O54967 (ACK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Activated CDC42 kinase 1
Short name=ACK-1
EC=2.7.10.2
EC=2.7.11.1

Alternative name(s):
Non-receptor protein tyrosine kinase Ack
Tyrosine kinase non-receptor protein 2

Gene names

Name:	Tnk2
Synonyms:	Ack1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1055 AA.
Sequence status	Complete.
Protein existence	Evidence 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.7 Ref.11
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Subunit structure	Homodimer. 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). 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 By similarity. Interacts with CDC42. Interacts with EGFR, and this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts (via kinase domain) with AKT1. Interacts with NEDD4 (via WW3 domain). NEDD4L and EGF promote association with NEDD4. Ref.5 Ref.7 Ref.10 Ref.11
Subcellular location	Cell membrane. Nucleus. Endosome. Cell junction › adherens junction. Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasmic vesicle › clathrin-coated vesicle By similarity. Membrane › clathrin-coated pit By similarity. Note: The Tyr-284 phosphorylated form is found both in the membrane and nucleus. Co-localizes with EGFR on endosomes. Nuclear translocation is CDC42-dependent. Ref.1 Ref.7 Ref.8 Ref.11 Ref.12
Tissue specificity	Ubiquitously present in all tissues tested. Highly expressed in the adult central nervous system (CNS); hippocampus, neocortex, and cerebellum, both at dendritic spines and presynaptic axon terminals. Levels are strongly increased during enhanced neural activity. Ref.1 Ref.5 Ref.6
Developmental stage	Highly expressed at E14-E16 in the forebrain, in the proliferative ventricular zone of the neocortex and hippocampus, and in the cortical and hippocampal plates. Also observed in the septal area, the ganglionic eminence, and in the dorsal thalamus and hypothalamus. In the hindbrain, expressed in many nuclei in the brain stem and in the cerebellar anlage, external granule cell layer, in Purkinje cells and the deep cerebellar nuclei. Ref.5 Ref.6
Induction	Down-regulated by EGF. Ref.10
Domain	The EBD (EGFR-binding domain) domain is necessary for interaction with EGFR. Ref.7 Ref.10 The SAM-like domain is necessary for NEDD4-mediated ubiquitination. Promotes membrane localization and dimerization to allow for autophosphorylation. Ref.7 Ref.10 The UBA domain binds both poly- and mono-ubiquitin. Ref.7 Ref.10
Post-translational modification	Autophosphorylation regulates kinase activity. Phosphorylation on Tyr-533 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.
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 AAH31168.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.

Ontologies

Keywords
Biological process	Endocytosis
Cellular component	Cell junction Cell membrane Coated pit Cytoplasmic vesicle Endosome Membrane Nucleus
Coding sequence diversity	Alternative splicing
Domain	SH3 domain
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	endocytosis Inferred from electronic annotation. Source: UniProtKB-KW phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	adherens junction Inferred from electronic annotation. Source: UniProtKB-SubCell axon Inferred from direct assay Ref.5. Source: MGI clathrin-coated vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell coated pit Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell dendrite Inferred from direct assay Ref.5. Source: MGI endosome Inferred from direct assay Ref.7. Source: UniProtKB growth cone Inferred from direct assay Ref.5. Source: MGI neuronal cell body Inferred from direct assay Ref.5. Source: MGI nucleus Inferred from direct assay Ref.11. Source: UniProtKB plasma membrane Inferred from direct assay Ref.11. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O54967-1)

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: O54967-2)

The sequence of this isoform differs from the canonical sequence as follows:
     515-531: REPPPRPPQPAIFTQKT → KP
     980-1011: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: O54967-3)

The sequence of this isoform differs from the canonical sequence as follows:
     515-531: REPPPRPPQPAIFTQKT → KP

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1055	1055	Activated CDC42 kinase 1		PRO_0000088059
Regions
	Domain	126 – 385	260	Protein kinase
	Domain	386 – 448	63	SH3
	Domain	454 – 466	13	CRIB
	Domain	973 – 1013	41	UBA
	Nucleotide binding	132 – 140	9	ATP By similarity
	Region	1 – 110	110	SAM-like domain
	Region	638 – 667	30	Required for interaction with SRC
	Region	647 – 650	4	Required for interaction with NEDD4
	Region	748 – 891	144	EBD domain
	Compositional bias	517 – 950	434	Pro-rich
Sites
	Active site	252	1	Proton acceptor By similarity
	Binding site	158	1	ATP
Amino acid modifications
	Modified residue	284	1	Phosphotyrosine; by SRC and autocatalysis By similarity
	Modified residue	533	1	Phosphotyrosine Ref.9 Ref.12
	Modified residue	842	1	Phosphotyrosine By similarity
	Modified residue	874	1	Phosphotyrosine Ref.9
	Modified residue	887	1	Phosphotyrosine By similarity
	Modified residue	896	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	515 – 531	17	REPPP…FTQKT → KP in isoform 2 and isoform 3.		VSP_008657
	Alternative sequence	980 – 1011	32	Missing in isoform 2.		VSP_008658
Experimental info
	Mutagenesis	158	1	K → A: Loss of kinase activity. Ref.1
	Mutagenesis	424	1	W → K: Increase in autophosphorylation activity. Ref.1
	Mutagenesis	464	1	H → D: Loss of CDC42-binding and impairment of autophosphorylation. Ref.1
	Mutagenesis	650	1	Y → A: Loss of interaction with NEDD4 and drastic reduction in its ubiquitination. Ref.7
	Sequence conflict	57 – 58	2	RR → SG in AAC04786. Ref.2
	Sequence conflict	531	1	T → P in ABG46266. Ref.1
	Sequence conflict	574	1	K → E in ABG46266. Ref.1
	Sequence conflict	649	1	A → V in AAC04786. Ref.2
	Sequence conflict	818	1	L → V in BAC40063. Ref.3
	Sequence conflict	955	1	A → T in AAH52421. Ref.2
	Sequence conflict	955	1	A → T in BAC40063. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 4, 2007. Version 2. Checksum: 4A029C67C350B89A	FASTA	1,055	116,975
	10 20 30 40 50 60 MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NITRLSHFEY VKNEDLEKIG MGRPGQRRLW 70 80 90 100 110 120 EAVKRRKAMC KRKSWMSKVF SGKRLEAEFP SQHSQSTFRK PSPTPGSLPG EGTLQSLTCL 130 140 150 160 170 180 IGEKDLRLLE KLGDGSFGVV RRGEWDAPAG KTVSVAVKCL KPDVLSQPEA MDDFIREVNA 190 200 210 220 230 240 MHSLDHRNLI RLYGVVLTLP MKMVTELAPL GSLLDRLRKH QGHFLLGTLS RYAVQVAEGM 250 260 270 280 290 300 AYLESKRFIH 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 LSTSRPTQHL GRVKREPPPR PPQPAIFTQK TTYDPVSEDP 550 560 570 580 590 600 DPLSSDFKRL GLRKPALPRG LWLAKPSARV PGTKADRSSG GEVTLIDFGE EPVVPTPRPC 610 620 630 640 650 660 APSLAQLAMD ACSLLDKTPP QSPTRALPRP LHPTPVVDWD ARPLPPPPAY DDVAQDEDDF 670 680 690 700 710 720 EVCSINSTLV GAGLPAGPSQ GETNYAFVPE QAQMPPALED NLFLPPQGGG KPPSSVQTAE 730 740 750 760 770 780 IFQALQQECM RQLQVPTGQL TPSPTPGGDD KPQVPPRVPI PPRPTRPRVE LSPAPSGEEE 790 800 810 820 830 840 TSRWPGPASP PRVPPREPLS PQGSRTPSPL VPPGSSPLPH RLSSSPGKTM PTTQSFASDP 850 860 870 880 890 900 KYATPQVIQA PGPRAGPCIL PIVRDGRKVS STHYYLLPER PPYLERYQRF LREAQSPEEP 910 920 930 940 950 960 AALPVPPLLP PPSTPAPAAP TATVRPMPQA APDPKANFST NNSNPGARPP SLRAAARLPQ 970 980 990 1000 1010 1020 RGCPGDGQEA ARPADKVQML QAMVHGVTTE ECQAALQSHS WSVQRAAQYL KVEQLFGLGL 1030 1040 1050 RPRVECHKVL EMFDWNLEQA GCHLLGSCGP AHHKR
	Isoform 2 [UniParc]. Checksum: 09718C0B88D4F2D1	FASTA	1,008	111,704
	10 20 30 40 50 60 MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NITRLSHFEY VKNEDLEKIG MGRPGQRRLW 70 80 90 100 110 120 EAVKRRKAMC KRKSWMSKVF SGKRLEAEFP SQHSQSTFRK PSPTPGSLPG EGTLQSLTCL 130 140 150 160 170 180 IGEKDLRLLE KLGDGSFGVV RRGEWDAPAG KTVSVAVKCL KPDVLSQPEA MDDFIREVNA 190 200 210 220 230 240 MHSLDHRNLI RLYGVVLTLP MKMVTELAPL GSLLDRLRKH QGHFLLGTLS RYAVQVAEGM 250 260 270 280 290 300 AYLESKRFIH 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 LSTSRPTQHL GRVKKPTYDP VSEDPDPLSS DFKRLGLRKP 550 560 570 580 590 600 ALPRGLWLAK PSARVPGTKA DRSSGGEVTL IDFGEEPVVP TPRPCAPSLA QLAMDACSLL 610 620 630 640 650 660 DKTPPQSPTR ALPRPLHPTP VVDWDARPLP PPPAYDDVAQ DEDDFEVCSI NSTLVGAGLP 670 680 690 700 710 720 AGPSQGETNY AFVPEQAQMP PALEDNLFLP PQGGGKPPSS VQTAEIFQAL QQECMRQLQV 730 740 750 760 770 780 PTGQLTPSPT PGGDDKPQVP PRVPIPPRPT RPRVELSPAP SGEEETSRWP GPASPPRVPP 790 800 810 820 830 840 REPLSPQGSR TPSPLVPPGS SPLPHRLSSS PGKTMPTTQS FASDPKYATP QVIQAPGPRA 850 860 870 880 890 900 GPCILPIVRD GRKVSSTHYY LLPERPPYLE RYQRFLREAQ SPEEPAALPV PPLLPPPSTP 910 920 930 940 950 960 APAAPTATVR PMPQAAPDPK ANFSTNNSNP GARPPSLRAA ARLPQRGCPG DGQEAARPAD 970 980 990 1000 KVQMVEQLFG LGLRPRVECH KVLEMFDWNL EQAGCHLLGS CGPAHHKR
	Isoform 3 [UniParc]. Checksum: A2401DAFB05715E0	FASTA	1,040	115,258
	10 20 30 40 50 60 MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NITRLSHFEY VKNEDLEKIG MGRPGQRRLW 70 80 90 100 110 120 EAVKRRKAMC KRKSWMSKVF SGKRLEAEFP SQHSQSTFRK PSPTPGSLPG EGTLQSLTCL 130 140 150 160 170 180 IGEKDLRLLE KLGDGSFGVV RRGEWDAPAG KTVSVAVKCL KPDVLSQPEA MDDFIREVNA 190 200 210 220 230 240 MHSLDHRNLI RLYGVVLTLP MKMVTELAPL GSLLDRLRKH QGHFLLGTLS RYAVQVAEGM 250 260 270 280 290 300 AYLESKRFIH 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 LSTSRPTQHL GRVKKPTYDP VSEDPDPLSS DFKRLGLRKP 550 560 570 580 590 600 ALPRGLWLAK PSARVPGTKA DRSSGGEVTL IDFGEEPVVP TPRPCAPSLA QLAMDACSLL 610 620 630 640 650 660 DKTPPQSPTR ALPRPLHPTP VVDWDARPLP PPPAYDDVAQ DEDDFEVCSI NSTLVGAGLP 670 680 690 700 710 720 AGPSQGETNY AFVPEQAQMP PALEDNLFLP PQGGGKPPSS VQTAEIFQAL QQECMRQLQV 730 740 750 760 770 780 PTGQLTPSPT PGGDDKPQVP PRVPIPPRPT RPRVELSPAP SGEEETSRWP GPASPPRVPP 790 800 810 820 830 840 REPLSPQGSR TPSPLVPPGS SPLPHRLSSS PGKTMPTTQS FASDPKYATP QVIQAPGPRA 850 860 870 880 890 900 GPCILPIVRD GRKVSSTHYY LLPERPPYLE RYQRFLREAQ SPEEPAALPV PPLLPPPSTP 910 920 930 940 950 960 APAAPTATVR PMPQAAPDPK ANFSTNNSNP GARPPSLRAA ARLPQRGCPG DGQEAARPAD 970 980 990 1000 1010 1020 KVQMLQAMVH GVTTEECQAA LQSHSWSVQR AAQYLKVEQL FGLGLRPRVE CHKVLEMFDW 1030 1040 NLEQAGCHLL GSCGPAHHKR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Activation of the nonreceptor protein tyrosine kinase Ack by multiple extracellular stimuli." Galisteo M.L., Yang Y., Urena J., Schlessinger J. Proc. Natl. Acad. Sci. U.S.A. 103:9796-9801(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-158; TRP-424 AND HIS-464.
[2]	"The protein tyrosine kinase Ack is associated with and activated in vivo by CDC42Hs." Her J.-H., Bolen J.B. Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"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] (ISOFORMS 2 AND 3). Strain: C57BL/6. Tissue: Brain and Colon.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 121-1055 (ISOFORM 3). Strain: NOD. Tissue: Thymus.
[5]	"Expression, synaptic localization, and developmental regulation of Ack1/Pyk1, a cytoplasmic tyrosine kinase highly expressed in the developing and adult brain." Urena J.M., La Torre A., Martinez A., Lowenstein E., Franco N., Winsky-Sommerer R., Fontana X., Casaroli-Marano R., Ibanez-Sabio M.A., Pascual M., Del Rio J.A., de Lecea L., Soriano E. J. Comp. Neurol. 490:119-132(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDC42, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[6]	"Expression pattern of ACK1 tyrosine kinase during brain development in the mouse." La Torre A., del Rio J.A., Soriano E., Urena J.M. Gene Expr. Patterns 6:886-892(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[7]	"Activated Cdc42-associated kinase 1 is a component of EGF receptor signaling complex and regulates EGF receptor degradation." Shen F., Lin Q., Gu Y., Childress C., Yang W. Mol. Biol. Cell 18:732-742(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH EGFR, SUBCELLULAR LOCATION, DOMAIN EBD AND UBA, MUTAGENESIS OF TYR-650.
[8]	"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: SUBCELLULAR LOCATION.
[9]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-533 AND TYR-874, MASS SPECTROMETRY. Tissue: Brain.
[10]	"HECT E3 ubiquitin ligase Nedd4-1 ubiquitinates ACK and regulates epidermal growth factor (EGF)-induced degradation of EGF receptor and ACK." Lin Q., Wang J., Childress C., Sudol M., Carey D.J., Yang W. Mol. Cell. Biol. 30:1541-1554(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NEDD4 AND NEDD4L, UBIQUITINATION, INDUCTION, DOMAIN SAM-LIKE AND UBA.
[11]	"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.
[12]	"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 AND TYR-533.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	DQ666696 mRNA. Translation: ABG46266.1. AF037260 mRNA. Translation: AAC04786.1. BC031168 mRNA. Translation: AAH31168.1. Sequence problems. BC052421 mRNA. Translation: AAH52421.1. AK087965 mRNA. Translation: BAC40063.1.
IPI	IPI00119965. IPI00377737. IPI00874745.
RefSeq	NP_001103617.1. NM_001110147.1. NP_058068.2. NM_016788.3.
UniGene	Mm.251115.
3D structure databases
ProteinModelPortal	O54967.
SMR	O54967. Positions 80-416, 447-489.
ModBase	Search...
PTM databases
PhosphoSite	O54967.
Proteomic databases
PaxDb	O54967.
PRIDE	O54967.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000115125; ENSMUSP00000110778; ENSMUSG00000022791.
GeneID	51789.
KEGG	mmu:51789.
UCSC	uc007yzc.2. mouse. uc012aeo.1. mouse.
Organism-specific databases
CTD	10188.
MGI	MGI:1858308. Tnk2.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00630000089536.
HOGENOM	HOG000168225.
HOVERGEN	HBG100429.
InParanoid	O54967.
KO	K08886.
OrthoDB	EOG4Q58NQ.
Gene expression databases
ArrayExpress	O54967.
Bgee	O54967.
CleanEx	MM_TNK2.
Genevestigator	O54967.
Family and domain databases
Gene3D	4.10.680.10. 1 hit.
InterPro	IPR015116. Cdc42_binding_dom_like. 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. IPR000449. UBA/transl_elong_EF1B_N. [Graphical view]
Pfam	PF09027. GTPase_binding. 1 hit. PF11555. Inhibitor_Mig-6. 1 hit. PF07714. Pkinase_Tyr. 1 hit. PF00627. UBA. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
SMART	SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF50044. SH3. 1 hit.
PROSITE	PS50108. CRIB. False negative. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS50002. SH3. 1 hit. PS50030. UBA. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TNK2. mouse.
NextBio	308016.
SOURCE	Search...

Entry information

Entry name

ACK1_MOUSE

Accession

Primary (citable) accession number: O54967
Secondary accession number(s): Q0Z844, Q8C2U0, Q8K0K4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 24, 2003
Last sequence update:	December 4, 2007
Last modified:	May 1, 2013
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program