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Q99ML2

- TNK1_MOUSE

UniProt

Q99ML2 - TNK1_MOUSE

Protein

Non-receptor tyrosine-protein kinase TNK1

Gene

Tnk1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 108 (01 Oct 2014)
      Sequence version 2 (15 Feb 2005)
      Previous versions | rss
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    Functioni

    May function in signaling pathways utilized broadly during fetal development and more selectively in adult tissues and in cells of the lymphohematopoietic system. Could specifically be involved in phospholipid signal transduction By similarity. Involved in negative regulation of cell growth. Has tumor suppressor properties. Plays a negative regulatory role in the Ras-MAPK pathway.By similarity2 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 sitei148 – 1481ATPBy similarityPROSITE-ProRule annotation
    Active sitei245 – 2451Proton acceptorBy similarityPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi122 – 1309ATPBy similarityPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB

    GO - Biological processi

    1. negative regulation of cell growth Source: UniProtKB
    2. negative regulation of Ras protein signal transduction Source: UniProtKB
    3. protein autophosphorylation Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Non-receptor tyrosine-protein kinase TNK1 (EC:2.7.10.2)
    Alternative name(s):
    Kinase of embryonic stem cells
    Gene namesi
    Name:Tnk1Imported
    Synonyms:Kos1Imported
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:1930958. Tnk1.

    Subcellular locationi

    Membrane By similarity. Cytoplasm 1 Publication

    GO - Cellular componenti

    1. cytosol Source: UniProtKB
    2. membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Mice develop spontaneous tumors, including lymphomas and carcinomas at high rates.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi148 – 1481K → A: Loss of autophosphorylation. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 666666Non-receptor tyrosine-protein kinase TNK1PRO_0000088174Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei255 – 2551PhosphoserineBy similarity
    Modified residuei498 – 4981PhosphoserineBy similarity
    Modified residuei510 – 5101PhosphothreonineBy similarity
    Modified residuei515 – 5151PhosphoserineBy similarity
    Modified residuei582 – 5821PhosphoserineBy similarity

    Post-translational modificationi

    Autophosphorylated on tyrosine residues.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiQ99ML2.

    PTM databases

    PhosphoSiteiQ99ML2.

    Expressioni

    Tissue specificityi

    Expressed in whole embryo and all adult tissues examined including liver, kidney, heart, brain, skeletal muscle and intestine. Also detected in various myeloid- and lymphoid-derived cell lines.1 Publication

    Developmental stagei

    Expression during embryogenesis increases between E7 and E11. Levels of expression subsequently decrease and reach a steady-state level by E17.1 Publication

    Gene expression databases

    ArrayExpressiQ99ML2.
    BgeeiQ99ML2.
    CleanExiMM_TNK1.
    GenevestigatoriQ99ML2.

    Interactioni

    Subunit structurei

    Interacts with the SH3 domain of PLCG1 via its Pro-rich domain.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ99ML2.
    SMRiQ99ML2. Positions 107-437.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini116 – 383268Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini387 – 43953SH3Sequence AnalysisAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi507 – 56054Pro-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 SH3 domain.Sequence Analysis

    Keywords - Domaini

    SH3 domain

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00740000115195.
    HOGENOMiHOG000231055.
    HOVERGENiHBG055513.
    KOiK08885.
    OMAiYTHIAFL.
    OrthoDBiEOG71G9T3.
    TreeFamiTF316643.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view]
    PfamiPF07714. Pkinase_Tyr. 1 hit.
    [Graphical view]
    PRINTSiPR00109. TYRKINASE.
    SMARTiSM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 11 Publication (identifier: Q99ML2-1) [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

    MLPEASSLWL LRLLRDVQLA QFYRPILEEL NVTRPEHFDF VRPEDLDNIG    50
    MGRPAQRRLN EALKRYRSGV KSKNWVYKIL GGFAPEQKEI PPRSDSPLCF 100
    HEPEGGLKCL IPEGAVRRGE LLGSGCFGVV HRGLWTLPSG QSIPVAVKSL 150
    RVGPEGPMGT ELGDFLREVS VMMKLEHPHV LRLHGLVLGQ PLQMVMELAP 200
    LGSLHARLTA PAPTPPLPVA LLCLFLRQLA GAMAYLGSCG LVHRDLATRN 250
    LLLASPRMIK VADFGLVRPL GGARGRYVMG GPRPIPYAWC APESLRQGAF 300
    SSASDVWMFG VTLWEMFSGG EEPWAGVPPY LILQRLEKDR ARLPKPPLCS 350
    RALYSLALRC WAPHPADRPS FSNLEGLLQE AWLSEGRCVR EVTEPGALRM 400
    EPGDPITIIE GSLDTATWKG QNGRTLKVGN FPASAVTLAD LGGSPVTHPA 450
    HRGSPAHGEK CRGGTDGDRE KATLQDLPPA RSHRTKMPLQ RMRGISKSLE 500
    SVLSLGPRPT GGGSSPPELR RTRAMPQRLP DLPPRPPDLP PRPPIICNSS 550
    QPTQPHKARP KRESSHNHRT GAPGASKATV PSGGPLSDPE WQRKVVEVEL 600
    SVHGVTYQEC QVALRTTGGD VASAIRNLKV DQLFHLSNRS RADCRRILEH 650
    HQWDLSAASR YILARS 666
    Length:666
    Mass (Da):73,099
    Last modified:February 15, 2005 - v2
    Checksum:i5AE6A48D99BADE8B
    GO
    Isoform 21 Publication (identifier: Q99ML2-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         381-434: AWLSEGRCVR...TLKVGNFPAS → VRIPNSPYTH...QSLPAGSAEP
         435-666: Missing.

    Show »
    Length:434
    Mass (Da):47,926
    Checksum:iE1F1BBF451401FBC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti46 – 461L → V in AAK35164. 1 PublicationCurated
    Sequence conflicti59 – 591L → I in AAK35164. 1 PublicationCurated
    Sequence conflicti206 – 2061A → T in AAH29623. (PubMed:15489334)Curated
    Sequence conflicti206 – 2061A → T in AAH55303. (PubMed:15489334)Curated
    Sequence conflicti534 – 5341P → S in AAK35164. 1 PublicationCurated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei381 – 43454AWLSE…NFPAS → VRIPNSPYTHIAFLPCILSP SVPCRRQTRLGAWAGIWNSA QNQVQSLPAGSAEP in isoform 2. 1 PublicationVSP_051664Add
    BLAST
    Alternative sequencei435 – 666232Missing in isoform 2. 1 PublicationVSP_051665Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF307745 Genomic DNA. Translation: AAL09412.1.
    AF307746 mRNA. Translation: AAL09413.1.
    AF332512 mRNA. Translation: AAK35164.1.
    BC029623 mRNA. Translation: AAH29623.1.
    BC055303 mRNA. Translation: AAH55303.1.
    AK033440 mRNA. Translation: BAC28288.1.
    CCDSiCCDS24917.1. [Q99ML2-1]
    RefSeqiNP_114086.3. NM_031880.3. [Q99ML2-1]
    XP_006534617.1. XM_006534554.1. [Q99ML2-1]
    UniGeneiMm.28874.
    Mm.358793.

    Genome annotation databases

    EnsembliENSMUST00000001626; ENSMUSP00000001626; ENSMUSG00000001583. [Q99ML2-1]
    ENSMUST00000108626; ENSMUSP00000104266; ENSMUSG00000001583. [Q99ML2-2]
    GeneIDi83813.
    KEGGimmu:83813.
    UCSCiuc007jsb.2. mouse. [Q99ML2-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF307745 Genomic DNA. Translation: AAL09412.1 .
    AF307746 mRNA. Translation: AAL09413.1 .
    AF332512 mRNA. Translation: AAK35164.1 .
    BC029623 mRNA. Translation: AAH29623.1 .
    BC055303 mRNA. Translation: AAH55303.1 .
    AK033440 mRNA. Translation: BAC28288.1 .
    CCDSi CCDS24917.1. [Q99ML2-1 ]
    RefSeqi NP_114086.3. NM_031880.3. [Q99ML2-1 ]
    XP_006534617.1. XM_006534554.1. [Q99ML2-1 ]
    UniGenei Mm.28874.
    Mm.358793.

    3D structure databases

    ProteinModelPortali Q99ML2.
    SMRi Q99ML2. Positions 107-437.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei Q99ML2.

    Proteomic databases

    PRIDEi Q99ML2.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000001626 ; ENSMUSP00000001626 ; ENSMUSG00000001583 . [Q99ML2-1 ]
    ENSMUST00000108626 ; ENSMUSP00000104266 ; ENSMUSG00000001583 . [Q99ML2-2 ]
    GeneIDi 83813.
    KEGGi mmu:83813.
    UCSCi uc007jsb.2. mouse. [Q99ML2-1 ]

    Organism-specific databases

    CTDi 8711.
    MGIi MGI:1930958. Tnk1.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00740000115195.
    HOGENOMi HOG000231055.
    HOVERGENi HBG055513.
    KOi K08885.
    OMAi YTHIAFL.
    OrthoDBi EOG71G9T3.
    TreeFami TF316643.

    Miscellaneous databases

    NextBioi 350786.
    PROi Q99ML2.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q99ML2.
    Bgeei Q99ML2.
    CleanExi MM_TNK1.
    Genevestigatori Q99ML2.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view ]
    Pfami PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view ]
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Kos1, a nonreceptor tyrosine kinase that suppresses Ras signaling."
      Hoare K., Hoare S., Smith O.M., Kalmaz G., Small D., May W.S. Jr.
      Oncogene 22:3562-3577(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2), FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-148, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Strain: 129/SvImported.
      Tissue: Embryonic stem cell.
    2. "Cloning of the murine Tnk1 tyrosine kinase and evidence that it plays a role in cell adhesion."
      Hoehn G.T., Felschow D.M., Civin C.I.
      Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "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).
      Strain: FVB/N-3Imported.
      Tissue: Mammary glandImported.
    4. "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] OF 151-666 (ISOFORM 1).
      Strain: C57BL/6J.
      Tissue: Colon.
    5. Cited for: FUNCTION, DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiTNK1_MOUSE
    AccessioniPrimary (citable) accession number: Q99ML2
    Secondary accession number(s): Q8CCC4, Q8K0X9, Q91V11
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 15, 2005
    Last sequence update: February 15, 2005
    Last modified: October 1, 2014
    This is version 108 of the entry and version 2 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