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Q5U2X5 (ACK1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 79. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Activated CDC42 kinase 1

Short name=ACK-1
EC=2.7.10.2
EC=2.7.11.1
Alternative name(s):
Tyrosine kinase non-receptor protein 2
Gene names
Name:Tnk2
Synonyms:Ack1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1040 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. UniProtKB Q07912

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity. UniProtKB Q07912

Subunit structure

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.

Subcellular location

Cell membrane By similarity. Nucleus By similarity. Endosome By similarity. Cell junctionadherens junction By similarity. Cytoplasmic vesicle membrane; Peripheral membrane protein; 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. UniProtKB O54967

Domain

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.

Post-translational modification

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.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. UniProtKB Q07912

Contains 1 protein kinase domain.

Contains 1 SH3 domain.

Contains 1 UBA domain.

Ontologies

Keywords
   Biological processEndocytosis
   Cellular componentCell junction
Cell membrane
Coated pit
Cytoplasmic vesicle
Endosome
Membrane
Nucleus
   DomainSH3 domain
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processendocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 16052498. Source: GOC

phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentadherens junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

clathrin-coated vesicle

Inferred from electronic annotation. Source: UniProtKB-SubCell

coated pit

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasmic vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

endosome

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

protein tyrosine kinase activity

Inferred from direct assay PubMed 16052498. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10401040Activated CDC42 kinase 1
PRO_0000312830

Regions

Domain126 – 385260Protein kinase
Domain373 – 44876SH3
Domain958 – 99841UBA
Nucleotide binding132 – 1409ATP By similarity UniProtKB P00517
Region1 – 110110SAM-like domain By similarity
Region623 – 65230Required for interaction with SRC By similarity
Region632 – 6354Required for interaction with NEDD4 By similarity
Region733 – 876144EBD domain By similarity
Compositional bias577 – 935359Pro-rich

Sites

Active site2521Proton acceptor By similarity UniProtKB P00517
Binding site1581ATP By similarity UniProtKB O54967

Amino acid modifications

Modified residue2841Phosphotyrosine; by SRC and autocatalysis By similarity UniProtKB Q07912
Modified residue5181Phosphotyrosine By similarity UniProtKB Q07912
Modified residue8271Phosphotyrosine By similarity UniProtKB Q07912
Modified residue8591Phosphotyrosine By similarity UniProtKB Q07912
Modified residue8721Phosphotyrosine By similarity
Modified residue8811Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q5U2X5 [UniParc].

Last modified December 7, 2004. Version 1.
Checksum: 0624944919F821F6

FASTA1,040115,068
        10         20         30         40         50         60 
MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NITRLSHFEY VKNEDLEKIG MGRPGQRRLW 

        70         80         90        100        110        120 
EAVKRRKAMC KRKSWMSKVF SGKRQEAEFP SHHSQSTFRK PSPTPGGLAG EGTLQSLTCL 

       130        140        150        160        170        180 
IGEKDLRLLE KLGDGSFGVV RRGEWDAPAG KTVSVAVKCL KPDVLSQPEA MDDFIREVNA 

       190        200        210        220        230        240 
MHSLDHRNLI RLYGVVLTPP MKMVTELAPL GSLLDRLRKH QGHFLLGTLS RYAVQVAEGM 

       250        260        270        280        290        300 
GYLESKRFIH RDLAARNLLL ATRDLVKIGD FGLMRALPQN DGHYVMQEHR KVPFAWCAPE 

       310        320        330        340        350        360 
SLKTRTFSHA SDTWMFGVTL WEMFTYGQEP WIGLNGSQIL HKIDKEGERL PRPEDCPQDI 

       370        380        390        400        410        420 
YNVMVQCWAH KPEDRPTFVA LRDFLLEAQP TDMRALQDFE EPDKLHIQMN DVITVIEGRA 

       430        440        450        460        470        480 
ENYWWRGQNT RTLCVGPFPR NVVTSVAGLS AQDISQPLQN SFIHTGHGDS DPRHCWGFPD 

       490        500        510        520        530        540 
RIDELYLGNP MDPPDLLSVE LSTSRPTQHL GRMKKPTYDP VSEDPDPLSS DFKRLGLRKP 

       550        560        570        580        590        600 
ALPRGLWLAK PSARVPGTKA GRSSGGEVTL IDFGEEPVAP TPRPCAPSLA QLAMDACSLL 

       610        620        630        640        650        660 
DKTPPQSPTR ALPRPLHPTP VVDWDARPLP PPPAYDDVAQ DEDDFEVCSI NSTLVSAGLP 

       670        680        690        700        710        720 
TGPSQGETNY AFVPEQAQLP PALEDNLFLP PQGGGQPPSS AQTAEIFQAL QQECMRQLQV 

       730        740        750        760        770        780 
PTGQLTPSPT PGGDDKPQVP PRVPIPPRPT RPRVGLSPAP LGEEEASRWP GPSSPPRVPP 

       790        800        810        820        830        840 
REPLSPQGSR TPSPLVPPGS SPLPHRLSSS PGKTMPTTQS FASDPKYATP QVIQAPGPRA 

       850        860        870        880        890        900 
GPCILPIVRD GRKVSSTHYY LLPERPPYLE RYQRFLREAQ SPEEPAALPV PPLLPPPSTP 

       910        920        930        940        950        960 
APAAPTATVR PMPQAAPDPK ANFSTNNSNP GAQPPSLRAS ARLPQRGCPG DGQEAARPAD 

       970        980        990       1000       1010       1020 
KVQMLQAMVH GVTTEECQAA LRSHSWSIQR AAQYLKVEQL FGLGLRPRVE CHKVLEMFDW 

      1030       1040 
NLEQAGCHLL GSCGPAHHKR 

« Hide

References

[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: Kidney.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC085825 mRNA. Translation: AAH85825.1.
RefSeqNP_001008337.1. NM_001008336.1.
UniGeneRn.98335.

3D structure databases

ProteinModelPortalQ5U2X5.
SMRQ5U2X5. Positions 117-388, 447-489.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid257704. 1 interaction.
STRING10116.ENSRNOP00000040625.

PTM databases

PhosphoSiteQ5U2X5.

Proteomic databases

PaxDbQ5U2X5.
PRIDEQ5U2X5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID303882.
KEGGrno:303882.

Organism-specific databases

CTD10188.
RGD1305957. Tnk2.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000168225.
HOVERGENHBG100429.
KOK08886.

Gene expression databases

GenevestigatorQ5U2X5.

Family and domain databases

Gene3D4.10.680.10. 1 hit.
InterProIPR015116. 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]
PfamPF09027. GTPase_binding. 1 hit.
PF11555. Inhibitor_Mig-6. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00627. UBA. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio652234.

Entry information

Entry nameACK1_RAT
AccessionPrimary (citable) accession number: Q5U2X5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: December 7, 2004
Last modified: April 16, 2014
This is version 79 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families