Q3UIZ8 (MYLK3_MOUSE) 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	795 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Kinase that phosphorylates MYL2 in vitro. Has been proposed to be calmodulin-dependent (Ref.3), although MYL2 phosphorylation has also been observed in the presence or absence of calmodulin (Ref.1). Promotes sarcomere formation in cardiomyocytes and increases cardiomyocyte contractility. Ref.1 Ref.3
Catalytic activity	ATP + [myosin light-chain] = ADP + [myosin light-chain] phosphate.
Cofactor	Magnesium By similarity.
Subcellular location	Cytoplasm Ref.1.
Tissue specificity	Restricted to cardiomyocytes (at protein level). Down-regulated in heart after experimental myocardial infarction at the protein level; no significant changes at the mRNA level. Ref.1
Developmental stage	Up-regulated in the heart from 10.5 dpc to neonates and further increased in adults. Down-regulated in aged hearts (at protein level). Ref.1
Post-translational modification	Phosphorylated on serine residues. Ref.1
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Contains 1 protein kinase domain.
Biophysicochemical properties	Kinetic parameters: KM=4.3 µM for MYL2 Ref.1 Vmax=0.26 µmol/min/mg enzyme

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
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 electronic annotation. Source: Compara cellular response to interleukin-1 Inferred from electronic annotation. Source: Compara positive regulation of sarcomere organization Inferred from electronic annotation. Source: Compara regulation of vascular permeability involved in acute inflammatory response Inferred from electronic annotation. Source: Compara sarcomere organization Inferred from direct assay Ref.1. Source: BHF-UCL sarcomerogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from direct assay Ref.1. Source: BHF-UCL cytosol Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin-dependent protein kinase activity Inferred from direct assay Ref.3. Source: BHF-UCL myosin light chain kinase activity Inferred from direct assay Ref.3Ref.1. Source: BHF-UCL
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q3UIZ8-1)

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: Q3UIZ8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     100-162: Missing.
     777-795: KHFHVVTAVNRLRKFPTCP → VFWVFFSKSCI

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 795	795	Myosin light chain kinase 3		PRO_0000272201
Regions
	Domain	491 – 746	256	Protein kinase
	Nucleotide binding	497 – 505	9	ATP By similarity
Sites
	Active site	612	1	Proton acceptor By similarity
	Binding site	520	1	ATP By similarity
Natural variations
	Alternative sequence	100 – 162	63	Missing in isoform 2.		VSP_022369
	Alternative sequence	777 – 795	19	KHFHV…FPTCP → VFWVFFSKSCI in isoform 2.		VSP_022370

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 11, 2005. Version 1. Checksum: 9B9874D50E6EBA20	FASTA	795	86,372
	10 20 30 40 50 60 MSGVSEEDPE GLAPQGLPAL GGACLATMDK KLNVLTEKVD RLLHFQEDVT EKLQCVCQGM 70 80 90 100 110 120 DHLEQDLHRL EASRELSLAG SGSTPPTTAQ AAWPEVLELV RAVRQEGAQH GARLEALFKM 130 140 150 160 170 180 VVAVDRAITL VGSTFQNSKV ADFIMQGTVP GRKGSLADGP EENKEQAEVA GVKPNHVLTT 190 200 210 220 230 240 GGVQADASRT LWEESQKEDI PVRTVEGLPL IINTSLKGAD LTQAGASLRQ GVEVLGPGQV 250 260 270 280 290 300 PLPTEAESRL PETASENTGA TLELSVAIDR ISEVLTSLKM SQGGGQETSS SKPDCWLSEE 310 320 330 340 350 360 AMRLSSGPLP QPLGPLTPDS DIHSGDALPR IPINMQEMAT PGELLETQSG SPIGSAEAPG 370 380 390 400 410 420 LGTVLEDQIP KGARPFPPLP KRSSNNGGMS AEEEIGSGAE PMRGPSLATR DWRDETVGTT 430 440 450 460 470 480 DLQQGIDPGA VSPEPGKDHA AQGPGRTEAG RLSSAAEAAI VVLDDSAAPP APFEHRVVSI 490 500 510 520 530 540 KDTLISAGYT VSQHEVLGGG RFGQVHRCTE RSTGLALAAK IIKVKNVKDR EDVKNEVNIM 550 560 570 580 590 600 NQLSHVNLIQ LYDAFESKSS FTLIMEYVDG GELFDRITDE KYHLTELDVV LFTRQICEGV 610 620 630 640 650 660 HYLHQHYILH LDLKPENILC VSQTGHQIKI IDFGLARRYK PREKLKVNFG TPEFLAPEVV 670 680 690 700 710 720 NYEFVSFPTD MWSVGVITYM LLSGLSPFLG ETDAETMNFI VNCSWDFDAD TFKGLSEEAK 730 740 750 760 770 780 DFVSRLLVKE KSCRMSATQC LKHEWLSHLP AKASGSNVRL RSQQLLQKYM AQSKWKKHFH 790 VVTAVNRLRK FPTCP
	Isoform 2 [UniParc]. Checksum: AE80A5AB899A23C4	FASTA	724	78,790
	10 20 30 40 50 60 MSGVSEEDPE GLAPQGLPAL GGACLATMDK KLNVLTEKVD RLLHFQEDVT EKLQCVCQGM 70 80 90 100 110 120 DHLEQDLHRL EASRELSLAG SGSTPPTTAQ AAWPEVLELN KEQAEVAGVK PNHVLTTGGV 130 140 150 160 170 180 QADASRTLWE ESQKEDIPVR TVEGLPLIIN TSLKGADLTQ AGASLRQGVE VLGPGQVPLP 190 200 210 220 230 240 TEAESRLPET ASENTGATLE LSVAIDRISE VLTSLKMSQG GGQETSSSKP DCWLSEEAMR 250 260 270 280 290 300 LSSGPLPQPL GPLTPDSDIH SGDALPRIPI NMQEMATPGE LLETQSGSPI GSAEAPGLGT 310 320 330 340 350 360 VLEDQIPKGA RPFPPLPKRS SNNGGMSAEE EIGSGAEPMR GPSLATRDWR DETVGTTDLQ 370 380 390 400 410 420 QGIDPGAVSP EPGKDHAAQG PGRTEAGRLS SAAEAAIVVL DDSAAPPAPF EHRVVSIKDT 430 440 450 460 470 480 LISAGYTVSQ HEVLGGGRFG QVHRCTERST GLALAAKIIK VKNVKDREDV KNEVNIMNQL 490 500 510 520 530 540 SHVNLIQLYD AFESKSSFTL IMEYVDGGEL FDRITDEKYH LTELDVVLFT RQICEGVHYL 550 560 570 580 590 600 HQHYILHLDL KPENILCVSQ TGHQIKIIDF GLARRYKPRE KLKVNFGTPE FLAPEVVNYE 610 620 630 640 650 660 FVSFPTDMWS VGVITYMLLS GLSPFLGETD AETMNFIVNC SWDFDADTFK GLSEEAKDFV 670 680 690 700 710 720 SRLLVKEKSC RMSATQCLKH EWLSHLPAKA SGSNVRLRSQ QLLQKYMAQS KWKVFWVFFS KSCI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of cardiac-specific myosin light chain kinase." Chan J.Y., Takeda M., Briggs L.E., Graham M.L., Lu J.T., Horikoshi N., Weinberg E.O., Aoki H., Sato N., Chien K.R., Kasahara H. Circ. Res. 102:571-580(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, PHOSPHORYLATION. Tissue: Heart.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Heart and Testis.
[3]	"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: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	EU403565 mRNA. Translation: ABY89726.1. AK031546 mRNA. Translation: BAE43277.1. AK052858 mRNA. Translation: BAC35177.1. AK146683 mRNA. Translation: BAE27357.1.
IPI	IPI00654336. IPI00828323.
RefSeq	NP_780650.2. NM_175441.5.
UniGene	Mm.32804.
3D structure databases
HSSP	HSSP built from PDB template 1YRP based on UniProtKB O43293.
ProteinModelPortal	Q3UIZ8.
SMR	Q3UIZ8. Positions 468-765.
ModBase	Search...
PTM databases
PhosphoSite	Q3UIZ8.
Proteomic databases
PaxDb	Q3UIZ8.
PRIDE	Q3UIZ8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000034133; ENSMUSP00000034133; ENSMUSG00000031698. ENSMUST00000121972; ENSMUSP00000113960; ENSMUSG00000031698.
GeneID	213435.
KEGG	mmu:213435.
Organism-specific databases
CTD	91807.
MGI	MGI:2443063. Mylk3.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00700000104434.
HOGENOM	HOG000233016.
HOVERGEN	HBG080416.
InParanoid	Q3UIZ8.
KO	K00907.
OMA	QHGARLE.
OrthoDB	EOG49ZXNP.
Gene expression databases
ArrayExpress	Q3UIZ8.
Bgee	Q3UIZ8.
CleanEx	MM_MYLK3.
Genevestigator	Q3UIZ8.
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
NextBio	373954.
SOURCE	Search...

Entry information

Entry name

MYLK3_MOUSE

Accession

Primary (citable) accession number: Q3UIZ8
Secondary accession number(s): B0LY41, Q3V3V0, Q8BWD1

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 23, 2007
Last sequence update:	October 11, 2005
Last modified:	May 1, 2013
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program