F1RDG9
Gene name |
fynb |
Protein name |
Tyrosine-protein kinase fynb |
Names |
EC 2.7.10.2 , Proto-oncogene c-Fynb |
Species |
Homo sapiens (Human) |
KEGG Pathway |
dre:574422 |
EC number |
2.7.10.1: Protein-tyrosine kinases |
Protein Class |
TYROSINE-PROTEIN KINASE RECEPTOR (PTHR24416) |
Descriptions
ALK is a receptor tyrosine kinase involved in the development of several human cancers. Its autoinhibition is mediated by an intramolecular interaction between β-sheet (β1' and β2') and DFG helix in an activation loop, which occludes the substrate binding site. The activation loop contains phosphorylation sites, which need to be phosphorylated for ALK activation.
Autoinhibitory domains (AIDs)
Target domain |
278-531 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Target domain |
278-531 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Target domain |
278-531 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
Target domain |
278-531 (Protein kinase domain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
No accessory elements
References
- Hong E et al. (2004) "Solution structure and backbone dynamics of the non-receptor protein-tyrosine kinase-6 Src homology 2 domain", The Journal of biological chemistry, 279, 29700-8
- Ko S et al. (2009) "Structural basis of the auto-inhibition mechanism of nonreceptor tyrosine kinase PTK6", Biochemical and biophysical research communications, 384, 236-42
- Qiu H et al. (2002) "Regulation of the nonreceptor tyrosine kinase Brk by autophosphorylation and by autoinhibition", The Journal of biological chemistry, 277, 34634-41
- Williams JC et al. (1997) "The 2.35 A crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions", Journal of molecular biology, 274, 757-75
- Boggon TJ et al. (2004) "Structure and regulation of Src family kinases", Oncogene, 23, 7918-27
- Meng Y et al. (2014) "Locking the active conformation of c-Src kinase through the phosphorylation of the activation loop", Journal of molecular biology, 426, 423-35
- Register AC et al. (2014) "SH2-catalytic domain linker heterogeneity influences allosteric coupling across the SFK family", Biochemistry, 53, 6910-23
- Wang Q et al. (2010) "Multicolor monitoring of dysregulated protein kinases in chronic myelogenous leukemia", ACS chemical biology, 5, 887-95
- Sotirellis N et al. (1995) "Autophosphorylation induces autoactivation and a decrease in the Src homology 2 domain accessibility of the Lyn protein kinase", The Journal of biological chemistry, 270, 29773-80
- Williams NK et al. (2009) "Crystal structures of the Lyn protein tyrosine kinase domain in its Apo- and inhibitor-bound state", The Journal of biological chemistry, 284, 284-291
- Laham LE et al. (2000) "The activation loop in Lck regulates oncogenic potential by inhibiting basal kinase activity and restricting substrate specificity", Oncogene, 19, 3961-70
- Furlan G et al. (2014) "Phosphatase CD45 both positively and negatively regulates T cell receptor phosphorylation in reconstituted membrane protein clusters", The Journal of biological chemistry, 289, 28514-25
- Engen JR et al. (2008) "Structure and dynamic regulation of Src-family kinases", Cellular and molecular life sciences : CMLS, 65, 3058-73
- Alvarado JJ et al. (2010) "Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region supports an SH3-dominant activation mechanism", The Journal of biological chemistry, 285, 35455-61
Autoinhibited structure
Activated structure
1 structures for F1RDG9
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-F1RDG9-F1 | Predicted | AlphaFoldDB |
No variants for F1RDG9
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for F1RDG9 | |||||
No associated diseases with F1RDG9
6 regional properties for F1RDG9
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Arf GTPase activating protein | 1 - 124 | IPR001164 |
| repeat | Ankyrin repeat | 132 - 228 | IPR002110 |
| domain | GIT, Spa2 homology (SHD) domain | 264 - 294 | IPR013724-1 |
| domain | GIT, Spa2 homology (SHD) domain | 328 - 358 | IPR013724-2 |
| domain | ARF GTPase-activating protein GIT1, C-terminal | 643 - 755 | IPR022018 |
| domain | Arf GTPase-activating protein GIT1/2, coiled-coil domain | 409 - 473 | IPR032352 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.10.1 | Protein-tyrosine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | PTHR24416 | TYROSINE-PROTEIN KINASE RECEPTOR |
| PANTHER Subfamily | PTHR24416:SF276 | ALK TYROSINE KINASE RECEPTOR |
| PANTHER Protein Class | transmembrane signal receptor | |
| PANTHER Pathway Category | No pathway information available | |
2 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| extrinsic component of cytoplasmic side of plasma membrane | The component of a plasma membrane consisting of gene products and protein complexes that are loosely bound to its cytoplasmic surface, but not integrated into the hydrophobic region. |
4 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 |
| signaling receptor binding | Binding to one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function. |
7 GO annotations of biological process
| Name | Definition |
|---|---|
| cell differentiation | The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state. |
| convergent extension involved in gastrulation | The morphogenetic process in which an epithelium narrows along one axis and lengthens in a perpendicular axis usually resulting in the formation of the three primary germ layers, ectoderm, mesoderm and endoderm. |
| fin regeneration | The regrowth of fin tissue following its loss or destruction. |
| innate immune response | Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. |
| 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. |
| T cell receptor signaling pathway | The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell. |
| transmembrane receptor protein tyrosine kinase signaling pathway | The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription. |
77 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q0VBZ0 | CSK | Tyrosine-protein kinase CSK | Bos taurus (Bovine) | SS |
| Q3ZC95 | BTK | Tyrosine-protein kinase | Bos taurus (Bovine) | EV SS |
| A0JNB0 | FYN | Tyrosine-protein kinase Fyn | Bos taurus (Bovine) | SS |
| P42683 | LCK | Proto-oncogene tyrosine-protein kinase LCK | Gallus gallus (Chicken) | SS |
| P41239 | CSK | Tyrosine-protein kinase CSK | Gallus gallus (Chicken) | SS |
| P00523 | SRC | Proto-oncogene tyrosine-protein kinase Src | Gallus gallus (Chicken) | EV |
| Q02977 | YRK | Proto-oncogene tyrosine-protein kinase Yrk | Gallus gallus (Chicken) | SS |
| Q8JH64 | BTK | Tyrosine-protein kinase BTK | Gallus gallus (Chicken) | SS |
| P09324 | YES1 | Tyrosine-protein kinase Yes | Gallus gallus (Chicken) | SS |
| Q75R65 | JAK2 | Tyrosine-protein kinase JAK2 | Gallus gallus (Chicken) | SS |
| Q05876 | FYN | Tyrosine-protein kinase Fyn | Gallus gallus (Chicken) | SS |
| Q24592 | hop | Tyrosine-protein kinase hopscotch | Drosophila melanogaster (Fruit fly) | PR |
| P08630 | Btk | Tyrosine-protein kinase Btk | Drosophila melanogaster (Fruit fly) | SS |
| P00528 | Src64B | Tyrosine-protein kinase Src64B | Drosophila melanogaster (Fruit fly) | SS |
| Q9V9J3 | Src42A | Tyrosine-protein kinase Src42A | Drosophila melanogaster (Fruit fly) | SS |
| P41240 | CSK | Tyrosine-protein kinase CSK | Homo sapiens (Human) | SS |
| P51451 | BLK | Tyrosine-protein kinase Blk | Homo sapiens (Human) | SS |
| P06239 | LCK | Tyrosine-protein kinase Lck | Homo sapiens (Human) | EV |
| P23458 | JAK1 | Tyrosine-protein kinase JAK1 | Homo sapiens (Human) | SS |
| P51813 | BMX | Cytoplasmic tyrosine-protein kinase BMX | Homo sapiens (Human) | SS |
| P12931 | SRC | Proto-oncogene tyrosine-protein kinase Src | Homo sapiens (Human) | EV |
| P09769 | FGR | Tyrosine-protein kinase Fgr | Homo sapiens (Human) | SS |
| P42680 | TEC | Tyrosine-protein kinase Tec | Homo sapiens (Human) | SS |
| O60674 | JAK2 | Tyrosine-protein kinase JAK2 | Homo sapiens (Human) | EV |
| P42679 | MATK | Megakaryocyte-associated tyrosine-protein kinase | Homo sapiens (Human) | SS |
| P52333 | JAK3 | Tyrosine-protein kinase JAK3 | Homo sapiens (Human) | SS |
| Q08881 | ITK | Tyrosine-protein kinase ITK/TSK | Homo sapiens (Human) | EV |
| P07948 | LYN | Tyrosine-protein kinase Lyn | Homo sapiens (Human) | SS |
| P29597 | TYK2 | Non-receptor tyrosine-protein kinase TYK2 | Homo sapiens (Human) | EV |
| Q13882 | PTK6 | Protein-tyrosine kinase 6 | Homo sapiens (Human) | EV |
| P08631 | HCK | Tyrosine-protein kinase HCK | Homo sapiens (Human) | EV |
| P07947 | YES1 | Tyrosine-protein kinase Yes | Homo sapiens (Human) | SS |
| P42685 | FRK | Tyrosine-protein kinase FRK | Homo sapiens (Human) | EV |
| Q06187 | BTK | Tyrosine-protein kinase BTK | Homo sapiens (Human) | EV |
| P06241 | FYN | Tyrosine-protein kinase Fyn | Homo sapiens (Human) | SS |
| Q9R117 | Tyk2 | Non-receptor tyrosine-protein kinase TYK2 | Mus musculus (Mouse) | SS |
| P08103 | Hck | Tyrosine-protein kinase HCK | Mus musculus (Mouse) | SS |
| P16277 | Blk | Tyrosine-protein kinase Blk | Mus musculus (Mouse) | SS |
| Q62270 | Srms | Tyrosine-protein kinase Srms | Mus musculus (Mouse) | SS |
| Q64434 | Ptk6 | Protein-tyrosine kinase 6 | Mus musculus (Mouse) | SS |
| P05480 | Src | Proto-oncogene tyrosine-protein kinase Src | Mus musculus (Mouse) | EV |
| P14234 | Fgr | Tyrosine-protein kinase Fgr | Mus musculus (Mouse) | SS |
| P35991 | Btk | Tyrosine-protein kinase BTK | Mus musculus (Mouse) | EV |
| P41241 | Csk | Tyrosine-protein kinase CSK | Mus musculus (Mouse) | EV |
| P25911 | Lyn | Tyrosine-protein kinase Lyn | Mus musculus (Mouse) | EV |
| Q62137 | Jak3 | Tyrosine-protein kinase JAK3 | Mus musculus (Mouse) | SS |
| Q62120 | Jak2 | Tyrosine-protein kinase JAK2 | Mus musculus (Mouse) | EV |
| P06240 | Lck | Proto-oncogene tyrosine-protein kinase LCK | Mus musculus (Mouse) | SS |
| P24604 | Tec | Tyrosine-protein kinase Tec | Mus musculus (Mouse) | SS |
| Q04736 | Yes1 | Tyrosine-protein kinase Yes | Mus musculus (Mouse) | SS |
| P52332 | Jak1 | Tyrosine-protein kinase JAK1 | Mus musculus (Mouse) | SS |
| Q03526 | Itk | Tyrosine-protein kinase ITK/TSK | Mus musculus (Mouse) | SS |
| P41242 | Matk | Megakaryocyte-associated tyrosine-protein kinase | Mus musculus (Mouse) | SS |
| Q922K9 | Frk | Tyrosine-protein kinase FRK | Mus musculus (Mouse) | SS |
| P39688 | Fyn | Tyrosine-protein kinase Fyn | Mus musculus (Mouse) | SS |
| O19064 | JAK2 | Tyrosine-protein kinase JAK2 | Sus scrofa (Pig) | SS |
| A1Y2K1 | FYN | Tyrosine-protein kinase Fyn | Sus scrofa (Pig) | SS |
| Q62662 | Frk | Tyrosine-protein kinase FRK | Rattus norvegicus (Rat) | SS |
| Q07014 | Lyn | Tyrosine-protein kinase Lyn | Rattus norvegicus (Rat) | SS |
| P50545 | Hck | Tyrosine-protein kinase HCK | Rattus norvegicus (Rat) | SS |
| Q9WUD9 | Src | Proto-oncogene tyrosine-protein kinase Src | Rattus norvegicus (Rat) | SS |
| Q01621 | Lck | Proto-oncogene tyrosine-protein kinase LCK | Rattus norvegicus (Rat) | SS |
| Q6P6U0 | Fgr | Tyrosine-protein kinase Fgr | Rattus norvegicus (Rat) | SS |
| Q62689 | Jak2 | Tyrosine-protein kinase JAK2 | Rattus norvegicus (Rat) | SS |
| Q63272 | Jak3 | Tyrosine-protein kinase JAK3 | Rattus norvegicus (Rat) | SS |
| P32577 | Csk | Tyrosine-protein kinase CSK | Rattus norvegicus (Rat) | SS |
| P41243 | Matk | Megakaryocyte-associated tyrosine-protein kinase | Rattus norvegicus (Rat) | SS |
| F1LM93 | Yes1 | Tyrosine-protein kinase Yes | Rattus norvegicus (Rat) | SS |
| Q62844 | Fyn | Tyrosine-protein kinase Fyn | Rattus norvegicus (Rat) | SS |
| G5ECJ6 | csk-1 | Tyrosine-protein kinase csk-1 | Caenorhabditis elegans | SS |
| O45539 | src-2 | Tyrosine protein-kinase src-2 | Caenorhabditis elegans | SS |
| G5EE56 | src-1 | Tyrosine protein-kinase src-1 | Caenorhabditis elegans | SS |
| Q2MHE4 | HT1 | Serine/threonine/tyrosine-protein kinase HT1 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| O12990 | jak1 | Tyrosine-protein kinase JAK1 | Danio rerio (Zebrafish) (Brachydanio rerio) | PR |
| A1A5H8 | yes1 | Tyrosine-protein kinase yes | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q1JPZ3 | src | Proto-oncogene tyrosine-protein kinase Src | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q6EWH2 | fyna | Tyrosine-protein kinase fyna | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MGAIGLLWLL | PLLLSTAAVG | SGMGTGQRAG | SPAAGPPLQP | REPLSYSRLQ | RKSLAVDFVV |
| 70 | 80 | 90 | 100 | 110 | 120 |
| PSLFRVYARD | LLLPPSSSEL | KAGRPEARGS | LALDCAPLLR | LLGPAPGVSW | TAGSPAPAEA |
| 130 | 140 | 150 | 160 | 170 | 180 |
| RTLSRVLKGG | SVRKLRRAKQ | LVLELGEEAI | LEGCVGPPGE | AAVGLLQFNL | SELFSWWIRQ |
| 190 | 200 | 210 | 220 | 230 | 240 |
| GEGRLRIRLM | PEKKASEVGR | EGRLSAAIRA | SQPRLLFQIF | GTGHSSLESP | TNMPSPSPDY |
| 250 | 260 | 270 | 280 | 290 | 300 |
| FTWNLTWIMK | DSFPFLSHRS | RYGLECSFDF | PCELEYSPPL | HDLRNQSWSW | RRIPSEEASQ |
| 310 | 320 | 330 | 340 | 350 | 360 |
| MDLLDGPGAE | RSKEMPRGSF | LLLNTSADSK | HTILSPWMRS | SSEHCTLAVS | VHRHLQPSGR |
| 370 | 380 | 390 | 400 | 410 | 420 |
| YIAQLLPHNE | AAREILLMPT | PGKHGWTVLQ | GRIGRPDNPF | RVALEYISSG | NRSLSAVDFF |
| 430 | 440 | 450 | 460 | 470 | 480 |
| ALKNCSEGTS | PGSKMALQSS | FTCWNGTVLQ | LGQACDFHQD | CAQGEDESQM | CRKLPVGFYC |
| 490 | 500 | 510 | 520 | 530 | 540 |
| NFEDGFCGWT | QGTLSPHTPQ | WQVRTLKDAR | FQDHQDHALL | LSTTDVPASE | SATVTSATFP |
| 550 | 560 | 570 | 580 | 590 | 600 |
| APIKSSPCEL | RMSWLIRGVL | RGNVSLVLVE | NKTGKEQGRM | VWHVAAYEGL | SLWQWMVLPL |
| 610 | 620 | 630 | 640 | 650 | 660 |
| LDVSDRFWLQ | MVAWWGQGSR | AIVAFDNISI | SLDCYLTISG | EDKILQNTAP | KSRNLFERNP |
| 670 | 680 | 690 | 700 | 710 | 720 |
| NKELKPGENS | PRQTPIFDPT | VHWLFTTCGA | SGPHGPTQAQ | CNNAYQNSNL | SVEVGSEGPL |
| 730 | 740 | 750 | 760 | 770 | 780 |
| KGIQIWKVPA | TDTYSISGYG | AAGGKGGKNT | MMRSHGVSVL | GIFNLEKDDM | LYILVGQQGE |
| 790 | 800 | 810 | 820 | 830 | 840 |
| DACPSTNQLI | QKVCIGENNV | IEEEIRVNRS | VHEWAGGGGG | GGGATYVFKM | KDGVPVPLII |
| 850 | 860 | 870 | 880 | 890 | 900 |
| AAGGGGRAYG | AKTDTFHPER | LENNSSVLGL | NGNSGAAGGG | GGWNDNTSLL | WAGKSLQEGA |
| 910 | 920 | 930 | 940 | 950 | 960 |
| TGGHSCPQAM | KKWGWETRGG | FGGGGGGCSS | GGGGGGYIGG | NAASNNDPEM | DGEDGVSFIS |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| PLGILYTPAL | KVMEGHGEVN | IKHYLNCSHC | EVDECHMDPE | SHKVICFCDH | GTVLAEDGVS |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| CIVSPTPEPH | LPLSLILSVV | TSALVAALVL | AFSGIMIVYR | RKHQELQAMQ | MELQSPEYKL |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| SKLRTSTIMT | DYNPNYCFAG | KTSSISDLKE | VPRKNITLIR | GLGHGAFGEV | YEGQVSGMPN |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| DPSPLQVAVK | TLPEVCSEQD | ELDFLMEALI | ISKFNHQNIV | RCIGVSLQSL | PRFILLELMA |
| 1210 | 1220 | 1230 | 1240 | 1250 | 1260 |
| GGDLKSFLRE | TRPRPSQPSS | LAMLDLLHVA | RDIACGCQYL | EENHFIHRDI | AARNCLLTCP |
| 1270 | 1280 | 1290 | 1300 | 1310 | 1320 |
| GPGRVAKIGD | FGMARDIYRA | SYYRKGGCAM | LPVKWMPPEA | FMEGIFTSKT | DTWSFGVLLW |
| 1330 | 1340 | 1350 | 1360 | 1370 | 1380 |
| EIFSLGYMPY | PSKSNQEVLE | FVTSGGRMDP | PKNCPGPVYR | IMTQCWQHQP | EDRPNFAIIL |
| 1390 | 1400 | 1410 | 1420 | 1430 | 1440 |
| ERIEYCTQDP | DVINTALPIE | YGPLVEEEEK | VPVRPKDPEG | VPPLLVSQQA | KREEERSPAA |
| 1450 | 1460 | 1470 | 1480 | 1490 | 1500 |
| PPPLPTTSSG | KAAKKPTAAE | ISVRVPRGPA | VEGGHVNMAF | SQSNPPSELH | KVHGSRNKPT |
| 1510 | 1520 | 1530 | 1540 | 1550 | 1560 |
| SLWNPTYGSW | FTEKPTKKNN | PIAKKEPHDR | GNLGLEGSCT | VPPNVATGRL | PGASLLLEPS |
| 1570 | 1580 | 1590 | 1600 | 1610 | |
| SLTANMKEVP | LFRLRHFPCG | NVNYGYQQQG | LPLEAATAPG | AGHYEDTILK | SKNSMNQPGP |