Q62371

SS
Gene name
Ddr2 (Ntrkr3, Tkt, Tyro10)
Protein name
Discoidin domain-containing receptor 2
Names
Discoidin domain receptor 2 , EC 2.7.10.1 , CD167 antigen-like family member B , Neurotrophic tyrosine kinase, receptor-related 3 , Receptor protein-tyrosine kinase TKT , Tyrosine-protein kinase TYRO10 , CD antigen CD167b
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:18214
EC number
2.7.10.-: Protein-tyrosine kinases
Protein Class

Descriptions

Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase with important functions in organogenesis and tissue homeostasis. The autoinhibition of DDR kinase activity is released by a two-step. First, phosphorylation of JM4 (kinase-proximal segment) tyrosines likely ejects JM4 from the cleft between the kinase N- and C-lobes, resulting in low activity similar to that of an inactive kinase alone where the A-loop still blocks the active site. In the second step, phosphorylation of the A-loop frees up the active site, resulting in a fully active kinase. Interestingly, the glycosylation at the Asn211 position could help to maintain the autoinhibitory state during the trafficking of the receptor to the cell surface by imposing steric or electrostatic effects that translate into downstream conformations.

Autoinhibitory domains (AIDs)

518-543 (Juxtamembrane 4 region) SS

Target domain

563-848 (Protein kinase domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q62371

Entry ID Method Resolution Chain Position Source
AF-Q62371-F1 Predicted AlphaFoldDB

44 variants for Q62371

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3388512702 16 L>F No EVA
rs3388510744 24 Q>H No EVA
rs3390938223 68 G>* No EVA
rs3388514700 72 W>C No EVA
rs47694293 74 P>L No EVA
rs31474649 87 L>M No EVA
rs3388516006 91 L>* No EVA
rs3388509255 102 T>A No EVA
rs3388515437 105 R>G No EVA
rs3388515182 113 E>V No EVA
rs3388509236 114 F>S No EVA
rs3388515448 171 D>E No EVA
rs3388515632 176 V>M No EVA
rs3388511303 188 L>V No EVA
rs3388515635 190 G>D No EVA
rs3388514286 202 F>L No EVA
rs3390965723 212 L>Q No EVA
rs3388515453 229 L>P No EVA
rs3388514701 234 D>E No EVA
rs3388514706 263 S>G No EVA
rs232897194 264 A>T No EVA
rs3388515639 293 A>D No EVA
rs3388511299 296 V>M No EVA
rs3388514333 342 M>T No EVA
rs3388511139 358 M>T No EVA
rs3388513471 435 R>M No EVA
rs3388517430 440 E>D No EVA
rs3388512264 440 E>Q No EVA
rs3388514731 474 I>L No EVA
rs3388517458 478 R>L No EVA
rs242021756 510 A>V No EVA
rs3391003431 576 E>G No EVA
rs3388511089 582 V>* No EVA
rs3388517429 585 M>V No EVA
rs3388515418 588 F>L No EVA
rs31474355 590 D>G No EVA
rs3388515414 609 M>I No EVA
rs3388515597 622 F>S No EVA
rs3388513531 669 H>P No EVA
rs3388512266 705 F>L No EVA
rs3388516024 728 F>L No EVA
rs3388512804 827 M>L No EVA
rs3388515583 834 E>K No EVA
rs3388510672 845 H>Q No EVA

1 associated diseases with Q62371

Without disease ID

7 regional properties for Q62371

Type Name Position InterPro Accession
domain Coagulation factor 5/8 C-terminal domain 29 - 185 IPR000421
domain Protein kinase domain 563 - 848 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 564 - 845 IPR001245
conserved_site Tyrosine-protein kinase, receptor class II, conserved site 733 - 741 IPR002011
active_site Tyrosine-protein kinase, active site 705 - 717 IPR008266
domain Tyrosine-protein kinase, catalytic domain 563 - 848 IPR020635
domain Discoidin domain-containing receptor 1/2, DS-like domain 190 - 366 IPR048525

Functions

Description
EC Number 2.7.10.- 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
actin cytoskeleton The part of the cytoskeleton (the internal framework of a cell) composed of actin and associated proteins. Includes actin cytoskeleton-associated complexes.
apical plasma membrane The region of the plasma membrane located at the apical end of the cell.
receptor complex Any protein complex that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.

4 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
collagen binding Binding to collagen, a group of fibrous proteins of very high tensile strength that form the main component of connective tissue in animals. Collagen is highly enriched in glycine (some regions are 33% glycine) and proline, occurring predominantly as 3-hydroxyproline (about 20%).
protein tyrosine kinase collagen receptor activity Combining with collagen and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity by catalysis of the reaction
transmembrane receptor protein tyrosine kinase activity Combining with a signal and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity by catalysis of the reaction

32 GO annotations of biological process

Name Definition
biomineral tissue development Formation of hard tissues that consist mainly of inorganic compounds, and also contain a small amounts of organic matrices that are believed to play important roles in their formation.
cellular response to angiotensin Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an angiotensin stimulus. Angiotensin is any of three physiologically active peptides (angiotensin II, III, or IV) processed from angiotensinogen.
cellular response to hypoxia Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level.
cellular response to transforming growth factor beta stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a transforming growth factor beta stimulus.
chondrocyte proliferation The multiplication or reproduction of chondrocytes by cell division, resulting in the expansion of their population. A chondrocyte is a polymorphic cell that forms cartilage.
collagen fibril organization Any process that determines the size and arrangement of collagen fibrils within an extracellular matrix.
collagen-activated tyrosine kinase receptor signaling pathway The series of molecular signals initiated by collagen binding to its receptor on the surface of a target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.
endochondral bone growth The increase in size or mass of an endochondral bone that contributes to the shaping of the bone.
negative regulation of apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
negative regulation of hydrogen peroxide-mediated programmed cell death Any process that stops, prevents or reduces the frequency, rate or extent of hydrogen peroxide-mediated programmed cell death.
ossification The formation of bone or of a bony substance, or the conversion of fibrous tissue or of cartilage into bone or a bony substance.
peptidyl-tyrosine phosphorylation The phosphorylation of peptidyl-tyrosine to form peptidyl-O4'-phospho-L-tyrosine.
positive regulation of cell population proliferation Any process that activates or increases the rate or extent of cell proliferation.
positive regulation of collagen biosynthetic process Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of collagen, any of a group of fibrous proteins of very high tensile strength that form the main component of connective tissue in animals.
positive regulation of DNA-binding transcription factor activity Any process that activates or increases the frequency, rate or extent of activity of a transcription factor, any factor involved in the initiation or regulation of transcription.
positive regulation of ERK1 and ERK2 cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
positive regulation of extracellular matrix disassembly Any process that increases the rate, frequency or extent of extracellular matrix disassembly. Extracellular matrix disassembly is a process that results in the breakdown of the extracellular matrix.
positive regulation of fibroblast migration Any process that increases the rate, frequency or extent of fibroblast cell migration. Fibroblast cell migration is accomplished by extension and retraction of a pseudopodium.
positive regulation of fibroblast proliferation Any process that activates or increases the frequency, rate or extent of multiplication or reproduction of fibroblast cells.
positive regulation of G1/S transition of mitotic cell cycle Any signalling pathway that increases or activates a cell cycle cyclin-dependent protein kinase to modulate the switch from G1 phase to S phase of the mitotic cell cycle.
positive regulation of hepatic stellate cell activation Any process that activates or increases the frequency, rate or extent of hepatic stellate cell activation.
positive regulation of hepatic stellate cell proliferation Any process that activates or increases the frequency, rate or extent of hepatic stellate cell proliferation.
positive regulation of neuron projection development Any process that increases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
positive regulation of osteoblast differentiation Any process that activates or increases the frequency, rate or extent of osteoblast differentiation.
positive regulation of protein kinase activity Any process that activates or increases the frequency, rate or extent of protein kinase activity.
positive regulation of vascular associated smooth muscle cell migration Any process that activates or increases the frequency, rate or extent of vascular associated smooth muscle cell migration.
positive regulation of vascular associated smooth muscle cell proliferation Any process that activates or increases the frequency, rate or extent of vascular smooth muscle cell proliferation.
positive regulation of wound healing Any process that increases the rate, frequency, or extent of the series of events that restore integrity to a damaged tissue, following an injury.
regulation of bone mineralization Any process that modulates the frequency, rate or extent of bone mineralization.
regulation of tissue remodeling Any process that modulates the frequency, rate, or extent of tissue remodeling.
response to muscle stretch Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a myofibril being extended beyond its slack length.
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.

47 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q5F3X2 DDR1 receptor protein-tyrosine kinase Gallus gallus (Chicken) SS
Q7YR43 DDR1 Epithelial discoidin domain-containing receptor 1 Pan troglodytes (Chimpanzee) SS
Q08345 DDR1 Epithelial discoidin domain-containing receptor 1 Homo sapiens (Human) EV
Q16832 DDR2 Discoidin domain-containing receptor 2 Homo sapiens (Human) SS
P35546 Ret Proto-oncogene tyrosine-protein kinase receptor Ret Mus musculus (Mouse) SS
Q61006 Musk Muscle, skeletal receptor tyrosine-protein kinase Mus musculus (Mouse) SS
Q9Z138 Ror2 Tyrosine-protein kinase transmembrane receptor ROR2 Mus musculus (Mouse) SS
Q9Z139 Ror1 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Mus musculus (Mouse) PR
Q03146 Ddr1 Epithelial discoidin domain-containing receptor 1 Mus musculus (Mouse) SS
P15209 Ntrk2 BDNF/NT-3 growth factors receptor Mus musculus (Mouse) SS
Q3UFB7 Ntrk1 High affinity nerve growth factor receptor Mus musculus (Mouse) SS
Q6VNS1 Ntrk3 NT-3 growth factor receptor Mus musculus (Mouse) SS
P35917 Flt4 Vascular endothelial growth factor receptor 3 Mus musculus (Mouse) SS
P35969 Flt1 Vascular endothelial growth factor receptor 1 Mus musculus (Mouse) SS
P35918 Kdr Vascular endothelial growth factor receptor 2 Mus musculus (Mouse) PR
Q03145 Epha2 Ephrin type-A receptor 2 Mus musculus (Mouse) PR
Q60750 Epha1 Ephrin type-A receptor 1 Mus musculus (Mouse) SS
P54761 Ephb4 Ephrin type-B receptor 4 Mus musculus (Mouse) PR
Q60629 Epha5 Ephrin type-A receptor 5 Mus musculus (Mouse) SS
P97793 Alk ALK tyrosine kinase receptor Mus musculus (Mouse) SS
Q9WTL4 Insrr Insulin receptor-related protein Mus musculus (Mouse) SS
Q60751 Igf1r Insulin-like growth factor 1 receptor Mus musculus (Mouse) SS
P15208 Insr Insulin receptor Mus musculus (Mouse) SS
P16092 Fgfr1 Fibroblast growth factor receptor 1 Mus musculus (Mouse) SS
P21803 Fgfr2 Fibroblast growth factor receptor 2 Mus musculus (Mouse) SS
Q03142 Fgfr4 Fibroblast growth factor receptor 4 Mus musculus (Mouse) PR
Q60805 Mertk Tyrosine-protein kinase Mer Mus musculus (Mouse) SS
Q62190 Mst1r Macrophage-stimulating protein receptor Mus musculus (Mouse) SS
Q00993 Axl Tyrosine-protein kinase receptor UFO Mus musculus (Mouse) PR
P55144 Tyro3 Tyrosine-protein kinase receptor TYRO3 Mus musculus (Mouse) SS
P70424 Erbb2 Receptor tyrosine-protein kinase erbB-2 Mus musculus (Mouse) SS
Q61527 Erbb4 Receptor tyrosine-protein kinase erbB-4 Mus musculus (Mouse) SS
Q61526 Erbb3 Receptor tyrosine-protein kinase erbB-3 Mus musculus (Mouse) SS
Q01279 Egfr Epidermal growth factor receptor Mus musculus (Mouse) SS
Q01887 Ryk Tyrosine-protein kinase RYK Mus musculus (Mouse) PR
Q02858 Tek Angiopoietin-1 receptor Mus musculus (Mouse) SS
Q06806 Tie1 Tyrosine-protein kinase receptor Tie-1 Mus musculus (Mouse) SS
P05532 Kit Mast/stem cell growth factor receptor Kit Mus musculus (Mouse) PR
P05622 Pdgfrb Platelet-derived growth factor receptor beta Mus musculus (Mouse) SS
P09581 Csf1r Macrophage colony-stimulating factor 1 receptor Mus musculus (Mouse) SS
P26618 Pdgfra Platelet-derived growth factor receptor alpha Mus musculus (Mouse) SS
Q00342 Flt3 Receptor-type tyrosine-protein kinase FLT3 Mus musculus (Mouse) SS
Q61851 Fgfr3 Fibroblast growth factor receptor 3 Mus musculus (Mouse) PR
P16056 Met Hepatocyte growth factor receptor Mus musculus (Mouse) PR
Q63474 Ddr1 Epithelial discoidin domain-containing receptor 1 Rattus norvegicus (Rat) SS
Q95ZV7 ddr-2 Discoidin domain-containing receptor tyrosine kinase B Caenorhabditis elegans PR
E7F3X9 ddr1 receptor protein-tyrosine kinase Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MIPIPRMPLV LLLLLLILGS AKAQVNPAIC RYPLGMSGGH IPDEDITASS QWSESTAAKY
70 80 90 100 110 120
GRLDSEEGDG AWCPEIPVQP DDLKEFLQID LRTLHFITLV GTQGRHAGGH GIEFAPMYKI
130 140 150 160 170 180
NYSRDGSRWI SWRNRHGKQV LDGNSNPYDV FLKDLEPPIV ARFVRLIPVT DHSMNVCMRV
190 200 210 220 230 240
ELYGCVWLDG LVSYNAPAGQ QFVLPGGSII YLNDSVYDGA VGYSMTEGLG QLTDGVSGLD
250 260 270 280 290 300
DFTQTHEYHV WPGYDYVGWR NESATNGFIE IMFEFDRIRN FTTMKVHCNN MFAKGVKIFK
310 320 330 340 350 360
EVQCYFRSEA SEWEPTAVYF PLVLDDVNPS ARFVTVPLHH RMASAIKCQY HFADTWMMFS
370 380 390 400 410 420
EITFQSDAAM YNNSGALPTS PMAPTTYDPM LKVDDSNTRI LIGCLVAIIF ILLAIIVIIL
430 440 450 460 470 480
WRQFWQKMLE KASRRMLDDE MTVSLSLPSE SSMFNNNRSS SPSEQESNST YDRIFPLRPD
490 500 510 520 530 540
YQEPSRLIRK LPEFAPGEEE SGCSGVVKPA QPNGPEGVPH YAEADIVNLQ GVTGGNTYCV
550 560 570 580 590 600
PAVTMDLLSG KDVAVEEFPR KLLAFKEKLG EGQFGEVHLC EVEGMEKFKD KDFALDVSAN
610 620 630 640 650 660
QPVLVAVKML RADANKNARN DFLKEIKIMS RLKDPNIIRL LAVCITEDPL CMITEYMENG
670 680 690 700 710 720
DLNQFLSRHE PLSSCSSDAT VSYANLKFMA TQIASGMKYL SSLNFVHRDL ATRNCLVGKN
730 740 750 760 770 780
YTIKIADFGM SRNLYSGDYY RIQGRAVLPI RWMSWESILL GKFTTASDVW AFGVTLWETF
790 800 810 820 830 840
TFCQEQPYSQ LSDEQVIENT GEFFRDQGRQ IYLPQPALCP DSVYKLMLSC WRRETKHRPS
850
FQEIHLLLLQ QGAE