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Q17R13 (ACK1_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 66. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·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):
Activated CDC42 kinase 2
Tyrosine kinase non-receptor protein 2
Gene names
Name:TNK2
Synonyms:ACK1, ACK2
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length1039 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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. Ref.3

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.1 UniProtKB Q07912

ATP + a protein = ADP + a phosphoprotein. Ref.1

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 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

Subcellular location

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

Tissue specificity

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

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.

Sequence caution

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

Ontologies

Keywords
   Biological processEndocytosis
   Cellular componentCell junction
Cell membrane
Coated pit
Cytoplasmic vesicle
Endosome
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   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

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

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: EC

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SNX9Q9Y5X15EBI-457220,EBI-77848From a different organism.

Alternative products

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
     857-1039: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10391039Activated CDC42 kinase 1
PRO_0000312829

Regions

Domain126 – 385260Protein kinase
Domain373 – 44876SH3
Domain957 – 99741UBA
Nucleotide binding132 – 1409ATP By similarity UniProtKB P00517
Region1 – 110110SAM-like domain By similarity
Region622 – 65130Required for interaction with SRC By similarity
Region631 – 6344Required for interaction with NEDD4 By similarity
Region732 – 875144EBD domain By similarity
Compositional bias576 – 918343Pro-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 residue7231Phosphoserine By similarity
Modified residue8261Phosphotyrosine By similarity UniProtKB Q07912
Modified residue8581Phosphotyrosine By similarity UniProtKB Q07912
Modified residue8711Phosphotyrosine By similarity
Modified residue8801Phosphoserine By similarity

Natural variations

Alternative sequence5141K → KREPPPRPPQPAIFTQ in isoform 2.
VSP_038165
Alternative sequence814 – 85643MPTTQ…KVSST → ENYVQNFKNLTAHHPPWRDQ DTGTGSSRGPTVLSPECGRE TPF in isoform 2.
VSP_038166
Alternative sequence857 – 1039183Missing in isoform 2.
VSP_038167

Experimental info

Mutagenesis1581K → R: Abolishes enzyme activity. Ref.3
Sequence conflict2031T → M in AAC05310. Ref.1
Sequence conflict5341R → K in AAC05310. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 25, 2006. Version 1.
Checksum: E7834771D76F8472

FASTA1,039114,868
        10         20         30         40         50         60 
MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NVTRLSHFEY VKNEDLEKIG MGRPGQRRLW 

        70         80         90        100        110        120 
EAVKRRKAMC KRKSWMSKVF SGKRLEAEFP PHHSQSTFRK TSPTPGGSAG EGSLQSLTCL 

       130        140        150        160        170        180 
IGEKDLHLFE KLGDGSFGVV RRGEWDAPSG KTVSVAVKCL KPDVLSQPEA MDDFIREVNA 

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

       250        260        270        280        290        300 
GYLEAKRFIH RDLAARNLLL ATRDLVKIGD FGLMRALPQN DDHYVMQEHR 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 
KIDELYLGNP MDPPDLLSVE LSTSRPTQHL GRVKKPTYDP VSEDQDPLSS DFKRLGLRKP 

       550        560        570        580        590        600 
GLPRGLWLAK PSARVPGTKA GRGGGEVTLI DFGEEPVVPA PRPCAPSLAQ LAMDACSLLD 

       610        620        630        640        650        660 
KTPPQSPTRA LPRPLHPTPV VDWDARPLPP PPAYDDVAQD EDDFEVCSIN STLVGAGVSA 

       670        680        690        700        710        720 
EPSQGETNYA FVPEPARLLP PLEDNLFLPP QSGGKPPNSA QTAEIFQALQ QECMRQLQVP 

       730        740        750        760        770        780 
PGSLVPSPSP GGDDKPQVPP RVPIPPRPTR SRGELSPVPP GEEEMGRWPG PASPPRVPPR 

       790        800        810        820        830        840 
EPLSPQGSRT PSPLVPPGSS PLPPRLSSSP GKTMPTTQSF ASDPKYATPQ VIQAPGPRAG 

       850        860        870        880        890        900 
PCILPIVRDG KKVSSTHYYL LPERPPYLER YQRFLHEAQS PRGPDPTPIP LLLPPPSTPA 

       910        920        930        940        950        960 
PAAPTATVRP MPQAAPDPKA NFSSNNSNPG ARPSSLRATA RLPQRGYPGD GPEAGRPADK 

       970        980        990       1000       1010       1020 
IQMLQAMVHG VTTEECQAAL QSHSWSVQRA AQYLKVEQLF GLGLRPRGEC HNVLEMFDWN 

      1030 
LEQAGCHLLG SCGPAHHKR

« Hide

Isoform 2 [UniParc].

Checksum: 3BE6448F4370A6E1
Show »

FASTA87196,809

References

« Hide 'large scale' references
[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: Hereford.
Tissue: Hypothalamus.
[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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		U96722 mRNA. Translation: AAC05310.1. Frameshift.
BC118081 mRNA. Translation: AAI18082.1.
IPIIPI00700705.
IPI00944890.
RefSeqNP_776310.2. NM_173885.3.
UniGeneBt.64988.

3D structure databases

ProteinModelPortalQ17R13.
SMRQ17R13. Positions 117-388, 447-489.
ModBaseSearch...

Protein-protein interaction databases

IntActQ17R13. 4 interactions.

Proteomic databases

PRIDEQ17R13.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID280710.
KEGGbta:280710.

Organism-specific databases

CTD10188.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000168225.
HOVERGENHBG100429.
InParanoidQ17R13.
KOK08886.
OrthoDBEOG4Q58NQ.

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_cat_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/transl_elong_EF1B_N.
IPR015940. UBA/transl_elong_EF1B_N_euk.
[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.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMSSF56112. Kinase_like. 1 hit.
SSF50044. SH3. 1 hit.
PROSITEPS00107. 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.
[Graphical view]
ProtoNetSearch...

Other

NextBio20804889.

Entry information

Entry nameACK1_BOVIN
AccessionPrimary (citable) accession number: Q17R13
Secondary accession number(s): O02742
Entry history
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: July 25, 2006
Last modified: May 1, 2013
This is version 66 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

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