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Q60805

- MERTK_MOUSE

UniProt

Q60805 - MERTK_MOUSE

Protein

Tyrosine-protein kinase Mer

Gene

Mertk

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.2 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei610 – 6101ATPPROSITE-ProRule annotation
    Active sitei718 – 7181Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi588 – 5969ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB-EC

    GO - Biological processi

    1. apoptotic cell clearance Source: UniProtKB
    2. natural killer cell differentiation Source: MGI
    3. negative regulation of lymphocyte activation Source: MGI
    4. platelet activation Source: MGI
    5. positive regulation of phagocytosis Source: Ensembl
    6. protein kinase B signaling Source: MGI
    7. retina development in camera-type eye Source: MGI
    8. secretion by cell Source: MGI
    9. spermatogenesis Source: MGI
    10. substrate adhesion-dependent cell spreading Source: MGI
    11. vagina development Source: MGI

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.1. 3474.
    ReactomeiREACT_225233. Cell surface interactions at the vascular wall.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase Mer (EC:2.7.10.1)
    Alternative name(s):
    Proto-oncogene c-Mer
    Receptor tyrosine kinase MerTK
    Gene namesi
    Name:Mertk
    Synonyms:Mer
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:96965. Mertk.

    Subcellular locationi

    Membrane By similarity; Single-pass type I membrane protein By similarity

    GO - Cellular componenti

    1. cytoplasm Source: Ensembl
    2. extracellular space Source: Ensembl
    3. integral component of membrane Source: UniProtKB-KW
    4. photoreceptor outer segment Source: Ensembl
    5. rhabdomere Source: Ensembl

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Disruption phenotypei

    knockout mice are fertile, but male animals that lack all three receptors TYRO3, AXL and MERTK produce no mature sperm.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi867 – 8671Y → F: Loss of GRB2 binding. 1 Publication

    Keywords - Diseasei

    Proto-oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1818Sequence AnalysisAdd
    BLAST
    Chaini19 – 994976Tyrosine-protein kinase MerPRO_0000024444Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi91 – 911N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi108 – 1081N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi109 ↔ 170PROSITE-ProRule annotation
    Glycosylationi165 – 1651N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi202 – 2021N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi210 – 2101N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi213 ↔ 257PROSITE-ProRule annotation
    Glycosylationi229 – 2291N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi289 – 2891N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi311 – 3111N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi324 – 3241N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi331 – 3311N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi349 – 3491N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi384 – 3841N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi390 – 3901N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi437 – 4371N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi449 – 4491N-linked (GlcNAc...)Sequence Analysis
    Modified residuei538 – 5381PhosphoserineBy similarity
    Modified residuei744 – 7441Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei748 – 7481Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei749 – 7491Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei867 – 8671Phosphotyrosine; by autocatalysis1 Publication

    Post-translational modificationi

    Autophosphorylated on Tyr-744, Tyr-748 and Tyr-749 in the activation loop allowing full activity By similarity. Autophosphorylated on Tyr-867 leading to recruitment of downstream partners of the signaling cascade such as PLCG2.By similarity1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    MaxQBiQ60805.
    PaxDbiQ60805.
    PRIDEiQ60805.

    PTM databases

    PhosphoSiteiQ60805.

    Expressioni

    Tissue specificityi

    Expressed predominantly in the hematopoietic lineages: macrophages, NK cells, NKT cells, dendritic cells and platelets.1 Publication

    Developmental stagei

    Expressed during most, if not all, stages of embryological development beginning in the morula and blastocyst and progressing through the yolk sac and fetal liver stages.

    Gene expression databases

    ArrayExpressiQ60805.
    BgeeiQ60805.
    CleanExiMM_MERTK.
    GenevestigatoriQ60805.

    Interactioni

    Subunit structurei

    Interacts (upon activation) with TNK2; stimulates TNK2 autophosphorylation. Interacts (via N-terminus) with extracellular ligands LGALS3, TUB, TULP1 and GAS6. Interacts with VAV1 in a phosphotyrosine-independent manner By similarity.By similarity

    Protein-protein interaction databases

    IntActiQ60805. 1 interaction.
    STRINGi10090.ENSMUSP00000014505.

    Structurei

    3D structure databases

    ProteinModelPortaliQ60805.
    SMRiQ60805. Positions 97-276, 287-487, 533-863.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini19 – 497479ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini519 – 994476CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei498 – 51821HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini75 – 181107Ig-like C2-type 1Add
    BLAST
    Domaini192 – 26877Ig-like C2-type 2Add
    BLAST
    Domaini281 – 37696Fibronectin type-III 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini381 – 47898Fibronectin type-III 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini582 – 852271Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.PROSITE-ProRule annotation
    Contains 2 fibronectin type-III domains.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00720000108377.
    HOGENOMiHOG000231685.
    HOVERGENiHBG006346.
    InParanoidiQ60805.
    KOiK05117.
    OMAiNEIGWSA.
    OrthoDBiEOG77DJ5C.
    PhylomeDBiQ60805.
    TreeFamiTF317402.

    Family and domain databases

    Gene3Di2.60.40.10. 4 hits.
    InterProiIPR003961. Fibronectin_type3.
    IPR007110. Ig-like_dom.
    IPR013783. Ig-like_fold.
    IPR003599. Ig_sub.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view]
    PfamiPF00041. fn3. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view]
    PRINTSiPR00109. TYRKINASE.
    SMARTiSM00060. FN3. 2 hits.
    SM00409. IG. 2 hits.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF49265. SSF49265. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS50853. FN3. 2 hits.
    PS50835. IG_LIKE. 2 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q60805-1 [UniParc]FASTAAdd to Basket

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    MVLAPLLLGL LLLPALWSGG TAEKWEETEL DQLFSGPLPG RLPVNHRPFS    50
    APHSSRDQLP PPQTGRSHPA HTAAPQVTST ASKLLPPVAF NHTIGHIVLS 100
    EHKNVKFNCS INIPNTYQET AGISWWKDGK ELLGAHHSIT QFYPDEEGVS 150
    IIALFSIASV QRSDNGSYFC KMKVNNREIV SDPIYVEVQG LPYFIKQPES 200
    VNVTRNTAFN LTCQAVGPPE PVNIFWVQNS SRVNEKPERS PSVLTVPGLT 250
    ETAVFSCEAH NDKGLTVSKG VHINIKVIPS PPTEVHILNS TAHSILVSWV 300
    PGFDGYSPLQ NCSIQVKEAD RLSNGSVMVF NTSASPHLYE IQQLQALANY 350
    SIAVSCRNEI GWSAVSPWIL ASTTEGAPSV APLNITVFLN ESNNILDIRW 400
    TKPPIKRQDG ELVGYRISHV WESAGTYKEL SEEVSQNGSW AQIPVQIHNA 450
    TCTVRIAAIT KGGIGPFSEP VNIIIPEHSK VDYAPSSTPA PGNTDSMFII 500
    LGCFCGFILI GLILCISLAL RRRVQETKFG GAFSEEDSQL VVNYRAKKSF 550
    CRRAIELTLQ SLGVSEELQN KLEDVVIDRN LLVLGKVLGE GEFGSVMEGN 600
    LKQEDGTSQK VAVKTMKLDN FSQREIEEFL SEAACMKDFN HPNVIRLLGV 650
    CIELSSQGIP KPMVILPFMK YGDLHTFLLY SRLNTGPKYI HLQTLLKFMM 700
    DIAQGMEYLS NRNFLHRDLA ARNCMLRDDM TVCVADFGLS KKIYSGDYYR 750
    QGRIAKMPVK WIAIESLADR VYTSKSDVWA FGVTMWEITT RGMTPYPGVQ 800
    NHEMYDYLLH GHRLKQPEDC LDELYDIMYS CWSADPLDRP TFSVLRLQLE 850
    KLSESLPDAQ DKESIIYINT QLLESCEGIA NGPSLTGLDM NIDPDSIIAS 900
    CTPGAAVSVV TAEVHENNLR EERYILNGGN EEWEDVSSTP FAAVTPEKDG 950
    VLPEDRLTKN GVSWSHHSTL PLGSPSPDEL LFVDDSLEDS EVLM 994
    Length:994
    Mass (Da):110,157
    Last modified:November 1, 1996 - v1
    Checksum:i603C09FA11F76FE0
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti473 – 4764IIIP → SARA1 PublicationCurated
    Sequence conflicti516 – 5161I → V in AAA85355. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U21301 mRNA. Translation: AAA80222.1.
    L11625 mRNA. Translation: AAA85355.1.
    CCDSiCCDS16716.1.
    PIRiI49276.
    RefSeqiNP_032613.1. NM_008587.1.
    UniGeneiMm.239655.

    Genome annotation databases

    EnsembliENSMUST00000014505; ENSMUSP00000014505; ENSMUSG00000014361.
    GeneIDi17289.
    KEGGimmu:17289.
    UCSCiuc008mgt.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U21301 mRNA. Translation: AAA80222.1 .
    L11625 mRNA. Translation: AAA85355.1 .
    CCDSi CCDS16716.1.
    PIRi I49276.
    RefSeqi NP_032613.1. NM_008587.1.
    UniGenei Mm.239655.

    3D structure databases

    ProteinModelPortali Q60805.
    SMRi Q60805. Positions 97-276, 287-487, 533-863.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q60805. 1 interaction.
    STRINGi 10090.ENSMUSP00000014505.

    PTM databases

    PhosphoSitei Q60805.

    Proteomic databases

    MaxQBi Q60805.
    PaxDbi Q60805.
    PRIDEi Q60805.

    Protocols and materials databases

    DNASUi 17289.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000014505 ; ENSMUSP00000014505 ; ENSMUSG00000014361 .
    GeneIDi 17289.
    KEGGi mmu:17289.
    UCSCi uc008mgt.1. mouse.

    Organism-specific databases

    CTDi 10461.
    MGIi MGI:96965. Mertk.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00720000108377.
    HOGENOMi HOG000231685.
    HOVERGENi HBG006346.
    InParanoidi Q60805.
    KOi K05117.
    OMAi NEIGWSA.
    OrthoDBi EOG77DJ5C.
    PhylomeDBi Q60805.
    TreeFami TF317402.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 3474.
    Reactomei REACT_225233. Cell surface interactions at the vascular wall.

    Miscellaneous databases

    NextBioi 291808.
    PROi Q60805.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q60805.
    Bgeei Q60805.
    CleanExi MM_MERTK.
    Genevestigatori Q60805.

    Family and domain databases

    Gene3Di 2.60.40.10. 4 hits.
    InterProi IPR003961. Fibronectin_type3.
    IPR007110. Ig-like_dom.
    IPR013783. Ig-like_fold.
    IPR003599. Ig_sub.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view ]
    Pfami PF00041. fn3. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view ]
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00060. FN3. 2 hits.
    SM00409. IG. 2 hits.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49265. SSF49265. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS50853. FN3. 2 hits.
    PS50835. IG_LIKE. 2 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and developmental expression analysis of the murine c-mer tyrosine kinase."
      Graham D.K., Bowman G.W., Dawson T.L., Stanford W.L., Earp H.S., Snodgrass H.R.
      Oncogene 10:2349-2359(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C57BL/6.
      Tissue: Spleen.
    2. "A cDNA encoding part of a novel putative receptor tyrosine kinase."
      Dowds C.A., Burks D.J., Saling P.M.
      Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 472-994.
      Strain: CD-1.
      Tissue: Testis.
    3. "Tyro-3 family receptors are essential regulators of mammalian spermatogenesis."
      Lu Q., Gore M., Zhang Q., Camenisch T., Boast S., Casagranda F., Lai C., Skinner M.K., Klein R., Matsushima G.K., Earp H.S., Goff S.P., Lemke G.
      Nature 398:723-728(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    4. "Biological effects of c-Mer receptor tyrosine kinase in hematopoietic cells depend on the Grb2 binding site in the receptor and activation of NF-kappaB."
      Georgescu M.M., Kirsch K.H., Shishido T., Zong C., Hanafusa H.
      Mol. Cell. Biol. 19:1171-1181(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GRB2, MUTAGENESIS OF TYR-867.
    5. "The mer receptor tyrosine kinase: expression and function suggest a role in innate immunity."
      Behrens E.M., Gadue P., Gong S.Y., Garrett S., Stein P.L., Cohen P.L.
      Eur. J. Immunol. 33:2160-2167(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    6. "The receptor tyrosine kinase MerTK activates phospholipase C gamma2 during recognition of apoptotic thymocytes by murine macrophages."
      Todt J.C., Hu B., Curtis J.L.
      J. Leukoc. Biol. 75:705-713(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PLCG2.
    7. "A role for Mer tyrosine kinase in alphavbeta5 integrin-mediated phagocytosis of apoptotic cells."
      Wu Y., Singh S., Georgescu M.M., Birge R.B.
      J. Cell Sci. 118:539-553(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FAK/PTK2.
    8. "Autophosphorylation docking site Tyr-867 in Mer receptor tyrosine kinase allows for dissociation of multiple signaling pathways for phagocytosis of apoptotic cells and down-modulation of lipopolysaccharide-inducible NF-kappaB transcriptional activation."
      Tibrewal N., Wu Y., D'mello V., Akakura R., George T.C., Varnum B., Birge R.B.
      J. Biol. Chem. 283:3618-3627(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-867.
    9. "Mertk drives myosin II redistribution during retinal pigment epithelial phagocytosis."
      Strick D.J., Feng W., Vollrath D.
      Invest. Ophthalmol. Vis. Sci. 50:2427-2435(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis."
      Caberoy N.B., Zhou Y., Li W.
      EMBO J. 29:3898-3910(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TUB AND TULP1.
    11. "Sertoli cell-initiated testicular innate immune response through toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and mer receptors."
      Sun B., Qi N., Shang T., Wu H., Deng T., Han D.
      Endocrinology 151:2886-2897(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN IMMUNE RESPONSE INHIBITION.
    12. "Galectin-3 is a new MerTK-specific eat-me signal."
      Caberoy N.B., Alvarado G., Bigcas J.L., Li W.
      J. Cell. Physiol. 227:401-407(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LGALS3.

    Entry informationi

    Entry nameiMERTK_MOUSE
    AccessioniPrimary (citable) accession number: Q60805
    Secondary accession number(s): Q62194
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 143 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3