DDR2 discoidin domain receptor tyrosine kinase 2 [Homo sapiens] - Gene

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Summary

Official Symbol: DDR2provided by HGNC
Official Full Name: discoidin domain receptor tyrosine kinase 2provided by HGNC
Primary source: HGNC:2731
Locus tag: RP11-572K18.1
See related: Ensembl:ENSG00000162733; HPRD:01868; MIM:191311; Vega:OTTHUMG00000034423
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TKT; MIG20a; NTRKR3; TYRO10
Summary: Receptor tyrosine kinases (RTKs) play a key role in the communication of cells with their microenvironment. These molecules are involved in the regulation of cell growth, differentiation, and metabolism. In several cases the biochemical mechanism by which RTKs transduce signals across the membrane has been shown to be ligand induced receptor oligomerization and subsequent intracellular phosphorylation. This autophosphorylation leads to phosphorylation of cytosolic targets as well as association with other molecules, which are involved in pleiotropic effects of signal transduction. RTKs have a tripartite structure with extracellular, transmembrane, and cytoplasmic regions. This gene encodes a member of a novel subclass of RTKs and contains a distinct extracellular region encompassing a factor VIII-like domain. Alternative splicing in the 5' UTR results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 1q23.3

Sequence :: Chromosome: 1; NC_000001.10 (162602228..162750255)

See DDR2 in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

DDR2 promotes A375 melanoma metastasis to the liver and the underlying mechanism implicates regulation of metalloproteinase release, cell growth and chemotactic invasion of the host tissue.
Title: Downregulation of discoidin domain receptor 2 in A375 human melanoma cells reduces its experimental liver metastasis ability.
Discoidin domain receptor 2 is a critical regulator of epithelial-mesenchymal transition
Title: Discoidin domain receptor 2 is a critical regulator of epithelial-mesenchymal transition.
Collagen I induces discoidin domain receptor (DDR) 1 expression through DDR2 and a JAK2-ERK1/2-mediated mechanism in primary human lung fibroblasts.
Title: Collagen I induces discoidin domain receptor (DDR) 1 expression through DDR2 and a JAK2-ERK1/2-mediated mechanism in primary human lung fibroblasts.
The stimulation of p38 MAPK by DDR2 was required for DDR2-induced activation of Runx2 and OCN promoters.
Title: Transcriptional upregulation of DDR2 by ATF4 facilitates osteoblastic differentiation through p38 MAPK-mediated Runx2 activation.
Spondylo-meta-epiphyseal dysplasia with short limbs and abnormal calcifications can result from at least two different loss-of-function mechanisms: defects in DDR2 targeting to the plasma membrane or the loss of its ligand-binding activity.
Title: Trafficking defects and loss of ligand binding are the underlying causes of all reported DDR2 missense mutations found in SMED-SL patients.
Meta-analysis of gene-disease association. (HuGE Navigator)
Title: Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot".
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
DDR2-mediated MMP-13 induction by collagen matrix in synovial fibroblasts of RA contributed to articular cartilage destruction
Title: Discoidin domain receptor 2 is associated with the increased expression of matrix metalloproteinase-13 in synovial fibroblasts of rheumatoid arthritis.
Observational study of gene-disease association. (HuGE Navigator)
Title: Follow-up of a major linkage peak on chromosome 1 reveals suggestive QTLs associated with essential hypertension: GenNet study.
There are three missense mutations c.2254 C > T [R752C], c. 2177 T > G [I726R], c.2138C > T [T713I] and one splice site mutation [IVS17+1g > a] in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene.
Title: Mutations in DDR2 gene cause SMED with short limbs and abnormal calcifications.

Submit: New GeneRIF Correction See all (22)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Spondylometaepiphyseal dysplasia, short limb-hand type

MIM: 271665

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Products	Interactant	Other Gene	Source	Pubs	Description
Q16832	P02452	COL1A1	HPRD	PubMed
Q16832	P02461	COL3A1	HPRD	PubMed
Q16832	P29353	SHC1	HPRD	PubMed
Q16832	P12931	SRC	HPRD	PubMed
BioGRID:110975	BioGRID:112361	SHC1	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:110975	BioGRID:112592	SRC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110975	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
collagen binding	IDA Inferred from Direct Assay more info
kinase activity	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein tyrosine kinase collagen receptor activity	IDA Inferred from Direct Assay more info	PubMed
receptor activity	IEA Inferred from Electronic Annotation more info
transmembrane receptor protein tyrosine kinase activity	IDA Inferred from Direct Assay more info

Process	Evidence Code	Pubs
cell adhesion	IEA Inferred from Electronic Annotation more info
chondrocyte proliferation	ISS Inferred from Sequence or Structural Similarity more info
chondrocyte proliferation	TAS Traceable Author Statement more info	PubMed
collagen-activated tyrosine kinase receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
endochondral bone growth	ISS Inferred from Sequence or Structural Similarity more info
ossification	IEA Inferred from Electronic Annotation more info
peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info
positive regulation of extracellular matrix disassembly	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of fibroblast migration	IEA Inferred from Electronic Annotation more info
positive regulation of fibroblast migration	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of fibroblast migration	TAS Traceable Author Statement more info	PubMed
positive regulation of fibroblast proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of fibroblast proliferation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of osteoblast differentiation	IMP Inferred from Mutant Phenotype more info
positive regulation of protein kinase activity	IMP Inferred from Mutant Phenotype more info
positive regulation of sequence-specific DNA binding transcription factor activity	IMP Inferred from Mutant Phenotype more info
protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
regulation of bone mineralization	IMP Inferred from Mutant Phenotype more info
regulation of extracellular matrix disassembly	TAS Traceable Author Statement more info	PubMed
signal transduction	TAS Traceable Author Statement more info	PubMed
transmembrane receptor protein tyrosine kinase signaling pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
integral to plasma membrane	TAS Traceable Author Statement more info	PubMed
plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: discoidin domain-containing receptor 2

Names: discoidin domain-containing receptor 2; tyrosylprotein kinase; hydroxyaryl-protein kinase; discoidin domain receptor 2; tyrosine-protein kinase TYRO10; CD167 antigen-like family member B; cell migration-inducing protein 20; migration-inducing gene 16 protein; receptor protein-tyrosine kinase TKT; discoidin domain receptor family, member 2; neurotrophic tyrosine kinase receptor related 3; neurotrophic tyrosine kinase, receptor-related 3; discoidin domain-containing receptor tyrosine kinase 2

NP_001014796.1

EC 2.7.10.1

NP_006173.2

EC 2.7.10.1

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016290.1 RefSeqGene

Range

5001..153028

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001014796.1 → NP_001014796.1 discoidin domain-containing receptor 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript.

Source sequence(s)

AA148473, BC052998, CF994640

Consensus CDS

CCDS1241.1

UniProtKB/Swiss-Prot

Q16832

Related

ENSP00000356899, OTTHUMP00000032332, ENST00000367922, OTTHUMT00000083213

Conserved Domains (4) summary

cd00057
Location:32 – 184
Blast Score: 389

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.

cd05095
Location:557 – 851
Blast Score: 1650

PTKc_DDR2; Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2

smart00221
Location:563 – 849
Blast Score: 972

STYKc; Protein kinase; unclassified specificity.

smart00231
Location:30 – 185
Blast Score: 339

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain
NM_006182.2 → NP_006173.2 discoidin domain-containing receptor 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform.

Source sequence(s)

AA148473, BC052998, CF994640, X74764

Consensus CDS

CCDS1241.1

UniProtKB/Swiss-Prot

Q16832

Related

ENSP00000356898, OTTHUMP00000038368, ENST00000367921, OTTHUMT00000097650

Conserved Domains (4) summary

cd00057
Location:32 – 184
Blast Score: 389

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.

cd05095
Location:557 – 851
Blast Score: 1650

PTKc_DDR2; Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2

smart00221
Location:563 – 849
Blast Score: 972

STYKc; Protein kinase; unclassified specificity.

smart00231
Location:30 – 185
Blast Score: 339

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000001.10 Reference GRCh37.p5 Primary Assembly

Range

162602228..162750255

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

133847299..133995362

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AL445197.4	CAI15939.1
		CAI15940.1
		CAI15941.1
		CAI15942.1
		CAI15943.1
genomic	AL596325.5 (100870..152769)	None
genomic	CH471067.1	EAW90713.1
		EAW90714.1
mRNA	AA148473.1	None
mRNA	AK095975.1	BAG53183.1
mRNA	AK225063.1	None
mRNA	AK225196.1	None
mRNA	AK314388.1	BAG37013.1
mRNA	AY423733.1	AAS00496.1
mRNA	AY871271.1	AAX11427.1
mRNA	BC052998.2	AAH52998.1
mRNA	BX640899.1	CAE45946.1
mRNA	CF994640.1	None
mRNA	X74764.1	CAA52777.1
other-genetic	EU832145.1	ACE87495.1
other-genetic	EU832238.1	ACE86808.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
Q16832.2	GenPept	UniProtKB/Swiss-Prot:Q16832
Q5J7V3	GenPept	UniProtKB/TrEMBL:Q5J7V3
Q5T242	GenPept	UniProtKB/TrEMBL:Q5T242
Q5T244	GenPept	UniProtKB/TrEMBL:Q5T244
Q5T245	GenPept	UniProtKB/TrEMBL:Q5T245
Q6MZT2	GenPept	UniProtKB/TrEMBL:Q6MZT2