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Protein

Activated CDC42 kinase 1

Gene

Tnk2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 similarity

Catalytic activityi

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

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei158 – 1581ATPPROSITE-ProRule annotationBy similarity
Active sitei252 – 2521Proton acceptorPROSITE-ProRule annotationBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi132 – 1409ATPPROSITE-ProRule annotationBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. hormone receptor binding Source: GO_Central
  3. metal ion binding Source: UniProtKB-KW
  4. non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  5. protein serine/threonine kinase activity Source: UniProtKB-KW
  6. protein tyrosine kinase activity Source: MGI

GO - Biological processi

  1. cell differentiation Source: GO_Central
  2. cell migration Source: GO_Central
  3. endocytosis Source: UniProtKB-KW
  4. innate immune response Source: GO_Central
  5. peptidyl-tyrosine autophosphorylation Source: GO_Central
  6. phosphorylation Source: UniProtKB
  7. regulation of cell proliferation Source: GO_Central
  8. transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
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):
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. extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  8. nucleus Source: UniProtKB
  9. plasma membrane Source: UniProtKB
Complete GO annotation...

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.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

eggNOGiCOG0515.
HOGENOMiHOG000168225.
HOVERGENiHBG100429.
InParanoidiQ5U2X5.
KOiK08886.

Family and domain databases

Gene3Di4.10.680.10. 1 hit.
InterProiIPR030220. Ack1.
IPR015116. 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.
IPR000449. UBA/Ts_N.
[Graphical view]
PANTHERiPTHR24418:SF66. PTHR24418:SF66. 1 hit.
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

        10         20         30         40         50
MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NITRLSHFEY VKNEDLEKIG
60 70 80 90 100
MGRPGQRRLW EAVKRRKAMC KRKSWMSKVF SGKRQEAEFP SHHSQSTFRK
110 120 130 140 150
PSPTPGGLAG EGTLQSLTCL IGEKDLRLLE KLGDGSFGVV RRGEWDAPAG
160 170 180 190 200
KTVSVAVKCL KPDVLSQPEA MDDFIREVNA MHSLDHRNLI RLYGVVLTPP
210 220 230 240 250
MKMVTELAPL GSLLDRLRKH QGHFLLGTLS RYAVQVAEGM GYLESKRFIH
260 270 280 290 300
RDLAARNLLL ATRDLVKIGD FGLMRALPQN DGHYVMQEHR 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 RIDELYLGNP MDPPDLLSVE
510 520 530 540 550
LSTSRPTQHL GRMKKPTYDP VSEDPDPLSS DFKRLGLRKP ALPRGLWLAK
560 570 580 590 600
PSARVPGTKA GRSSGGEVTL IDFGEEPVAP TPRPCAPSLA QLAMDACSLL
610 620 630 640 650
DKTPPQSPTR ALPRPLHPTP VVDWDARPLP PPPAYDDVAQ DEDDFEVCSI
660 670 680 690 700
NSTLVSAGLP TGPSQGETNY AFVPEQAQLP PALEDNLFLP PQGGGQPPSS
710 720 730 740 750
AQTAEIFQAL QQECMRQLQV PTGQLTPSPT PGGDDKPQVP PRVPIPPRPT
760 770 780 790 800
RPRVGLSPAP LGEEEASRWP GPSSPPRVPP REPLSPQGSR TPSPLVPPGS
810 820 830 840 850
SPLPHRLSSS PGKTMPTTQS FASDPKYATP QVIQAPGPRA GPCILPIVRD
860 870 880 890 900
GRKVSSTHYY LLPERPPYLE RYQRFLREAQ SPEEPAALPV PPLLPPPSTP
910 920 930 940 950
APAAPTATVR PMPQAAPDPK ANFSTNNSNP GAQPPSLRAS ARLPQRGCPG
960 970 980 990 1000
DGQEAARPAD KVQMLQAMVH GVTTEECQAA LRSHSWSIQR AAQYLKVEQL
1010 1020 1030 1040
FGLGLRPRVE CHKVLEMFDW NLEQAGCHLL GSCGPAHHKR
Length:1,040
Mass (Da):115,068
Last modified:December 7, 2004 - v1
Checksum:i0624944919F821F6
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
BC085825 mRNA. Translation: AAH85825.1.
RefSeqiNP_001008337.1. NM_001008336.1.
UniGeneiRn.98335.

3D structure databases

ProteinModelPortaliQ5U2X5.
SMRiQ5U2X5. Positions 117-388, 447-489.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi257704. 1 interaction.
STRINGi10116.ENSRNOP00000040625.

PTM databases

PhosphoSiteiQ5U2X5.

Proteomic databases

PaxDbiQ5U2X5.
PRIDEiQ5U2X5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi303882.
KEGGirno:303882.

Organism-specific databases

CTDi10188.
RGDi1305957. Tnk2.

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000168225.
HOVERGENiHBG100429.
InParanoidiQ5U2X5.
KOiK08886.

Miscellaneous databases

NextBioi652234.

Gene expression databases

GenevestigatoriQ5U2X5.

Family and domain databases

Gene3Di4.10.680.10. 1 hit.
InterProiIPR030220. Ack1.
IPR015116. 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.
IPR000449. UBA/Ts_N.
[Graphical view]
PANTHERiPTHR24418:SF66. PTHR24418:SF66. 1 hit.
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]
ProtoNetiSearch...

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: March 4, 2015
This is version 86 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

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 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.