Q5U2X5

SS
Gene name
Tnk2 (Ack1)
Protein name
Activated CDC42 kinase 1
Names
ACK-1 , EC 2.7.10.2 , EC 2.7.11.1 , Tyrosine kinase non-receptor protein 2
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:303882
EC number
2.7.10.2: Protein-tyrosine kinases
Protein Class

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)

803-880 (Mig6 homology region) SS

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

References

Autoinhibited structure

Activated structure

1 structures for Q5U2X5

Entry ID Method Resolution Chain Position Source
AF-Q5U2X5-F1 Predicted AlphaFoldDB

No variants for Q5U2X5

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q5U2X5

No associated diseases with Q5U2X5

10 regional properties for Q5U2X5

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 - 513 IPR015116
binding_site Protein kinase, ATP binding site 132 - 158 IPR017441
domain Tyrosine-protein kinase, catalytic domain 126 - 385 IPR020635
domain Mig-6 domain 775 - 837 IPR021619
domain Activated CDC42 kinase 1, UBA domain 961 - 1004 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
  • Co-localizes with EGFR on endosomes
  • Nuclear translocation is CDC42-dependent
  • Detected in long filamentous cytosolic structures where it co-localizes with CTPS1
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

15 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.
cytoophidium A subcellular filamentary structure where CTP synthase is compartmentalized in a range of organisms including bacteria, yeast, fruit fly, rat and human.
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.
Grb2-EGFR complex A protein complex that contains the epidermal growth factor receptor (EGFR) and Grb2, and is involved in linking EGFR activation to the p21-Ras pathway.
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.

11 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
epidermal growth factor receptor binding Binding to an epidermal growth factor receptor.
identical protein binding Binding to an identical protein or proteins.
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
ubiquitin protein ligase binding Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.
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.

8 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.
positive regulation of peptidyl-tyrosine phosphorylation Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-tyrosine.
regulation of clathrin-dependent endocytosis Any process that modulates the frequency, rate or extent of clathrin-mediated endocytosis.
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.

19 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
Q99ML2 Tnk1 Non-receptor tyrosine-protein kinase TNK1 Mus musculus (Mouse) PR
O54967 Tnk2 Activated CDC42 kinase 1 Mus musculus (Mouse) SS
Q64725 Syk Tyrosine-protein kinase SYK Rattus norvegicus (Rat) SS
Q6P6U0 Fgr Tyrosine-protein kinase Fgr Rattus norvegicus (Rat) SS
Q07014 Lyn Tyrosine-protein kinase Lyn Rattus norvegicus (Rat) SS
Q62844 Fyn Tyrosine-protein kinase Fyn Rattus norvegicus (Rat) SS
Q9WUD9 Src Proto-oncogene tyrosine-protein kinase Src Rattus norvegicus (Rat) SS
P50545 Hck Tyrosine-protein kinase HCK Rattus norvegicus (Rat) SS
F1LM93 Yes1 Tyrosine-protein kinase Yes Rattus norvegicus (Rat) SS
Q62662 Frk Tyrosine-protein kinase FRK Rattus norvegicus (Rat) SS
P41243 Matk Megakaryocyte-associated tyrosine-protein kinase Rattus norvegicus (Rat) SS
P32577 Csk Tyrosine-protein kinase CSK Rattus norvegicus (Rat) SS
P70600 Ptk2b Protein-tyrosine kinase 2-beta Rattus norvegicus (Rat) PR
O35346 Ptk2 Focal adhesion kinase 1 Rattus norvegicus (Rat) SS
Q01621 Lck Proto-oncogene tyrosine-protein kinase LCK Rattus norvegicus (Rat) SS
P09760 Fer Tyrosine-protein kinase Fer Rattus norvegicus (Rat) PR
10 20 30 40 50 60
MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NITRLSHFEY VKNEDLEKIG MGRPGQRRLW
70 80 90 100 110 120
EAVKRRKAMC KRKSWMSKVF SGKRQEAEFP SHHSQSTFRK PSPTPGGLAG EGTLQSLTCL
130 140 150 160 170 180
IGEKDLRLLE KLGDGSFGVV RRGEWDAPAG 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 DGHYVMQEHR 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 GRMKKPTYDP VSEDPDPLSS DFKRLGLRKP
550 560 570 580 590 600
ALPRGLWLAK PSARVPGTKA GRSSGGEVTL IDFGEEPVAP TPRPCAPSLA QLAMDACSLL
610 620 630 640 650 660
DKTPPQSPTR ALPRPLHPTP VVDWDARPLP PPPAYDDVAQ DEDDFEVCSI NSTLVSAGLP
670 680 690 700 710 720
TGPSQGETNY AFVPEQAQLP PALEDNLFLP PQGGGQPPSS AQTAEIFQAL QQECMRQLQV
730 740 750 760 770 780
PTGQLTPSPT PGGDDKPQVP PRVPIPPRPT RPRVGLSPAP LGEEEASRWP GPSSPPRVPP
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 GAQPPSLRAS ARLPQRGCPG DGQEAARPAD
970 980 990 1000 1010 1020
KVQMLQAMVH GVTTEECQAA LRSHSWSIQR AAQYLKVEQL FGLGLRPRVE CHKVLEMFDW
1030
NLEQAGCHLL GSCGPAHHKR