Q9H1R3 (MYLK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myosin light chain kinase 2, skeletal/cardiac muscle
Short name=MLCK2
EC=2.7.11.18

Gene names

Name:

MYLK2

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	596 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Cardiomyopathy Disease mutation
Ligand	ATP-binding Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle cell differentiation Inferred from electronic annotation. Source: Compara cardiac 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: Compara 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: Compara skeletal muscle cell differentiation Inferred from direct assay PubMed 21556048. Source: UniProtKB
Cellular_component	nucleus Inferred from direct assay PubMed 21556048. Source: UniProtKB sarcomere Inferred by curator PubMed 16448786. Source: BHF-UCL
Molecular_function	ATP 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
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 596

595

Myosin light chain kinase 2, skeletal/cardiac muscle

PRO_0000086408

Regions

Domain

285 – 540

256

Protein kinase

Nucleotide binding

291 – 299

9

ATP By similarity

Region

574 – 586

13

Calmodulin-binding By similarity

Compositional bias

261 – 268

8

Poly-Pro

Sites

Active site

406

1

Proton acceptor By similarity

Binding site

314

1

ATP By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Natural variations

Natural variant

87

1

A → V in CMH. Ref.1

VAR_014197

Natural variant

95

1

A → E in CMH. Ref.1

VAR_014198

Natural variant

117

1

A → V in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.6

VAR_040860

Natural variant

142

1

G → V. Ref.6
Corresponds to variant rs56385445 [ dbSNP | Ensembl ].

VAR_040861

Natural variant

144

1

P → A. Ref.6
Corresponds to variant rs34396614 [ dbSNP | Ensembl ].

VAR_040862

Natural variant

324

1

K → N. Ref.6
Corresponds to variant rs34146416 [ dbSNP | Ensembl ].

VAR_040863

Experimental info

Sequence conflict

355 – 361

7

IVLFMEY → GGVCAHS in AAH07753. Ref.4

Secondary structure

1

.

.

.

596

Helix Strand Turn

Details...

Helix

567 – 586

20

Sequences

	Sequence		Length	Mass (Da)
	Q9H1R3 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 671A2B5DE9453ADE	FASTA	596	64,685
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
+	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.

IPI

IPI00221127.

RefSeq

NP_149109.1. NM_033118.3.

UniGene

Hs.86092.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LV6	Other	-	B	566-591	[»]
3KF9	X-ray	2.60	B/D	566-587	[»]

ProteinModelPortal

Q9H1R3.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9H1R3. 5 interactions.

MINT

MINT-1158812.

STRING

9606.ENSP00000365152.

PTM databases

PhosphoSite

Q9H1R3.

Polymorphism databases

DMDM

24211884.

Proteomic databases

PaxDb

Q9H1R3.

PRIDE

Q9H1R3.

Protocols and materials databases

DNASU

85366.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000375985; ENSP00000365152; ENSG00000101306.
ENST00000375994; ENSP00000365162; ENSG00000101306.

GeneID

85366.

KEGG

hsa:85366.

UCSC

uc002wwq.2. human.

Organism-specific databases

CTD

85366.

GeneCards

GC20P030407.

HGNC

HGNC:16243. MYLK2.

MIM

192600. phenotype.
606566. gene.

neXtProt

NX_Q9H1R3.

Orphanet

155. Familial isolated hypertrophic cardiomyopathy.

PharmGKB

PA31389.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233016.

HOVERGEN

HBG080416.

InParanoid

Q9H1R3.

KO

K00907.

OMA

TTGHMVK.

OrthoDB

EOG4868C5.

Enzyme and pathway databases

BRENDA

2.7.11.18. 2681.

Gene expression databases

Bgee

Q9H1R3.

CleanEx

HS_MYLK2.

Genevestigator

Q9H1R3.

GermOnline

ENSG00000101306. Homo sapiens.

Family and domain databases

InterPro

IPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

PANTHER

PTHR24347. PTHR24347. 1 hit.

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9H1R3.

ChEMBL

CHEMBL2777.

EvolutionaryTrace

Q9H1R3.

GenomeRNAi

85366.

NextBio

75899.

SOURCE

Search...

Entry information

Entry name

MYLK2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 127 of the entry and version 3 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.