Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Myosin light chain kinase 2, skeletal/cardiac muscle

Gene

MYLK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei314 – 3141ATPPROSITE-ProRule annotation
Active sitei406 – 4061Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi291 – 2999ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

  • cardiac muscle contraction Source: BHF-UCL
  • cardiac muscle tissue morphogenesis Source: BHF-UCL
  • neuromuscular synaptic transmission Source: Ensembl
  • peptidyl-threonine phosphorylation Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • regulation of muscle filament sliding Source: BHF-UCL
  • skeletal muscle cell differentiation Source: UniProtKB
  • skeletal muscle satellite cell differentiation Source: Ensembl
  • striated muscle contraction Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Calmodulin-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.18. 2681.
SignaLinkiQ9H1R3.

Names & Taxonomyi

Protein namesi
Recommended name:
Myosin light chain kinase 2, skeletal/cardiac muscle (EC:2.7.11.18)
Short name:
MLCK2
Gene namesi
Name:MYLK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:16243. MYLK2.

Subcellular locationi

  • Cytoplasm

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

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
  • sarcomere Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Cardiomyopathy, familial hypertrophic (CMH)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:192600
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti87 – 871A → V in CMH. 1 Publication
Corresponds to variant rs121908107 [ dbSNP | Ensembl ].
VAR_014197
Natural varianti95 – 951A → E in CMH. 1 Publication
Corresponds to variant rs121908108 [ dbSNP | Ensembl ].
VAR_014198

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

MIMi192600. phenotype.
Orphaneti155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA31389.

Polymorphism and mutation databases

BioMutaiMYLK2.
DMDMi24211884.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 596595Myosin light chain kinase 2, skeletal/cardiac musclePRO_0000086408Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiQ9H1R3.
PRIDEiQ9H1R3.

PTM databases

PhosphoSiteiQ9H1R3.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ9H1R3.
CleanExiHS_MYLK2.
GenevisibleiQ9H1R3. HS.

Organism-specific databases

HPAiHPA059704.
HPA059890.

Interactioni

Subunit structurei

May interact with centrin.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
MEF2CQ064132EBI-356910,EBI-2684075

Protein-protein interaction databases

BioGridi124494. 17 interactions.
IntActiQ9H1R3. 8 interactions.
MINTiMINT-1158812.
STRINGi9606.ENSP00000365152.

Structurei

Secondary structure

1
596
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi567 – 58620Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LV6Other-B566-591[»]
3KF9X-ray2.60B/D566-587[»]
ProteinModelPortaliQ9H1R3.
SMRiQ9H1R3. Positions 261-591.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H1R3.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini285 – 540256Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni574 – 58613Calmodulin-bindingBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi261 – 2688Poly-Pro

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118877.
HOGENOMiHOG000233016.
HOVERGENiHBG080416.
InParanoidiQ9H1R3.
KOiK00907.
OMAiSNWYFDE.
OrthoDBiEOG73FQMV.
PhylomeDBiQ9H1R3.
TreeFamiTF314166.

Family and domain databases

InterProiIPR020636. 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.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9H1R3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATENGAVEL GIQNPSTDKA PKGPTGERPL AAGKDPGPPD PKKAPDPPTL
60 70 80 90 100
KKDAKAPASE KGDGTLAQPS TSSQGPKGEG DRGGGPAEGS AGPPAALPQQ
110 120 130 140 150
TATPETSVKK PKAEQGASGS QDPGKPRVGK KAAEGQAAAR RGSPAFLHSP
160 170 180 190 200
SCPAIISSSE KLLAKKPPSE ASELTFEGVP MTHSPTDPRP AKAEEGKNIL
210 220 230 240 250
AESQKEVGEK TPGQAGQAKM QGDTSRGIEF QAVPSEKSEV GQALCLTARE
260 270 280 290 300
EDCFQILDDC PPPPAPFPHR MVELRTGNVS SEFSMNSKEA LGGGKFGAVC
310 320 330 340 350
TCMEKATGLK LAAKVIKKQT PKDKEMVLLE IEVMNQLNHR NLIQLYAAIE
360 370 380 390 400
TPHEIVLFME YIEGGELFER IVDEDYHLTE VDTMVFVRQI CDGILFMHKM
410 420 430 440 450
RVLHLDLKPE NILCVNTTGH LVKIIDFGLA RRYNPNEKLK VNFGTPEFLS
460 470 480 490 500
PEVVNYDQIS DKTDMWSMGV ITYMLLSGLS PFLGDDDTET LNNVLSGNWY
510 520 530 540 550
FDEETFEAVS DEAKDFVSNL IVKDQRARMN AAQCLAHPWL NNLAEKAKRC
560 570 580 590
NRRLKSQILL KKYLMKRRWK KNFIAVSAAN RFKKISSSGA LMALGV
Length:596
Mass (Da):64,685
Last modified:January 23, 2007 - v3
Checksum:i671A2B5DE9453ADE
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti355 – 3617IVLFMEY → GGVCAHS in AAH07753 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti87 – 871A → V in CMH. 1 Publication
Corresponds to variant rs121908107 [ dbSNP | Ensembl ].
VAR_014197
Natural varianti95 – 951A → E in CMH. 1 Publication
Corresponds to variant rs121908108 [ dbSNP | Ensembl ].
VAR_014198
Natural varianti117 – 1171A → V in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication
VAR_040860
Natural varianti142 – 1421G → V.1 Publication
Corresponds to variant rs56385445 [ dbSNP | Ensembl ].
VAR_040861
Natural varianti144 – 1441P → A.1 Publication
Corresponds to variant rs34396614 [ dbSNP | Ensembl ].
VAR_040862
Natural varianti324 – 3241K → N.1 Publication
Corresponds to variant rs34146416 [ dbSNP | Ensembl ].
VAR_040863

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13191.1.
RefSeqiNP_149109.1. NM_033118.3.
UniGeneiHs.86092.

Genome annotation databases

EnsembliENST00000375985; ENSP00000365152; ENSG00000101306.
ENST00000375994; ENSP00000365162; ENSG00000101306.
GeneIDi85366.
KEGGihsa:85366.
UCSCiuc002wwq.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13191.1.
RefSeqiNP_149109.1. NM_033118.3.
UniGeneiHs.86092.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LV6Other-B566-591[»]
3KF9X-ray2.60B/D566-587[»]
ProteinModelPortaliQ9H1R3.
SMRiQ9H1R3. Positions 261-591.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124494. 17 interactions.
IntActiQ9H1R3. 8 interactions.
MINTiMINT-1158812.
STRINGi9606.ENSP00000365152.

Chemistry

BindingDBiQ9H1R3.
ChEMBLiCHEMBL2777.
GuidetoPHARMACOLOGYi1553.

PTM databases

PhosphoSiteiQ9H1R3.

Polymorphism and mutation databases

BioMutaiMYLK2.
DMDMi24211884.

Proteomic databases

PaxDbiQ9H1R3.
PRIDEiQ9H1R3.

Protocols and materials databases

DNASUi85366.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375985; ENSP00000365152; ENSG00000101306.
ENST00000375994; ENSP00000365162; ENSG00000101306.
GeneIDi85366.
KEGGihsa:85366.
UCSCiuc002wwq.2. human.

Organism-specific databases

CTDi85366.
GeneCardsiGC20P030407.
GeneReviewsiMYLK2.
HGNCiHGNC:16243. MYLK2.
HPAiHPA059704.
HPA059890.
MIMi192600. phenotype.
606566. gene.
neXtProtiNX_Q9H1R3.
Orphaneti155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA31389.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118877.
HOGENOMiHOG000233016.
HOVERGENiHBG080416.
InParanoidiQ9H1R3.
KOiK00907.
OMAiSNWYFDE.
OrthoDBiEOG73FQMV.
PhylomeDBiQ9H1R3.
TreeFamiTF314166.

Enzyme and pathway databases

BRENDAi2.7.11.18. 2681.
SignaLinkiQ9H1R3.

Miscellaneous databases

EvolutionaryTraceiQ9H1R3.
GeneWikiiMYLK2.
GenomeRNAii85366.
NextBioi75899.
PROiQ9H1R3.
SOURCEiSearch...

Gene expression databases

BgeeiQ9H1R3.
CleanExiHS_MYLK2.
GenevisibleiQ9H1R3. HS.

Family and domain databases

InterProiIPR020636. 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.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
    , 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.

Entry informationi

Entry nameiMYLK2_HUMAN
AccessioniPrimary (citable) accession number: Q9H1R3
Secondary accession number(s): Q569L1, Q96I84
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 19, 2002
Last sequence update: January 23, 2007
Last modified: June 24, 2015
This is version 147 of the entry and version 3 of the sequence. [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

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.