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Q5U2X5

- ACK1_RAT

UniProt

Q5U2X5 - ACK1_RAT

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Protein
Activated CDC42 kinase 1
Gene
Tnk2, Ack1
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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.

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.By similarity
ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium By similarity.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei158 – 1581ATP By similarityBy similarity
Active sitei252 – 2521Proton acceptor By similarityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi132 – 1409ATP By similarityBy similarity

GO - Molecular functioni

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

GO - Biological processi

  1. endocytosis Source: UniProtKB-KW
  2. peptidyl-tyrosine phosphorylation Source: GOC
  3. phosphorylation Source: UniProtKB
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:Tnk2
Synonyms:Ack1
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; 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.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. nucleus Source: UniProtKB
  8. 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 1
PRO_0000312830Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei284 – 2841Phosphotyrosine; by SRC and autocatalysis By similarityBy similarity
Modified residuei518 – 5181Phosphotyrosine By similarityBy similarity
Modified residuei827 – 8271Phosphotyrosine By similarityBy similarity
Modified residuei859 – 8591Phosphotyrosine By similarityBy similarity
Modified residuei872 – 8721Phosphotyrosine By similarity
Modified residuei881 – 8811Phosphoserine By 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.
Polyubiquitinated by NEDD4 and NEDD4L. Degradation can be induced by EGF and is lysosome-dependent 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.

Protein-protein interaction databases

BioGridi257704. 1 interaction.
STRINGi10116.ENSRNOP00000040625.

Structurei

3D structure databases

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

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini126 – 385260Protein kinase
Add
BLAST
Domaini373 – 44876SH3
Add
BLAST
Domaini958 – 99841UBA
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 110110SAM-like domain By similarity
Add
BLAST
Regioni623 – 65230Required for interaction with SRC By similarity
Add
BLAST
Regioni632 – 6354Required for interaction with NEDD4 By similarity
Regioni733 – 876144EBD domain By similarity
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi577 – 935359Pro-rich
Add
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.
The UBA domain binds both poly- and mono-ubiquitin By similarity.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family.By similarity
Contains 1 SH3 domain.
Contains 1 UBA domain.

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000168225.
HOVERGENiHBG100429.
KOiK08886.

Family and domain databases

Gene3Di4.10.680.10. 1 hit.
InterProiIPR015116. 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]
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

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MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NITRLSHFEY VKNEDLEKIG     50
MGRPGQRRLW EAVKRRKAMC KRKSWMSKVF SGKRQEAEFP SHHSQSTFRK 100
PSPTPGGLAG EGTLQSLTCL IGEKDLRLLE KLGDGSFGVV RRGEWDAPAG 150
KTVSVAVKCL KPDVLSQPEA MDDFIREVNA MHSLDHRNLI RLYGVVLTPP 200
MKMVTELAPL GSLLDRLRKH QGHFLLGTLS RYAVQVAEGM GYLESKRFIH 250
RDLAARNLLL ATRDLVKIGD FGLMRALPQN DGHYVMQEHR KVPFAWCAPE 300
SLKTRTFSHA SDTWMFGVTL WEMFTYGQEP WIGLNGSQIL HKIDKEGERL 350
PRPEDCPQDI YNVMVQCWAH KPEDRPTFVA LRDFLLEAQP TDMRALQDFE 400
EPDKLHIQMN DVITVIEGRA ENYWWRGQNT RTLCVGPFPR NVVTSVAGLS 450
AQDISQPLQN SFIHTGHGDS DPRHCWGFPD RIDELYLGNP MDPPDLLSVE 500
LSTSRPTQHL GRMKKPTYDP VSEDPDPLSS DFKRLGLRKP ALPRGLWLAK 550
PSARVPGTKA GRSSGGEVTL IDFGEEPVAP TPRPCAPSLA QLAMDACSLL 600
DKTPPQSPTR ALPRPLHPTP VVDWDARPLP PPPAYDDVAQ DEDDFEVCSI 650
NSTLVSAGLP TGPSQGETNY AFVPEQAQLP PALEDNLFLP PQGGGQPPSS 700
AQTAEIFQAL QQECMRQLQV PTGQLTPSPT PGGDDKPQVP PRVPIPPRPT 750
RPRVGLSPAP LGEEEASRWP GPSSPPRVPP REPLSPQGSR TPSPLVPPGS 800
SPLPHRLSSS PGKTMPTTQS FASDPKYATP QVIQAPGPRA GPCILPIVRD 850
GRKVSSTHYY LLPERPPYLE RYQRFLREAQ SPEEPAALPV PPLLPPPSTP 900
APAAPTATVR PMPQAAPDPK ANFSTNNSNP GAQPPSLRAS ARLPQRGCPG 950
DGQEAARPAD KVQMLQAMVH GVTTEECQAA LRSHSWSIQR AAQYLKVEQL 1000
FGLGLRPRVE CHKVLEMFDW NLEQAGCHLL GSCGPAHHKR 1040
Length:1,040
Mass (Da):115,068
Last modified:December 7, 2004 - v1
Checksum:i0624944919F821F6
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
BC085825 mRNA. Translation: AAH85825.1 .
RefSeqi NP_001008337.1. NM_001008336.1.
UniGenei Rn.98335.

3D structure databases

ProteinModelPortali Q5U2X5.
SMRi Q5U2X5. Positions 117-388, 447-489.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 257704. 1 interaction.
STRINGi 10116.ENSRNOP00000040625.

PTM databases

PhosphoSitei Q5U2X5.

Proteomic databases

PaxDbi Q5U2X5.
PRIDEi Q5U2X5.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 303882.
KEGGi rno:303882.

Organism-specific databases

CTDi 10188.
RGDi 1305957. Tnk2.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000168225.
HOVERGENi HBG100429.
KOi K08886.

Miscellaneous databases

NextBioi 652234.

Gene expression databases

Genevestigatori Q5U2X5.

Family and domain databases

Gene3Di 4.10.680.10. 1 hit.
InterProi IPR015116. 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 ]
Pfami PF09027. 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 ]
PRINTSi PR00109. TYRKINASE.
SMARTi SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: Kidney.

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: June 11, 2014
This is version 80 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