Descriptions

The c-Kit receptor protein-tyrosine kinase is tightly regulated in normal cells, whereas deregulated c-Kit kinase activity is implicated in the pathogenesis of human cancers. Crystal structures of c-Kit kinase reveal a manner in which the small juxtamembrane domain functions to maintain the kinase in an autoinhibited state. Insertion of this autoinhibitory domain into the cleft between the kinase N- and C-lobes flips the DFG motif into its off state, thereby inducing the activation loop to fold back over from its extended conformation in the active kinase where it binds as a pseudosubstrate at the kinase-active center.

Autoinhibitory domains (AIDs)

Target domain

339-679 (Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha)

Relief mechanism

Ligand binding

Assay

Target domain

339-679 (Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha)

Relief mechanism

Ligand binding

Assay

Target domain

352-594 (Protein kinase domain)

Relief mechanism

Ligand binding

Assay

Target domain

352-594 (Protein kinase domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

491-514 (Activation loop from InterPro)

Target domain

350-608 (Protein kinase domain)

Relief mechanism

Assay

491-514 (Activation loop from InterPro)

Target domain

350-608 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

1 structures for P05130

Entry ID Method Resolution Chain Position Source
AF-P05130-F1 Predicted AlphaFoldDB

1 variants for P05130

Variant ID(s) Position Change Description Diseaes Association Provenance
437 M>I No

No associated diseases with P05130

15 regional properties for P05130

Type Name Position InterPro Accession
domain Protein kinase domain 590 - 938 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 591 - 923 IPR001245
conserved_site Tyrosine-protein kinase, receptor class III, conserved site 649 - 662 IPR001824
domain Immunoglobulin subtype 2 224 - 298 IPR003598-1
domain Immunoglobulin subtype 2 423 - 499 IPR003598-2
domain Immunoglobulin subtype 43 - 112 IPR003599-1
domain Immunoglobulin subtype 121 - 205 IPR003599-2
domain Immunoglobulin subtype 218 - 309 IPR003599-3
domain Immunoglobulin subtype 321 - 409 IPR003599-4
domain Immunoglobulin-like domain 212 - 309 IPR007110-1
domain Immunoglobulin-like domain 414 - 508 IPR007110-2
active_site Tyrosine-protein kinase, active site 789 - 801 IPR008266
domain Immunoglobulin-like beta-sandwich domain 220 - 303 IPR013151
binding_site Protein kinase, ATP binding site 596 - 624 IPR017441
domain Tyrosine-protein kinase, catalytic domain 590 - 925 IPR020635

Functions

Description
EC Number 2.7.10.1 Protein-tyrosine kinases
Subcellular Localization
  • Cell membrane ; Single-pass type I membrane protein
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

3 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
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.

5 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
diacylglycerol-dependent serine/threonine kinase activity Catalysis of the reaction
protein serine kinase activity Catalysis of the reactions
protein serine/threonine kinase activity Catalysis of the reactions
zinc ion binding Binding to a zinc ion (Zn).

4 GO annotations of biological process

Name Definition
intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
positive regulation of clathrin-dependent endocytosis Any process that activates or increases the frequency, rate or extent of clathrin-mediated endocytosis.
protein phosphorylation The process of introducing a phosphate group on to a protein.
regulation of hemocyte proliferation Any process that modulates the frequency, rate or extent of hemocyte proliferation. Hemocytes are blood cells associated with a hemocoel (the cavity containing most of the major organs of the arthropod body) which are involved in defense and clotting of hemolymph, but not involved in transport of oxygen. An example of this is found in Drosophila melanogaster.

31 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P24583 PKC1 Protein kinase C-like 1 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) SS
P04409 PRKCA Protein kinase C alpha type Bos taurus (Bovine) EV SS
P05128 PRKCG Protein kinase C gamma type Bos taurus (Bovine) SS
P05126 PRKCB Protein kinase C beta type Bos taurus (Bovine) SS
Q9W0V1 Pdk1 3-phosphoinositide-dependent protein kinase 1 Drosophila melanogaster (Fruit fly) SS
A1Z9X0 aPKC Atypical protein kinase C Drosophila melanogaster (Fruit fly) SS
A1Z7T0 Pkn Serine/threonine-protein kinase N Drosophila melanogaster (Fruit fly) SS
P83099 Pkcdelta Putative protein kinase C delta type homolog Drosophila melanogaster (Fruit fly) PR
Q8INB9 Akt RAC serine/threonine-protein kinase Drosophila melanogaster (Fruit fly) SS
Q9NBK5 trc Serine/threonine-protein kinase tricornered Drosophila melanogaster (Fruit fly) SS
P13677 inaC Protein kinase C, eye isozyme Drosophila melanogaster (Fruit fly) SS
P05129 PRKCG Protein kinase C gamma type Homo sapiens (Human) SS
P05771 PRKCB Protein kinase C beta type Homo sapiens (Human) SS
Q02156 PRKCE Protein kinase C epsilon type Homo sapiens (Human) SS
P24723 PRKCH Protein kinase C eta type Homo sapiens (Human) SS
P17252 PRKCA Protein kinase C alpha type Homo sapiens (Human) EV
P20444 Prkca Protein kinase C alpha type Mus musculus (Mouse) SS
P68404 Prkcb Protein kinase C beta type Mus musculus (Mouse) SS
P16054 Prkce Protein kinase C epsilon type Mus musculus (Mouse) PR
P23298 Prkch Protein kinase C eta type Mus musculus (Mouse) PR
P63318 Prkcg Protein kinase C gamma type Mus musculus (Mouse) SS
Q64617 Prkch Protein kinase C eta type Rattus norvegicus (Rat) PR
P63319 Prkcg Protein kinase C gamma type Rattus norvegicus (Rat) SS
P05696 Prkca Protein kinase C alpha type Rattus norvegicus (Rat) SS
P68403 Prkcb Protein kinase C beta type Rattus norvegicus (Rat) SS
P90980 pkc-2 Protein kinase C-like 2 Caenorhabditis elegans SS
Q9SUA3 D6PKL1 Serine/threonine-protein kinase D6PKL1 Arabidopsis thaliana (Mouse-ear cress) PR
O64682 PID Protein kinase PINOID Arabidopsis thaliana (Mouse-ear cress) PR
Q9LUL2 WAG2 Serine/threonine-protein kinase WAG2 Arabidopsis thaliana (Mouse-ear cress) PR
A8KBH6 prkcb Protein kinase C beta type Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) SS
Q7SY24 prkcbb Protein kinase C beta type Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MRGARGAWDF LCVLLLLLRV QTGSSQPSAS PGEWSLPSIH PATSELIVSA GDEIRLLCTD
70 80 90 100 110 120
PGFVKWTFET LGQSSEITHN EWITEKAEAT NTGNYTCTNG GGLSSSIYVF VRDPAKLFLV
130 140 150 160 170 180
DLPLYGKEDH DTLVRCPLTD PEVTNYSLRG CEGKPLPKDL TFVTDPKAGI TIRNVKREYH
190 200 210 220 230 240
RLCLHCSADR KGKSVLSKKF TLKVRAAIRA VPVVSVSKAS HLLREGEEFS VMCLIKDVSS
250 260 270 280 290 300
SVDSMWIKEN SPQTNAQPQS NSWHQGDFNF VRQERLTISS ARVNDSGVFM CYANNTFGSA
310 320 330 340 350 360
NVTTTLEVVA KGFINIFPMM NTTIFVNDGE NVDLIVEYEA YPKPEHQRWV YMNRTLTDKW
370 380 390 400 410 420
EDYPKSDNES NIRYVSELHL TRLKGNEGGT YTFQVSNSDV NSSVTLNVYV NTKPEILTHE
430 440 450 460 470 480
SLVSGILQCL VAGFPEPTVD WYFCPGAEQR CPVPVGPLDV QMQNSSVSPS GKLVVQSSID
490 500 510 520 530 540
YSAFKHNGTV ECRASNNVGK TSAFFNFAFK GNSKEQMHPH TLFTPLLIGF VIAAGMMCII
550 560 570 580 590 600
VMILTYKYLQ KPMYEVQWKV VEEINGNNYV YIDPTQLPYD HKWEFPRNRL SFGKTLGAGA
610 620 630 640 650 660
FGKVVEATAY GLIKSDAAMT VAVKMLKPSA HLTEREALMS ELKVLSYLGN HMNIVNLLGA
670 680 690 700 710 720
CTVGGPTLVI TEYCCYGDLL NFLRRKRDSF ICSKQEDHAE VALYKNLLQS KESSCNDSTN
730 740 750 760 770 780
EYMDMKPGVS YVVPTKADKR RSARIGSYIE RDVTPAIMED DELALDLEDL LSFSYQVAKG
790 800 810 820 830 840
MAFLASKNCI HRDLAARNIL LTHGRITKIC DFGLARDIKN DSNYVVKGNA RLPVKWMAPE
850 860 870 880 890 900
SIFNCVYTFE SDVWSYGIFL WELFSLGSSP YPGMPVDSKF YKMIKEGFRM LSPEHAPAEM
910 920 930 940 950 960
YDIMKTCWDA DPLKRPTFKQ IVQLIEKQIS DSTNHIYSNL ANCSPNRERP TAVDHCVRIN
970
SVGSSTSSTQ PLLVHEDA