Q17R13 (ACK1_BOVIN) Reviewed, UniProtKB/Swiss-Prot
Last modified May 1, 2013. Version 66. History...
Names and origin
|Protein names||Recommended name:|
Activated CDC42 kinase 1
Activated CDC42 kinase 2
Tyrosine kinase non-receptor protein 2
|Organism||Bos taurus (Bovine) [Reference proteome]|
|Taxonomic identifier||9913 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos|
|Sequence length||1039 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. Ref.3
ATP + a protein = ADP + a phosphoprotein. Ref.1
Magnesium By similarity. UniProtKB Q07912
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). Ref.1 Ref.3
Cell membrane By similarity. Nucleus By similarity. Endosome By similarity. Cell junction › adherens junction By similarity. Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasmic vesicle › clathrin-coated vesicle By similarity. Membrane › clathrin-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. UniProtKB O54967
Expressed in brain and skeletal muscle. Weakly expressed in pancreas, heart, placenta and lung.
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.
The UBA domain binds both poly- and mono-ubiquitin By similarity.
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.
Polyubiquitinated by NEDD4 and NEDD4L. Degradation can be induced by EGF and is lysosome-dependent By similarity.
Contains 1 protein kinase domain.
Contains 1 SH3 domain.
Contains 1 UBA domain.
|This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform 1 (identifier: Q17R13-1) |
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.
|Isoform 2 (identifier: Q17R13-2) |
The sequence of this isoform differs from the canonical sequence as follows:
514-514: K → KREPPPRPPQPAIFTQ
814-856: MPTTQSFASD...VRDGKKVSST → ENYVQNFKNL...SPECGRETPF
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 1039||1039||Activated CDC42 kinase 1||PRO_0000312829|
|Domain||126 – 385||260||Protein kinase|
|Domain||373 – 448||76||SH3|
|Domain||957 – 997||41||UBA|
|Nucleotide binding||132 – 140||9||ATP By similarity UniProtKB P00517|
|Region||1 – 110||110||SAM-like domain By similarity|
|Region||622 – 651||30||Required for interaction with SRC By similarity|
|Region||631 – 634||4||Required for interaction with NEDD4 By similarity|
|Region||732 – 875||144||EBD domain By similarity|
|Compositional bias||576 – 918||343||Pro-rich|
|Active site||252||1||Proton acceptor By similarity UniProtKB P00517|
|Binding site||158||1||ATP By similarity UniProtKB O54967|
Amino acid modifications
|Modified residue||284||1||Phosphotyrosine; by SRC and autocatalysis By similarity UniProtKB Q07912|
|Modified residue||518||1||Phosphotyrosine By similarity UniProtKB Q07912|
|Modified residue||723||1||Phosphoserine By similarity|
|Modified residue||826||1||Phosphotyrosine By similarity UniProtKB Q07912|
|Modified residue||858||1||Phosphotyrosine By similarity UniProtKB Q07912|
|Modified residue||871||1||Phosphotyrosine By similarity|
|Modified residue||880||1||Phosphoserine By similarity|
|Alternative sequence||514||1||K → KREPPPRPPQPAIFTQ in isoform 2.||VSP_038165|
|Alternative sequence||814 – 856||43||MPTTQ…KVSST → ENYVQNFKNLTAHHPPWRDQ DTGTGSSRGPTVLSPECGRE TPF in isoform 2.||VSP_038166|
|Alternative sequence||857 – 1039||183||Missing in isoform 2.||VSP_038167|
|Mutagenesis||158||1||K → R: Abolishes enzyme activity. Ref.3|
|Sequence conflict||203||1||T → M in AAC05310. Ref.1|
|Sequence conflict||534||1||R → K in AAC05310. Ref.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.
|||NIH - Mammalian Gene Collection (MGC) project|
Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
|||"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.
|U96722 mRNA. Translation: AAC05310.1. Frameshift.|
BC118081 mRNA. Translation: AAI18082.1.
|RefSeq||NP_776310.2. NM_173885.3. |
3D structure databases
|SMR||Q17R13. Positions 117-388, 447-489. |
Protein-protein interaction databases
|IntAct||Q17R13. 4 interactions.|
Protocols and materials databases
Genome annotation databases
Family and domain databases
|Gene3D||4.10.680.10. 1 hit. |
|InterPro||IPR015116. Cdc42_binding_dom_like. |
|Pfam||PF09027. GTPase_binding. 1 hit. |
PF11555. Inhibitor_Mig-6. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00627. UBA. 1 hit.
|PRINTS||PR00109. TYRKINASE. |
|SMART||SM00326. SH3. 1 hit. |
SM00219. TyrKc. 1 hit.
SM00165. UBA. 1 hit.
|SUPFAM||SSF56112. Kinase_like. 1 hit. |
SSF50044. SH3. 1 hit.
|PROSITE||PS00107. PROTEIN_KINASE_ATP. 1 hit. |
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50002. SH3. 1 hit.
PS50030. UBA. False negative.
|Accession||Primary (citable) accession number: Q17R13|
Secondary accession number(s): O02742
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families