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Q32MK0

- MYLK3_HUMAN

UniProt

Q32MK0 - MYLK3_HUMAN

Protein

Myosin light chain kinase 3

Gene

MYLK3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 85 (01 Oct 2014)
      Sequence version 3 (28 Jul 2009)
      Previous versions | rss
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    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

    Magnesium.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

    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

    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. 4 interactions.
    IntActiQ32MK0. 2 interactions.
    STRINGi9606.ENSP00000378288.

    Structurei

    3D structure databases

    ProteinModelPortaliQ32MK0.
    SMRiQ32MK0. Positions 491-793.
    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.
    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_dom.
    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. Align

    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

    MSGTSKESLG HGGLPGLGKT CLTTMDTKLN MLNEKVDQLL HFQEDVTEKL    50
    QSMCRDMGHL ERGLHRLEAS RAPGPGGADG VPHIDTQAGW PEVLELVRAM 100
    QQDAAQHGAR LEALFRMVAA VDRAIALVGA TFQKSKVADF LMQGRVPWRR 150
    GSPGDSPEEN KERVEEEGGK PKHVLSTSGV QSDAREPGEE SQKADVLEGT 200
    AERLPPIRAS GLGADPAQAV VSPGQGDGVP GPAQAFPGHL PLPTKVEAKA 250
    PETPSENLRT GLELAPAPGR VNVVSPSLEV APGAGQGASS SRPDPEPLEE 300
    GTRLTPGPGP QCPGPPGLPA QARATHSGGE TPPRISIHIQ EMDTPGEMLM 350
    TGRGSLGPTL TTEAPAAAQP GKQGPPGTGR CLQAPGTEPG EQTPEGAREL 400
    SPLQESSSPG GVKAEEEQRA GAEPGTRPSL ARSDDNDHEV GALGLQQGKS 450
    PGAGNPEPEQ DCAARAPVRA EAVRRMPPGA EAGSVVLDDS PAPPAPFEHR 500
    VVSVKETSIS AGYEVCQHEV LGGGRFGQVH RCTEKSTGLP LAAKIIKVKS 550
    AKDREDVKNE INIMNQLSHV NLIQLYDAFE SKHSCTLVME YVDGGELFDR 600
    ITDEKYHLTE LDVVLFTRQI CEGVHYLHQH YILHLDLKPE NILCVNQTGH 650
    QIKIIDFGLA RRYKPREKLK VNFGTPEFLA PEVVNYEFVS FPTDMWSVGV 700
    ITYMLLSGLS PFLGETDAET MNFIVNCSWD FDADTFEGLS EEAKDFVSRL 750
    LVKEKSCRMS ATQCLKHEWL NNLPAKASRS KTRLKSQLLL QKYIAQRKWK 800
    KHFYVVTAAN RLRKFPTSP 819
    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.
    The sequence CAC42766.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

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

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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.
    CCDSi CCDS10723.2. [Q32MK0-3 ]
    RefSeqi NP_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 ]
    UniGenei Hs.130465.

    3D structure databases

    ProteinModelPortali Q32MK0.
    SMRi Q32MK0. Positions 491-793.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 124881. 4 interactions.
    IntActi Q32MK0. 2 interactions.
    STRINGi 9606.ENSP00000378288.

    Chemistry

    BindingDBi Q32MK0.
    ChEMBLi CHEMBL4627.
    GuidetoPHARMACOLOGYi 2110.

    PTM databases

    PhosphoSitei Q32MK0.

    Polymorphism databases

    DMDMi 254763411.

    Proteomic databases

    MaxQBi Q32MK0.
    PaxDbi Q32MK0.
    PRIDEi Q32MK0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000394809 ; ENSP00000378288 ; ENSG00000140795 . [Q32MK0-3 ]
    ENST00000536476 ; ENSP00000439297 ; ENSG00000140795 . [Q32MK0-4 ]
    GeneIDi 91807.
    KEGGi hsa:91807.
    UCSCi uc002eei.4. human. [Q32MK0-3 ]
    uc002eej.1. human. [Q32MK0-4 ]

    Organism-specific databases

    CTDi 91807.
    GeneCardsi GC16M046736.
    HGNCi HGNC:29826. MYLK3.
    HPAi HPA040258.
    MIMi 612147. gene.
    neXtProti NX_Q32MK0.
    PharmGKBi PA162396375.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233016.
    HOVERGENi HBG080416.
    InParanoidi Q32MK0.
    KOi K00907.
    OMAi FRMVVAV.
    OrthoDBi EOG73FQMV.
    PhylomeDBi Q32MK0.
    TreeFami TF314166.

    Enzyme and pathway databases

    SignaLinki Q32MK0.

    Miscellaneous databases

    GeneWikii MYLK3.
    GenomeRNAii 91807.
    NextBioi 77465.
    PROi Q32MK0.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q32MK0.
    CleanExi HS_MYLK3.
    Genevestigatori Q32MK0.

    Family and domain databases

    InterProi IPR020636. 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_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    PANTHERi PTHR24347. PTHR24347. 1 hit.
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 85 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