Q32MK0 (MYLK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myosin light chain kinase 3
EC=2.7.11.18

Alternative name(s):
Cardiac-MyBP-C-associated Ca/CaM kinase
Short name=Cardiac-MLCK

Gene names

Name:	MYLK3
Synonyms:	MLCK

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	819 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Kinase that phosphorylates MYL2 in vitro. Promotes sarcomere formation in cardiomyocytes and increases cardiomyocyte contractility By similarity.
Catalytic activity	ATP + [myosin light-chain] = ADP + [myosin light-chain] phosphate.
Cofactor	Magnesium By similarity.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Restricted to heart. Ref.6
Post-translational modification	Phosphorylated on serine residues By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Contains 1 protein kinase domain.
Sequence caution	The sequence AAI09098.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence CAC42766.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Magnesium Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac myofibril assembly Inferred from sequence or structural similarity. Source: BHF-UCL cellular response to interleukin-1 Inferred from mutant phenotype PubMed 18390750. Source: BHF-UCL positive regulation of sarcomere organization Inferred from sequence or structural similarity. Source: BHF-UCL regulation of vascular permeability involved in acute inflammatory response Inferred from mutant phenotype PubMed 18390750. Source: BHF-UCL sarcomere organization Inferred from sequence or structural similarity. Source: BHF-UCL sarcomerogenesis Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	actin cytoskeleton Inferred from electronic annotation. Source: Compara cytosol Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin-dependent protein kinase activity Inferred from sequence or structural similarity. Source: BHF-UCL myosin light chain kinase activity Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q32MK0-3)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q32MK0-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-341: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 819	819	Myosin light chain kinase 3		PRO_0000272200
Regions
	Domain	515 – 770	256	Protein kinase
	Nucleotide binding	521 – 529	9	ATP By similarity
Sites
	Active site	636	1	Proton acceptor By similarity
	Binding site	544	1	ATP By similarity
Natural variations
	Alternative sequence	1 – 341	341	Missing in isoform 2.		VSP_044312
	Natural variant	70	1	S → T. Corresponds to variant rs9923813 [ dbSNP | Ensembl ].		VAR_058335
	Natural variant	180	1	V → L. Ref.1 Ref.5 Corresponds to variant rs28407821 [ dbSNP | Ensembl ].		VAR_058336
	Natural variant	390	1	G → R in a colorectal cancer sample; somatic mutation. Ref.7		VAR_035630
Experimental info
	Sequence conflict	149	1	R → G in BAG70269. Ref.2
	Sequence conflict	199	1	G → R in CAC42766. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 28, 2009. Version 3. Checksum: 21148BBACB0FF0D9	FASTA	819	88,393
	10 20 30 40 50 60 MSGTSKESLG HGGLPGLGKT CLTTMDTKLN MLNEKVDQLL HFQEDVTEKL QSMCRDMGHL 70 80 90 100 110 120 ERGLHRLEAS RAPGPGGADG VPHIDTQAGW PEVLELVRAM QQDAAQHGAR LEALFRMVAA 130 140 150 160 170 180 VDRAIALVGA TFQKSKVADF LMQGRVPWRR GSPGDSPEEN KERVEEEGGK PKHVLSTSGV 190 200 210 220 230 240 QSDAREPGEE SQKADVLEGT AERLPPIRAS GLGADPAQAV VSPGQGDGVP GPAQAFPGHL 250 260 270 280 290 300 PLPTKVEAKA PETPSENLRT GLELAPAPGR VNVVSPSLEV APGAGQGASS SRPDPEPLEE 310 320 330 340 350 360 GTRLTPGPGP QCPGPPGLPA QARATHSGGE TPPRISIHIQ EMDTPGEMLM TGRGSLGPTL 370 380 390 400 410 420 TTEAPAAAQP GKQGPPGTGR CLQAPGTEPG EQTPEGAREL SPLQESSSPG GVKAEEEQRA 430 440 450 460 470 480 GAEPGTRPSL ARSDDNDHEV GALGLQQGKS PGAGNPEPEQ DCAARAPVRA EAVRRMPPGA 490 500 510 520 530 540 EAGSVVLDDS PAPPAPFEHR VVSVKETSIS AGYEVCQHEV LGGGRFGQVH RCTEKSTGLP 550 560 570 580 590 600 LAAKIIKVKS AKDREDVKNE INIMNQLSHV NLIQLYDAFE SKHSCTLVME YVDGGELFDR 610 620 630 640 650 660 ITDEKYHLTE LDVVLFTRQI CEGVHYLHQH YILHLDLKPE NILCVNQTGH QIKIIDFGLA 670 680 690 700 710 720 RRYKPREKLK VNFGTPEFLA PEVVNYEFVS FPTDMWSVGV ITYMLLSGLS PFLGETDAET 730 740 750 760 770 780 MNFIVNCSWD FDADTFEGLS EEAKDFVSRL LVKEKSCRMS ATQCLKHEWL NNLPAKASRS 790 800 810 KTRLKSQLLL QKYIAQRKWK KHFYVVTAAN RLRKFPTSP
	Isoform 2 [UniParc]. Checksum: 4AD65710D538D28B	FASTA	478	52,723
	10 20 30 40 50 60 MDTPGEMLMT GRGSLGPTLT TEAPAAAQPG KQGPPGTGRC LQAPGTEPGE QTPEGARELS 70 80 90 100 110 120 PLQESSSPGG VKAEEEQRAG AEPGTRPSLA RSDDNDHEVG ALGLQQGKSP GAGNPEPEQD 130 140 150 160 170 180 CAARAPVRAE AVRRMPPGAE AGSVVLDDSP APPAPFEHRV VSVKETSISA GYEVCQHEVL 190 200 210 220 230 240 GGGRFGQVHR CTEKSTGLPL AAKIIKVKSA KDREDVKNEI NIMNQLSHVN LIQLYDAFES 250 260 270 280 290 300 KHSCTLVMEY VDGGELFDRI TDEKYHLTEL DVVLFTRQIC EGVHYLHQHY ILHLDLKPEN 310 320 330 340 350 360 ILCVNQTGHQ IKIIDFGLAR RYKPREKLKV NFGTPEFLAP EVVNYEFVSF PTDMWSVGVI 370 380 390 400 410 420 TYMLLSGLSP FLGETDAETM NFIVNCSWDF DADTFEGLSE EAKDFVSRLL VKEKSCRMSA 430 440 450 460 470 TQCLKHEWLN NLPAKASRSK TRLKSQLLLQ KYIAQRKWKK HFYVVTAANR LRKFPTSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The cardiac-MyBP-C associated Ca/CaM kinase is a novel MLCK with cardiac-specific domains." Mues A., Seidel R., Gautel M. Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-180. Tissue: Cardiac myocyte.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Tongue.
[3]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 1), VARIANT LEU-180.
[6]	"A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart." Seguchi O., Takashima S., Yamazaki S., Asakura M., Asano Y., Shintani Y., Wakeno M., Minamino T., Kondo H., Furukawa H., Nakamaru K., Naito A., Takahashi T., Ohtsuka T., Kawakami K., Isomura T., Kitamura S., Tomoike H., Mochizuki N., Kitakaze M. J. Clin. Invest. 117:2812-2824(2007) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-390.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ247087 mRNA. Translation: CAC42766.1. Different initiation. AK299443 mRNA. Translation: BAH13034.1. AB451455 mRNA. Translation: BAG70269.1. AC007225 Genomic DNA. No translation available. BC109097 mRNA. Translation: AAI09098.2. Different initiation.
IPI	IPI00304648.
RefSeq	NP_872299.2. NM_182493.2.
UniGene	Hs.130465.
3D structure databases
HSSP	HSSP built from PDB template 1YRP based on UniProtKB O43293.
ProteinModelPortal	Q32MK0.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q32MK0. 2 interactions.
STRING	9606.ENSP00000378288.
PTM databases
PhosphoSite	Q32MK0.
Polymorphism databases
DMDM	254763411.
Proteomic databases
PaxDb	Q32MK0.
PRIDE	Q32MK0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000394809; ENSP00000378288; ENSG00000140795. ENST00000536476; ENSP00000439297; ENSG00000140795.
GeneID	91807.
KEGG	hsa:91807.
UCSC	uc002eei.4. human.
Organism-specific databases
CTD	91807.
GeneCards	GC16M046736.
HGNC	HGNC:29826. MYLK3.
HPA	HPA040258.
MIM	612147. gene.
neXtProt	NX_Q32MK0.
PharmGKB	PA162396375.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233016.
HOVERGEN	HBG080416.
InParanoid	Q32MK0.
KO	K00907.
OMA	QHGARLE.
OrthoDB	EOG49ZXNP.
Gene expression databases
ArrayExpress	Q32MK0.
Bgee	Q32MK0.
CleanEx	HS_MYLK3.
Genevestigator	Q32MK0.
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	Q32MK0.
ChEMBL	CHEMBL4627.
GenomeRNAi	91807.
NextBio	77465.
SOURCE	Search...

Entry information

Entry name

MYLK3_HUMAN

Accession

Primary (citable) accession number: Q32MK0
Secondary accession number(s): B5BUL9 , B7Z5U8, Q32MK1, Q96DV1

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 23, 2007
Last sequence update:	July 28, 2009
Last modified:	May 1, 2013
This is version 72 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.