EKS-HOS-00352

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00352

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Ack	453.2	1.2E-135	127	385	259

Status

Reviewed

Ensembl Protein

ENSP00000323216

UniProt Accession

Q07912; Q6ZMQ0; Q8N6U7; Q96H59;

Protein Name

Activated CDC42 kinase 1

Protein Synonyms/Alias

ACK-1; Tyrosine kinase non-receptor protein 2;

Gene Name

TNK2

Gene Synonyms/Alias

TNK2; ACK1;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000061938	ENSP00000376201	ENST00000392400
ENSG00000061938	ENSP00000392253	ENST00000438207
ENSG00000061938	ENSP00000393707	ENST00000447060
ENSG00000061938	ENSP00000415126	ENST00000411741
ENSG00000061938	ENSP00000392546	ENST00000428187
ENSG00000061938	ENSP00000398614	ENST00000416152
ENSG00000061938	ENSP00000329425	ENST00000333602
ENSG00000061938	ENSP00000323216	ENST00000316664
ENSG00000061938	ENSP00000390435	ENST00000424563
ENSG00000061938	ENSP00000395154	ENST00000433111
ENSG00000061938	ENSP00000395588	ENST00000439230
ENSG00000061938	ENSP00000371341	ENST00000381916
ENSG00000061938	ENSP00000390088	ENST00000427576
ENSG00000061938	ENSP00000409462	ENST00000430929

Organism

Homo sapiens

Functional Description

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.

Protein Length

528

Protein Sequence
(FASTA)

MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NVTRLSHFEY VKNEDLEKIG MGRPGQRRLW 60

EAVKRRKALC KRKSWMSKVF SGKRLEAEFP PHHSQSTFRK TSPAPGGPAG EGPLQSLTCL 120

IGEKDLRLLE KLGDGSFGVV RRGEWDAPSG KTVSVAVKCL KPDVLSQPEA MDDFIREVNA 180

MHSLDHRNLI RLYGVVLTPP MKMVTELAPL GSLLDRLRKH QGHFLLGTLS RYAVQVAEGM 240

GYLESKRFIH RDLAARNLLL ATRDLVKIGD FGLMRALPQN DDHYVMQEHR KVPFAWCAPE 300

SLKTRTFSHA SDTWMFGVTL WEMFTYGQEP WIGLNGSQIL HKIDKEGERL PRPEDCPQDI 360

YNVMVQCWAH KPEDRPTFVA LRDFLLEAQP TDMRALQDFE EPDKLHIQMN DVITVIEGRA 420

ENYWWRGQNT RTLCVGPFPR NVVTSVAGLS AQDISQPLQN SFIHTGHGDS DPRHCWGFPD 480

RIDECPFSAF SPGHPPAETC GQVLWTGRRE ACASDPRLHP VSSRTKGL 528

Nucleotide Sequence
(FASTA)

ATGCAGCCAG AGGAGGGCAC AGGCTGGCTG CTGGAGCTGC TGTCCGAGGT GCAGCTGCAA 60

CAGTACTTCC TGCGGCTCCG AGATGACCTC AACGTCACCC GCCTGTCCCA CTTTGAGTAC 120

GTCAAGAATG AGGACCTGGA GAAGATCGGC ATGGGTCGGC CTGGCCAGCG GCGGCTGTGG 180

GAGGCTGTGA AGAGGAGGAA GGCCTTGTGC AAACGCAAGT CGTGGATGAG TAAGGTGTTC 240

AGTGGAAAGC GACTGGAGGC TGAGTTCCCA CCTCATCACT CTCAGAGCAC CTTCCGGAAG 300

ACCTCGCCCG CCCCTGGGGG CCCAGCAGGG GAGGGGCCCC TGCAGAGCCT CACCTGCCTC 360

ATTGGGGAGA AGGACCTGCG CCTCCTGGAG AAGCTGGGTG ATGGTTCCTT TGGCGTGGTG 420

CGCAGGGGCG AGTGGGACGC GCCCTCAGGG AAGACGGTGA GTGTGGCTGT GAAGTGCCTG 480

AAGCCCGATG TCCTGAGCCA GCCAGAAGCC ATGGACGACT TCATCCGGGA GGTCAATGCC 540

ATGCACTCGC TCGACCACCG AAACCTCATC CGCCTCTACG GGGTGGTGCT CACGCCGCCC 600

ATGAAGATGG TGACAGAGCT GGCACCTCTG GGATCGTTGT TGGACCGGCT ACGTAAGCAC 660

CAGGGCCACT TCCTCCTGGG GACTCTGAGC CGCTACGCTG TGCAGGTGGC TGAGGGCATG 720

GGCTACCTGG AGTCCAAGCG CTTTATTCAC CGTGACCTGG CTGCCCGCAA TCTGCTGTTG 780

GCTACCCGCG ACCTGGTCAA GATCGGGGAC TTTGGGCTGA TGCGAGCACT ACCTCAGAAT 840

GACGACCATT ACGTCATGCA GGAACATCGC AAGGTGCCCT TCGCCTGGTG TGCCCCCGAG 900

AGCCTGAAGA CACGCACCTT CTCCCATGCC AGCGACACCT GGATGTTCGG GGTGACACTG 960

TGGGAAATGT TCACCTACGG CCAGGAGCCC TGGATCGGCC TCAACGGCAG TCAGATCCTG 1020

CATAAGATCG ACAAGGAGGG GGAGCGGCTG CCCCGGCCCG AGGACTGTCC CCAGGACATC 1080

TACAACGTCA TGGTCCAGTG CTGGGCTCAC AAGCCAGAGG ACAGACCCAC GTTTGTGGCC 1140

CTGCGGGACT TCCTGCTGGA GGCCCAGCCC ACAGACATGC GGGCCCTTCA GGACTTTGAG 1200

GAACCGGACA AGCTGCACAT CCAGATGAAT GATGTCATCA CCGTCATCGA GGGAAGGGCC 1260

GAGAACTACT GGTGGCGTGG CCAGAACACA CGGACGCTGT GTGTGGGGCC CTTCCCTCGC 1320

AACGTGGTGA CCTCCGTGGC CGGCCTGTCG GCCCAGGACA TCAGCCAGCC CCTGCAGAAC 1380

AGCTTCATCC ACACAGGGCA TGGCGACAGT GACCCCCGCC ACTGCTGGGG CTTCCCGGAC 1440

AGGATTGACG AGTGTCCTTT CTCTGCCTTC TCTCCAGGAC ACCCCCCAGC TGAGACGTGC 1500

GGTCAGGTTC TGTGGACTGG GAGGCGGGAG GCCTGTGCTT CAGACCCAAG ACTACACCCG 1560

GTTTCCTCCA GGACGAAGGG GCTCTGA 1587

Domain Profile

S: 2     klleklGeGsfgvvkrgeWsapsgksvqvavkvlksdkllstel.ddflrevsvllkleh  60

         +lleklG+Gsfgvv+rgeW+apsgk+v+vavk+lk+d+l+++e+ ddf+rev+++++l+h

Q: 127   RLLEKLGDGSFGVVRRGEWDAPSGKTVSVAVKCLKPDVLSQPEAmDDFIREVNAMHSLDH  186

         789****************************************99***************

S: 61    enlvrlyGvvltqplklvtelaelgslldrlrkeakrdsllvallleyavqiaeglayle  120

         +nl+rlyGvvlt p+k+vtela+lgslldrlrk++   ++l+ +l++yavq+aeg+ yle

Q: 187   RNLIRLYGVVLTPPMKMVTELAPLGSLLDRLRKHQG--HFLLGTLSRYAVQVAEGMGYLE  244

         ***********************************9..9*********************

S: 121   skrlvhrdlaarnlllaskklvkisdfGlvralgeeedlyvlaenkkvPfaWcaPeslrt  180

         skr++hrdlaarnllla+++lvki+dfGl+ral++++d+yv++e++kvPfaWcaPesl+t

Q: 245   SKRFIHRDLAARNLLLATRDLVKIGDFGLMRALPQNDDHYVMQEHRKVPFAWCAPESLKT  304

         ************************************************************

S: 181   rkfssasdvWafGvtlWemfsyGeePWvglsglqilkkidkekerlekPeacpediysll  240

         r+fs+asd+W+fGvtlWemf+yG+ePW+gl+g+qil+kidke+erl++Pe+cp+diy+++

Q: 305   RTFSHASDTWMFGVTLWEMFTYGQEPWIGLNGSQILHKIDKEGERLPRPEDCPQDIYNVM  364

         ************************************************************

S: 241   lkcWakkpadrpkfsalkekl  261

         ++cWa+kp+drp+f+al+++l

Q: 365   VQCWAHKPEDRPTFVALRDFL  385

         ******************986

Domain Sequence
(FASTA)

RLLEKLGDGS FGVVRRGEWD APSGKTVSVA VKCLKPDVLS QPEAMDDFIR EVNAMHSLDH 60

RNLIRLYGVV LTPPMKMVTE LAPLGSLLDR LRKHQGHFLL GTLSRYAVQV AEGMGYLESK 120

RFIHRDLAAR NLLLATRDLV KIGDFGLMRA LPQNDDHYVM QEHRKVPFAW CAPESLKTRT 180

FSHASDTWMF GVTLWEMFTY GQEPWIGLNG SQILHKIDKE GERLPRPEDC PQDIYNVMVQ 240

CWAHKPEDRP TFVALRDFL 259

Keyword

3D-structure; Alternative splicing; ATP-binding; Cell junction; Cell membrane; Coated pit; Complete proteome; Cytoplasmic vesicle; Endocytosis; Endosome; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; SH3 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Ochotona princeps"; ?>Oreochromis niloticus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005912	; C:adherens junction
GO:0030424	; C:axon
GO:0030136	; C:clathrin-coated vesicle
GO:0005905	; C:coated pit
GO:0030659	; C:cytoplasmic vesicle membrane
GO:0030425	; C:dendrite
GO:0005768	; C:endosome
GO:0070436	; C:Grb2-EGFR complex
GO:0030426	; C:growth cone
GO:0043025	; C:neuronal cell body
GO:0005634	; C:nucleus
GO:0005524	; F:ATP binding
GO:0005154	; F:epidermal growth factor receptor binding
GO:0005095	; F:GTPase inhibitor activity
GO:0046872	; F:metal ion binding
GO:0004715	; F:non-membrane spanning protein tyrosine kinase activity
GO:0004674	; F:protein serine/threonine kinase activity
GO:0004712	; F:protein serine/threonine/tyrosine kinase activity
GO:0050699	; F:WW domain binding
GO:0007166	; P:cell surface receptor signaling pathway
GO:0006897	; P:endocytosis
GO:0050731	; P:positive regulation of peptidyl-tyrosine phosphorylation
GO:2000369	; P:regulation of clathrin-mediated endocytosis
GO:0007264	; P:small GTPase mediated signal transduction

KEGG

hsa:10188

;

InterPros

IPR015116	; GTPase_binding.
IPR021619	; Inhibitor_Mig-6.
IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_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.

Pfam

PF09027	; GTPase_binding; 1.
PF11555	; Inhibitor_Mig-6; 1.
PF07714	; Pkinase_Tyr; 1.

SMARTs

SM00326	; SH3; 1.
SM00219	; TyrKc; 1.

Prosites

PS50108	; CRIB; FALSE_NEG.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00109	; PROTEIN_KINASE_TYR; 1.
PS50002	; SH3; 1.
PS50030	; UBA; FALSE_NEG.

Prints

PR00109

; TYRKINASE.

Created Date

20-Feb-2013