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Protein

Activated CDC42 kinase 1

Gene

TNK2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 similarity1 Publication

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotationBy similarity1 Publication
ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei158ATPPROSITE-ProRule annotationBy similarity1
Active sitei252Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi132 – 140ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

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
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi158K → R: Abolishes enzyme activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003128291 – 1039Activated CDC42 kinase 1Add BLAST1039

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei284Phosphotyrosine; by SRC and autocatalysisBy similarity1
Modified residuei518PhosphotyrosineBy similarity1
Modified residuei723PhosphoserineBy similarity1
Modified residuei826PhosphotyrosineBy similarity1
Modified residuei838Omega-N-methylarginineBy similarity1
Modified residuei858PhosphotyrosineBy similarity1
Modified residuei871PhosphotyrosineBy similarity1
Modified residuei880PhosphoserineBy similarity1

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

Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ17R13.
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.

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ17R13. 4 interactors.
STRINGi9913.ENSBTAP00000043771.

Structurei

3D structure databases

ProteinModelPortaliQ17R13.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini126 – 385Protein kinasePROSITE-ProRule annotationAdd BLAST260
Domaini373 – 448SH3PROSITE-ProRule annotationAdd BLAST76
Domaini957 – 997UBASequence analysisAdd BLAST41

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 110SAM-like domainBy similarityAdd BLAST110
Regioni622 – 651Required for interaction with SRCBy similarityAdd BLAST30
Regioni631 – 634Required for interaction with NEDD4By similarity4
Regioni732 – 875EBD domainBy similarityAdd BLAST144

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi576 – 918Pro-richSequence analysisAdd BLAST343

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.PROSITE-ProRule annotationBy similarity
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

eggNOGiKOG0199. Eukaryota.
ENOG410XPRC. LUCA.
HOGENOMiHOG000168225.
HOVERGENiHBG100429.
InParanoidiQ17R13.
KOiK08886.

Family and domain databases

Gene3Di4.10.680.10. 1 hit.
InterProiIPR015116. Cdc42_binding_dom-like.
IPR011009. Kinase-like_dom.
IPR021619. Mig-6.
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.
[Graphical view]
PfamiPF09027. GTPase_binding. 1 hit.
PF11555. Inhibitor_Mig-6. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF14604. SH3_9. 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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

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

        10         20         30         40         50
MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NVTRLSHFEY VKNEDLEKIG
60 70 80 90 100
MGRPGQRRLW EAVKRRKAMC KRKSWMSKVF SGKRLEAEFP PHHSQSTFRK
110 120 130 140 150
TSPTPGGSAG EGSLQSLTCL IGEKDLHLFE KLGDGSFGVV RRGEWDAPSG
160 170 180 190 200
KTVSVAVKCL KPDVLSQPEA MDDFIREVNA MHSLDHRNLI RLYGVVLTPP
210 220 230 240 250
MKTVTELAPL GSLLDRLRKH QGHFLLGTLS RYAVQVAEGM GYLEAKRFIH
260 270 280 290 300
RDLAARNLLL ATRDLVKIGD FGLMRALPQN DDHYVMQEHR KVPFAWCAPE
310 320 330 340 350
SLKTRTFSHA SDTWMFGVTL WEMFTYGQEP WIGLNGSQIL HKIDKEGERL
360 370 380 390 400
PRPEDCPQDI YNVMVQCWAH KPEDRPTFVA LRDFLLEAQP TDMRALQDFE
410 420 430 440 450
EPDKLHIQMN DVITVIEGRA ENYWWRGQNT RTLCVGPFPR NVVTSVAGLS
460 470 480 490 500
AQDISQPLQN SFIHTGHGDS DPRHCWGFPD KIDELYLGNP MDPPDLLSVE
510 520 530 540 550
LSTSRPTQHL GRVKKPTYDP VSEDQDPLSS DFKRLGLRKP GLPRGLWLAK
560 570 580 590 600
PSARVPGTKA GRGGGEVTLI DFGEEPVVPA PRPCAPSLAQ LAMDACSLLD
610 620 630 640 650
KTPPQSPTRA LPRPLHPTPV VDWDARPLPP PPAYDDVAQD EDDFEVCSIN
660 670 680 690 700
STLVGAGVSA EPSQGETNYA FVPEPARLLP PLEDNLFLPP QSGGKPPNSA
710 720 730 740 750
QTAEIFQALQ QECMRQLQVP PGSLVPSPSP GGDDKPQVPP RVPIPPRPTR
760 770 780 790 800
SRGELSPVPP GEEEMGRWPG PASPPRVPPR EPLSPQGSRT PSPLVPPGSS
810 820 830 840 850
PLPPRLSSSP GKTMPTTQSF ASDPKYATPQ VIQAPGPRAG PCILPIVRDG
860 870 880 890 900
KKVSSTHYYL LPERPPYLER YQRFLHEAQS PRGPDPTPIP LLLPPPSTPA
910 920 930 940 950
PAAPTATVRP MPQAAPDPKA NFSSNNSNPG ARPSSLRATA RLPQRGYPGD
960 970 980 990 1000
GPEAGRPADK IQMLQAMVHG VTTEECQAAL QSHSWSVQRA AQYLKVEQLF
1010 1020 1030
GLGLRPRGEC HNVLEMFDWN LEQAGCHLLG SCGPAHHKR
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 differs from that shown. Reason: Frameshift at position 682.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti203T → M in AAC05310 (PubMed:9312079).Curated1
Sequence conflicti534R → K in AAC05310 (PubMed:9312079).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038165514K → KREPPPRPPQPAIFTQ in isoform 2. 1 Publication1
Alternative sequenceiVSP_038166814 – 856MPTTQ…KVSST → ENYVQNFKNLTAHHPPWRDQ DTGTGSSRGPTVLSPECGRE TPF in isoform 2. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_038167857 – 1039Missing in isoform 2. 1 PublicationAdd BLAST183

Sequence databases

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

3D structure databases

ProteinModelPortaliQ17R13.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ17R13. 4 interactors.
STRINGi9913.ENSBTAP00000043771.

Proteomic databases

PaxDbiQ17R13.
PRIDEiQ17R13.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi280710.
KEGGibta:280710.

Organism-specific databases

CTDi10188.

Phylogenomic databases

eggNOGiKOG0199. Eukaryota.
ENOG410XPRC. LUCA.
HOGENOMiHOG000168225.
HOVERGENiHBG100429.
InParanoidiQ17R13.
KOiK08886.

Family and domain databases

Gene3Di4.10.680.10. 1 hit.
InterProiIPR015116. Cdc42_binding_dom-like.
IPR011009. Kinase-like_dom.
IPR021619. Mig-6.
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.
[Graphical view]
PfamiPF09027. GTPase_binding. 1 hit.
PF11555. Inhibitor_Mig-6. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF14604. SH3_9. 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]
ProtoNetiSearch...

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: November 30, 2016
This is version 94 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.