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)

Target domain

606-901 (Protein kinase domain)

Relief mechanism

PTM

Assay

Accessory elements

779-804 (Activation loop from InterPro)

Target domain

606-901 (Protein kinase domain)

Relief mechanism

Assay

779-804 (Activation loop from InterPro)

Target domain

606-901 (Protein kinase domain)

Relief mechanism

Assay

Autoinhibited structure

Activated structure

1 structures for Q7YR43

Entry ID Method Resolution Chain Position Source
AF-Q7YR43-F1 Predicted AlphaFoldDB

No variants for Q7YR43

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q7YR43

No associated diseases with Q7YR43

3 regional properties for Q7YR43

Type Name Position InterPro Accession
domain Myosin head, motor domain 78 - 780 IPR001609
domain Myosin tail 847 - 1924 IPR002928
domain Myosin, N-terminal, SH3-like 31 - 80 IPR004009

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

2 GO annotations of cellular component

Name Definition
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
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%).
metal ion binding Binding to a metal ion.
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

9 GO annotations of biological process

Name Definition
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.
female pregnancy The set of physiological processes that allow an embryo or foetus to develop within the body of a female animal. It covers the time from fertilization of a female ovum by a male spermatozoon until birth.
lactation The regulated release of milk from the mammary glands and the period of time that a mother lactates to feed her young.
peptidyl-tyrosine autophosphorylation The phosphorylation by a protein of one or more of its own tyrosine amino acid residues, or a tyrosine residue on an identical protein.
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).
regulation of extracellular matrix disassembly Any process that modulates the rate, frequency or extent of extracellular matrix disassembly. Extracellular matrix disassembly is a process that results in the breakdown of the extracellular matrix.
smooth muscle cell migration The orderly movement of a smooth muscle cell from one site to another, often during the development of a multicellular organism.
smooth muscle cell-matrix adhesion The binding of a smooth muscle cell to the extracellular matrix via adhesion molecules.
wound healing, spreading of cells The migration of a cell along or through a wound gap that contributes to the reestablishment of a continuous surface.

9 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q5F3X2 DDR1 receptor protein-tyrosine kinase Gallus gallus (Chicken) SS
Q5IS37 NTRK3 NT-3 growth factor receptor Pan troglodytes (Chimpanzee) SS
Q16832 DDR2 Discoidin domain-containing receptor 2 Homo sapiens (Human) SS
Q08345 DDR1 Epithelial discoidin domain-containing receptor 1 Homo sapiens (Human) EV
Q62371 Ddr2 Discoidin domain-containing receptor 2 Mus musculus (Mouse) SS
Q03146 Ddr1 Epithelial discoidin domain-containing receptor 1 Mus musculus (Mouse) SS
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
MGPEALSSLL LLLLVASGDA DMKGHFDPAK CRYALGMQDR TIPDSDISAS SSWSDSTAAR
70 80 90 100 110 120
HSSDGDGAWC PAGSVFPKEE EYLQVDLQRL HLVALVGTQG RHAGGLGKEF SRSYRLRYSR
130 140 150 160 170 180
DGRRWMGWKD RWGQEVISGN EDPEGVVLKD LGPPMVARLV RFYPRADRVM SVCLRVELYG
190 200 210 220 230 240
CLWRDGLLSY TAPVGQTMYL SEAVYLNDST YDGHTVGGLQ YGGLGQLADG VVGLDDFRKS
250 260 270 280 290 300
QELRVWPGYD YVGWSNHSFS SGYVEMEFEF DRLRAFQAMQ VHCNNMHTLG ARLPGGVECR
310 320 330 340 350 360
FRRGPAMAWE GEPMRHNLGG NLGDPRARAV SVPLGGRVAR FLQCRFLFAG PWLLFSEISF
370 380 390 400 410 420
ISDVVNNSSP ALGGTFPPAP WWPPGPPPTN FSSLELEPRG QQPVAKAEGS PTAILIGCLV
430 440 450 460 470 480
AIILLLLLII ALMLWRLHWR RLLSKAERRV LEEELTVHLS VPGDTILINN RPGPREPPPY
490 500 510 520 530 540
QEPRPRGNPP HSAPCVPNGS ALLLSNPAYR LLLATYARPP RGPGPPTPAW AKPTNTQAYS
550 560 570 580 590 600
GDYMEPEKPG APLLPPPPQN SVPHYAEADI VTLQGVTGGN TYAVPALPPG AVGDGPPRVD
610 620 630 640 650 660
FPRSRLRFKE KLGEGQFGEV HLCEVDSPQD LVSLDFPLNV RKGHPLLVAV KILRPDATKN
670 680 690 700 710 720
ARNDFLKEVK IMSRLKDPNI IRLLGVCVQD DPLCMITDYM ENGDLNQFLS AHQLEDKAAE
730 740 750 760 770 780
GAPGDGQAAQ GPTISYPMLL HVAAQIASGM RYLATLNFVH RDLATRNCLV GENFTIKIAD
790 800 810 820 830 840
FGMSRNLYAG DYYRVQGRAV LPIRWMAWEC ILMGKFTTAS DVWAFGVTLW EVLMLCRAQP
850 860 870 880 890 900
FGQLTDEQVI ENAGEFFRDQ GRQVYLSRPP ACPQGLYELM LRCWSRESEQ RPPFSQLHRF
LAEDALNTV