Reviewed, UniProtKB/Swiss-Prot Q16832 (DDR2_HUMAN)

Names and origin

Protein names

Recommended name:
    Discoidin domain-containing receptor 2
      Short name=Discoidin domain receptor 2
    EC=2.7.10.1
Alternative name(s):
    Receptor protein-tyrosine kinase TKT
    Tyrosine-protein kinase TYRO10
    Neurotrophic tyrosine kinase, receptor-related 3
    CD167 antigen-like family member B
    CD_antigen=CD167b

Gene names

Name:	DDR2
Synonyms:	NTRKR3, TKT, TYRO10

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	855 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	This tyrosine kinase receptor for fibrillar collagen mediates fibroblast migration and proliferation. Contributes to cutaneous wound healing By similarity.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	The major 10 kDa transcript is expressed in high levels in heart and lung, less in brain, placenta, liver, skeletal muscle, pancreas, and kidney.
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

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell adhesion Traceable author statement. Source: ProtInc protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW transmembrane receptor protein tyrosine kinase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 855

834

Discoidin domain-containing receptor 2

PRO_0000016746

Regions

Topological domain

22 – 399

378

Extracellular Potential

Transmembrane

400 – 421

22

Potential

Topological domain

422 – 855

434

Cytoplasmic Potential

Domain

30 – 185

156

F5/8 type C

Domain

563 – 849

287

Protein kinase

Nucleotide binding

569 – 577

9

ATP By similarity

Sites

Active site

710

1

Proton acceptor By similarity

Binding site

608

1

ATP By similarity

Amino acid modifications

Modified residue

736

1

Phosphotyrosine Ref.6

Modified residue

740

1

Phosphotyrosine; by autocatalysis By similarity

Glycosylation

121

1

N-linked (GlcNAc...) Potential

Glycosylation

213

1

N-linked (GlcNAc...) Potential

Glycosylation

261

1

N-linked (GlcNAc...) Potential

Glycosylation

280

1

N-linked (GlcNAc...) Potential

Glycosylation

372

1

N-linked (GlcNAc...) Potential

Disulfide bond

30 ↔ 185

Ref.7

Disulfide bond

73 ↔ 177

Ref.7

Natural variations

Natural variant

105

1

R → S in a lung large cell carcinoma sample; somatic mutation. Ref.8

VAR_041498

Natural variant

441

1

M → I: dbSNP rs34722354. Ref.8

VAR_041499

Natural variant

478

1

R → C: dbSNP rs34869543. Ref.8

VAR_041500

Natural variant

543

1

V → F: dbSNP rs55973200. Ref.8

VAR_041501

Experimental info

Sequence conflict

642

1

A → S in CAA52777. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

855

Helix Strand Turn

Details...

Beta strand

33 – 35

3

Turn

36 – 39

4

Beta strand

46 – 49

4

Beta strand

52 – 57

6

Turn

58 – 60

3

Beta strand

67 – 71

5

Beta strand

86 – 104

19

Turn

108 – 111

4

Beta strand

116 – 128

13

Beta strand

139 – 142

4

Beta strand

145 – 149

5

Beta strand

151 – 169

19

Beta strand

171 – 174

4

Beta strand

178 – 185

8

Sequences

	Sequence		Length	Mass (Da)
	Q16832-1 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: 78662021BC53E1A0	FASTA	855	96,736
	10 20 30 40 50 60 MILIPRMLLV LFLLLPILSS AKAQVNPAIC RYPLGMSGGQ IPDEDITASS QWSESTAAKY 70 80 90 100 110 120 GRLDSEEGDG AWCPEIPVEP DDLKEFLQID LHTLHFITLV GTQGRHAGGH GIEFAPMYKI 130 140 150 160 170 180 NYSRDGTRWI SWRNRHGKQV LDGNSNPYDI FLKDLEPPIV ARFVRFIPVT DHSMNVCMRV 190 200 210 220 230 240 ELYGCVWLDG LVSYNAPAGQ QFVLPGGSII YLNDSVYDGA VGYSMTEGLG QLTDGVSGLD 250 260 270 280 290 300 DFTQTHEYHV WPGYDYVGWR NESATNGYIE IMFEFDRIRN FTTMKVHCNN MFAKGVKIFK 310 320 330 340 350 360 EVQCYFRSEA SEWEPNAISF PLVLDDVNPS ARFVTVPLHH RMASAIKCQY HFADTWMMFS 370 380 390 400 410 420 EITFQSDAAM YNNSEALPTS PMAPTTYDPM LKVDDSNTRI LIGCLVAIIF ILLAIIVIIL 430 440 450 460 470 480 WRQFWQKMLE KASRRMLDDE MTVSLSLPSD SSMFNNNRSS SPSEQGSNST YDRIFPLRPD 490 500 510 520 530 540 YQEPSRLIRK LPEFAPGEEE SGCSGVVKPV QPSGPEGVPH YAEADIVNLQ GVTGGNTYSV 550 560 570 580 590 600 PAVTMDLLSG KDVAVEEFPR KLLTFKEKLG EGQFGEVHLC EVEGMEKFKD KDFALDVSAN 610 620 630 640 650 660 QPVLVAVKML RADANKNARN DFLKEIKIMS RLKDPNIIHL LAVCITDDPL CMITEYMENG 670 680 690 700 710 720 DLNQFLSRHE PPNSSSSDVR TVSYTNLKFM ATQIASGMKY LSSLNFVHRD LATRNCLVGK 730 740 750 760 770 780 NYTIKIADFG MSRNLYSGDY YRIQGRAVLP IRWMSWESIL LGKFTTASDV WAFGVTLWET 790 800 810 820 830 840 FTFCQEQPYS QLSDEQVIEN TGEFFRDQGR QTYLPQPAIC PDSVYKLMLS CWRRDTKNRP 850 SFQEIHLLLL QQGDE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure, expression and chromosomal mapping of TKT from man and mouse: a new subclass of receptor tyrosine kinases with a factor VIII-like domain." Karn T., Holtrich U., Braeuninger A., Boehme B., Wolf G., Ruebsamen-Waigmann H., Strebhardt K. Oncogene 8:3433-3440(1993) [PubMed: 8247548] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart and Thymus.
[2]	"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. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hair follicle dermal papilla and Uterus.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Skin.
[6]	"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. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-736 AND TYR-740, MASS SPECTROMETRY.
[7]	"Structural basis of the collagen-binding mode of discoidin domain receptor 2." Ichikawa O., Osawa M., Nishida N., Goshima N., Nomura N., Shimada I. EMBO J. 26:4168-4176(2007) [PubMed: 17703188] [Abstract] Cited for: STRUCTURE BY NMR OF 22-186, INTERACTION WITH COLLAGEN, DISULFIDE BONDS.
[8]	"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. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-105; ILE-441; CYS-478 AND PHE-543.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X74764 mRNA. Translation: CAA52777.1.
AK314388 mRNA. Translation: BAG37013.1.
AK095975 mRNA. Translation: BAG53183.1.
AL445197 Genomic DNA. Translation: CAI15941.1.
CH471067 Genomic DNA. Translation: EAW90713.1.
BC052998 mRNA. Translation: AAH52998.1.

IPI

IPI00004409.

PIR

S42621.

RefSeq

NP_001014796.1.
NP_006173.2.

UniGene

Hs.275757
Hs.593833

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Z4F	NMR	-	A	26-186	[»]

ModBase

Search...

PTM databases

PhosphoSite

Q16832.

Proteomic databases

PRIDE

Q16832.

Genome annotation databases

Ensembl

ENSG00000162733. Homo sapiens. [Contig view]

GeneID

4921.

KEGG

hsa:4921.

Organism-specific databases

GeneCards

GC01P160868.

HGNC

HGNC:2731. DDR2.

HPA

CAB010432.

MIM

191311. gene.

Orphanet

252. Spondyloepimetaphyseal dysplasia.
93358. Spondyloepimetaphyseal dysplasia - short limb - abnormal calcification.

PharmGKB

PA27196.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q16832.

HOVERGEN

Q16832.

OMA

Q16832. TRWISWR.

Enzyme and pathway databases

BRENDA

2.7.10.1. 247.

Gene expression databases

ArrayExpress

Q16832.

Bgee

Q16832.

CleanEx

HS_DDR2.
HS_TKT.

GermOnline

ENSG00000162733. Homo sapiens.

Family and domain databases

InterPro

IPR000421. Coagulation_factor_5/8-type_C.
IPR000719. Prot_kinase_core.
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. 2 hits.
[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.
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

NextBio

18949.

SOURCE

Search...

Entry information

Entry name

DDR2_HUMAN

Accession

Primary (citable) accession number: Q16832
Secondary accession number(s): Q7Z730

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 25, 2008
Last modified:	July 7, 2009
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)