Reviewed,
UniProtKB/Swiss-Prot Q08345 (DDR1_HUMAN)
Last modified
July 7, 2009.
Version 109.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: Epithelial discoidin domain-containing receptor 1 Short name=Epithelial discoidin domain receptor 1 EC=2.7.10.1 Alternative name(s): Tyrosine kinase DDR Discoidin receptor tyrosine kinase Tyrosine-protein kinase CAK Cell adhesion kinase TRK E Protein-tyrosine kinase RTK 6 HGK2 CD167 antigen-like family member A CD_antigen=CD167a | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 913 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | May be involved in cell-cell interactions and recognition. |
| Catalytic activity | ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. |
| Subcellular location | Isoform 1: Membrane; Single-pass type I membrane protein. Isoform 2: Membrane; Single-pass type I membrane protein. Isoform 3: Secreted Potential. Isoform 4: Secreted Potential. |
| Tissue specificity | Expressed at low levels in most adult tissues and is highest in the brain and lung. Abundant in breast carcinoma cell lines. |
| Domain | The Gly/Pro-rich domains may be required for an unusual geometry of interaction with ligand or substrates. |
| Sequence similarities | Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily. Contains 1 F5/8 type C domain. Contains 1 protein kinase domain. |
Ontologies
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q08345-1) Also known as: CAK I; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q08345-2) Also known as: CAK II; Short; The sequence of this isoform differs from the canonical sequence as follows: 506-542: Missing. | ||||||
| Isoform 3 (identifier: Q08345-3) Also known as: Soluble DDR1 variant 1; The sequence of this isoform differs from the canonical sequence as follows: 285-286: VH → MW 287-913: Missing. | ||||||
| Isoform 4 (identifier: Q08345-4) Also known as: Soluble DDR1 variant 2; The sequence of this isoform differs from the canonical sequence as follows: 190-243: GLLSYTAPVG...GVVGLDDFRK → CSMGVWASWQ...MWRWSLSLTG 244-913: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 18 | 18 | Potential | ||||||||
| Chain | 19 – 913 | 895 | Epithelial discoidin domain-containing receptor 1 | PRO_0000016742 | |||||||
Regions | |||||||||||
| Topological domain | 19 – 416 | 398 | Extracellular Potential | ||||||||
| Transmembrane | 417 – 443 | 27 | Potential | ||||||||
| Topological domain | 444 – 913 | 470 | Cytoplasmic Potential | ||||||||
| Domain | 31 – 185 | 155 | F5/8 type C | ||||||||
| Domain | 610 – 905 | 296 | Protein kinase | ||||||||
| Nucleotide binding | 616 – 624 | 9 | ATP By similarity | ||||||||
| Compositional bias | 377 – 415 | 39 | Gly/Pro-rich | ||||||||
| Compositional bias | 476 – 601 | 126 | Gly/Pro-rich | ||||||||
Sites | |||||||||||
| Active site | 766 | 1 | Proton acceptor By similarity | ||||||||
| Binding site | 655 | 1 | ATP By similarity | ||||||||
Amino acid modifications | |||||||||||
| Modified residue | 513 | 1 | Phosphotyrosine; by autocatalysis By similarity | ||||||||
| Modified residue | 792 | 1 | Phosphotyrosine; by autocatalysis By similarity | ||||||||
| Modified residue | 796 | 1 | Phosphotyrosine; by autocatalysis By similarity | ||||||||
| Modified residue | 797 | 1 | Phosphotyrosine; by autocatalysis By similarity | ||||||||
| Glycosylation | 211 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 260 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 371 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 394 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Disulfide bond | 31 ↔ 185 | By similarity | |||||||||
Natural variations | |||||||||||
| Alternative sequence | 190 – 243 | 54 | GLLSY…DDFRK → CSMGVWASWQMVWWGWMTLG RVRSCGSGQAMTMWDGATTA SPVAMWRWSLSLTG in isoform 4. | VSP_036916 | |||||||
| Alternative sequence | 244 – 913 | 670 | Missing in isoform 4. | VSP_036917 | |||||||
| Alternative sequence | 285 – 286 | 2 | VH → MW in isoform 3. | VSP_036918 | |||||||
| Alternative sequence | 287 – 913 | 627 | Missing in isoform 3. | VSP_036919 | |||||||
| Alternative sequence | 506 – 542 | 37 | Missing in isoform 2. | VSP_002953 | |||||||
| Natural variant | 17 | 1 | S → G Ref.17 | VAR_041492 | |||||||
| Natural variant | 100 | 1 | V → A Ref.17 | VAR_041493 | |||||||
| Natural variant | 169 | 1 | R → Q Ref.17 | VAR_041494 | |||||||
| Natural variant | 170 | 1 | A → D Ref.17 | VAR_041495 | |||||||
| Natural variant | 306 | 1 | R → W Ref.17 | VAR_041496 | |||||||
| Natural variant | 496 | 1 | S → A in a lung squamous cell carcinoma sample; somatic mutation. Ref.17 | VAR_041497 | |||||||
| Natural variant | 833 | 1 | L → V: dbSNP rs2524235. Ref.2 Ref.3 | VAR_049716 | |||||||
Experimental info | |||||||||||
| Sequence conflict | 94 | 1 | L → V in AAA02866. Ref.2 | ||||||||
| Sequence conflict | 94 | 1 | L → V in AAC50917. Ref.3 | ||||||||
| Sequence conflict | 165 | 1 | R → H in AAH70070. Ref.14 | ||||||||
| Sequence conflict | 741 | 1 | P → Q in AAH70070. Ref.14 | ||||||||
| Sequence conflict | 847 – 867 | 21 | QLTDE…DQGRQ → SAHRRAGHRERGGVLPGPGP A in CAA66871. Ref.4 | ||||||||
Sequences
| ||||||||||||||||||||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "Identification and chromosomal mapping of a receptor tyrosine kinase with a putative phospholipid binding sequence in its ectodomain." Perez J.L., Shen X., Finkernagel S., Sciorra L., Jenkins N.A., Gilbert D.J., Copeland N.G., Wong T.W. Oncogene 9:211-219(1994) [PubMed: 8302582] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal liver. |
| [2] | "A receptor tyrosine kinase found in breast carcinoma cells has an extracellular discoidin I-like domain." Johnson J.D., Edman J.C., Rutter W.J. Proc. Natl. Acad. Sci. U.S.A. 90:5677-5681(1993) [PubMed: 8390675] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT VAL-833. Tissue: Placenta. |
| [3] | "Receptor protein tyrosine kinase DDR is up-regulated by p53 protein." Sakuma S., Tada M., Saya H., Sawamura Y., Shinohe Y., Abe H. FEBS Lett. 398:165-169(1996) [PubMed: 8977099] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-833. |
| [4] | "The genomic structure of discoidin receptor tyrosine kinase." Playford M.P., Butler R.J., Wang X.C., Katso R.M., Cooke I.E., Ganesan T.S. Genome Res. 6:620-627(1996) [PubMed: 8796349] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [5] | "Identification of two isoforms of the Cak receptor kinase that are coexpressed in breast tumor cell lines." Perez J.L., Jing S.Q., Wong T.W. Oncogene 12:1469-1477(1996) [PubMed: 8622863] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Lung. |
| [6] | "Molecular cloning of trkE, a novel trk-related putative tyrosine kinase receptor isolated from normal human keratinocytes and widely expressed by normal human tissues." di Marco E., Cutuli N., Guerra L., Cancedda R., de Luca M. J. Biol. Chem. 268:24290-24295(1993) [PubMed: 8226977] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Brain and Keratinocyte. |
| [7] | "Isolation and characterization of an epithelial-specific receptor tyrosine kinase from an ovarian cancer cell line." Laval S., Butler R., Shelling A.N., Hanby A.M., Poulsom R., Ganesan T.S. Cell Growth Differ. 5:1173-1183(1994) [PubMed: 7848919] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Ovary. |
| [8] | "Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis." Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., Phillips S., Feldmann M., Shepard H.M., Paleolog E.M. Arthritis Res. Ther. 10:R73-R73(2008) [PubMed: 18593464] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4). |
| [9] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Placenta. |
| [10] | "Preparation of a set of expression-ready clones of mammalian long cDNAs encoding large proteins by the ORF trap cloning method." Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R., Okazaki N., Koga H., Nagase T., Ohara O. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain. |
| [11] | "Rapid evolution of major histocompatibility complex class I genes in primates generates new disease alleles in humans via hitchhiking diversity." Shiina T., Ota M., Shimizu S., Katsuyama Y., Hashimoto N., Takasu M., Anzai T., Kulski J.K., Kikkawa E., Naruse T., Kimura N., Yanagiya K., Watanabe A., Hosomichi K., Kohara S., Iwamoto C., Umehara Y., Meyer A. Bahram S.Genetics 173:1555-1570(2006) [PubMed: 16702430] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Tissue: Peripheral blood leukocyte. |
| [12] | "The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. Beck S.Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [13] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [14] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain and Muscle. |
| [15] | "Expression of growth factor receptors, the focal adhesion kinase, and other tyrosine kinases in human soft tissue tumors." Weiner T.M., Liu E.T., Craven R.J., Cance W.G. Ann. Surg. Oncol. 1:18-27(1994) [PubMed: 7834423] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 771-824. |
| [16] | "Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. Comb M.J.Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-792; TYR-796 AND TYR-797, MASS SPECTROMETRY. |
| [17] | "Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLY-17; ALA-100; GLN-169; ASP-170; TRP-306 AND ALA-496. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| L20817 mRNA. Translation: AAA18019.1. L11315 mRNA. Translation: AAA02866.1. U48705 Genomic DNA. Translation: AAC50917.1. X98208 X99034 Genomic DNA. Translation: CAA66871.1. L57508 mRNA. Translation: AAB05208.1. X74979 mRNA. Translation: CAA52915.1. Z29093 mRNA. Translation: CAA82335.1. EU826613 mRNA. Translation: ACF47649.1. EU826614 mRNA. Translation: ACF47650.1. AK291621 mRNA. Translation: BAF84310.1. AB210021 mRNA. Translation: BAE06103.1. Different initiation. BA000025 Genomic DNA. Translation: BAB63318.1. CR759747 Genomic DNA. Translation: CAQ06757.1. CR759747 Genomic DNA. Translation: CAQ06756.1. AB088102 Genomic DNA. Translation: BAC54935.1. AB103608 Genomic DNA. Translation: BAF31270.1. AL662854 Genomic DNA. Translation: CAI17434.1. AL662870 Genomic DNA. Translation: CAI18441.1. AL773541, AL773589 Genomic DNA. Translation: CAI18450.1. AL773589, AL773541 Genomic DNA. Translation: CAI18534.1. AL662854 Genomic DNA. Translation: CAI17433.1. AL662870 Genomic DNA. Translation: CAI18442.1. AL773541, AL773589 Genomic DNA. Translation: CAI18451.1. AL773589, AL773541 Genomic DNA. Translation: CAI18533.1. AB202100 Genomic DNA. Translation: BAE78621.1. BX927194 Genomic DNA. Translation: CAQ09768.1. BX927194 Genomic DNA. Translation: CAQ09767.1. CH471081 Genomic DNA. Translation: EAX03335.1. CH471081 Genomic DNA. Translation: EAX03338.1. BC008716 mRNA. Translation: AAH08716.1. BC013400 mRNA. Translation: AAH13400.1. BC070070 mRNA. Translation: AAH70070.1. | |
| IPI | IPI00001477. IPI00219996. IPI00910318. IPI00925878. |
| PIR | A48280. A49508. |
| RefSeq | NP_001945.3. NP_054699.2. NP_054700.2. |
| UniGene | Hs.631988 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1LUF based on UniProtKB Q62838. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q08345. 12 interactions. |
PTM databases | |
| PhosphoSite | Q08345. |
Proteomic databases | |
| PRIDE | Q08345. |
Genome annotation databases | |
| Ensembl | ENSG00000137332. Homo sapiens. [Contig view] ENSG00000204580. Homo sapiens. [Contig view] ENSG00000215522. Homo sapiens. [Contig view] |
| GeneID | 780. |
| KEGG | hsa:780. |
| UCSC | uc003nrr.1. human. |
Organism-specific databases | |
| GeneCards | GC06P030960. |
| H-InvDB | HIX0025035. HIX0058006. HIX0058118. |
| HGNC | HGNC:2730. DDR1. |
| HPA | CAB010162. |
| MIM | 600408. gene. |
| PharmGKB | PA24348. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | Q08345. |
| HOVERGEN | Q08345. |
| OMA | Q08345. LGLYELM. |
Enzyme and pathway databases | |
| BRENDA | 2.7.10.1. 247. |
Gene expression databases | |
| ArrayExpress | Q08345. |
| CleanEx | HS_DDR1. |
| GermOnline | ENSG00000204580. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR000421. Coagulation_factor_5/8-type_C. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR002011. Recept_tyr_kinase-II_CS. IPR001245. Tyr_pkinase. IPR008266. Tyr_pkinase_AS. [Graphical view] |
| Pfam | PF00754. F5_F8_type_C. 1 hit. PF07714. Pkinase_Tyr. 1 hit. [Graphical view] |
| PRINTS | PR00109. TYRKINASE. |
| ProDom | PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain] |
| SMART | SM00231. FA58C. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view] |
| PROSITE | PS01285. FA58C_1. 1 hit. PS01286. FA58C_2. 1 hit. PS50022. FA58C_3. 1 hit. PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS00239. RECEPTOR_TYR_KIN_II. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| DrugBank | DB00619. Imatinib. |
| NextBio | 3152. |
| PMAP-CutDB | Q08345. |
| SOURCE | Search... |
Entry information
| Entry name | DDR1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q08345 Secondary accession number(s): B5A975 Q9UD37 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human cell differentiation molecules CD nomenclature of surface proteins of human leucocytes and list of entries |
| Human chromosome 6 Human chromosome 6: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


