DDR2_HUMAN
ID DDR2_HUMAN Reviewed; 855 AA.
AC Q16832; Q7Z730;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Discoidin domain-containing receptor 2;
DE Short=Discoidin domain receptor 2;
DE EC=2.7.10.1;
DE AltName: Full=CD167 antigen-like family member B;
DE AltName: Full=Discoidin domain-containing receptor tyrosine kinase 2;
DE AltName: Full=Neurotrophic tyrosine kinase, receptor-related 3;
DE AltName: Full=Receptor protein-tyrosine kinase TKT;
DE AltName: Full=Tyrosine-protein kinase TYRO10;
DE AltName: CD_antigen=CD167b;
DE Flags: Precursor;
GN Name=DDR2; Synonyms=NTRKR3, TKT, TYRO10;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Heart, and Thymus;
RX PubMed=8247548;
RA Karn T., Holtrich U., Braeuninger A., Boehme B., Wolf G.,
RA Ruebsamen-Waigmann H., Strebhardt K.;
RT "Structure, expression and chromosomal mapping of TKT from man and mouse: a
RT new subclass of receptor tyrosine kinases with a factor VIII-like domain.";
RL Oncogene 8:3433-3440(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hair follicle dermal papilla, and Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION AS COLLAGEN RECEPTOR AND IN UP-REGULATION OF MMP1,
RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=9659899; DOI=10.1016/s1097-2765(00)80003-9;
RA Vogel W., Gish G.D., Alves F., Pawson T.;
RT "The discoidin domain receptor tyrosine kinases are activated by
RT collagen.";
RL Mol. Cell 1:13-23(1997).
RN [7]
RP FUNCTION IN REGULATION OF MMP1 AND MMP2, PHOSPHORYLATION AT TYR-736;
RP TYR-740 AND TYR-741, CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION
RP WITH SHC1, AND MUTAGENESIS OF LYS-608; TYR-736; TYR-740 AND TYR-741.
RX PubMed=16186108; DOI=10.1074/jbc.m506921200;
RA Yang K., Kim J.H., Kim H.J., Park I.S., Kim I.Y., Yang B.S.;
RT "Tyrosine 740 phosphorylation of discoidin domain receptor 2 by Src
RT stimulates intramolecular autophosphorylation and Shc signaling complex
RT formation.";
RL J. Biol. Chem. 280:39058-39066(2005).
RN [8]
RP FUNCTION AS COLLAGEN RECEPTOR, AND PHOSPHORYLATION.
RX PubMed=16186104; DOI=10.1074/jbc.m508226200;
RA Wall S.J., Werner E., Werb Z., DeClerck Y.A.;
RT "Discoidin domain receptor 2 mediates tumor cell cycle arrest induced by
RT fibrillar collagen.";
RL J. Biol. Chem. 280:40187-40194(2005).
RN [9]
RP FUNCTION IN UP-REGULATION OF MMP13, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=17665456; DOI=10.1002/art.22761;
RA Xu L., Peng H., Glasson S., Lee P.L., Hu K., Ijiri K., Olsen B.R.,
RA Goldring M.B., Li Y.;
RT "Increased expression of the collagen receptor discoidin domain receptor 2
RT in articular cartilage as a key event in the pathogenesis of
RT osteoarthritis.";
RL Arthritis Rheum. 56:2663-2673(2007).
RN [10]
RP FUNCTION AS COLLAGEN RECEPTOR, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND
RP SUBUNIT.
RX PubMed=18201965; DOI=10.1074/jbc.m709290200;
RA Konitsiotis A.D., Raynal N., Bihan D., Hohenester E., Farndale R.W.,
RA Leitinger B.;
RT "Characterization of high affinity binding motifs for the discoidin domain
RT receptor DDR2 in collagen.";
RL J. Biol. Chem. 283:6861-6868(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [13]
RP FUNCTION IN OSTEOBLAST DIFFERENTIATION VIA ACTIVATION OF RUNX2, INDUCTION,
RP AND TISSUE SPECIFICITY.
RX PubMed=20564243; DOI=10.1002/jbmr.159;
RA Lin K.L., Chou C.H., Hsieh S.C., Hwa S.Y., Lee M.T., Wang F.F.;
RT "Transcriptional upregulation of DDR2 by ATF4 facilitates osteoblastic
RT differentiation through p38 MAPK-mediated Runx2 activation.";
RL J. Bone Miner. Res. 25:2489-2503(2010).
RN [14]
RP FUNCTION IN OSTEOBLAST DIFFERENTIATION AND CHONDROCYTE MATURATION VIA
RP ACTIVATION OF RUNX2.
RX PubMed=20734453; DOI=10.1002/jbmr.225;
RA Zhang Y., Su J., Yu J., Bu X., Ren T., Liu X., Yao L.;
RT "An essential role of discoidin domain receptor 2 (DDR2) in osteoblast
RT differentiation and chondrocyte maturation via modulation of Runx2
RT activation.";
RL J. Bone Miner. Res. 26:604-617(2011).
RN [15]
RP REVIEW.
RX PubMed=16626936; DOI=10.1016/j.cellsig.2006.02.012;
RA Vogel W.F., Abdulhussein R., Ford C.E.;
RT "Sensing extracellular matrix: an update on discoidin domain receptor
RT function.";
RL Cell. Signal. 18:1108-1116(2006).
RN [16]
RP REVIEW.
RX PubMed=21568710; DOI=10.1146/annurev-cellbio-092910-154013;
RA Leitinger B.;
RT "Transmembrane collagen receptors.";
RL Annu. Rev. Cell Dev. Biol. 27:265-290(2011).
RN [17]
RP STRUCTURE BY NMR OF 22-186, INTERACTION WITH COLLAGEN, AND DISULFIDE BONDS.
RX PubMed=17703188; DOI=10.1038/sj.emboj.7601833;
RA Ichikawa O., Osawa M., Nishida N., Goshima N., Nomura N., Shimada I.;
RT "Structural basis of the collagen-binding mode of discoidin domain receptor
RT 2.";
RL EMBO J. 26:4168-4176(2007).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 26-190 IN COMPLEX WITH COLLAGEN
RP PEPTIDE, DISULFIDE BONDS, MUTAGENESIS OF TRP-52, FUNCTION IN COLLAGEN
RP BINDING, CATALYTIC ACTIVITY, AND PHOSPHORYLATION.
RX PubMed=20004161; DOI=10.1016/j.str.2009.10.012;
RA Carafoli F., Bihan D., Stathopoulos S., Konitsiotis A.D., Kvansakul M.,
RA Farndale R.W., Leitinger B., Hohenester E.;
RT "Crystallographic insight into collagen recognition by discoidin domain
RT receptor 2.";
RL Structure 17:1573-1581(2009).
RN [19]
RP VARIANT [LARGE SCALE ANALYSIS] SER-105.
RX PubMed=16140923; DOI=10.1158/0008-5472.can-05-1855;
RA Davies H., Hunter C., Smith R., Stephens P., Greenman C., Bignell G.,
RA Teague J., Butler A., Edkins S., Stevens C., Parker A., O'Meara S.,
RA Avis T., Barthorpe S., Brackenbury L., Buck G., Clements J., Cole J.,
RA Dicks E., Edwards K., Forbes S., Gorton M., Gray K., Halliday K.,
RA Harrison R., Hills K., Hinton J., Jones D., Kosmidou V., Laman R., Lugg R.,
RA Menzies A., Perry J., Petty R., Raine K., Shepherd R., Small A.,
RA Solomon H., Stephens Y., Tofts C., Varian J., Webb A., West S., Widaa S.,
RA Yates A., Brasseur F., Cooper C.S., Flanagan A.M., Green A., Knowles M.,
RA Leung S.Y., Looijenga L.H., Malkowicz B., Pierotti M.A., Teh B.T.,
RA Yuen S.T., Lakhani S.R., Easton D.F., Weber B.L., Goldstraw P.,
RA Nicholson A.G., Wooster R., Stratton M.R., Futreal P.A.;
RT "Somatic mutations of the protein kinase gene family in human lung
RT cancer.";
RL Cancer Res. 65:7591-7595(2005).
RN [20]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-105; ILE-441; CYS-478 AND PHE-543.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [21]
RP VARIANTS SEMD-SL ILE-713; ARG-726 AND CYS-752.
RX PubMed=19110212; DOI=10.1016/j.ajhg.2008.12.004;
RA Bargal R., Cormier-Daire V., Ben-Neriah Z., Le Merrer M., Sosna J.,
RA Melki J., Zangen D.H., Smithson S.F., Borochowitz Z., Belostotsky R.,
RA Raas-Rothschild A.;
RT "Mutations in DDR2 gene cause SMED with short limbs and abnormal
RT calcifications.";
RL Am. J. Hum. Genet. 84:80-84(2009).
RN [22]
RP VARIANT SEMD-SL LYS-113, CHARACTERIZATION OF VARIANTS SEMD-SL LYS-113;
RP ILE-713; ARG-726 AND CYS-752, MUTAGENESIS OF TRP-52, GLYCOSYLATION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=20223752; DOI=10.1093/hmg/ddq103;
RA Ali B.R., Xu H., Akawi N.A., John A., Karuvantevida N.S., Langer R.,
RA Al-Gazali L., Leitinger B.;
RT "Trafficking defects and loss of ligand binding are the underlying causes
RT of all reported DDR2 missense mutations found in SMED-SL patients.";
RL Hum. Mol. Genet. 19:2239-2250(2010).
RN [23]
RP VARIANT SEMD-SL TRP-124.
RX PubMed=26463668; DOI=10.1002/ajmg.a.37426;
RA Mansouri M., Kayserili H., Elalaoui S.C., Nishimura G., Iida A.,
RA Lyahyai J., Miyake N., Matsumoto N., Sefiani A., Ikegawa S.;
RT "Novel DDR2 mutation identified by whole exome sequencing in a Moroccan
RT patient with spondylo-meta-epiphyseal dysplasia, short limb-abnormal
RT calcification type.";
RL Am. J. Med. Genet. A 170:460-465(2016).
RN [24]
RP VARIANTS WRCN PRO-610 AND CYS-740, CHARACTERIZATION OF VARIANTS WRCN
RP PRO-610 AND CYS-740, FUNCTION, AND INVOLVEMENT IN WRCN.
RX PubMed=30449416; DOI=10.1016/j.ajhg.2018.10.013;
RA Xu L., Jensen H., Johnston J.J., Di Maria E., Kloth K., Cristea I.,
RA Sapp J.C., Darling T.N., Huryn L.A., Tranebjaerg L., Cinotti E.,
RA Kubisch C., Roedahl E., Bruland O., Biesecker L.G., Houge G., Bredrup C.;
RT "Recurrent, activating variants in the receptor tyrosine kinase DDR2 cause
RT Warburg-Cinotti syndrome.";
RL Am. J. Hum. Genet. 103:976-983(2018).
CC -!- FUNCTION: Tyrosine kinase involved in the regulation of tissues
CC remodeling (PubMed:30449416). It functions as cell surface receptor for
CC fibrillar collagen and regulates cell differentiation, remodeling of
CC the extracellular matrix, cell migration and cell proliferation.
CC Required for normal bone development. Regulates osteoblast
CC differentiation and chondrocyte maturation via a signaling pathway that
CC involves MAP kinases and leads to the activation of the transcription
CC factor RUNX2. Regulates remodeling of the extracellular matrix by up-
CC regulation of the collagenases MMP1, MMP2 and MMP13, and thereby
CC facilitates cell migration and tumor cell invasion. Promotes fibroblast
CC migration and proliferation, and thereby contributes to cutaneous wound
CC healing. {ECO:0000269|PubMed:16186104, ECO:0000269|PubMed:16186108,
CC ECO:0000269|PubMed:17665456, ECO:0000269|PubMed:18201965,
CC ECO:0000269|PubMed:20004161, ECO:0000269|PubMed:20564243,
CC ECO:0000269|PubMed:20734453, ECO:0000269|PubMed:30449416,
CC ECO:0000269|PubMed:9659899}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:20004161};
CC -!- ACTIVITY REGULATION: Present in an inactive state in the absence of
CC collagen binding and phosphorylation by SRC. Tyrosine phosphorylation
CC enhances the affinity for ATP and the catalytic activity.
CC {ECO:0000269|PubMed:16186108}.
CC -!- SUBUNIT: Binds hydroxyproline-rich sequence motifs in fibrillar,
CC glycosylated collagen, such as the GQOGVMGFO motif, where O stands for
CC hydroxyproline. Interacts with SRC. Interacts (tyrosine phosphorylated)
CC with SHC1. {ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:17703188,
CC ECO:0000269|PubMed:18201965, ECO:0000269|PubMed:20004161}.
CC -!- INTERACTION:
CC Q16832; P13942: COL11A2; NbExp=2; IntAct=EBI-1381484, EBI-2515504;
CC Q16832; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1381484, EBI-352572;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18201965,
CC ECO:0000269|PubMed:20223752, ECO:0000269|PubMed:9659899}; Single-pass
CC type I membrane protein {ECO:0000269|PubMed:18201965,
CC ECO:0000269|PubMed:20223752, ECO:0000269|PubMed:9659899}.
CC -!- TISSUE SPECIFICITY: Detected in osteocytes, osteoblastic cells in
CC subchondral bone, bone lining cells, tibia and cartilage (at protein
CC level). Detected at high levels in heart and lung, and at low levels in
CC brain, placenta, liver, skeletal muscle, pancreas, and kidney.
CC {ECO:0000269|PubMed:17665456, ECO:0000269|PubMed:20564243,
CC ECO:0000269|PubMed:8247548}.
CC -!- INDUCTION: Up-regulated during osteoblast differentiation (in vitro).
CC Up-regulated in cartilage from osteoarthritis patients.
CC {ECO:0000269|PubMed:17665456, ECO:0000269|PubMed:20564243}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:20223752}.
CC -!- PTM: Tyrosine phosphorylated in response to collagen binding.
CC Phosphorylated by SRC; this is required for activation and subsequent
CC autophosphorylation on additional tyrosine residues.
CC {ECO:0000269|PubMed:16186104, ECO:0000269|PubMed:16186108,
CC ECO:0000269|PubMed:18201965, ECO:0000269|PubMed:20004161,
CC ECO:0000269|PubMed:9659899}.
CC -!- DISEASE: Spondyloepimetaphyseal dysplasia, short limb-hand type (SEMD-
CC SL) [MIM:271665]: A bone disease characterized by short-limbed
CC dwarfism, a narrow chest with pectus excavatum, brachydactyly in the
CC hands and feet, a characteristic craniofacial appearance and premature
CC calcifications. The radiological findings are distinctive and comprise
CC short long bones throughout the skeleton with striking epiphyses that
CC are stippled, flattened and fragmented and flared, irregular
CC metaphyses. Platyspondyly in the spine with wide intervertebral spaces
CC is observed and some vertebral bodies are pear-shaped with central
CC humps, anterior protrusions and posterior scalloping.
CC {ECO:0000269|PubMed:19110212, ECO:0000269|PubMed:20223752,
CC ECO:0000269|PubMed:26463668}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Warburg-Cinotti syndrome (WRCN) [MIM:618175]: An autosomal
CC dominant disease characterized by progressive corneal
CC neovascularization, keloid formation, chronic skin ulcers, wasting of
CC subcutaneous tissue, flexion contractures of the fingers, and acro-
CC osteolysis. {ECO:0000269|PubMed:30449416}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; X74764; CAA52777.1; -; mRNA.
DR EMBL; AK314388; BAG37013.1; -; mRNA.
DR EMBL; AK095975; BAG53183.1; -; mRNA.
DR EMBL; AL445197; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW90713.1; -; Genomic_DNA.
DR EMBL; BC052998; AAH52998.1; -; mRNA.
DR CCDS; CCDS1241.1; -.
DR PIR; S42621; S42621.
DR RefSeq; NP_001014796.1; NM_001014796.1.
DR RefSeq; NP_006173.2; NM_006182.2.
DR RefSeq; XP_006711407.1; XM_006711344.3.
DR RefSeq; XP_011507888.1; XM_011509586.2.
DR RefSeq; XP_011507889.1; XM_011509587.2.
DR PDB; 2WUH; X-ray; 1.60 A; A=26-190.
DR PDB; 2Z4F; NMR; -; A=26-186.
DR PDB; 6FER; X-ray; 2.87 A; A/B/C/D/E/F/G/H/I/J/K/L=553-855.
DR PDB; 7AZB; X-ray; 2.62 A; A=26-190.
DR PDBsum; 2WUH; -.
DR PDBsum; 2Z4F; -.
DR PDBsum; 6FER; -.
DR PDBsum; 7AZB; -.
DR AlphaFoldDB; Q16832; -.
DR BMRB; Q16832; -.
DR SMR; Q16832; -.
DR BioGRID; 110975; 24.
DR DIP; DIP-39699N; -.
DR IntAct; Q16832; 18.
DR MINT; Q16832; -.
DR STRING; 9606.ENSP00000356899; -.
DR BindingDB; Q16832; -.
DR ChEMBL; CHEMBL5122; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB08896; Regorafenib.
DR DrugCentral; Q16832; -.
DR GuidetoPHARMACOLOGY; 1844; -.
DR GlyGen; Q16832; 5 sites.
DR iPTMnet; Q16832; -.
DR PhosphoSitePlus; Q16832; -.
DR SwissPalm; Q16832; -.
DR BioMuta; DDR2; -.
DR DMDM; 215273969; -.
DR EPD; Q16832; -.
DR jPOST; Q16832; -.
DR MassIVE; Q16832; -.
DR MaxQB; Q16832; -.
DR PaxDb; Q16832; -.
DR PeptideAtlas; Q16832; -.
DR PRIDE; Q16832; -.
DR ProteomicsDB; 61095; -.
DR Antibodypedia; 4177; 463 antibodies from 36 providers.
DR DNASU; 4921; -.
DR Ensembl; ENST00000367921.8; ENSP00000356898.3; ENSG00000162733.19.
DR Ensembl; ENST00000367922.7; ENSP00000356899.2; ENSG00000162733.19.
DR Ensembl; ENST00000446985.6; ENSP00000400309.2; ENSG00000162733.19.
DR GeneID; 4921; -.
DR KEGG; hsa:4921; -.
DR MANE-Select; ENST00000367921.8; ENSP00000356898.3; NM_006182.4; NP_006173.2.
DR UCSC; uc001gcg.4; human.
DR CTD; 4921; -.
DR DisGeNET; 4921; -.
DR GeneCards; DDR2; -.
DR HGNC; HGNC:2731; DDR2.
DR HPA; ENSG00000162733; Low tissue specificity.
DR MalaCards; DDR2; -.
DR MIM; 191311; gene.
DR MIM; 271665; phenotype.
DR MIM; 618175; phenotype.
DR neXtProt; NX_Q16832; -.
DR OpenTargets; ENSG00000162733; -.
DR Orphanet; 93358; Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome.
DR PharmGKB; PA27196; -.
DR VEuPathDB; HostDB:ENSG00000162733; -.
DR eggNOG; KOG1094; Eukaryota.
DR GeneTree; ENSGT00940000154842; -.
DR HOGENOM; CLU_008873_2_0_1; -.
DR InParanoid; Q16832; -.
DR OMA; FTFCREQ; -.
DR OrthoDB; 227725at2759; -.
DR PhylomeDB; Q16832; -.
DR TreeFam; TF317840; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; Q16832; -.
DR Reactome; R-HSA-3000171; Non-integrin membrane-ECM interactions.
DR SignaLink; Q16832; -.
DR SIGNOR; Q16832; -.
DR BioGRID-ORCS; 4921; 9 hits in 1100 CRISPR screens.
DR ChiTaRS; DDR2; human.
DR EvolutionaryTrace; Q16832; -.
DR GeneWiki; Discoidin_domain-containing_receptor_2; -.
DR GenomeRNAi; 4921; -.
DR Pharos; Q16832; Tchem.
DR PRO; PR:Q16832; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q16832; protein.
DR Bgee; ENSG00000162733; Expressed in cauda epididymis and 197 other tissues.
DR ExpressionAtlas; Q16832; baseline and differential.
DR Genevisible; Q16832; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005518; F:collagen binding; IDA:UniProtKB.
DR GO; GO:0038062; F:protein tyrosine kinase collagen receptor activity; IDA:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0031214; P:biomineral tissue development; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:1904385; P:cellular response to angiotensin; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR GO; GO:0035988; P:chondrocyte proliferation; ISS:UniProtKB.
DR GO; GO:0030199; P:collagen fibril organization; ISS:UniProtKB.
DR GO; GO:0038063; P:collagen-activated tyrosine kinase receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0003416; P:endochondral bone growth; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:1901299; P:negative regulation of hydrogen peroxide-mediated programmed cell death; IEA:Ensembl.
DR GO; GO:0033673; P:negative regulation of kinase activity; IEA:Ensembl.
DR GO; GO:0060547; P:negative regulation of necrotic cell death; IEA:Ensembl.
DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0090091; P:positive regulation of extracellular matrix disassembly; ISS:UniProtKB.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; ISS:UniProtKB.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISS:UniProtKB.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:2000491; P:positive regulation of hepatic stellate cell activation; IEA:Ensembl.
DR GO; GO:1904899; P:positive regulation of hepatic stellate cell proliferation; IEA:Ensembl.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:1901216; P:positive regulation of neuron death; IEA:Ensembl.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IMP:UniProtKB.
DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0090303; P:positive regulation of wound healing; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0030500; P:regulation of bone mineralization; IMP:UniProtKB.
DR GO; GO:0010715; P:regulation of extracellular matrix disassembly; TAS:UniProtKB.
DR GO; GO:0034103; P:regulation of tissue remodeling; IMP:UniProtKB.
DR GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd00057; FA58C; 1.
DR InterPro; IPR034299; DDR1/DDR2.
DR InterPro; IPR000421; FA58C.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
DR PANTHER; PTHR24416:SF295; PTHR24416:SF295; 1.
DR Pfam; PF00754; F5_F8_type_C; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00231; FA58C; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS01285; FA58C_1; 1.
DR PROSITE; PS01286; FA58C_2; 1.
DR PROSITE; PS50022; FA58C_3; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane; Disease variant; Disulfide bond;
KW Dwarfism; Glycoprotein; Kinase; Membrane; Nucleotide-binding; Osteogenesis;
KW Phosphoprotein; Receptor; Reference proteome; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..855
FT /note="Discoidin domain-containing receptor 2"
FT /id="PRO_0000016746"
FT TOPO_DOM 22..399
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 400..421
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 422..855
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..185
FT /note="F5/8 type C"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DOMAIN 563..849
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 452..471
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 710
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 569..577
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 608
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 471
FT /note="Phosphotyrosine; by SRC and autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q62371"
FT MOD_RES 736
FT /note="Phosphotyrosine; by SRC and autocatalysis"
FT /evidence="ECO:0000269|PubMed:16186108"
FT MOD_RES 740
FT /note="Phosphotyrosine; by SRC and autocatalysis"
FT /evidence="ECO:0000269|PubMed:16186108"
FT MOD_RES 741
FT /note="Phosphotyrosine; by SRC and autocatalysis"
FT /evidence="ECO:0000269|PubMed:16186108"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 213
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 30..185
FT DISULFID 73..177
FT VARIANT 105
FT /note="R -> S (in a lung large cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:16140923,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_041498"
FT VARIANT 113
FT /note="E -> K (in SEMD-SL; abolishes collagen binding;
FT dbSNP:rs397514747)"
FT /evidence="ECO:0000269|PubMed:20223752"
FT /id="VAR_065719"
FT VARIANT 124
FT /note="R -> W (in SEMD-SL)"
FT /evidence="ECO:0000269|PubMed:26463668"
FT /id="VAR_075417"
FT VARIANT 441
FT /note="M -> I (in dbSNP:rs34722354)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041499"
FT VARIANT 478
FT /note="R -> C (in dbSNP:rs34869543)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041500"
FT VARIANT 543
FT /note="V -> F (in dbSNP:rs55973200)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041501"
FT VARIANT 610
FT /note="L -> P (in WRCN; increased autophosphorylation in
FT patient fibroblasts)"
FT /evidence="ECO:0000269|PubMed:30449416"
FT /id="VAR_081931"
FT VARIANT 713
FT /note="T -> I (in SEMD-SL; causes retention in an
FT intracellular compartment and thereby abolishes signaling
FT in response collagen binding; dbSNP:rs121964865)"
FT /evidence="ECO:0000269|PubMed:19110212,
FT ECO:0000269|PubMed:20223752"
FT /id="VAR_063050"
FT VARIANT 726
FT /note="I -> R (in SEMD-SL; causes retention in an
FT intracellular compartment and thereby abolishes signaling
FT in response collagen binding; dbSNP:rs121964864)"
FT /evidence="ECO:0000269|PubMed:19110212,
FT ECO:0000269|PubMed:20223752"
FT /id="VAR_063051"
FT VARIANT 740
FT /note="Y -> C (in WRCN; increased autophosphorylation in
FT patient fibroblasts)"
FT /evidence="ECO:0000269|PubMed:30449416"
FT /id="VAR_081932"
FT VARIANT 752
FT /note="R -> C (in SEMD-SL; causes retention in an
FT intracellular compartment and thereby abolishes signaling
FT in response collagen binding; dbSNP:rs121964863)"
FT /evidence="ECO:0000269|PubMed:19110212,
FT ECO:0000269|PubMed:20223752"
FT /id="VAR_063052"
FT MUTAGEN 52
FT /note="W->A: Abolishes collagen binding."
FT /evidence="ECO:0000269|PubMed:20004161,
FT ECO:0000269|PubMed:20223752"
FT MUTAGEN 608
FT /note="K->A: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:16186108"
FT MUTAGEN 736
FT /note="Y->F: Reduces autophosphorylation. Abolishes
FT phosphorylation by SRC; when associated with F-740 and F-
FT 741."
FT /evidence="ECO:0000269|PubMed:16186108"
FT MUTAGEN 740
FT /note="Y->F: Promotes autophosphorylation. Abolishes
FT phosphorylation by SRC; when associated with F-736 and F-
FT 741."
FT /evidence="ECO:0000269|PubMed:16186108"
FT MUTAGEN 741
FT /note="Y->F: Reduces autophosphorylation. Abolishes
FT phosphorylation by SRC; when associated with F-736 and F-
FT 740."
FT /evidence="ECO:0000269|PubMed:16186108"
FT CONFLICT 642
FT /note="A -> S (in Ref. 1; CAA52777)"
FT /evidence="ECO:0000305"
FT TURN 27..29
FT /evidence="ECO:0007829|PDB:2WUH"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:2Z4F"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:2WUH"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:2WUH"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:2WUH"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:2WUH"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:2WUH"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:2WUH"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:2WUH"
FT STRAND 87..103
FT /evidence="ECO:0007829|PDB:2WUH"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:2WUH"
FT STRAND 116..128
FT /evidence="ECO:0007829|PDB:2WUH"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:7AZB"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:7AZB"
FT STRAND 145..149
FT /evidence="ECO:0007829|PDB:2WUH"
FT STRAND 151..169
FT /evidence="ECO:0007829|PDB:2WUH"
FT STRAND 171..174
FT /evidence="ECO:0007829|PDB:7AZB"
FT STRAND 178..186
FT /evidence="ECO:0007829|PDB:2WUH"
FT HELIX 560..562
FT /evidence="ECO:0007829|PDB:6FER"
FT STRAND 565..571
FT /evidence="ECO:0007829|PDB:6FER"
FT STRAND 576..581
FT /evidence="ECO:0007829|PDB:6FER"
FT STRAND 604..609
FT /evidence="ECO:0007829|PDB:6FER"
FT HELIX 616..630
FT /evidence="ECO:0007829|PDB:6FER"
FT STRAND 642..644
FT /evidence="ECO:0007829|PDB:6FER"
FT STRAND 646..649
FT /evidence="ECO:0007829|PDB:6FER"
FT STRAND 651..655
FT /evidence="ECO:0007829|PDB:6FER"
FT HELIX 662..667
FT /evidence="ECO:0007829|PDB:6FER"
FT HELIX 684..703
FT /evidence="ECO:0007829|PDB:6FER"
FT HELIX 713..715
FT /evidence="ECO:0007829|PDB:6FER"
FT STRAND 716..718
FT /evidence="ECO:0007829|PDB:6FER"
FT HELIX 720..722
FT /evidence="ECO:0007829|PDB:6FER"
FT STRAND 724..726
FT /evidence="ECO:0007829|PDB:6FER"
FT HELIX 734..739
FT /evidence="ECO:0007829|PDB:6FER"
FT STRAND 744..746
FT /evidence="ECO:0007829|PDB:6FER"
FT TURN 751..753
FT /evidence="ECO:0007829|PDB:6FER"
FT HELIX 756..759
FT /evidence="ECO:0007829|PDB:6FER"
FT HELIX 766..782
FT /evidence="ECO:0007829|PDB:6FER"
FT TURN 788..791
FT /evidence="ECO:0007829|PDB:6FER"
FT HELIX 794..806
FT /evidence="ECO:0007829|PDB:6FER"
FT STRAND 818..820
FT /evidence="ECO:0007829|PDB:6FER"
FT HELIX 822..831
FT /evidence="ECO:0007829|PDB:6FER"
FT HELIX 836..838
FT /evidence="ECO:0007829|PDB:6FER"
FT HELIX 842..849
FT /evidence="ECO:0007829|PDB:6FER"
SQ SEQUENCE 855 AA; 96736 MW; 78662021BC53E1A0 CRC64;
MILIPRMLLV LFLLLPILSS AKAQVNPAIC RYPLGMSGGQ IPDEDITASS QWSESTAAKY
GRLDSEEGDG AWCPEIPVEP DDLKEFLQID LHTLHFITLV GTQGRHAGGH GIEFAPMYKI
NYSRDGTRWI SWRNRHGKQV LDGNSNPYDI FLKDLEPPIV ARFVRFIPVT DHSMNVCMRV
ELYGCVWLDG LVSYNAPAGQ QFVLPGGSII YLNDSVYDGA VGYSMTEGLG QLTDGVSGLD
DFTQTHEYHV WPGYDYVGWR NESATNGYIE IMFEFDRIRN FTTMKVHCNN MFAKGVKIFK
EVQCYFRSEA SEWEPNAISF PLVLDDVNPS ARFVTVPLHH RMASAIKCQY HFADTWMMFS
EITFQSDAAM YNNSEALPTS PMAPTTYDPM LKVDDSNTRI LIGCLVAIIF ILLAIIVIIL
WRQFWQKMLE KASRRMLDDE MTVSLSLPSD SSMFNNNRSS SPSEQGSNST YDRIFPLRPD
YQEPSRLIRK LPEFAPGEEE SGCSGVVKPV QPSGPEGVPH YAEADIVNLQ GVTGGNTYSV
PAVTMDLLSG KDVAVEEFPR KLLTFKEKLG EGQFGEVHLC EVEGMEKFKD KDFALDVSAN
QPVLVAVKML RADANKNARN DFLKEIKIMS RLKDPNIIHL LAVCITDDPL CMITEYMENG
DLNQFLSRHE PPNSSSSDVR TVSYTNLKFM ATQIASGMKY LSSLNFVHRD LATRNCLVGK
NYTIKIADFG MSRNLYSGDY YRIQGRAVLP IRWMSWESIL LGKFTTASDV WAFGVTLWET
FTFCQEQPYS QLSDEQVIEN TGEFFRDQGR QTYLPQPAIC PDSVYKLMLS CWRRDTKNRP
SFQEIHLLLL QQGDE
