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Protein

Myosin light chain kinase 3

Gene

MYLK3

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

Functioni

Kinase that phosphorylates MYL2 in vitro. Promotes sarcomere formation in cardiomyocytes and increases cardiomyocyte contractility (By similarity).By similarity

Catalytic activityi

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

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei544 – 5441ATPPROSITE-ProRule annotation
Active sitei636 – 6361Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi521 – 5299ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. calmodulin-dependent protein kinase activity Source: BHF-UCL
  3. myosin light chain kinase activity Source: BHF-UCL

GO - Biological processi

  1. cardiac myofibril assembly Source: BHF-UCL
  2. cellular response to interleukin-1 Source: BHF-UCL
  3. positive regulation of sarcomere organization Source: BHF-UCL
  4. protein phosphorylation Source: BHF-UCL
  5. regulation of vascular permeability involved in acute inflammatory response Source: BHF-UCL
  6. sarcomere organization Source: BHF-UCL
  7. sarcomerogenesis Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ32MK0.

Names & Taxonomyi

Protein namesi
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 namesi
Name:MYLK3
Synonyms:MLCK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:29826. MYLK3.

Subcellular locationi

Cytoplasm By similarity

GO - Cellular componenti

  1. actin cytoskeleton Source: Ensembl
  2. cytoplasm Source: BHF-UCL
  3. cytosol Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA162396375.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 819819Myosin light chain kinase 3PRO_0000272200Add
BLAST

Post-translational modificationi

Phosphorylated on serine residues.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ32MK0.
PaxDbiQ32MK0.
PRIDEiQ32MK0.

PTM databases

PhosphoSiteiQ32MK0.

Expressioni

Tissue specificityi

Restricted to heart.1 Publication

Gene expression databases

BgeeiQ32MK0.
CleanExiHS_MYLK3.
GenevestigatoriQ32MK0.

Organism-specific databases

HPAiHPA040258.

Interactioni

Protein-protein interaction databases

BioGridi124881. 6 interactions.
IntActiQ32MK0. 2 interactions.
STRINGi9606.ENSP00000378288.

Structurei

3D structure databases

ProteinModelPortaliQ32MK0.
SMRiQ32MK0. Positions 458-793.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini515 – 770256Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118877.
HOGENOMiHOG000233016.
HOVERGENiHBG080416.
InParanoidiQ32MK0.
KOiK00907.
OMAiFRMVVAV.
OrthoDBiEOG73FQMV.
PhylomeDBiQ32MK0.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q32MK0-3) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSGTSKESLG HGGLPGLGKT CLTTMDTKLN MLNEKVDQLL HFQEDVTEKL
60 70 80 90 100
QSMCRDMGHL ERGLHRLEAS RAPGPGGADG VPHIDTQAGW PEVLELVRAM
110 120 130 140 150
QQDAAQHGAR LEALFRMVAA VDRAIALVGA TFQKSKVADF LMQGRVPWRR
160 170 180 190 200
GSPGDSPEEN KERVEEEGGK PKHVLSTSGV QSDAREPGEE SQKADVLEGT
210 220 230 240 250
AERLPPIRAS GLGADPAQAV VSPGQGDGVP GPAQAFPGHL PLPTKVEAKA
260 270 280 290 300
PETPSENLRT GLELAPAPGR VNVVSPSLEV APGAGQGASS SRPDPEPLEE
310 320 330 340 350
GTRLTPGPGP QCPGPPGLPA QARATHSGGE TPPRISIHIQ EMDTPGEMLM
360 370 380 390 400
TGRGSLGPTL TTEAPAAAQP GKQGPPGTGR CLQAPGTEPG EQTPEGAREL
410 420 430 440 450
SPLQESSSPG GVKAEEEQRA GAEPGTRPSL ARSDDNDHEV GALGLQQGKS
460 470 480 490 500
PGAGNPEPEQ DCAARAPVRA EAVRRMPPGA EAGSVVLDDS PAPPAPFEHR
510 520 530 540 550
VVSVKETSIS AGYEVCQHEV LGGGRFGQVH RCTEKSTGLP LAAKIIKVKS
560 570 580 590 600
AKDREDVKNE INIMNQLSHV NLIQLYDAFE SKHSCTLVME YVDGGELFDR
610 620 630 640 650
ITDEKYHLTE LDVVLFTRQI CEGVHYLHQH YILHLDLKPE NILCVNQTGH
660 670 680 690 700
QIKIIDFGLA RRYKPREKLK VNFGTPEFLA PEVVNYEFVS FPTDMWSVGV
710 720 730 740 750
ITYMLLSGLS PFLGETDAET MNFIVNCSWD FDADTFEGLS EEAKDFVSRL
760 770 780 790 800
LVKEKSCRMS ATQCLKHEWL NNLPAKASRS KTRLKSQLLL QKYIAQRKWK
810
KHFYVVTAAN RLRKFPTSP
Length:819
Mass (Da):88,393
Last modified:July 28, 2009 - v3
Checksum:i21148BBACB0FF0D9
GO
Isoform 2 (identifier: Q32MK0-4) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.

Show »
Length:478
Mass (Da):52,723
Checksum:i4AD65710D538D28B
GO

Sequence cautioni

The sequence AAI09098.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAC42766.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti149 – 1491R → G in BAG70269 (PubMed:14702039).Curated
Sequence conflicti199 – 1991G → R in CAC42766 (Ref. 1) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti70 – 701S → T.
Corresponds to variant rs9923813 [ dbSNP | Ensembl ].
VAR_058335
Natural varianti180 – 1801V → L.2 Publications
Corresponds to variant rs28407821 [ dbSNP | Ensembl ].
VAR_058336
Natural varianti390 – 3901G → R in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_035630

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 341341Missing in isoform 2. 1 PublicationVSP_044312Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10723.2. [Q32MK0-3]
RefSeqiNP_872299.2. NM_182493.2. [Q32MK0-3]
XP_005256292.1. XM_005256235.2. [Q32MK0-4]
XP_006721396.1. XM_006721333.1. [Q32MK0-3]
XP_006721397.1. XM_006721334.1. [Q32MK0-4]
UniGeneiHs.130465.

Genome annotation databases

EnsembliENST00000394809; ENSP00000378288; ENSG00000140795. [Q32MK0-3]
ENST00000536476; ENSP00000439297; ENSG00000140795. [Q32MK0-4]
GeneIDi91807.
KEGGihsa:91807.
UCSCiuc002eei.4. human. [Q32MK0-3]
uc002eej.1. human. [Q32MK0-4]

Polymorphism databases

DMDMi254763411.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10723.2. [Q32MK0-3]
RefSeqiNP_872299.2. NM_182493.2. [Q32MK0-3]
XP_005256292.1. XM_005256235.2. [Q32MK0-4]
XP_006721396.1. XM_006721333.1. [Q32MK0-3]
XP_006721397.1. XM_006721334.1. [Q32MK0-4]
UniGeneiHs.130465.

3D structure databases

ProteinModelPortaliQ32MK0.
SMRiQ32MK0. Positions 458-793.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124881. 6 interactions.
IntActiQ32MK0. 2 interactions.
STRINGi9606.ENSP00000378288.

Chemistry

BindingDBiQ32MK0.
ChEMBLiCHEMBL4627.
GuidetoPHARMACOLOGYi2110.

PTM databases

PhosphoSiteiQ32MK0.

Polymorphism databases

DMDMi254763411.

Proteomic databases

MaxQBiQ32MK0.
PaxDbiQ32MK0.
PRIDEiQ32MK0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000394809; ENSP00000378288; ENSG00000140795. [Q32MK0-3]
ENST00000536476; ENSP00000439297; ENSG00000140795. [Q32MK0-4]
GeneIDi91807.
KEGGihsa:91807.
UCSCiuc002eei.4. human. [Q32MK0-3]
uc002eej.1. human. [Q32MK0-4]

Organism-specific databases

CTDi91807.
GeneCardsiGC16M046736.
HGNCiHGNC:29826. MYLK3.
HPAiHPA040258.
MIMi612147. gene.
neXtProtiNX_Q32MK0.
PharmGKBiPA162396375.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118877.
HOGENOMiHOG000233016.
HOVERGENiHBG080416.
InParanoidiQ32MK0.
KOiK00907.
OMAiFRMVVAV.
OrthoDBiEOG73FQMV.
PhylomeDBiQ32MK0.
TreeFamiTF314166.

Enzyme and pathway databases

SignaLinkiQ32MK0.

Miscellaneous databases

ChiTaRSiMYLK3. human.
GeneWikiiMYLK3.
GenomeRNAii91807.
NextBioi77465.
PROiQ32MK0.
SOURCEiSearch...

Gene expression databases

BgeeiQ32MK0.
CleanExiHS_MYLK3.
GenevestigatoriQ32MK0.

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 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. Cited for: TISSUE SPECIFICITY.
  7. Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-390.

Entry informationi

Entry nameiMYLK3_HUMAN
AccessioniPrimary (citable) accession number: Q32MK0
Secondary accession number(s): B5BUL9
, B7Z5U8, Q32MK1, Q96DV1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: July 28, 2009
Last modified: January 7, 2015
This is version 88 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: 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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. 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.