DDR1 discoidin domain receptor tyrosine kinase 1 [Homo sapiens] - Gene

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Summary

Official Symbol: DDR1provided by HGNC
Official Full Name: discoidin domain receptor tyrosine kinase 1provided by HGNC
Primary source: HGNC:2730
Locus tag: DAAP-278B20.1
See related: Ensembl:ENSG00000204580; HPRD:02678; MIM:600408; Vega:OTTHUMG00000031236
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: CAK; DDR; NEP; HGK2; PTK3; RTK6; TRKE; CD167; EDDR1; MCK10; NTRK4; PTK3A
Summary: Receptor tyrosine kinases play a key role in the communication of cells with their microenvironment. These kinases are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene belongs to a subfamily of tyrosine kinase receptors with homology to Dictyostelium discoideum protein discoidin I in their extracellular domain, and that are activated by various types of collagen. Expression of this protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, it has been shown to be significantly overexpressed in several human tumors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

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Genomic context

Location :: 6p21.3

Sequence :: Chromosome: 6; NC_000006.11 (30851861..30867933)

See DDR1 in Epigenomics, MapViewer

Chromosome 6 - NC_000006.11 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?

DDR1 polymorphisms are not likely to contribute to predispositions of aspirin-exacerbated respiratory disease, but may be potentially associated with FEV(1) decline by aspirin provocation in asthmatics.
Title: Potential association of DDR1 genetic variant with FEV1 decline by aspirin provocation in asthmatics.
The results of this study suggested that the DDR1 A2RE sequence is functionally involved in the hnRNP A2/B1-mediated splicing and transport of the DDR1c mRNA.
Title: The discoidin domain receptor 1 gene has a functional A2RE sequence.
malfunction of neprilysin in infected macrophages may contribute to acceleration of beta amyloidosis in HIV-inflicted brains
Title: HIV-1 reduces Abeta-degrading enzymatic activities in primary human mononuclear phagocytes.
These data suggest that extracellular matrix signalling via DDR1 regulates aspects of bronchial epithelial repair, integrity and MMP expression in the airways.
Title: Discoidin domain receptor 1 regulates bronchial epithelial repair and matrix metalloproteinase production.
DDR1 exerts prosurvival effect, at least in part, through the functional interaction with Notch1.
Title: DDR1 receptor tyrosine kinase promotes prosurvival pathway through Notch1 activation.
Discoidin domain receptor 1 transmembrane signalling, collagen binding and receptor activation occurred with triple-helical peptides containing the GVMGFO motif
Title: Collagen binding specificity of the discoidin domain receptors: binding sites on collagens II and III and molecular determinants for collagen IV recognition by DDR1.
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 DDR1 mediates MMP-2 and -9 secretions and invasion induced by native type IV collagen in MDA-MB-231 breast cancer cells.
Title: Role of DDR1 in the gelatinases secretion induced by native type IV collagen in MDA-MB-231 breast cancer cells.
Type I collagen induces smooth muscle cell migration through DDR1
Title: Collagen stimulates discoidin domain receptor 1-mediated migration of smooth muscle cells through Src.
These data elucidate DDR1 function pertinent to cirrhosis and indicate the importance of epithelial cell-collagen interactions in chronic liver injury.
Title: Discoidin domain receptor 1: isoform expression and potential functions in cirrhotic human liver.

Submit: New GeneRIF Correction See all (46)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Common genetic variation and the control of HIV-1 in humans.

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_054699.1	NP_054699.1	DDR1	BIND	PubMed	The DDR1 receptor tyrosine kinase autophosphorylates
NP_054699.1	NP_003020.2	SHC1	BIND	PubMed	DDR1 interacts with Shc.
Q08345	Chromosome 1 open reading frame 165	BEND5	HPRD	PubMed
Q08345	P12107	COL11A1	HPRD	PubMed
Q08345	P02458	COL2A1	HPRD	PubMed
Q08345	P02461	COL3A1	HPRD	PubMed
Q08345	P05997	COL5A2	HPRD	PubMed
Q08345	Q08345	DDR1	HPRD	PubMed
Q08345	Q8WU20	FRS2	HPRD	PubMed
Q08345	O43639	NCK2	HPRD	PubMed
Q08345	P19174	PLCG1	HPRD	PubMed
Q08345	Q06124	PTPN11	HPRD	PubMed
Q08345	P41220	RGS2	HPRD	PubMed
Q08345	P29353	SHC1	HPRD	PubMed
Q08345	O95295	SNAPIN	HPRD	PubMed
Q08345	Q96DI7	SNRNP40	HPRD	PubMed
Q08345	P30408	TM4SF1	HPRD	PubMed
Q08345	P02766	TTR	HPRD	PubMed
BioGRID:107234	BioGRID:111583	MAPK6	BioGRID	PubMed	Two-hybrid
BioGRID:107234	BioGRID:116336	NUDT3	BioGRID	PubMed	Two-hybrid
BioGRID:107234	BioGRID:111929	RGS2	BioGRID	PubMed	Two-hybrid
BioGRID:107234	BioGRID:112361	SHC1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107234	BioGRID:117101	SNAPIN	BioGRID	PubMed	Two-hybrid
BioGRID:107234	BioGRID:114805	SNRNP40	BioGRID	PubMed	Two-hybrid
BioGRID:107234	BioGRID:110249	TM4SF1	BioGRID	PubMed	Two-hybrid
BioGRID:107234	BioGRID:113127	TTR	BioGRID	PubMed	Two-hybrid
BioGRID:107234	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	PubMed
collagen binding	IMP Inferred from Mutant Phenotype more info	PubMed
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase activity	IEA Inferred from Electronic Annotation more info
protein tyrosine kinase collagen receptor activity	IDA Inferred from Direct Assay more info
receptor activity	IEA Inferred from Electronic Annotation more info
transferase activity, transferring phosphorus-containing groups	IEA Inferred from Electronic Annotation more info
transmembrane receptor protein tyrosine kinase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
branching involved in mammary gland duct morphogenesis	IEA Inferred from Electronic Annotation more info
cell adhesion	IEA Inferred from Electronic Annotation more info
collagen-activated tyrosine kinase receptor signaling pathway	IDA Inferred from Direct Assay more info
collagen-activated tyrosine kinase receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
ear development	IEA Inferred from Electronic Annotation more info
embryo implantation	IEA Inferred from Electronic Annotation more info
mammary gland alveolus development	IEA Inferred from Electronic Annotation more info
negative regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
organ regeneration	IEA Inferred from Electronic Annotation more info
peptidyl-tyrosine autophosphorylation	IDA Inferred from Direct Assay more info
protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
regulation of cell growth	IEA Inferred from Electronic Annotation more info
regulation of cell-matrix adhesion	IEA Inferred from Electronic Annotation more info
regulation of extracellular matrix disassembly	IMP Inferred from Mutant Phenotype more info	PubMed
skin development	IEA Inferred from Electronic Annotation more info
smooth muscle cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
smooth muscle cell-matrix adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
wound healing, spreading of cells	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
basolateral plasma membrane	IEA Inferred from Electronic Annotation more info
extracellular region	IEA Inferred from Electronic Annotation more info
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: epithelial discoidin domain-containing receptor 1

Names: epithelial discoidin domain-containing receptor 1; tyrosine kinase DDR; cell adhesion kinase; mammary carcinoma kinase 10; tyrosine-protein kinase CAK; protein-tyrosine kinase RTK-6; neuroepithelial tyrosine kinase; PTK3A protein tyrosine kinase 3A; CD167 antigen-like family member A; neurotrophic tyrosine kinase, receptor, type 4

NP_001189450.1

EC 2.7.10.1

NP_001189451.1

EC 2.7.10.1

NP_001189452.1

EC 2.7.10.1

NP_001945.3

EC 2.7.10.1

NP_054699.2

EC 2.7.10.1

NP_054700.2

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_029066.1 RefSeqGene

Range

5001..21073

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001202521.1 → NP_001189450.1 epithelial discoidin domain-containing receptor 1 isoform 4 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4) is missing an internal coding exon compared to variant 1. This results in a frame-shift, and early translation termination, rendering this transcript a candidate for nonsense-mediated mRNA decay (NMD). However, the encoded isoform (4, also known as DDR1d) is represented as it has been detected in vivo in several colon carcinoma cell lines (PMID:11344127). This isoform is truncated and lacks the catalytic tyrosine kinase domain, therefore, most likely lacks intrinsic tyrosine kinase activity. It may function in some other regulatory capacity.

Source sequence(s)

AF353182, BC008716, L20817

UniProtKB/Swiss-Prot

Q08345

UniProtKB/TrEMBL

Q96T62

Conserved Domains (2) summary

cd00057
Location:68 – 184
Blast Score: 300

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.

smart00231
Location:30 – 185
Blast Score: 280

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain
NM_001202522.1 → NP_001189451.1 epithelial discoidin domain-containing receptor 1 isoform 5 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (5) is missing an internal coding exon, and uses an alternate acceptor splice site at one of the coding exons compared to variant 1. This results in localized frame-shift, and a shorter isoform (5, also known as DDR1e) compared to isoform 1. This isoform lacks the ATP binding site, therefore, most likely lacks intrinsic tyrosine kinase activity. It may function in some other regulatory capacity.

Source sequence(s)

AF353183, BC008716, L20817

UniProtKB/Swiss-Prot

Q08345

UniProtKB/TrEMBL

Q96T61

Conserved Domains (4) summary

cd00057
Location:68 – 184
Blast Score: 305

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.

smart00219
Location:498 – 759
Blast Score: 858

TyrKc; Tyrosine kinase, catalytic domain

smart00231
Location:30 – 185
Blast Score: 285

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

cl09925
Location:478 – 761
Blast Score: 1470

PKc_like; Protein Kinases, catalytic domain
NM_001202523.1 → NP_001189452.1 epithelial discoidin domain-containing receptor 1 isoform 6 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (6) contains an alternate 5' terminal exon compared to variant 1. This results in translation initiation from an in-frame upstream start codon, and a longer isoform (6) with a distinct N-terminus compared to isoform 1.

Source sequence(s)

AK294793, BC008716, DC369107

Consensus CDS

CCDS56411.1

UniProtKB/Swiss-Prot

Q08345

Related

ENSP00000422442, OTTHUMP00000222080, ENST00000508312, OTTHUMT00000369045

Conserved Domains (4) summary

cd00057
Location:86 – 202
Blast Score: 307

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.

cd05096
Location:585 – 888
Blast Score: 1580

PTKc_DDR1; Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1

smart00219
Location:591 – 886
Blast Score: 919

TyrKc; Tyrosine kinase, catalytic domain

smart00231
Location:48 – 203
Blast Score: 285

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain
NM_001954.4 → NP_001945.3 epithelial discoidin domain-containing receptor 1 isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the predominant transcript, and encodes isoform 1 (also known as DDR1a).

Source sequence(s)

BC008716, BC070070

Consensus CDS

CCDS4690.1

UniProtKB/Swiss-Prot

Q08345

Related

ENSP00000365754, ENST00000376570

Conserved Domains (4) summary

cd00057
Location:68 – 184
Blast Score: 306

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.

cd05096
Location:567 – 870
Blast Score: 1583

PTKc_DDR1; Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1

smart00219
Location:573 – 868
Blast Score: 919

TyrKc; Tyrosine kinase, catalytic domain

smart00231
Location:30 – 185
Blast Score: 285

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain
NM_013993.2 → NP_054699.2 epithelial discoidin domain-containing receptor 1 isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an additional in-frame coding exon compared to variant 1, resulting in a longer isoform (2, also known as DDR1b) with a 37 aa protein segment not found in isoform 1.

Source sequence(s)

BC008716, CN362335, L11315

Consensus CDS

CCDS34385.1

UniProtKB/Swiss-Prot

Q08345

Related

ENSP00000405039, ENST00000452441

Conserved Domains (4) summary

cd00057
Location:68 – 184
Blast Score: 305

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.

cd05096
Location:604 – 907
Blast Score: 1584

PTKc_DDR1; Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1

smart00219
Location:610 – 905
Blast Score: 921

TyrKc; Tyrosine kinase, catalytic domain

smart00231
Location:30 – 185
Blast Score: 284

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain
NM_013994.2 → NP_054700.2 epithelial discoidin domain-containing receptor 1 isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an additional in-frame coding exon, and uses an alternate in-frame acceptor splice site at one of the coding exons compared to variant 1. This results in the longest isoform (3, also known as DDR1c) with additional protein segments not found in isoform 1.

Source sequence(s)

BC008716, BI193181, L11315, Z29093

Consensus CDS

CCDS47396.1

UniProtKB/Swiss-Prot

Q08345

Related

ENSP00000427552, OTTHUMP00000164867, ENST00000513240, OTTHUMT00000257577

Conserved Domains (4) summary

cd00057
Location:68 – 184
Blast Score: 305

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.

smart00219
Location:610 – 911
Blast Score: 904

TyrKc; Tyrosine kinase, catalytic domain

smart00231
Location:30 – 185
Blast Score: 285

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

cl09925
Location:604 – 913
Blast Score: 1567

PKc_like; Protein Kinases, catalytic 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_000006.11 Reference GRCh37.p5 Primary Assembly

Range

30851861..30867933

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p5 ALT_REF_LOCI_1

Genomic

NT_167244.1 Reference GRCh37.p5 ALT_REF_LOCI_1

Range

2164481..2168878

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p5 ALT_REF_LOCI_2

Genomic

NT_113891.2 Reference GRCh37.p5 ALT_REF_LOCI_2

Range

2363959..2380033

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p5 ALT_REF_LOCI_3

Genomic

NT_167245.1 Reference GRCh37.p5 ALT_REF_LOCI_3

Range

2145963..2162051

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p5 ALT_REF_LOCI_4

Genomic

NT_167246.1 Reference GRCh37.p5 ALT_REF_LOCI_4

Range

2199946..2216014

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p5 ALT_REF_LOCI_5

Genomic

NT_167247.1 Reference GRCh37.p5 ALT_REF_LOCI_5

Range

2233818..2254651

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p5 ALT_REF_LOCI_6

Genomic

NT_167248.1 Reference GRCh37.p5 ALT_REF_LOCI_6

Range

2144848..2160922

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000138.1 Alternate HuRef

Range

30652534..30668027

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AB088102.1	BAC54935.1
genomic	AB103608.1	BAF31270.1
genomic	AB202100.1	BAE78621.1
genomic	AL662854.7 (8675..24749)	None
genomic	AL662870.16 (37540..53612)	None
genomic	AL773541.6	CAI18450.1
		CAI18451.1
genomic	AL773589.3	CAI18533.1
		CAI18534.1
genomic	AL805917.3 (64390..65372)	None
genomic	BA000025.2	BAB63318.1
genomic	BX927194.9	CAQ09767.1
		CAQ09768.1
genomic	CH471081.1	EAX03335.1
		EAX03336.1
		EAX03337.1
		EAX03338.1
		EAX03339.1
		EAX03340.1
		EAX03341.1
		EAX03342.1
		EAX03343.1
		EAX03344.1
		EAX03345.1
		EAX03346.1
genomic	CR753093.2 (26149..28271)	None
genomic	CR759747.7	CAQ06756.1
		CAQ06757.1
genomic	CR936875.3	None
genomic	CR936908.2	CAQ07770.1
		CAQ07771.1
genomic	CR942271.10	CAX15129.1
		CAX15130.1
		CAX15131.1
		CAX15132.1
		CAX15133.1
		CAX15134.1
		CAX15135.1
genomic	U48705.1	AAC50917.1
genomic	X98208.1	CAA66871.1
genomic	X99031.1	None
mRNA	AB210021.1	BAE06103.1
mRNA	AF353182.1	AAK48842.1
mRNA	AF353183.1	AAK48843.1
mRNA	AK130776.1	BAC85426.1
mRNA	AK291621.1	BAF84310.1
mRNA	AK294793.1	BAH11886.1
mRNA	AK295643.1	BAH12138.1
mRNA	BC008716.2	AAH08716.1
mRNA	BC013400.2	AAH13400.1
mRNA	BC070070.1	AAH70070.1
mRNA	BI193181.1	None
mRNA	BM875592.1	None
mRNA	CN362335.1	None
mRNA	DC369107.1	None
mRNA	EU826613.1	ACF47649.1
mRNA	EU826614.1	ACF47650.1
mRNA	L11315.1	AAA02866.1
mRNA	L20817.1	AAA18019.1
mRNA	L57508.1	AAB05208.1
mRNA	X74979.1	CAA52915.1
mRNA	Z29093.1	CAA82335.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
Q08345.1	GenPept	UniProtKB/Swiss-Prot:Q08345
Q6ZNR9	GenPept	UniProtKB/TrEMBL:Q6ZNR9
Q96T61	GenPept	UniProtKB/TrEMBL:Q96T61
Q96T62	GenPept	UniProtKB/TrEMBL:Q96T62