InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DDR2

Summary

InnateDB Protein

IDBP-104398.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DDR2

Protein Name

discoidin domain receptor tyrosine kinase 2

Synonyms

MIG20a; NTRKR3; TKT; TYRO10;

Species

Homo sapiens

Ensembl Protein

ENSP00000356899

InnateDB Gene

IDBG-104396 (DDR2)

Protein Structure

UniProt Annotation

Function

Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing. {ECO:0000269PubMed:16186104, ECO:0000269PubMed:16186108, ECO:0000269PubMed:17665456, ECO:0000269PubMed:18201965, ECO:0000269PubMed:20004161, ECO:0000269PubMed:20564243, ECO:0000269PubMed:20734453, ECO:0000269PubMed:9659899}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:18201965, ECO:0000269PubMed:20223752, ECO:0000269PubMed:9659899}; Single- pass type I membrane protein {ECO:0000269PubMed:18201965, ECO:0000269PubMed:20223752, ECO:0000269PubMed:9659899}.

Disease Associations

Spondyloepimetaphyseal dysplasia short limb-hand type (SEMD-SL) [MIM:271665]: A bone disease characterized by short- limbed dwarfism, a narrow chest with pectus excavatum, brachydactyly in the hands and feet, a characteristic craniofacial appearance and premature calcifications. The radiological findings are distinctive and comprise short long bones throughout the skeleton with striking epiphyses that are stippled, flattened and fragmented and flared, irregular metaphyses. Platyspondyly in the spine with wide intervertebral spaces is observed and some vertebral bodies are pear-shaped with central humps, anterior protrusions and posterior scalloping. {ECO:0000269PubMed:19110212, ECO:0000269PubMed:20223752}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Detected in osteocytes, osteoblastic cells in subchondral bone, bone lining cells, tibia and cartilage (at protein level). Detected at high levels in heart and lung, and at low levels in brain, placenta, liver, skeletal muscle, pancreas, and kidney. {ECO:0000269PubMed:17665456, ECO:0000269PubMed:20564243, ECO:0000269PubMed:8247548}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 8 experimentally validated interaction(s) in this database.

Experimentally validated
Total	8 [view]
Protein-Protein	8 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005518	collagen binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0038062	protein tyrosine kinase collagen receptor activity

Biological Process

GO:0001503	ossification
GO:0003416	endochondral bone growth
GO:0006468	protein phosphorylation
GO:0007155	cell adhesion
GO:0007165	signal transduction
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0008284	positive regulation of cell proliferation
GO:0010715	regulation of extracellular matrix disassembly
GO:0010763	positive regulation of fibroblast migration
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030198	extracellular matrix organization
GO:0030199	collagen fibril organization
GO:0030500	regulation of bone mineralization
GO:0031214	biomineral tissue development
GO:0035988	chondrocyte proliferation
GO:0038063	collagen-activated tyrosine kinase receptor signaling pathway
GO:0045669	positive regulation of osteoblast differentiation
GO:0045860	positive regulation of protein kinase activity
GO:0046777	protein autophosphorylation
GO:0048146	positive regulation of fibroblast proliferation
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0090091	positive regulation of extracellular matrix disassembly

Cellular Component

GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0016324	apical plasma membrane
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000421 Coagulation factor 5/8 C-terminal type domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR008979 Galactose-binding domain-like
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00754
PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00231
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt