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Q17R13

- ACK1_BOVIN

UniProt

Q17R13 - ACK1_BOVIN

Protein

Activated CDC42 kinase 1

Gene

TNK2

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 77 (01 Oct 2014)
      Sequence version 1 (25 Jul 2006)
      Previous versions | rss
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    Functioni

    Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR By similarity.By similarity

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.By similarity1 PublicationPROSITE-ProRule annotation
    ATP + a protein = ADP + a phosphoprotein.1 Publication

    Cofactori

    Magnesium.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei158 – 1581ATPBy similarityPROSITE-ProRule annotation
    Active sitei252 – 2521Proton acceptorBy similarityPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi132 – 1409ATPBy similarityPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. metal ion binding Source: UniProtKB-KW
    3. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
    4. protein binding Source: IntAct
    5. protein serine/threonine kinase activity Source: UniProtKB-KW

    GO - Biological processi

    1. endocytosis Source: UniProtKB-KW
    2. phosphorylation Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Endocytosis

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Activated CDC42 kinase 1 (EC:2.7.10.2, EC:2.7.11.1)
    Short name:
    ACK-1
    Alternative name(s):
    Activated CDC42 kinase 2
    Tyrosine kinase non-receptor protein 2
    Gene namesi
    Name:TNK2By similarity
    Synonyms:ACK1By similarity, ACK2
    OrganismiBos taurus (Bovine)
    Taxonomic identifieri9913 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
    ProteomesiUP000009136: Unplaced

    Subcellular locationi

    Cell membrane By similarity. Nucleus By similarity. Endosome By similarity. Cell junctionadherens junction By similarity. Cytoplasmic vesicle membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity. Cytoplasmic vesicleclathrin-coated vesicle By similarity. Membraneclathrin-coated pit By similarity
    Note: The Tyr-284 phosphorylated form is found both in the membrane and nucleus. Co-localizes with EGFR on the endosomes. Nuclear translocation is CDC42-dependent By similarity.By similarity

    GO - Cellular componenti

    1. adherens junction Source: UniProtKB-SubCell
    2. clathrin-coated vesicle Source: UniProtKB-SubCell
    3. coated pit Source: UniProtKB-SubCell
    4. cytoplasm Source: UniProtKB
    5. cytoplasmic vesicle membrane Source: UniProtKB-SubCell
    6. endosome Source: UniProtKB
    7. nucleus Source: UniProtKB
    8. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Coated pit, Cytoplasmic vesicle, Endosome, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi158 – 1581K → R: Abolishes enzyme activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10391039Activated CDC42 kinase 1PRO_0000312829Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei284 – 2841Phosphotyrosine; by SRC and autocatalysisBy similarity
    Modified residuei518 – 5181PhosphotyrosineBy similarity
    Modified residuei723 – 7231PhosphoserineBy similarity
    Modified residuei826 – 8261PhosphotyrosineBy similarity
    Modified residuei858 – 8581PhosphotyrosineBy similarity
    Modified residuei871 – 8711PhosphotyrosineBy similarity
    Modified residuei880 – 8801PhosphoserineBy similarity

    Post-translational modificationi

    Autophosphorylation regulates kinase activity. Phosphorylation on Tyr-518 is required for interaction with SRC and is observed during association with clathrin-coated pits By similarity.By similarity
    Polyubiquitinated by NEDD4 and NEDD4L. Degradation can be induced by EGF and is lysosome-dependent By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiQ17R13.

    Expressioni

    Tissue specificityi

    Expressed in brain and skeletal muscle. Weakly expressed in pancreas, heart, placenta and lung.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with CDC42. Interacts with CSPG4 (activated). Interacts with MERTK (activated); stimulates autophosphorylation. May interact (phosphorylated) with HSP90AB1; maintains kinase activity. Interacts with NPHP1. Interacts with SRC (via SH2 and SH3 domain). Interacts (via kinase domain) with AKT1. Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas. Interacts with BCAR1/p130cas via SH3 domains. Forms complexes with GRB2 and numerous receptor tyrosine kinases (RTK) including LTK, AXL or PDGFRL, in which GRB2 promotes RTK recruitment by TNK2. Interacts with NEDD4 (via WW3 domain). NEDD4L and EGF promote association with NEDD4 By similarity. Interacts with EGFR, and this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts with SNX9 (via SH3 domain).By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    SNX9Q9Y5X15EBI-457220,EBI-77848From a different organism.

    Protein-protein interaction databases

    IntActiQ17R13. 4 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliQ17R13.
    SMRiQ17R13. Positions 117-388, 447-489.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini126 – 385260Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini373 – 44876SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini957 – 99741UBASequence AnalysisAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 110110SAM-like domainBy similarityAdd
    BLAST
    Regioni622 – 65130Required for interaction with SRCBy similarityAdd
    BLAST
    Regioni631 – 6344Required for interaction with NEDD4By similarity
    Regioni732 – 875144EBD domainBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi576 – 918343Pro-richSequence AnalysisAdd
    BLAST

    Domaini

    The EBD (EGFR-binding domain) domain is necessary for interaction with EGFR.By similarity
    The SAM-like domain is necessary for NEDD4-mediated ubiquitination. Promotes membrane localization and dimerization to allow for autophosphorylation By similarity.By similarity
    The UBA domain binds both poly- and mono-ubiquitin.By similarity

    Sequence similaritiesi

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

    Keywords - Domaini

    SH3 domain

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000168225.
    HOVERGENiHBG100429.
    InParanoidiQ17R13.
    KOiK08886.

    Family and domain databases

    Gene3Di4.10.680.10. 1 hit.
    InterProiIPR015116. Cdc42_binding_dom_like.
    IPR021619. Inhibitor_Mig-6.
    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.
    IPR009060. UBA-like.
    IPR015940. UBA/transl_elong_EF1B_N_euk.
    IPR000449. UBA/Ts_N.
    [Graphical view]
    PfamiPF09027. GTPase_binding. 1 hit.
    PF11555. Inhibitor_Mig-6. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF14604. SH3_9. 1 hit.
    PF00627. UBA. 1 hit.
    [Graphical view]
    PRINTSiPR00109. TYRKINASE.
    SMARTiSM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    SM00165. UBA. 1 hit.
    [Graphical view]
    SUPFAMiSSF46934. SSF46934. 1 hit.
    SSF50044. 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.
    PS50002. SH3. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q17R13-1) [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

    MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NVTRLSHFEY VKNEDLEKIG     50
    MGRPGQRRLW EAVKRRKAMC KRKSWMSKVF SGKRLEAEFP PHHSQSTFRK 100
    TSPTPGGSAG EGSLQSLTCL IGEKDLHLFE KLGDGSFGVV RRGEWDAPSG 150
    KTVSVAVKCL KPDVLSQPEA MDDFIREVNA MHSLDHRNLI RLYGVVLTPP 200
    MKTVTELAPL GSLLDRLRKH QGHFLLGTLS RYAVQVAEGM GYLEAKRFIH 250
    RDLAARNLLL ATRDLVKIGD FGLMRALPQN DDHYVMQEHR KVPFAWCAPE 300
    SLKTRTFSHA SDTWMFGVTL WEMFTYGQEP WIGLNGSQIL HKIDKEGERL 350
    PRPEDCPQDI YNVMVQCWAH KPEDRPTFVA LRDFLLEAQP TDMRALQDFE 400
    EPDKLHIQMN DVITVIEGRA ENYWWRGQNT RTLCVGPFPR NVVTSVAGLS 450
    AQDISQPLQN SFIHTGHGDS DPRHCWGFPD KIDELYLGNP MDPPDLLSVE 500
    LSTSRPTQHL GRVKKPTYDP VSEDQDPLSS DFKRLGLRKP GLPRGLWLAK 550
    PSARVPGTKA GRGGGEVTLI DFGEEPVVPA PRPCAPSLAQ LAMDACSLLD 600
    KTPPQSPTRA LPRPLHPTPV VDWDARPLPP PPAYDDVAQD EDDFEVCSIN 650
    STLVGAGVSA EPSQGETNYA FVPEPARLLP PLEDNLFLPP QSGGKPPNSA 700
    QTAEIFQALQ QECMRQLQVP PGSLVPSPSP GGDDKPQVPP RVPIPPRPTR 750
    SRGELSPVPP GEEEMGRWPG PASPPRVPPR EPLSPQGSRT PSPLVPPGSS 800
    PLPPRLSSSP GKTMPTTQSF ASDPKYATPQ VIQAPGPRAG PCILPIVRDG 850
    KKVSSTHYYL LPERPPYLER YQRFLHEAQS PRGPDPTPIP LLLPPPSTPA 900
    PAAPTATVRP MPQAAPDPKA NFSSNNSNPG ARPSSLRATA RLPQRGYPGD 950
    GPEAGRPADK IQMLQAMVHG VTTEECQAAL QSHSWSVQRA AQYLKVEQLF 1000
    GLGLRPRGEC HNVLEMFDWN LEQAGCHLLG SCGPAHHKR 1039
    Length:1,039
    Mass (Da):114,868
    Last modified:July 25, 2006 - v1
    Checksum:iE7834771D76F8472
    GO
    Isoform 2 (identifier: Q17R13-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         514-514: K → KREPPPRPPQPAIFTQ
         814-856: MPTTQSFASD...VRDGKKVSST → ENYVQNFKNL...SPECGRETPF
         857-1039: Missing.

    Show »
    Length:871
    Mass (Da):96,809
    Checksum:i3BE6448F4370A6E1
    GO

    Sequence cautioni

    The sequence AAC05310.1 differs from that shown. Reason: Frameshift at position 682.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti203 – 2031T → M in AAC05310. (PubMed:9312079)Curated
    Sequence conflicti534 – 5341R → K in AAC05310. (PubMed:9312079)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei514 – 5141K → KREPPPRPPQPAIFTQ in isoform 2. 1 PublicationVSP_038165
    Alternative sequencei814 – 85643MPTTQ…KVSST → ENYVQNFKNLTAHHPPWRDQ DTGTGSSRGPTVLSPECGRE TPF in isoform 2. 1 PublicationVSP_038166Add
    BLAST
    Alternative sequencei857 – 1039183Missing in isoform 2. 1 PublicationVSP_038167Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U96722 mRNA. Translation: AAC05310.1. Frameshift.
    BC118081 mRNA. Translation: AAI18082.1.
    RefSeqiNP_776310.2. NM_173885.3. [Q17R13-1]
    UniGeneiBt.64988.

    Genome annotation databases

    GeneIDi280710.
    KEGGibta:280710.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U96722 mRNA. Translation: AAC05310.1 . Frameshift.
    BC118081 mRNA. Translation: AAI18082.1 .
    RefSeqi NP_776310.2. NM_173885.3. [Q17R13-1 ]
    UniGenei Bt.64988.

    3D structure databases

    ProteinModelPortali Q17R13.
    SMRi Q17R13. Positions 117-388, 447-489.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q17R13. 4 interactions.

    Proteomic databases

    PRIDEi Q17R13.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 280710.
    KEGGi bta:280710.

    Organism-specific databases

    CTDi 10188.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000168225.
    HOVERGENi HBG100429.
    InParanoidi Q17R13.
    KOi K08886.

    Miscellaneous databases

    NextBioi 20804889.

    Family and domain databases

    Gene3Di 4.10.680.10. 1 hit.
    InterProi IPR015116. Cdc42_binding_dom_like.
    IPR021619. Inhibitor_Mig-6.
    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.
    IPR009060. UBA-like.
    IPR015940. UBA/transl_elong_EF1B_N_euk.
    IPR000449. UBA/Ts_N.
    [Graphical view ]
    Pfami PF09027. GTPase_binding. 1 hit.
    PF11555. Inhibitor_Mig-6. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF14604. SH3_9. 1 hit.
    PF00627. UBA. 1 hit.
    [Graphical view ]
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    SM00165. UBA. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46934. SSF46934. 1 hit.
    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.
    PS50002. SH3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and characterization of a novel Cdc42-associated tyrosine kinase, ACK-2, from bovine brain."
      Yang W., Cerione R.A.
      J. Biol. Chem. 272:24819-24824(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CATALYTIC ACTIVITY, INTERACTION WITH CDC42.
      Tissue: Brain.
    2. NIH - Mammalian Gene Collection (MGC) project
      Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Strain: HerefordImported.
      Tissue: HypothalamusImported.
    3. "The Cdc42 target ACK2 interacts with sorting nexin 9 (SH3PX1) to regulate epidermal growth factor receptor degradation."
      Lin Q., Lo C.G., Cerione R.A., Yang W.
      J. Biol. Chem. 277:10134-10138(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH SNX9 AND EGFR, IDENTIFICATION IN A COMPLEX WITH SNX9 AND CLATHRIN HEAVY CHAIN, MUTAGENESIS OF LYS-158.

    Entry informationi

    Entry nameiACK1_BOVIN
    AccessioniPrimary (citable) accession number: Q17R13
    Secondary accession number(s): O02742
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 4, 2007
    Last sequence update: July 25, 2006
    Last modified: October 1, 2014
    This is version 77 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3