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Q5U2X5

- ACK1_RAT

UniProt

Q5U2X5 - ACK1_RAT

Protein

Activated CDC42 kinase 1

Gene

Tnk2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 81 (01 Oct 2014)
      Sequence version 1 (07 Dec 2004)
      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 similarityPROSITE-ProRule annotation
    ATP + a protein = ADP + a phosphoprotein.

    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 serine/threonine kinase activity Source: UniProtKB-KW
    5. protein tyrosine kinase activity Source: MGI

    GO - Biological processi

    1. endocytosis Source: UniProtKB-KW
    2. peptidyl-tyrosine phosphorylation Source: GOC
    3. 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):
    Tyrosine kinase non-receptor protein 2
    Gene namesi
    Name:Tnk2By similarity
    Synonyms:Ack1By similarity
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi1305957. Tnk2.

    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 in both the membrane and nucleus. Colocalizes with EGFR on 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

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10401040Activated CDC42 kinase 1PRO_0000312830Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei284 – 2841Phosphotyrosine; by SRC and autocatalysisBy similarity
    Modified residuei518 – 5181PhosphotyrosineBy similarity
    Modified residuei827 – 8271PhosphotyrosineBy similarity
    Modified residuei859 – 8591PhosphotyrosineBy similarity
    Modified residuei872 – 8721PhosphotyrosineBy similarity
    Modified residuei881 – 8811PhosphoserineBy 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

    PaxDbiQ5U2X5.
    PRIDEiQ5U2X5.

    PTM databases

    PhosphoSiteiQ5U2X5.

    Expressioni

    Gene expression databases

    GenevestigatoriQ5U2X5.

    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 SNX9 (via SH3 domain). Interacts with SRC (via SH2 and SH3 domain). Interacts with EGFR, and this interaction is dependent on EGF stimulation and kinase activity of EGFR. 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.By similarity

    Protein-protein interaction databases

    BioGridi257704. 1 interaction.
    STRINGi10116.ENSRNOP00000040625.

    Structurei

    3D structure databases

    ProteinModelPortaliQ5U2X5.
    SMRiQ5U2X5. 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
    Domaini958 – 99841UBASequence AnalysisAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 110110SAM-like domainBy similarityAdd
    BLAST
    Regioni623 – 65230Required for interaction with SRCBy similarityAdd
    BLAST
    Regioni632 – 6354Required for interaction with NEDD4By similarity
    Regioni733 – 876144EBD domainBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi577 – 935359Pro-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.
    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.
    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.
    [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.
    PS50002. SH3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q5U2X5-1 [UniParc]FASTAAdd to Basket

    « Hide

    MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NITRLSHFEY VKNEDLEKIG     50
    MGRPGQRRLW EAVKRRKAMC KRKSWMSKVF SGKRQEAEFP SHHSQSTFRK 100
    PSPTPGGLAG EGTLQSLTCL IGEKDLRLLE KLGDGSFGVV RRGEWDAPAG 150
    KTVSVAVKCL KPDVLSQPEA MDDFIREVNA MHSLDHRNLI RLYGVVLTPP 200
    MKMVTELAPL GSLLDRLRKH QGHFLLGTLS RYAVQVAEGM GYLESKRFIH 250
    RDLAARNLLL ATRDLVKIGD FGLMRALPQN DGHYVMQEHR KVPFAWCAPE 300
    SLKTRTFSHA SDTWMFGVTL WEMFTYGQEP WIGLNGSQIL HKIDKEGERL 350
    PRPEDCPQDI YNVMVQCWAH KPEDRPTFVA LRDFLLEAQP TDMRALQDFE 400
    EPDKLHIQMN DVITVIEGRA ENYWWRGQNT RTLCVGPFPR NVVTSVAGLS 450
    AQDISQPLQN SFIHTGHGDS DPRHCWGFPD RIDELYLGNP MDPPDLLSVE 500
    LSTSRPTQHL GRMKKPTYDP VSEDPDPLSS DFKRLGLRKP ALPRGLWLAK 550
    PSARVPGTKA GRSSGGEVTL IDFGEEPVAP TPRPCAPSLA QLAMDACSLL 600
    DKTPPQSPTR ALPRPLHPTP VVDWDARPLP PPPAYDDVAQ DEDDFEVCSI 650
    NSTLVSAGLP TGPSQGETNY AFVPEQAQLP PALEDNLFLP PQGGGQPPSS 700
    AQTAEIFQAL QQECMRQLQV PTGQLTPSPT PGGDDKPQVP PRVPIPPRPT 750
    RPRVGLSPAP LGEEEASRWP GPSSPPRVPP REPLSPQGSR TPSPLVPPGS 800
    SPLPHRLSSS PGKTMPTTQS FASDPKYATP QVIQAPGPRA GPCILPIVRD 850
    GRKVSSTHYY LLPERPPYLE RYQRFLREAQ SPEEPAALPV PPLLPPPSTP 900
    APAAPTATVR PMPQAAPDPK ANFSTNNSNP GAQPPSLRAS ARLPQRGCPG 950
    DGQEAARPAD KVQMLQAMVH GVTTEECQAA LRSHSWSIQR AAQYLKVEQL 1000
    FGLGLRPRVE CHKVLEMFDW NLEQAGCHLL GSCGPAHHKR 1040
    Length:1,040
    Mass (Da):115,068
    Last modified:December 7, 2004 - v1
    Checksum:i0624944919F821F6
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BC085825 mRNA. Translation: AAH85825.1.
    RefSeqiNP_001008337.1. NM_001008336.1.
    UniGeneiRn.98335.

    Genome annotation databases

    GeneIDi303882.
    KEGGirno:303882.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BC085825 mRNA. Translation: AAH85825.1 .
    RefSeqi NP_001008337.1. NM_001008336.1.
    UniGenei Rn.98335.

    3D structure databases

    ProteinModelPortali Q5U2X5.
    SMRi Q5U2X5. Positions 117-388, 447-489.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 257704. 1 interaction.
    STRINGi 10116.ENSRNOP00000040625.

    PTM databases

    PhosphoSitei Q5U2X5.

    Proteomic databases

    PaxDbi Q5U2X5.
    PRIDEi Q5U2X5.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 303882.
    KEGGi rno:303882.

    Organism-specific databases

    CTDi 10188.
    RGDi 1305957. Tnk2.

    Phylogenomic databases

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

    Miscellaneous databases

    NextBioi 652234.

    Gene expression databases

    Genevestigatori Q5U2X5.

    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.
    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.
    [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.
    PS50002. SH3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "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].
      Tissue: KidneyImported.

    Entry informationi

    Entry nameiACK1_RAT
    AccessioniPrimary (citable) accession number: Q5U2X5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 4, 2007
    Last sequence update: December 7, 2004
    Last modified: October 1, 2014
    This is version 81 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