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Q17R13

- ACK1_BOVIN

UniProt

Q17R13 - ACK1_BOVIN

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Protein

Activated CDC42 kinase 1

Gene

TNK2

Organism
Bos taurus (Bovine)
Status
Reviewed - 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 similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.By similarity1 PublicationPROSITE-ProRule annotation
ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei158 – 1581ATPBy similarityPROSITE-ProRule annotation
Active sitei252 – 2521Proton acceptorBy similarityPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi132 – 1409ATPBy similarityPROSITE-ProRule annotation

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

GO - Biological processi

  1. endocytosis Source: UniProtKB-KW
  2. 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):
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
ProteomesiUP000009136: Unplaced

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 both in the membrane and nucleus. Co-localizes with EGFR on the endosomes. Nuclear translocation is CDC42-dependent (By similarity).By similarity

GO - Cellular componenti

  1. cell junction Source: UniProtKB-KW
  2. coated pit Source: UniProtKB-KW
  3. cytoplasm Source: UniProtKB
  4. cytoplasmic vesicle Source: UniProtKB-KW
  5. endosome Source: UniProtKB
  6. nucleus Source: UniProtKB
  7. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi158 – 1581K → R: Abolishes enzyme activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10391039Activated CDC42 kinase 1PRO_0000312829Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei284 – 2841Phosphotyrosine; by SRC and autocatalysisBy similarity
Modified residuei518 – 5181PhosphotyrosineBy similarity
Modified residuei723 – 7231PhosphoserineBy similarity
Modified residuei826 – 8261PhosphotyrosineBy similarity
Modified residuei858 – 8581PhosphotyrosineBy similarity
Modified residuei871 – 8711PhosphotyrosineBy similarity
Modified residuei880 – 8801PhosphoserineBy 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

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.

Protein-protein interaction databases

IntActiQ17R13. 4 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ17R13.
SMRiQ17R13. 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
Domaini957 – 99741UBASequence AnalysisAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 110110SAM-like domainBy similarityAdd
BLAST
Regioni622 – 65130Required for interaction with SRCBy similarityAdd
BLAST
Regioni631 – 6344Required for interaction with NEDD4By similarity
Regioni732 – 875144EBD domainBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi576 – 918343Pro-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.By similarityPROSITE-ProRule annotation
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.
InParanoidiQ17R13.
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.
IPR009060. UBA-like.
IPR015940. UBA/transl_elong_EF1B_N_euk.
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.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
SSF50044. 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. Align

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti203 – 2031T → M in AAC05310. (PubMed:9312079)Curated
Sequence conflicti534 – 5341R → K in AAC05310. (PubMed:9312079)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei514 – 5141K → KREPPPRPPQPAIFTQ in isoform 2. 1 PublicationVSP_038165
Alternative sequencei814 – 85643MPTTQ…KVSST → ENYVQNFKNLTAHHPPWRDQ DTGTGSSRGPTVLSPECGRE TPF in isoform 2. 1 PublicationVSP_038166Add
BLAST
Alternative sequencei857 – 1039183Missing in isoform 2. 1 PublicationVSP_038167Add
BLAST

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 .
RefSeqi NP_776310.2. NM_173885.3. [Q17R13-1 ]
UniGenei Bt.64988.

3D structure databases

ProteinModelPortali Q17R13.
SMRi Q17R13. Positions 117-388, 447-489.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q17R13. 4 interactions.

Proteomic databases

PRIDEi Q17R13.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 280710.
KEGGi bta:280710.

Organism-specific databases

CTDi 10188.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000168225.
HOVERGENi HBG100429.
InParanoidi Q17R13.
KOi K08886.

Miscellaneous databases

NextBioi 20804889.

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.
IPR009060. UBA-like.
IPR015940. UBA/transl_elong_EF1B_N_euk.
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.
SM00165. UBA. 1 hit.
[Graphical view ]
SUPFAMi SSF46934. SSF46934. 1 hit.
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

« Hide 'large scale' publications
  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: HerefordImported.
    Tissue: HypothalamusImported.
  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.

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 26, 2014
This is version 79 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