Descriptions

Ack1 belongs to a family of nonreceptor tyrosine kinases. Ack1 is a 120-kDa protein with an N-terminal sterile α-motif (SAM) domain, a kinase domain, an SH3 domain, and a Cdc42-binding domain (CRIB). The large C-terminal portion of Ack1 contains several proline-rich sequences as well as a clathrin-binding motif, a ubiquitin-binding domain, and a region homologous to Mig6. The C-terminal Mig6 homology region (803-880) participates in inhibitory intramolecular interactions with the kinase domain.<br>The addition of Cdc42 (ligand for CRIB domain) or poly-proline peptides (ligands for SH3 domain) did not activate the purified construct of Ack1 in vitro. However, in cells expressing full-length Ack1, the co-expression of Cdc42 did activate Ack1

Autoinhibitory domains (AIDs)

Target domain

126-385 (Protein kinase domain)

Relief mechanism

Partner binding

Assay

Accessory elements

269-295 (Activation loop from InterPro)

Target domain

126-385 (Protein kinase domain)

Relief mechanism

Assay

Autoinhibited structure

Activated structure

1 structures for O54967

Entry ID Method Resolution Chain Position Source
AF-O54967-F1 Predicted AlphaFoldDB

No variants for O54967

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for O54967

No associated diseases with O54967

10 regional properties for O54967

Type Name Position InterPro Accession
domain Protein kinase domain 126 - 385 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 127 - 384 IPR001245
domain SH3 domain 388 - 448 IPR001452
active_site Tyrosine-protein kinase, active site 248 - 260 IPR008266
domain Cdc42 binding domain-like 450 - 514 IPR015116
binding_site Protein kinase, ATP binding site 132 - 158 IPR017441
domain Tyrosine-protein kinase, catalytic domain 126 - 385 IPR020635
domain Mig-6 domain 790 - 852 IPR021619
domain Activated CDC42 kinase 1, UBA domain 976 - 1019 IPR030220
domain TNK(ACK)-like non-receptor tyrosine-protein kinases, SAM domain 6 - 67 IPR049587

Functions

Description
EC Number 2.7.10.2 Protein-tyrosine kinases
Subcellular Localization
  • Cell membrane
  • Nucleus
  • Endosome
  • Cell junction, adherens junction
  • Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side
  • Cytoplasmic vesicle, clathrin-coated vesicle
  • Membrane, clathrin-coated pit
  • Cytoplasm, cytosol
  • The Tyr-284 phosphorylated form is found both in the membrane and nucleus (PubMed:20333297)
  • Co-localizes with EGFR on endosomes (PubMed:17182860)
  • Nuclear translocation is CDC42-dependent (PubMed:21169560)
  • Detected in long filamentous cytosolic structures where it co-localizes with CTPS1 (PubMed:25223282)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

13 GO annotations of cellular component

Name Definition
adherens junction A cell-cell junction composed of the epithelial cadherin-catenin complex. The epithelial cadherins, or E-cadherins, of each interacting cell extend through the plasma membrane into the extracellular space and bind to each other. The E-cadherins bind to catenins on the cytoplasmic side of the membrane, where the E-cadherin-catenin complex binds to cytoskeletal components and regulatory and signaling molecules.
axon The long process of a neuron that conducts nerve impulses, usually away from the cell body to the terminals and varicosities, which are sites of storage and release of neurotransmitter.
clathrin-coated pit A part of the endomembrane system in the form of an invagination of a membrane upon which a clathrin coat forms, and that can be converted by vesicle budding into a clathrin-coated vesicle. Coated pits form on the plasma membrane, where they are involved in receptor-mediated selective transport of many proteins and other macromolecules across the cell membrane, in the trans-Golgi network, and on some endosomes.
clathrin-coated vesicle A vesicle with a coat formed of clathrin connected to the membrane via one of the clathrin adaptor complexes.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytoplasmic vesicle membrane The lipid bilayer surrounding a cytoplasmic vesicle.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
dendrite A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body.
endosome A vacuole to which materials ingested by endocytosis are delivered.
growth cone The migrating motile tip of a growing neuron projection, where actin accumulates, and the actin cytoskeleton is the most dynamic.
neuronal cell body The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

8 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
metal ion binding Binding to a metal ion.
non-membrane spanning protein tyrosine kinase activity Catalysis of the reaction
protein serine kinase activity Catalysis of the reactions
protein serine/threonine kinase activity Catalysis of the reactions
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions
protein tyrosine kinase activity Catalysis of the reaction
WW domain binding Binding to a WW domain of a protein, a small module composed of 40 amino acids and plays a role in mediating protein-protein interactions via proline-rich regions.

6 GO annotations of biological process

Name Definition
endocytosis A vesicle-mediated transport process in which cells take up external materials or membrane constituents by the invagination of a part of the plasma membrane to form a new membrane-bounded vesicle.
negative regulation of epidermal growth factor receptor signaling pathway Any process that stops, prevents, or reduces the frequency, rate or extent of epidermal growth factor receptor signaling pathway activity.
phosphorylation The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.
regulation of keratinocyte differentiation Any process that modulates the frequency, rate or extent of keratinocyte differentiation.
signal transduction The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.
spermatid development The process whose specific outcome is the progression of a spermatid over time, from its formation to the mature structure.

29 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q17R13 TNK2 Activated CDC42 kinase 1 Bos taurus (Bovine) SS
Q13470 TNK1 Non-receptor tyrosine-protein kinase TNK1 Homo sapiens (Human) PR
Q07912 TNK2 Activated CDC42 kinase 1 Homo sapiens (Human) EV
P48025 Syk Tyrosine-protein kinase SYK Mus musculus (Mouse) SS
P43404 Zap70 Tyrosine-protein kinase ZAP-70 Mus musculus (Mouse) SS
Q64434 Ptk6 Protein-tyrosine kinase 6 Mus musculus (Mouse) SS
P14234 Fgr Tyrosine-protein kinase Fgr Mus musculus (Mouse) SS
P25911 Lyn Tyrosine-protein kinase Lyn Mus musculus (Mouse) EV
P39688 Fyn Tyrosine-protein kinase Fyn Mus musculus (Mouse) SS
P05480 Src Proto-oncogene tyrosine-protein kinase Src Mus musculus (Mouse) EV
P06240 Lck Proto-oncogene tyrosine-protein kinase LCK Mus musculus (Mouse) SS
P16277 Blk Tyrosine-protein kinase Blk Mus musculus (Mouse) SS
P08103 Hck Tyrosine-protein kinase HCK Mus musculus (Mouse) SS
Q04736 Yes1 Tyrosine-protein kinase Yes Mus musculus (Mouse) SS
Q922K9 Frk Tyrosine-protein kinase FRK Mus musculus (Mouse) SS
Q03526 Itk Tyrosine-protein kinase ITK/TSK Mus musculus (Mouse) SS
P35991 Btk Tyrosine-protein kinase BTK Mus musculus (Mouse) EV
P24604 Tec Tyrosine-protein kinase Tec Mus musculus (Mouse) SS
P41242 Matk Megakaryocyte-associated tyrosine-protein kinase Mus musculus (Mouse) SS
P41241 Csk Tyrosine-protein kinase CSK Mus musculus (Mouse) EV
Q9QVP9 Ptk2b Protein-tyrosine kinase 2-beta Mus musculus (Mouse) PR
P34152 Ptk2 Focal adhesion kinase 1 Mus musculus (Mouse) SS
Q99ML2 Tnk1 Non-receptor tyrosine-protein kinase TNK1 Mus musculus (Mouse) PR
P70451 Fer Tyrosine-protein kinase Fer Mus musculus (Mouse) PR
Q6J9G1 Styk1 Tyrosine-protein kinase STYK1 Mus musculus (Mouse) PR
P00520 Abl1 Tyrosine-protein kinase ABL1 Mus musculus (Mouse) EV
Q62270 Srms Tyrosine-protein kinase Srms Mus musculus (Mouse) SS
Q4JIM5 Abl2 Tyrosine-protein kinase ABL2 Mus musculus (Mouse) SS
Q5U2X5 Tnk2 Activated CDC42 kinase 1 Rattus norvegicus (Rat) SS
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