... 596
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9H1R3 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 671A2B5DE9453ADE

FASTA59664,685
        10         20         30         40         50         60 
MATENGAVEL GIQNPSTDKA PKGPTGERPL AAGKDPGPPD PKKAPDPPTL KKDAKAPASE 

        70         80         90        100        110        120 
KGDGTLAQPS TSSQGPKGEG DRGGGPAEGS AGPPAALPQQ TATPETSVKK PKAEQGASGS 

       130        140        150        160        170        180 
QDPGKPRVGK KAAEGQAAAR RGSPAFLHSP SCPAIISSSE KLLAKKPPSE ASELTFEGVP 

       190        200        210        220        230        240 
MTHSPTDPRP AKAEEGKNIL AESQKEVGEK TPGQAGQAKM QGDTSRGIEF QAVPSEKSEV 

       250        260        270        280        290        300 
GQALCLTARE EDCFQILDDC PPPPAPFPHR MVELRTGNVS SEFSMNSKEA LGGGKFGAVC 

       310        320        330        340        350        360 
TCMEKATGLK LAAKVIKKQT PKDKEMVLLE IEVMNQLNHR NLIQLYAAIE TPHEIVLFME 

       370        380        390        400        410        420 
YIEGGELFER IVDEDYHLTE VDTMVFVRQI CDGILFMHKM RVLHLDLKPE NILCVNTTGH 

       430        440        450        460        470        480 
LVKIIDFGLA RRYNPNEKLK VNFGTPEFLS PEVVNYDQIS DKTDMWSMGV ITYMLLSGLS 

       490        500        510        520        530        540 
PFLGDDDTET LNNVLSGNWY FDEETFEAVS DEAKDFVSNL IVKDQRARMN AAQCLAHPWL 

       550        560        570        580        590 
NNLAEKAKRC NRRLKSQILL KKYLMKRRWK KNFIAVSAAN RFKKISSSGA LMALGV 

« Hide

References

« Hide 'large scale' references
[1]"The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation."
Davis J.S., Hassanzadeh S., Winitsky S., Lin H., Satorius C., Vemuri R., Aletras A.H., Wen H., Epstein N.D.
Cell 107:631-641(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, VARIANTS CMH VAL-87 AND GLU-95.
Tissue: Skeletal muscle.
[2]"Full-length sequencing of 100 cDNA clones from human adult skeletal muscle."
Stanchi F., Lanfranchi G.
Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Skeletal muscle.
[3]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Muscle.
[5]"Structural features of the complexes formed by Scherffelia dubia centrin."
Radu L., Miron S., Durand D., Assairi L., Blouquit Y., Charbonnier J.B.
Submitted (JAN-2011) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 566-587 IN COMPLEX WITH CENTRIN, SUBUNIT.
[6]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-117; VAL-142; ALA-144 AND ASN-324.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF325549 mRNA. Translation: AAK15494.1.
AJ272502 mRNA. Translation: CAC81354.1.
AL160175 Genomic DNA. Translation: CAC10006.1.
BC007753 mRNA. Translation: AAH07753.1.
BC069627 mRNA. Translation: AAH69627.1.
BC092413 mRNA. Translation: AAH92413.1.
BC127622 mRNA. Translation: AAI27623.1.
CCDSCCDS13191.1.
RefSeqNP_149109.1. NM_033118.3.
UniGeneHs.86092.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2LV6Other-B566-591[»]
3KF9X-ray2.60B/D566-587[»]
ProteinModelPortalQ9H1R3.
SMRQ9H1R3. Positions 261-591.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124494. 12 interactions.
IntActQ9H1R3. 8 interactions.
MINTMINT-1158812.
STRING9606.ENSP00000365152.

Chemistry

BindingDBQ9H1R3.
ChEMBLCHEMBL2777.
GuidetoPHARMACOLOGY1553.

PTM databases

PhosphoSiteQ9H1R3.

Polymorphism databases

DMDM24211884.

Proteomic databases

PaxDbQ9H1R3.
PRIDEQ9H1R3.

Protocols and materials databases

DNASU85366.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000375985; ENSP00000365152; ENSG00000101306.
ENST00000375994; ENSP00000365162; ENSG00000101306.
GeneID85366.
KEGGhsa:85366.
UCSCuc002wwq.2. human.

Organism-specific databases

CTD85366.
GeneCardsGC20P030407.
GeneReviewsMYLK2.
HGNCHGNC:16243. MYLK2.
HPAHPA059704.
HPA059890.
MIM192600. phenotype.
606566. gene.
neXtProtNX_Q9H1R3.
Orphanet155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBPA31389.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233016.
HOVERGENHBG080416.
InParanoidQ9H1R3.
KOK00907.
OMAEGVPMTH.
OrthoDBEOG73FQMV.
PhylomeDBQ9H1R3.
TreeFamTF314166.

Enzyme and pathway databases

BRENDA2.7.11.18. 2681.
SignaLinkQ9H1R3.

Gene expression databases

BgeeQ9H1R3.
CleanExHS_MYLK2.
GenevestigatorQ9H1R3.

Family and domain databases

InterProIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR24347. PTHR24347. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9H1R3.
GeneWikiMYLK2.
GenomeRNAi85366.
NextBio75899.
PROQ9H1R3.
SOURCESearch...

Entry information

Entry nameMYLK2_HUMAN
AccessionPrimary (citable) accession number: Q9H1R3
Secondary accession number(s): Q569L1, Q96I84
Entry history
Integrated into UniProtKB/Swiss-Prot: October 19, 2002
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 140 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM