InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DDR1

Summary

InnateDB Protein

IDBP-76167.7

Last Modified

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

Gene Symbol

DDR1

Protein Name

discoidin domain receptor tyrosine kinase 1

Synonyms

CAK; CD167; DDR; EDDR1; HGK2; MCK10; NEP; NTRK4; PTK3; PTK3A; RTK6; TRKE;

Species

Homo sapiens

Ensembl Protein

ENSP00000365754

InnateDB Gene

IDBG-76157 (DDR1)

Protein Structure

UniProt Annotation

Function

Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing. Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing (By similarity). Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Also plays a role in tumor cell invasion. Phosphorylates PTPN11. {ECO:0000250, ECO:0000269PubMed:12065315, ECO:0000269PubMed:16234985, ECO:0000269PubMed:16337946, ECO:0000269PubMed:19401332, ECO:0000269PubMed:20093046, ECO:0000269PubMed:20432435, ECO:0000269PubMed:20884741, ECO:0000269PubMed:21044884, ECO:0000269PubMed:9659899}.

Subcellular Localization

Isoform 1: Cell membrane; Single-pass type I membrane protein.Isoform 2: Cell membrane; Single-pass type I membrane protein.Isoform 3: Secreted {ECO:0000305}.Isoform 4: Cell membrane; Single-pass type I membrane protein.

Disease Associations

Tissue Specificity

Detected in T-47D, MDA-MB-175 and HBL-100 breast carcinoma cells, A-431 epidermoid carcinoma cells, SW48 and SNU-C2B colon carcinoma cells and Hs 294T melanoma cells (at protein level). Expressed at low levels in most adult tissues and is highest in the brain, lung, placenta and kidney. Lower levels of expression are detected in melanocytes, heart, liver, skeletal muscle and pancreas. Abundant in breast carcinoma cell lines. In the colonic mucosa, expressed in epithelia but not in the connective tissue of the lamina propria. In the thyroid gland, expressed in the epithelium of the thyroid follicles. In pancreas, expressed in the islets of Langerhans cells, but not in the surrounding epithelial cells of the exocrine pancreas. In kidney, expressed in the epithelia of the distal tubules. Not expressed in connective tissue, endothelial cells, adipose tissue, muscle cells or cells of hematopoietic origin. {ECO:0000269PubMed:7845687, ECO:0000269PubMed:7848919, ECO:0000269PubMed:8247543}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 19 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	19 [view]
Protein-Protein	19 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

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
GO:0046872	metal ion binding

Biological Process

GO:0006468	protein phosphorylation
GO:0007155	cell adhesion
GO:0007595	lactation
GO:0010715	regulation of extracellular matrix disassembly
GO:0014909	smooth muscle cell migration
GO:0030198	extracellular matrix organization
GO:0038063	collagen-activated tyrosine kinase receptor signaling pathway
GO:0038083	peptidyl-tyrosine autophosphorylation
GO:0044319	wound healing, spreading of cells
GO:0046777	protein autophosphorylation
GO:0061302	smooth muscle cell-matrix adhesion

Cellular Component

GO:0005615	extracellular space
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0043235	receptor complex
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