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Q07912 (ACK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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):
Tyrosine kinase non-receptor protein 2
Gene names
Name:TNK2
Synonyms:ACK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1038 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. Ref.6 Ref.7 Ref.11 Ref.13 Ref.15 Ref.16 Ref.19 Ref.20 Ref.24 Ref.27 Ref.28

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.35

ATP + a protein = ADP + a phosphoprotein. Ref.35

Cofactor

Magnesium.

Enzyme regulation

Inhibited by AIM-100 (4-amino-5,6-biaryl-furo[2,3-d]pyrimidine), which suppresses activating phosphorylation at Tyr-284. Repressed by dasatinib. Ref.27 Ref.29

Subunit structure

Interacts with NEDD4 (via WW3 domain). NEDD4L and EGF promote association with NEDD4 By similarity. Homodimer. Interacts with AR, CDC42, WWASL and WWOX. 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. Ref.1 Ref.5 Ref.9 Ref.10 Ref.11 Ref.15 Ref.17 Ref.18 Ref.23 Ref.24 Ref.26 Ref.28 Ref.30

Subcellular location

Cell membrane. Nucleus. Endosome. Cell junctionadherens junction By similarity. Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmic vesicleclathrin-coated vesicle. Membraneclathrin-coated pit. Note: The Tyr-284 phosphorylated form is found both in the membrane and nucleus. Colocalizes with EGFR on endosomes. Nuclear translocation is CDC42-dependent. Ref.8 Ref.10 Ref.20 Ref.26 Ref.28 Ref.31

Tissue specificity

The Tyr-284 phosphorylated form shows a significant increase in expression in breast cancers during the progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM) stages. It also shows a significant increase in expression in prostate cancers during the progressive stages. Ref.13 Ref.28 Ref.29

Domain

The EBD (EGFR-binding domain) domain is necessary for interaction with EGFR By similarity. Ref.26

The SAM-like domain is necessary for NEDD4-mediated ubiquitination. Promotes membrane localization and dimerization to allow for autophosphorylation. Ref.26

The UBA domain binds both poly- and mono-ubiquitin. Ref.26

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.

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.

Contains 1 CRIB domain.

Contains 1 protein kinase domain.

Contains 1 SH3 domain.

Contains 1 UBA domain.

Sequence caution

The sequence AAH08884.1 differs from that shown. Reason: Unlikely isoform. Aberrant splice sites.

Ontologies

Keywords
   Biological processEndocytosis
   Cellular componentCell junction
Cell membrane
Coated pit
Cytoplasmic vesicle
Endosome
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSH3 domain
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell surface receptor signaling pathway

Traceable author statement Ref.32. Source: UniProtKB

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of catalytic activity

Traceable author statement Ref.1. Source: GOC

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.35. Source: GOC

phosphorylation

Inferred from direct assay Ref.28Ref.26. Source: UniProtKB

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of clathrin-mediated endocytosis

Inferred from direct assay Ref.20. Source: UniProtKB

small GTPase mediated signal transduction

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentGrb2-EGFR complex

Inferred from direct assay PubMed 20086093. Source: BHF-UCL

adherens junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

axon

Inferred from electronic annotation. Source: Ensembl

clathrin-coated vesicle

Inferred from direct assay Ref.20. Source: UniProtKB

coated pit

Inferred from direct assay Ref.31. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.26. Source: UniProtKB

cytoplasmic vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

dendrite

Inferred from electronic annotation. Source: Ensembl

endosome

Inferred from sequence or structural similarity. Source: UniProtKB

growth cone

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.28. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.28Ref.26. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

GTPase inhibitor activity

Traceable author statement Ref.1. Source: ProtInc

WW domain binding

Inferred from sequence or structural similarity. Source: BHF-UCL

epidermal growth factor receptor binding

Inferred from direct assay PubMed 20086093. Source: BHF-UCL

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Traceable author statement Ref.1. Source: ProtInc

protein binding

Inferred from physical interaction Ref.5Ref.28. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

protein serine/threonine/tyrosine kinase activity

Inferred from direct assay Ref.11. Source: UniProtKB

protein tyrosine kinase activity

Inferred from direct assay Ref.35. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q07912-1)

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: Q07912-2)

The sequence of this isoform differs from the canonical sequence as follows:
     485-528: LYLGNPMDPP...DPVSEDQDPL → CPFSAFSPGH...HPVSSRTKGL
     529-1038: Missing.
Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 3 (identifier: Q07912-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLEARPPRTQGSDAAGAAAGRGLRALLLSLTAAAGIWGSMGERSAYQRLAGGEEGPQRLGGGRM
     514-514: K → KREPPPRPPQPAFFTQ
     965-994: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10381038Activated CDC42 kinase 1
PRO_0000088058

Regions

Domain126 – 385260Protein kinase
Domain386 – 44863SH3
Domain454 – 46613CRIB
Domain958 – 99639UBA
Nucleotide binding132 – 1409ATP
Region1 – 110110SAM-like domain
Region623 – 65230Required for interaction with SRC
Region632 – 6354Required for interaction with NEDD4 By similarity
Region733 – 876144EBD domain By similarity
Compositional bias577 – 958382Pro-rich

Sites

Active site2521Proton acceptor
Binding site1581ATP

Amino acid modifications

Modified residue2841Phosphotyrosine; by SRC and autocatalysis Ref.16 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.31 Ref.34
Modified residue5181Phosphotyrosine Ref.31
Modified residue7241Phosphoserine Ref.25
Modified residue8271Phosphotyrosine Ref.31
Modified residue8591Phosphotyrosine Ref.31
Modified residue8721Phosphotyrosine Ref.31
Modified residue8811Phosphoserine Ref.21

Natural variations

Alternative sequence11M → MLEARPPRTQGSDAAGAAAG RGLRALLLSLTAAAGIWGSM GERSAYQRLAGGEEGPQRLG GGRM in isoform 3.
VSP_037284
Alternative sequence485 – 52844LYLGN…DQDPL → CPFSAFSPGHPPAETCGQVL WTGRREACASDPRLHPVSSR TKGL in isoform 2.
VSP_008655
Alternative sequence5141K → KREPPPRPPQPAFFTQ in isoform 3.
VSP_037285
Alternative sequence529 – 1038510Missing in isoform 2.
VSP_008656
Alternative sequence965 – 99430Missing in isoform 3.
VSP_037286
Natural variant341R → L in a lung adenocarcinoma sample; somatic mutation. Ref.36
VAR_032792
Natural variant711K → R. Ref.36
Corresponds to variant rs56036945 [ dbSNP | Ensembl ].
VAR_032793
Natural variant991R → Q in an ovarian mucinous carcinoma sample; somatic mutation; undergoes autoactivation and causes phosphorylation on Tyr-284 leading to activation of AKT1. Ref.36
VAR_032794
Natural variant991R → W. Ref.36
Corresponds to variant rs3747673 [ dbSNP | Ensembl ].
VAR_032795
Natural variant1521T → M. Ref.36
Corresponds to variant rs56161912 [ dbSNP | Ensembl ].
VAR_032796
Natural variant3461E → K in an ovarian endometrioid cancer sample; somatic mutation. Ref.28 Ref.36
VAR_032797
Natural variant4091M → I in a gastric adenocarcinoma sample; somatic mutation. Ref.36
VAR_032798
Natural variant5071P → S. Ref.36
Corresponds to variant rs35759128 [ dbSNP | Ensembl ].
VAR_032799
Natural variant7251P → L. Ref.2 Ref.36
Corresponds to variant rs56260729 [ dbSNP | Ensembl ].
VAR_032800
Natural variant7481R → Q. Ref.36
Corresponds to variant rs57872314 [ dbSNP | Ensembl ].
VAR_032801
Natural variant8021P → L.
Corresponds to variant rs3749333 [ dbSNP | Ensembl ].
VAR_057115
Natural variant10381R → H. Ref.36
Corresponds to variant rs13433937 [ dbSNP | Ensembl ].
VAR_032802

Experimental info

Mutagenesis1581K → R: Loss of autophosphorylation. Ref.9
Mutagenesis4871L → F: Constantly active kinase. Ref.9
Sequence conflict1381G → V in AAH08884. Ref.4
Sequence conflict304 – 35249TRTFS…ERLPR → PPWRDISASSSTQFPHAVPC FPTSLLAKLLLRHSVPASSR EIKLVSILC in AAH08884. Ref.4
Sequence conflict353 – 1038686Missing in AAH08884. Ref.4
Sequence conflict5861A → P in AAA53570. Ref.1
Sequence conflict7221Missing in AAA53570. Ref.1
Sequence conflict838 – 8403PRA → AG in AAA53570. Ref.1

Secondary structure

.......................................................................... 1038
Helix Strand Turn

Details...

Sequences

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

Last modified May 5, 2009. Version 3.
Checksum: 74A1980665BC3E6B

FASTA1,038114,569
        10         20         30         40         50         60 
MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NVTRLSHFEY VKNEDLEKIG MGRPGQRRLW 

        70         80         90        100        110        120 
EAVKRRKALC KRKSWMSKVF SGKRLEAEFP PHHSQSTFRK TSPAPGGPAG EGPLQSLTCL 

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

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

       250        260        270        280        290        300 
GYLESKRFIH 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 
RIDELYLGNP MDPPDLLSVE LSTSRPPQHL GGVKKPTYDP VSEDQDPLSS DFKRLGLRKP 

       550        560        570        580        590        600 
GLPRGLWLAK PSARVPGTKA SRGSGAEVTL IDFGEEPVVP ALRPCAPSLA QLAMDACSLL 

       610        620        630        640        650        660 
DETPPQSPTR ALPRPLHPTP VVDWDARPLP PPPAYDDVAQ DEDDFEICSI NSTLVGAGVP 

       670        680        690        700        710        720 
AGPSQGQTNY AFVPEQARPP PPLEDNLFLP PQGGGKPPSS AQTAEIFQAL QQECMRQLQA 

       730        740        750        760        770        780 
PAGSPAPSPS PGGDDKPQVP PRVPIPPRPT RPHVQLSPAP PGEEETSQWP GPASPPRVPP 

       790        800        810        820        830        840 
REPLSPQGSR TPSPLVPPGS SPLPPRLSSS PGKTMPTTQS FASDPKYATP QVIQAPGPRA 

       850        860        870        880        890        900 
GPCILPIVRD GKKVSSTHYY LLPERPSYLE RYQRFLREAQ SPEEPTPLPV PLLLPPPSTP 

       910        920        930        940        950        960 
APAAPTATVR PMPQAALDPK ANFSTNNSNP GARPPPPRAT ARLPQRGCPG DGPEAGRPAD 

       970        980        990       1000       1010       1020 
KIQMAMVHGV TTEECQAALQ CHGWSVQRAA QYLKVEQLFG LGLRPRGECH KVLEMFDWNL 

      1030 
EQAGCHLLGS WGPAHHKR 

« Hide

Isoform 2 [UniParc].

Checksum: 6CE378AE9D186C20
Show »

FASTA52860,062
Isoform 3 [UniParc].

Checksum: 6FC37F9EFDF69D5E
Show »

FASTA1,086119,349

References

« Hide 'large scale' references
[1]"A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42."
Manser E., Leung T., Salihuddin H., Tan L., Lim L.
Nature 363:364-367(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH CDC42.
Tissue: Hippocampus.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT LEU-725.
Tissue: Brain.
[3]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] (ISOFORM 2).
Tissue: Brain and Uterus.
[5]"Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas."
Eisenmann K.M., McCarthy J.B., Simpson M.A., Keely P.J., Guan J.-L., Tachibana K., Lim L., Manser E., Furcht L.T., Iida J.
Nat. Cell Biol. 1:507-513(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CSPG4.
[6]"Activation of the guanine nucleotide exchange factor Dbl following ACK1-dependent tyrosine phosphorylation."
Kato J., Kaziro Y., Satoh T.
Biochem. Biophys. Res. Commun. 268:141-147(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS MCF2 KINASE.
[7]"The tyrosine kinase ACK1 associates with clathrin-coated vesicles through a binding motif shared by arrestin and other adaptors."
Teo M., Tan L., Lim L., Manser E.
J. Biol. Chem. 276:18392-18398(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Cdc42-dependent nuclear translocation of non-receptor tyrosine kinase, ACK."
Ahmed I., Calle Y., Sayed M.A., Kamal J.M., Rengaswamy P., Manser E., Meiners S., Nur-E-Kamal A.
Biochem. Biophys. Res. Commun. 314:571-579(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[9]"Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox."
Mahajan N.P., Whang Y.E., Mohler J.L., Earp H.S.
Cancer Res. 65:10514-10523(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPHOSPHORYLATION, INTERACTION WITH HSP90AB1; MTERK AND WWOX, MUTAGENESIS OF LYS-158 AND LEU-487.
[10]"SNX9 as an adaptor for linking synaptojanin-1 to the Cdc42 effector ACK1."
Yeow-Fong L., Lim L., Manser E.
FEBS Lett. 579:5040-5048(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SNX9, SUBCELLULAR LOCATION.
[11]"Phosphorylation of WASP by the Cdc42-associated kinase ACK1: dual hydroxyamino acid specificity in a tyrosine kinase."
Yokoyama N., Lougheed J., Miller W.T.
J. Biol. Chem. 280:42219-42226(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS WAS KINASE, INTERACTION WITH WASL.
[12]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Metastatic properties and genomic amplification of the tyrosine kinase gene ACK1."
van der Horst E.H., Degenhardt Y.Y., Strelow A., Slavin A., Chinn L., Orf J., Rong M., Li S., See L.-H., Nguyen K.Q.C., Hoey T., Wesche H., Powers S.
Proc. Natl. Acad. Sci. U.S.A. 102:15901-15906(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[14]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas."
Modzelewska K., Newman L.P., Desai R., Keely P.J.
J. Biol. Chem. 281:37527-37535(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL MIGRATION, INTERACTION WITH BCAR1; CDC42 AND CRK.
[16]"Purification and enzyme activity of ACK1."
Yokoyama N., Miller W.T.
Methods Enzymol. 406:250-260(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, AUTOPHOSPHORYLATION AT TYR-284.
[17]"Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation."
Mahajan N.P., Liu Y., Majumder S., Warren M.R., Parker C.E., Mohler J.L., Earp H.S., Whang Y.E.
Proc. Natl. Acad. Sci. U.S.A. 104:8438-8443(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AR.
[18]"Nephrocystin-1 interacts directly with Ack1 and is expressed in human collecting duct."
Eley L., Moochhala S.H., Simms R., Hildebrandt F., Sayer J.A.
Biochem. Biophys. Res. Commun. 371:877-882(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NPHP1.
[19]"TNK2 preserves epidermal growth factor receptor expression on the cell surface and enhances migration and invasion of human breast cancer cells."
Howlin J., Rosenkvist J., Andersson T.
Breast Cancer Res. 10:R36-R36(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[20]"Dysregulation of Ack1 inhibits down-regulation of the EGF receptor."
Groevdal L.M., Johannessen L.E., Roedland M.S., Madshus I.H., Stang E.
Exp. Cell Res. 314:1292-1300(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[21]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-881, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[23]"Down-regulation of active ACK1 is mediated by association with the E3 ubiquitin ligase Nedd4-2."
Chan W., Tian R., Lee Y.-F., Sit S.T., Lim L., Manser E.
J. Biol. Chem. 284:8185-8194(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NEDD4, UBIQUITINATION.
[24]"Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling."
Pao-Chun L., Chan P.M., Chan W., Manser E.
J. Biol. Chem. 284:34954-34963(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AXL; LTK; PDGFRL AND GRB2.
[25]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-284 AND SER-724, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]"Regulation of Ack1 localization and activity by the amino-terminal SAM domain."
Prieto-Echaguee V., Gucwa A., Brown D.A., Miller W.T.
BMC Biochem. 11:42-42(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-284, DOMAIN SAM-LIKE.
[27]"Dasatinib inhibits site-specific tyrosine phosphorylation of androgen receptor by Ack1 and Src kinases."
Liu Y., Karaca M., Zhang Z., Gioeli D., Earp H.S., Whang Y.E.
Oncogene 29:3208-3216(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS AR KINASE, ENZYME REGULATION.
[28]"Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation."
Mahajan K., Coppola D., Challa S., Fang B., Chen Y.A., Zhu W., Lopez A.S., Koomen J., Engelman R.W., Rivera C., Muraoka-Cook R.S., Cheng J.Q., Schoenbrunn E., Sebti S.M., Earp H.S., Mahajan N.P.
PLoS ONE 5:E9646-E9646(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AKT1, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT LYS-346, PHOSPHORYLATION AT TYR-284, TISSUE SPECIFICITY.
[29]"Effect of Ack1 tyrosine kinase inhibitor on ligand-independent androgen receptor activity."
Mahajan K., Challa S., Coppola D., Lawrence H., Luo Y., Gevariya H., Zhu W., Chen Y.A., Lawrence N.J., Mahajan N.P.
Prostate 70:1274-1285(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-284, TISSUE SPECIFICITY, ENZYME REGULATION.
[30]"The Cdc42-associated kinase ACK1 is not auto-inhibited but requires Src for activation."
Chan W., Sit S.T., Manser E.
Biochem. J. 435:355-364(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-284, INTERACTION WITH SRC.
[31]"Constitutive activated Cdc42-associated kinase (Ack) phosphorylation at arrested endocytic clathrin-coated pits of cells that lack dynamin."
Shen H., Ferguson S.M., Dephoure N., Park R., Yang Y., Volpicelli-Daley L., Gygi S., Schlessinger J., De Camilli P.
Mol. Biol. Cell 22:493-502(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-284; TYR-518; TYR-827; TYR-859 AND TYR-872.
[32]"Shepherding AKT and androgen receptor by Ack1 tyrosine kinase."
Mahajan K., Mahajan N.P.
J. Cell. Physiol. 224:327-333(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON TUMOR GROWTH.
[33]"Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK."
Mott H.R., Owen D., Nietlispach D., Lowe P.N., Manser E., Lim L., Laue E.D.
Nature 399:384-388(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 448-489.
[34]"Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1."
Lougheed J.C., Chen R.-H., Mak P., Stout T.J.
J. Biol. Chem. 279:44039-44045(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 107-395, PHOSPHORYLATION AT TYR-284.
[35]"Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors."
Kopecky D.J., Hao X., Chen Y., Fu J., Jiao X., Jaen J.C., Cardozo M.G., Liu J., Wang Z., Walker N.P., Wesche H., Li S., Farrelly E., Xiao S.H., Kayser F.
Bioorg. Med. Chem. Lett. 18:6352-6356(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 117-392 IN COMPLEX WITH INHIBITOR, CATALYTIC ACTIVITY.
[36]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LEU-34; ARG-71; GLN-99; TRP-99; MET-152; LYS-346; ILE-409; SER-507; LEU-725; GLN-748 AND HIS-1038.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L13738 mRNA. Translation: AAA53570.2.
AK131539 mRNA. Translation: BAD18675.1.
AC124944 Genomic DNA. No translation available.
BC008884 mRNA. Translation: AAH08884.1. Sequence problems.
BC028164 mRNA. Translation: AAH28164.1.
CCDSCCDS33927.1. [Q07912-3]
CCDS33928.1. [Q07912-1]
PIRS33596.
RefSeqNP_001010938.1. NM_001010938.1. [Q07912-3]
NP_005772.3. NM_005781.4. [Q07912-1]
UniGeneHs.518513.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CF4NMR-B448-489[»]
1U46X-ray2.00A/B109-395[»]
1U4DX-ray2.10A/B109-395[»]
1U54X-ray2.80A/B109-395[»]
3EQPX-ray2.30A/B117-392[»]
3EQRX-ray2.00A/B117-392[»]
4EWHX-ray2.50A/B117-391[»]
4HZRX-ray1.31A/B115-389[»]
4HZSX-ray3.23A/B/C/D115-453[»]
4ID7X-ray3.00A117-389[»]
ProteinModelPortalQ07912.
SMRQ07912. Positions 81-489.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115485. 50 interactions.
DIPDIP-33858N.
IntActQ07912. 19 interactions.
MINTMINT-1382124.
STRING9606.ENSP00000371341.

Chemistry

BindingDBQ07912.
ChEMBLCHEMBL4599.
DrugBankDB00171. Adenosine triphosphate.
GuidetoPHARMACOLOGY2246.

PTM databases

PhosphoSiteQ07912.

Polymorphism databases

DMDM229462980.

Proteomic databases

MaxQBQ07912.
PaxDbQ07912.
PRIDEQ07912.

Protocols and materials databases

DNASU10188.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000316664; ENSP00000323216; ENSG00000061938. [Q07912-2]
ENST00000333602; ENSP00000329425; ENSG00000061938. [Q07912-1]
ENST00000381916; ENSP00000371341; ENSG00000061938. [Q07912-3]
ENST00000392400; ENSP00000376201; ENSG00000061938. [Q07912-1]
ENST00000439230; ENSP00000395588; ENSG00000061938. [Q07912-2]
GeneID10188.
KEGGhsa:10188.
UCSCuc003fvt.1. human. [Q07912-3]
uc003fvu.1. human. [Q07912-1]

Organism-specific databases

CTD10188.
GeneCardsGC03M195590.
H-InvDBHIX0003961.
HGNCHGNC:19297. TNK2.
HPACAB009948.
HPA041954.
MIM606994. gene.
neXtProtNX_Q07912.
Orphanet391316. Infantile-onset mesial temporal lobe epilepsy with severe cognitive regression.
PharmGKBPA134909759.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000168225.
HOVERGENHBG100429.
KOK08886.
OMAVRPMPQA.
OrthoDBEOG71G9T3.
PhylomeDBQ07912.
TreeFamTF316643.

Enzyme and pathway databases

SignaLinkQ07912.

Gene expression databases

ArrayExpressQ07912.
BgeeQ07912.
CleanExHS_TNK2.
GenevestigatorQ07912.

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_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]
PfamPF09027. GTPase_binding. 1 hit.
PF11555. Inhibitor_Mig-6. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTNK2. human.
EvolutionaryTraceQ07912.
GeneWikiTNK2.
GenomeRNAi10188.
NextBio38556.
PROQ07912.
SOURCESearch...

Entry information

Entry nameACK1_HUMAN
AccessionPrimary (citable) accession number: Q07912
Secondary accession number(s): Q6ZMQ0, Q8N6U7, Q96H59
Entry history
Integrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: May 5, 2009
Last modified: July 9, 2014
This is version 152 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM