DDR1_HUMAN
ID DDR1_HUMAN Reviewed; 913 AA.
AC Q08345; B5A975; B5A976; B7Z2K0; Q14196; Q16562; Q2L6H3; Q4LE50; Q5ST11;
AC Q5ST12; Q6NSK4; Q9UD35; Q9UD36; Q9UD37; Q9UD86; Q9UDL2;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=Epithelial discoidin domain-containing receptor 1;
DE Short=Epithelial discoidin domain receptor 1;
DE EC=2.7.10.1;
DE AltName: Full=CD167 antigen-like family member A;
DE AltName: Full=Cell adhesion kinase;
DE AltName: Full=Discoidin receptor tyrosine kinase;
DE AltName: Full=HGK2;
DE AltName: Full=Mammary carcinoma kinase 10;
DE Short=MCK-10;
DE AltName: Full=Protein-tyrosine kinase 3A;
DE AltName: Full=Protein-tyrosine kinase RTK-6;
DE AltName: Full=TRK E;
DE AltName: Full=Tyrosine kinase DDR;
DE AltName: Full=Tyrosine-protein kinase CAK;
DE AltName: CD_antigen=CD167a;
DE Flags: Precursor;
GN Name=DDR1; Synonyms=CAK, EDDR1, NEP, NTRK4, PTK3A, RTK6, TRKE;
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] (ISOFORM 2).
RC TISSUE=Brain, and Keratinocyte;
RX PubMed=8226977; DOI=10.1016/s0021-9258(20)80524-9;
RA di Marco E., Cutuli N., Guerra L., Cancedda R., de Luca M.;
RT "Molecular cloning of trkE, a novel trk-related putative tyrosine kinase
RT receptor isolated from normal human keratinocytes and widely expressed by
RT normal human tissues.";
RL J. Biol. Chem. 268:24290-24295(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT VAL-833.
RC TISSUE=Placenta;
RX PubMed=8390675; DOI=10.1073/pnas.90.12.5677;
RA Johnson J.D., Edman J.C., Rutter W.J.;
RT "A receptor tyrosine kinase found in breast carcinoma cells has an
RT extracellular discoidin I-like domain.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:5677-5681(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Ovary;
RX PubMed=7848919;
RA Laval S., Butler R., Shelling A.N., Hanby A.M., Poulsom R., Ganesan T.S.;
RT "Isolation and characterization of an epithelial-specific receptor tyrosine
RT kinase from an ovarian cancer cell line.";
RL Cell Growth Differ. 5:1173-1183(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal liver;
RX PubMed=8302582;
RA Perez J.L., Shen X., Finkernagel S., Sciorra L., Jenkins N.A.,
RA Gilbert D.J., Copeland N.G., Wong T.W.;
RT "Identification and chromosomal mapping of a receptor tyrosine kinase with
RT a putative phospholipid binding sequence in its ectodomain.";
RL Oncogene 9:211-219(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-833.
RX PubMed=8977099; DOI=10.1016/s0014-5793(96)01234-3;
RA Sakuma S., Tada M., Saya H., Sawamura Y., Shinohe Y., Abe H.;
RT "Receptor protein tyrosine kinase DDR is up-regulated by p53 protein.";
RL FEBS Lett. 398:165-169(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8796349; DOI=10.1101/gr.6.7.620;
RA Playford M.P., Butler R.J., Wang X.C., Katso R.M., Cooke I.E.,
RA Ganesan T.S.;
RT "The genomic structure of discoidin receptor tyrosine kinase.";
RL Genome Res. 6:620-627(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Lung;
RX PubMed=8622863;
RA Perez J.L., Jing S.Q., Wong T.W.;
RT "Identification of two isoforms of the Cak receptor kinase that are
RT coexpressed in breast tumor cell lines.";
RL Oncogene 12:1469-1477(1996).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE [MRNA] OF
RP 1-286 (ISOFORMS 1/2/4).
RX PubMed=18593464; DOI=10.1186/ar2447;
RA Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D.,
RA Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.;
RT "Novel splice variants derived from the receptor tyrosine kinase
RT superfamily are potential therapeutics for rheumatoid arthritis.";
RL Arthritis Res. Ther. 10:R73-R73(2008).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 5).
RC TISSUE=Brain, and Placenta;
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R.,
RA Okazaki N., Koga H., Nagase T., Ohara O.;
RT "Preparation of a set of expression-ready clones of mammalian long cDNAs
RT encoding large proteins by the ORF trap cloning method.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC TISSUE=Peripheral blood leukocyte;
RX PubMed=16702430; DOI=10.1534/genetics.106.057034;
RA Shiina T., Ota M., Shimizu S., Katsuyama Y., Hashimoto N., Takasu M.,
RA Anzai T., Kulski J.K., Kikkawa E., Naruse T., Kimura N., Yanagiya K.,
RA Watanabe A., Hosomichi K., Kohara S., Iwamoto C., Umehara Y., Meyer A.,
RA Wanner V., Sano K., Macquin C., Ikeo K., Tokunaga K., Gojobori T.,
RA Inoko H., Bahram S.;
RT "Rapid evolution of major histocompatibility complex class I genes in
RT primates generates new disease alleles in humans via hitchhiking
RT diversity.";
RL Genetics 173:1555-1570(2006).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [13]
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 [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain, and Muscle;
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 [15]
RP PROTEIN SEQUENCE OF 480-490; 515-525 AND 790-798, IDENTIFICATION BY MASS
RP SPECTROMETRY, SUBUNIT, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-484;
RP TYR-513; TYR-520; TYR-792; TYR-796 AND TYR-797, GLYCOSYLATION AT ASN-211
RP AND ASN-260, AND MUTAGENESIS OF ARG-105; ASN-211; SER-213; ASN-260;
RP ASN-371; THR-379; THR-393; ASN-394 AND LYS-655.
RX PubMed=24509848; DOI=10.1074/jbc.m113.541102;
RA Fu H.L., Valiathan R.R., Payne L., Kumarasiri M., Mahasenan K.V.,
RA Mobashery S., Huang P., Fridman R.;
RT "Glycosylation at Asn211 regulates the activation state of the discoidin
RT domain receptor 1 (DDR1).";
RL J. Biol. Chem. 289:9275-9287(2014).
RN [16]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 501-550 (ISOFORMS 1/4), NUCLEOTIDE SEQUENCE
RP [MRNA] OF 501-550 AND 651-694 (ISOFORM 2), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 651-694 (ISOFORM 4), ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RC TISSUE=Mammary carcinoma;
RX PubMed=7845687;
RA Alves F., Vogel W., Mossie K., Millauer B., Hoefler H., Ullrich A.;
RT "Distinct structural characteristics of discoidin I subfamily receptor
RT tyrosine kinases and complementary expression in human cancer.";
RL Oncogene 10:609-618(1995).
RN [17]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 771-824 (ISOFORMS 1/2/4).
RX PubMed=7834423; DOI=10.1007/bf02303537;
RA Weiner T.M., Liu E.T., Craven R.J., Cance W.G.;
RT "Expression of growth factor receptors, the focal adhesion kinase, and
RT other tyrosine kinases in human soft tissue tumors.";
RL Ann. Surg. Oncol. 1:18-27(1994).
RN [18]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 772-823 (ISOFORMS 1/2/4), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Melanocyte;
RX PubMed=8247543;
RA Lee S.-T., Strunk K.M., Spritz R.A.;
RT "A survey of protein tyrosine kinase mRNAs expressed in normal human
RT melanocytes.";
RL Oncogene 8:3403-3410(1993).
RN [19]
RP FUNCTION AS COLLAGEN RECEPTOR, PHOSPHORYLATION AT TYR-513, INTERACTION WITH
RP SHC1, AUTOPHOSPHORYLATION, 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 [20]
RP FUNCTION.
RX PubMed=12065315; DOI=10.1161/01.res.0000022166.74073.f8;
RA Hou G., Vogel W.F., Bendeck M.P.;
RT "Tyrosine kinase activity of discoidin domain receptor 1 is necessary for
RT smooth muscle cell migration and matrix metalloproteinase expression.";
RL Circ. Res. 90:1147-1149(2002).
RN [21]
RP FUNCTION, INTERACTION WITH PTPN11 AND NCK2, PHOSPHORYLATION AT TYR-740, AND
RP MUTAGENESIS OF TYR-740.
RX PubMed=16337946; DOI=10.1016/j.febslet.2005.11.035;
RA Koo D.H., McFadden C., Huang Y., Abdulhussein R., Friese-Hamim M.,
RA Vogel W.F.;
RT "Pinpointing phosphotyrosine-dependent interactions downstream of the
RT collagen receptor DDR1.";
RL FEBS Lett. 580:15-22(2006).
RN [22]
RP FUNCTION.
RX PubMed=16234985; DOI=10.1007/s11060-005-6874-1;
RA Ram R., Lorente G., Nikolich K., Urfer R., Foehr E., Nagavarapu U.;
RT "Discoidin domain receptor-1a (DDR1a) promotes glioma cell invasion and
RT adhesion in association with matrix metalloproteinase-2.";
RL J. Neurooncol. 76:239-248(2006).
RN [23]
RP INTERACTION WITH WWC1 AND PRKCZ.
RX PubMed=18190796; DOI=10.1016/j.bbamcr.2007.12.007;
RA Hilton H.N., Stanford P.M., Harris J., Oakes S.R., Kaplan W., Daly R.J.,
RA Ormandy C.J.;
RT "KIBRA interacts with discoidin domain receptor 1 to modulate collagen-
RT induced signalling.";
RL Biochim. Biophys. Acta 1783:383-393(2008).
RN [24]
RP FUNCTION, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, AND INTERACTION WITH
RP MYH9.
RX PubMed=19401332; DOI=10.1242/jcs.046219;
RA Huang Y., Arora P., McCulloch C.A., Vogel W.F.;
RT "The collagen receptor DDR1 regulates cell spreading and motility by
RT associating with myosin IIA.";
RL J. Cell Sci. 122:1637-1646(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-631, AND IDENTIFICATION BY
RP 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 [26]
RP FUNCTION, AND INTERACTION WITH CDH1.
RX PubMed=20432435; DOI=10.1002/jcp.22134;
RA Eswaramoorthy R., Wang C.K., Chen W.C., Tang M.J., Ho M.L., Hwang C.C.,
RA Wang H.M., Wang C.Z.;
RT "DDR1 regulates the stabilization of cell surface E-cadherin and E-
RT cadherin-mediated cell aggregation.";
RL J. Cell. Physiol. 224:387-397(2010).
RN [27]
RP FUNCTION, AND INTERACTION WITH SRC.
RX PubMed=20093046; DOI=10.1016/j.carpath.2009.12.006;
RA Lu K.K., Trcka D., Bendeck M.P.;
RT "Collagen stimulates discoidin domain receptor 1-mediated migration of
RT smooth muscle cells through Src.";
RL Cardiovasc. Pathol. 20:71-76(2011).
RN [28]
RP FUNCTION.
RX PubMed=20884741; DOI=10.1183/09031936.00039710;
RA Roberts M.E., Magowan L., Hall I.P., Johnson S.R.;
RT "Discoidin domain receptor 1 regulates bronchial epithelial repair and
RT matrix metalloproteinase production.";
RL Eur. Respir. J. 37:1482-1493(2011).
RN [29]
RP FUNCTION AS COLLAGEN RECEPTOR, AND AUTOPHOSPHORYLATION.
RX PubMed=21044884; DOI=10.1016/j.matbio.2010.10.004;
RA Xu H., Raynal N., Stathopoulos S., Myllyharju J., Farndale R.W.,
RA Leitinger B.;
RT "Collagen binding specificity of the discoidin domain receptors: binding
RT sites on collagens II and III and molecular determinants for collagen IV
RT recognition by DDR1.";
RL Matrix Biol. 30:16-26(2011).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 29-367 IN COMPLEX WITH INHIBITORY
RP ANTIBODY, SUBUNIT, CALCIUM-BINDING SITES, GLYCOSYLATION AT ASN-211 AND
RP ASN-260, AND DISULFIDE BONDS.
RX PubMed=22483115; DOI=10.1016/j.str.2012.02.011;
RA Carafoli F., Mayer M.C., Shiraishi K., Pecheva M.A., Chan L.Y., Nan R.,
RA Leitinger B., Hohenester E.;
RT "Structure of the discoidin domain receptor 1 extracellular region bound to
RT an inhibitory Fab fragment reveals features important for signaling.";
RL Structure 20:688-697(2012).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 601-913 IN COMPLEX WITH
RP INHIBITOR, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF GLY-707.
RX PubMed=23899692; DOI=10.1021/cb400430t;
RA Kim H.G., Tan L., Weisberg E.L., Liu F., Canning P., Choi H.G., Ezell S.A.,
RA Wu H., Zhao Z., Wang J., Mandinova A., Griffin J.D., Bullock A.N., Liu Q.,
RA Lee S.W., Gray N.S.;
RT "Discovery of a potent and selective DDR1 receptor tyrosine kinase
RT inhibitor.";
RL ACS Chem. Biol. 8:2145-2150(2013).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 601-913 IN COMPLEXES WITH
RP INHIBITORS IMATINIB AND PONATINIB, ACTIVITY REGULATION, AND
RP AUTOPHOSPHORYLATION.
RX PubMed=24768818; DOI=10.1016/j.jmb.2014.04.014;
RA Canning P., Tan L., Chu K., Lee S.W., Gray N.S., Bullock A.N.;
RT "Structural mechanisms determining inhibition of the collagen receptor DDR1
RT by selective and multi-targeted type II kinase inhibitors.";
RL J. Mol. Biol. 426:2457-2470(2014).
RN [33]
RP VARIANTS [LARGE SCALE ANALYSIS] GLY-17; ALA-100; GLN-169; ASP-170; TRP-306
RP AND ALA-496.
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).
CC -!- FUNCTION: Tyrosine kinase that functions as cell surface receptor for
CC fibrillar collagen and regulates cell attachment to the extracellular
CC matrix, remodeling of the extracellular matrix, cell migration,
CC differentiation, survival and cell proliferation. Collagen binding
CC triggers a signaling pathway that involves SRC and leads to the
CC activation of MAP kinases. Regulates remodeling of the extracellular
CC matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and
CC MMP9, and thereby facilitates cell migration and wound healing.
CC Required for normal blastocyst implantation during pregnancy, for
CC normal mammary gland differentiation and normal lactation. Required for
CC normal ear morphology and normal hearing (By similarity). Promotes
CC smooth muscle cell migration, and thereby contributes to arterial wound
CC healing. Also plays a role in tumor cell invasion. Phosphorylates
CC PTPN11. {ECO:0000250, ECO:0000269|PubMed:12065315,
CC ECO:0000269|PubMed:16234985, ECO:0000269|PubMed:16337946,
CC ECO:0000269|PubMed:19401332, ECO:0000269|PubMed:20093046,
CC ECO:0000269|PubMed:20432435, ECO:0000269|PubMed:20884741,
CC ECO:0000269|PubMed:21044884, 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 -!- ACTIVITY REGULATION: Inhibited by the multi-targeted cancer drugs
CC imatinib and ponatinib. {ECO:0000269|PubMed:24768818}.
CC -!- SUBUNIT: Homodimer. Interacts (via PPxY motif) with WWC1 (via WW
CC domains) in a collagen-regulated manner. Forms a tripartite complex
CC with WWC1 and PRKCZ, but predominantly in the absence of collagen.
CC Interacts (tyrosine phosphorylated) with SHC1. Interacts with SRC.
CC Interacts with MYH9. Interacts with CDH1. Interacts with PTPN11.
CC Interacts with NCK2. {ECO:0000269|PubMed:16337946,
CC ECO:0000269|PubMed:18190796, ECO:0000269|PubMed:19401332,
CC ECO:0000269|PubMed:20093046, ECO:0000269|PubMed:20432435,
CC ECO:0000269|PubMed:22483115, ECO:0000269|PubMed:23899692,
CC ECO:0000269|PubMed:24509848, ECO:0000269|PubMed:9659899}.
CC -!- INTERACTION:
CC Q08345; O43639: NCK2; NbExp=3; IntAct=EBI-711879, EBI-713635;
CC Q08345; Q06124: PTPN11; NbExp=4; IntAct=EBI-711879, EBI-297779;
CC Q08345-2; Q9UHD9: UBQLN2; NbExp=5; IntAct=EBI-711903, EBI-947187;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=CAK I, DDR1b;
CC IsoId=Q08345-1; Sequence=Displayed;
CC Name=2; Synonyms=CAK II, DDR1a, Short;
CC IsoId=Q08345-2; Sequence=VSP_002953;
CC Name=3; Synonyms=DDR1d;
CC IsoId=Q08345-4; Sequence=VSP_036916, VSP_036917;
CC Name=4;
CC IsoId=Q08345-5; Sequence=VSP_038057;
CC Name=5;
CC IsoId=Q08345-6; Sequence=VSP_043582, VSP_002953;
CC -!- TISSUE SPECIFICITY: Detected in T-47D, MDA-MB-175 and HBL-100 breast
CC carcinoma cells, A-431 epidermoid carcinoma cells, SW48 and SNU-C2B
CC colon carcinoma cells and Hs 294T melanoma cells (at protein level).
CC Expressed at low levels in most adult tissues and is highest in the
CC brain, lung, placenta and kidney. Lower levels of expression are
CC detected in melanocytes, heart, liver, skeletal muscle and pancreas.
CC Abundant in breast carcinoma cell lines. In the colonic mucosa,
CC expressed in epithelia but not in the connective tissue of the lamina
CC propria. In the thyroid gland, expressed in the epithelium of the
CC thyroid follicles. In pancreas, expressed in the islets of Langerhans
CC cells, but not in the surrounding epithelial cells of the exocrine
CC pancreas. In kidney, expressed in the epithelia of the distal tubules.
CC Not expressed in connective tissue, endothelial cells, adipose tissue,
CC muscle cells or cells of hematopoietic origin.
CC {ECO:0000269|PubMed:7845687, ECO:0000269|PubMed:7848919,
CC ECO:0000269|PubMed:8247543}.
CC -!- DOMAIN: The Gly/Pro-rich domains may be required for an unusual
CC geometry of interaction with ligand or substrates.
CC -!- PTM: Autophosphorylated in response to fibrillar collagen binding.
CC -!- PTM: Glycosylation of Asn-211, but apparently not of Asn-260 or Asn-
CC 394, prevents autophosphorylation from occurring in the absence of
CC collagen. {ECO:0000269|PubMed:22483115, ECO:0000269|PubMed:24509848}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- CAUTION: The mutant Gln-371 studied is still likely to be glycosylated
CC at Asn-370, but study did not include mutagenesis of Asn-370.
CC {ECO:0000305|PubMed:24509848}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ACF47649.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE06103.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/DDR1ID40280ch6p21.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
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DR EMBL; X74979; CAA52915.1; -; mRNA.
DR EMBL; L11315; AAA02866.1; -; mRNA.
DR EMBL; Z29093; CAA82335.1; -; mRNA.
DR EMBL; L20817; AAA18019.1; -; mRNA.
DR EMBL; U48705; AAC50917.1; -; Genomic_DNA.
DR EMBL; X98208; CAA66871.1; -; Genomic_DNA.
DR EMBL; X99023; CAA66871.1; JOINED; Genomic_DNA.
DR EMBL; X99024; CAA66871.1; JOINED; Genomic_DNA.
DR EMBL; X99025; CAA66871.1; JOINED; Genomic_DNA.
DR EMBL; X99026; CAA66871.1; JOINED; Genomic_DNA.
DR EMBL; X99027; CAA66871.1; JOINED; Genomic_DNA.
DR EMBL; X99028; CAA66871.1; JOINED; Genomic_DNA.
DR EMBL; X99029; CAA66871.1; JOINED; Genomic_DNA.
DR EMBL; X99030; CAA66871.1; JOINED; Genomic_DNA.
DR EMBL; X99031; CAA66871.1; JOINED; Genomic_DNA.
DR EMBL; X99032; CAA66871.1; JOINED; Genomic_DNA.
DR EMBL; X99033; CAA66871.1; JOINED; Genomic_DNA.
DR EMBL; X99034; CAA66871.1; JOINED; Genomic_DNA.
DR EMBL; L57508; AAB05208.1; -; mRNA.
DR EMBL; EU826613; ACF47649.1; ALT_SEQ; mRNA.
DR EMBL; EU826614; ACF47650.1; -; mRNA.
DR EMBL; AK291621; BAF84310.1; -; mRNA.
DR EMBL; AK294793; BAH11886.1; -; mRNA.
DR EMBL; AB210021; BAE06103.1; ALT_INIT; mRNA.
DR EMBL; BA000025; BAB63318.1; -; Genomic_DNA.
DR EMBL; CR759747; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB088102; BAC54935.1; -; Genomic_DNA.
DR EMBL; AB103608; BAF31270.1; -; Genomic_DNA.
DR EMBL; AL662854; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL662870; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL773541; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL773589; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB202100; BAE78621.1; -; Genomic_DNA.
DR EMBL; BX927194; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03335.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03338.1; -; Genomic_DNA.
DR EMBL; BC008716; AAH08716.1; -; mRNA.
DR EMBL; BC013400; AAH13400.1; -; mRNA.
DR EMBL; BC070070; AAH70070.1; -; mRNA.
DR CCDS; CCDS34385.1; -. [Q08345-1]
DR CCDS; CCDS4690.1; -. [Q08345-2]
DR CCDS; CCDS47396.1; -. [Q08345-5]
DR CCDS; CCDS56411.1; -. [Q08345-2]
DR PIR; A48280; A48280.
DR PIR; A49508; A49508.
DR RefSeq; NP_001189450.1; NM_001202521.1.
DR RefSeq; NP_001189451.1; NM_001202522.1.
DR RefSeq; NP_001189452.1; NM_001202523.1. [Q08345-2]
DR RefSeq; NP_001284581.1; NM_001297652.1. [Q08345-2]
DR RefSeq; NP_001284582.1; NM_001297653.1. [Q08345-2]
DR RefSeq; NP_001284583.1; NM_001297654.1. [Q08345-1]
DR RefSeq; NP_001945.3; NM_001954.4. [Q08345-2]
DR RefSeq; NP_054699.2; NM_013993.2. [Q08345-1]
DR RefSeq; NP_054700.2; NM_013994.2. [Q08345-5]
DR PDB; 3ZOS; X-ray; 1.92 A; A/B=601-913.
DR PDB; 4AG4; X-ray; 2.80 A; A=29-367.
DR PDB; 4BKJ; X-ray; 1.70 A; A/B=601-913.
DR PDB; 4CKR; X-ray; 2.20 A; A=601-913.
DR PDB; 5BVK; X-ray; 2.29 A; A=595-913.
DR PDB; 5BVN; X-ray; 2.21 A; A=595-913.
DR PDB; 5BVO; X-ray; 1.98 A; A=595-913.
DR PDB; 5BVW; X-ray; 1.94 A; A=595-913.
DR PDB; 5FDP; X-ray; 2.25 A; A=601-913.
DR PDB; 5FDX; X-ray; 2.65 A; A/B=601-913.
DR PDB; 6BRJ; X-ray; 2.23 A; A=1-913.
DR PDB; 6BSD; X-ray; 2.61 A; A=1-913.
DR PDB; 6FEW; X-ray; 1.44 A; A=593-913.
DR PDB; 6FEX; X-ray; 1.29 A; A=593-913.
DR PDB; 6FIL; X-ray; 1.73 A; A=593-913.
DR PDB; 6FIN; X-ray; 1.67 A; A=593-913.
DR PDB; 6FIO; X-ray; 1.99 A; A=593-913.
DR PDB; 6FIQ; X-ray; 1.79 A; A=593-913.
DR PDB; 6GWR; X-ray; 2.07 A; A/B=601-913.
DR PDB; 6HP9; X-ray; 1.96 A; A/B=601-913.
DR PDB; 6Y23; X-ray; 2.58 A; A/B/C=566-913.
DR PDB; 7BCM; X-ray; 2.30 A; A/B=601-913.
DR PDB; 7BE6; X-ray; 1.87 A; A=601-913.
DR PDBsum; 3ZOS; -.
DR PDBsum; 4AG4; -.
DR PDBsum; 4BKJ; -.
DR PDBsum; 4CKR; -.
DR PDBsum; 5BVK; -.
DR PDBsum; 5BVN; -.
DR PDBsum; 5BVO; -.
DR PDBsum; 5BVW; -.
DR PDBsum; 5FDP; -.
DR PDBsum; 5FDX; -.
DR PDBsum; 6BRJ; -.
DR PDBsum; 6BSD; -.
DR PDBsum; 6FEW; -.
DR PDBsum; 6FEX; -.
DR PDBsum; 6FIL; -.
DR PDBsum; 6FIN; -.
DR PDBsum; 6FIO; -.
DR PDBsum; 6FIQ; -.
DR PDBsum; 6GWR; -.
DR PDBsum; 6HP9; -.
DR PDBsum; 6Y23; -.
DR PDBsum; 7BCM; -.
DR PDBsum; 7BE6; -.
DR AlphaFoldDB; Q08345; -.
DR SMR; Q08345; -.
DR BioGRID; 107234; 126.
DR CORUM; Q08345; -.
DR DIP; DIP-39698N; -.
DR IntAct; Q08345; 77.
DR MINT; Q08345; -.
DR STRING; 9606.ENSP00000427552; -.
DR BindingDB; Q08345; -.
DR ChEMBL; CHEMBL5319; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB00619; Imatinib.
DR DrugBank; DB15822; Pralsetinib.
DR DrugCentral; Q08345; -.
DR GuidetoPHARMACOLOGY; 1843; -.
DR GlyGen; Q08345; 4 sites.
DR iPTMnet; Q08345; -.
DR PhosphoSitePlus; Q08345; -.
DR BioMuta; DDR1; -.
DR DMDM; 729008; -.
DR EPD; Q08345; -.
DR jPOST; Q08345; -.
DR MassIVE; Q08345; -.
DR MaxQB; Q08345; -.
DR PaxDb; Q08345; -.
DR PeptideAtlas; Q08345; -.
DR PRIDE; Q08345; -.
DR ProteomicsDB; 58595; -. [Q08345-1]
DR ProteomicsDB; 58596; -. [Q08345-2]
DR ProteomicsDB; 58597; -. [Q08345-4]
DR ProteomicsDB; 58598; -. [Q08345-5]
DR ProteomicsDB; 58599; -. [Q08345-6]
DR ABCD; Q08345; 1 sequenced antibody.
DR Antibodypedia; 48090; 761 antibodies from 43 providers.
DR DNASU; 780; -.
DR Ensembl; ENST00000259875.11; ENSP00000259875.7; ENSG00000137332.19. [Q08345-2]
DR Ensembl; ENST00000324771.12; ENSP00000318217.8; ENSG00000204580.14. [Q08345-1]
DR Ensembl; ENST00000376567.6; ENSP00000365751.2; ENSG00000204580.14. [Q08345-2]
DR Ensembl; ENST00000376568.8; ENSP00000365752.3; ENSG00000204580.14. [Q08345-1]
DR Ensembl; ENST00000376569.7; ENSP00000365753.3; ENSG00000204580.14. [Q08345-2]
DR Ensembl; ENST00000376570.8; ENSP00000365754.4; ENSG00000204580.14. [Q08345-2]
DR Ensembl; ENST00000376575.7; ENSP00000365759.4; ENSG00000204580.14. [Q08345-4]
DR Ensembl; ENST00000383377.6; ENSP00000372868.2; ENSG00000137332.19. [Q08345-1]
DR Ensembl; ENST00000400410.5; ENSP00000383261.1; ENSG00000137332.19. [Q08345-2]
DR Ensembl; ENST00000400411.5; ENSP00000383262.1; ENSG00000137332.19. [Q08345-2]
DR Ensembl; ENST00000400414.5; ENSP00000383265.1; ENSG00000137332.19. [Q08345-1]
DR Ensembl; ENST00000400486.5; ENSP00000383334.1; ENSG00000215522.11. [Q08345-2]
DR Ensembl; ENST00000400488.5; ENSP00000383336.1; ENSG00000215522.11. [Q08345-2]
DR Ensembl; ENST00000400489.7; ENSP00000383337.3; ENSG00000215522.11. [Q08345-2]
DR Ensembl; ENST00000400491.5; ENSP00000383338.1; ENSG00000215522.11. [Q08345-1]
DR Ensembl; ENST00000400492.5; ENSP00000383339.1; ENSG00000215522.11. [Q08345-1]
DR Ensembl; ENST00000412329.5; ENSP00000391805.1; ENSG00000230456.10. [Q08345-1]
DR Ensembl; ENST00000415092.5; ENSP00000405540.1; ENSG00000230456.10. [Q08345-2]
DR Ensembl; ENST00000418800.6; ENSP00000407699.2; ENSG00000204580.14. [Q08345-2]
DR Ensembl; ENST00000419412.5; ENSP00000416183.1; ENSG00000234078.10. [Q08345-2]
DR Ensembl; ENST00000421229.6; ENSP00000415730.2; ENSG00000234078.10. [Q08345-2]
DR Ensembl; ENST00000427053.6; ENSP00000416145.2; ENSG00000230456.10. [Q08345-2]
DR Ensembl; ENST00000429699.5; ENSP00000401397.1; ENSG00000234078.10. [Q08345-1]
DR Ensembl; ENST00000430933.5; ENSP00000397769.1; ENSG00000234078.10. [Q08345-1]
DR Ensembl; ENST00000449518.5; ENSP00000414285.1; ENSG00000230456.10. [Q08345-1]
DR Ensembl; ENST00000452441.5; ENSP00000405039.1; ENSG00000204580.14. [Q08345-1]
DR Ensembl; ENST00000453510.5; ENSP00000401208.1; ENSG00000230456.10. [Q08345-2]
DR Ensembl; ENST00000454612.6; ENSP00000406091.2; ENSG00000204580.14. [Q08345-2]
DR Ensembl; ENST00000454774.5; ENSP00000400393.1; ENSG00000234078.10. [Q08345-2]
DR Ensembl; ENST00000482873.6; ENSP00000421978.1; ENSG00000204580.14. [Q08345-4]
DR Ensembl; ENST00000508312.5; ENSP00000422442.1; ENSG00000204580.14. [Q08345-6]
DR Ensembl; ENST00000513240.5; ENSP00000427552.1; ENSG00000204580.14. [Q08345-5]
DR Ensembl; ENST00000548133.4; ENSP00000449611.2; ENSG00000230456.10. [Q08345-1]
DR Ensembl; ENST00000548962.5; ENSP00000448115.2; ENSG00000230456.10. [Q08345-6]
DR Ensembl; ENST00000549026.3; ENSP00000449238.2; ENSG00000215522.11. [Q08345-6]
DR Ensembl; ENST00000550384.5; ENSP00000447474.2; ENSG00000234078.10. [Q08345-6]
DR Ensembl; ENST00000550395.5; ENSP00000449255.2; ENSG00000215522.11. [Q08345-1]
DR Ensembl; ENST00000552068.5; ENSP00000449190.2; ENSG00000234078.10. [Q08345-1]
DR Ensembl; ENST00000552721.4; ENSP00000449307.2; ENSG00000137332.19. [Q08345-6]
DR Ensembl; ENST00000553015.5; ENSP00000448377.2; ENSG00000137332.19. [Q08345-1]
DR Ensembl; ENST00000617572.3; ENSP00000479195.1; ENSG00000215522.11. [Q08345-4]
DR Ensembl; ENST00000618059.2; ENSP00000479204.1; ENSG00000234078.10. [Q08345-4]
DR Ensembl; ENST00000620318.4; ENSP00000484588.1; ENSG00000137332.19. [Q08345-4]
DR Ensembl; ENST00000621544.4; ENSP00000484013.1; ENSG00000230456.10. [Q08345-4]
DR GeneID; 780; -.
DR KEGG; hsa:780; -.
DR MANE-Select; ENST00000376568.8; ENSP00000365752.3; NM_001297654.2; NP_001284583.1.
DR UCSC; uc003nrq.4; human. [Q08345-1]
DR CTD; 780; -.
DR DisGeNET; 780; -.
DR GeneCards; DDR1; -.
DR HGNC; HGNC:2730; DDR1.
DR HPA; ENSG00000204580; Low tissue specificity.
DR MIM; 600408; gene.
DR neXtProt; NX_Q08345; -.
DR OpenTargets; ENSG00000204580; -.
DR PharmGKB; PA24348; -.
DR VEuPathDB; HostDB:ENSG00000204580; -.
DR eggNOG; KOG1094; Eukaryota.
DR GeneTree; ENSGT00940000159733; -.
DR HOGENOM; CLU_008873_2_0_1; -.
DR InParanoid; Q08345; -.
DR OMA; QILRCHF; -.
DR OrthoDB; 227725at2759; -.
DR PhylomeDB; Q08345; -.
DR TreeFam; TF317840; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; Q08345; -.
DR Reactome; R-HSA-3000171; Non-integrin membrane-ECM interactions.
DR SignaLink; Q08345; -.
DR SIGNOR; Q08345; -.
DR BioGRID-ORCS; 780; 17 hits in 1113 CRISPR screens.
DR ChiTaRS; DDR1; human.
DR GeneWiki; DDR1; -.
DR GenomeRNAi; 780; -.
DR Pharos; Q08345; Tchem.
DR PRO; PR:Q08345; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q08345; protein.
DR Bgee; ENSG00000137332; Expressed in cerebral cortex and 4 other tissues.
DR ExpressionAtlas; Q08345; baseline and differential.
DR Genevisible; Q08345; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005518; F:collagen binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0038062; F:protein tyrosine kinase collagen receptor activity; IDA:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0061564; P:axon development; IEA:Ensembl.
DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IEA:Ensembl.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0038063; P:collagen-activated tyrosine kinase receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0043583; P:ear development; IEA:Ensembl.
DR GO; GO:0007566; P:embryo implantation; IEA:Ensembl.
DR GO; GO:0007595; P:lactation; IEA:UniProtKB-KW.
DR GO; GO:0060749; P:mammary gland alveolus development; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:1990138; P:neuron projection extension; IEA:Ensembl.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; IEA:Ensembl.
DR GO; GO:0001952; P:regulation of cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0010715; P:regulation of extracellular matrix disassembly; IMP:UniProtKB.
DR GO; GO:0014909; P:smooth muscle cell migration; IMP:UniProtKB.
DR GO; GO:0061302; P:smooth muscle cell-matrix adhesion; IMP:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0044319; P:wound healing, spreading of cells; IMP:UniProtKB.
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; Alternative splicing; ATP-binding; Calcium; Cell membrane;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Kinase; Lactation;
KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Pregnancy;
KW Receptor; Reference proteome; Secreted; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..913
FT /note="Epithelial discoidin domain-containing receptor 1"
FT /id="PRO_0000016742"
FT TOPO_DOM 21..417
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 418..438
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 439..913
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 31..185
FT /note="F5/8 type C"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DOMAIN 610..905
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 192..367
FT /note="DS-like domain"
FT REGION 470..499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 481..484
FT /note="PPxY motif"
FT COMPBIAS 476..496
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 766
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 211
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 235
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 253
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 255
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 360
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 361
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 616..624
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 655
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 484
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:24509848"
FT MOD_RES 513
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:24509848,
FT ECO:0000269|PubMed:9659899"
FT MOD_RES 520
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:24509848"
FT MOD_RES 631
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 740
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:16337946"
FT MOD_RES 792
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:24509848"
FT MOD_RES 796
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:24509848"
FT MOD_RES 797
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:24509848"
FT CARBOHYD 211
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22483115,
FT ECO:0000269|PubMed:24509848"
FT CARBOHYD 260
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22483115,
FT ECO:0000269|PubMed:24509848"
FT CARBOHYD 370
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 394
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..185
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081,
FT ECO:0000269|PubMed:22483115"
FT DISULFID 74..177
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081,
FT ECO:0000269|PubMed:22483115"
FT DISULFID 303..348
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081,
FT ECO:0000269|PubMed:22483115"
FT VAR_SEQ 1
FT /note="M -> MSLPRCCPHPLRPEGSGAM (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043582"
FT VAR_SEQ 190..243
FT /note="GLLSYTAPVGQTMYLSEAVYLNDSTYDGHTVGGLQYGGLGQLADGVVGLDDF
FT RK -> CSMGVWASWQMVWWGWMTLGRVRSCGSGQAMTMWDGATTASPVAMWRWSLSLT
FT G (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_036916"
FT VAR_SEQ 244..913
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_036917"
FT VAR_SEQ 506..542
FT /note="Missing (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:7845687,
FT ECO:0000303|PubMed:7848919, ECO:0000303|PubMed:8226977,
FT ECO:0000303|PubMed:8622863, ECO:0000303|Ref.10"
FT /id="VSP_002953"
FT VAR_SEQ 665
FT /note="A -> ASFSLFS (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:7845687"
FT /id="VSP_038057"
FT VARIANT 17
FT /note="S -> G (in dbSNP:rs55901302)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041492"
FT VARIANT 100
FT /note="V -> A (in dbSNP:rs34544756)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041493"
FT VARIANT 169
FT /note="R -> Q (in dbSNP:rs55980643)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041494"
FT VARIANT 170
FT /note="A -> D (in dbSNP:rs56231803)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041495"
FT VARIANT 306
FT /note="R -> W (in dbSNP:rs56024191)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041496"
FT VARIANT 496
FT /note="S -> A (in a lung squamous cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041497"
FT VARIANT 833
FT /note="L -> V (in dbSNP:rs2524235)"
FT /evidence="ECO:0000269|PubMed:8390675,
FT ECO:0000269|PubMed:8977099"
FT /id="VAR_049716"
FT MUTAGEN 105
FT /note="R->A: Inhibits collagen-induced phosphorylation."
FT /evidence="ECO:0000269|PubMed:24509848"
FT MUTAGEN 211
FT /note="N->A: Phosphorylates regardless of collagen
FT presence, collagen addition does not alter significantly
FT the levels of constitutive phosphorylation."
FT /evidence="ECO:0000269|PubMed:24509848"
FT MUTAGEN 211
FT /note="N->Q: Sustained phosphorylation regardless of
FT collagen presence, collagen addition does not alter
FT significantly the levels of constitutive phosphorylation.
FT Located intracellularly and at the cell surface. Displays a
FT reduced rate of receptor internalization, which is not
FT altered in the presence of collagen. Able to bind collagen
FT as wild-type. Exhibits enhanced collagen-independent
FT receptor dimerization. Complete loss of the collagen-
FT independent constitutive activation; when associated with
FT A-655."
FT /evidence="ECO:0000269|PubMed:24509848"
FT MUTAGEN 213
FT /note="S->A: Phosphorylates regardless of collagen
FT presence, collagen addition does not alter significantly
FT the levels of constitutive phosphorylation."
FT /evidence="ECO:0000269|PubMed:24509848"
FT MUTAGEN 260
FT /note="N->Q: Phosphorylates in response to collagen, but at
FT lower levels compared to wild-type. No activation in the
FT absence of collagen."
FT /evidence="ECO:0000269|PubMed:24509848"
FT MUTAGEN 371
FT /note="N->Q: Phosphorylates in response to collagen, but at
FT lower levels compared to wild-type. No activation in the
FT absence of collagen."
FT /evidence="ECO:0000269|PubMed:24509848"
FT MUTAGEN 379
FT /note="T->A: Phosphorylates in response to collagen, but at
FT lower levels compared to wild-type. Phosphorylates in
FT response to collagen, but at lower levels compared to wild-
FT type; when associated with A-393."
FT /evidence="ECO:0000269|PubMed:24509848"
FT MUTAGEN 393
FT /note="T->A: Phosphorylates in response to collagen, but at
FT lower levels compared to wild-type. Phosphorylates in
FT response to collagen, but at lower levels compared to wild-
FT type; when associated with A-379."
FT /evidence="ECO:0000269|PubMed:24509848"
FT MUTAGEN 394
FT /note="N->Q: Phosphorylates in response to collagen, but at
FT lower levels compared to wild-type. No activation in the
FT absence of collagen."
FT /evidence="ECO:0000269|PubMed:24509848"
FT MUTAGEN 655
FT /note="K->A: Loss of kinase activity. Complete loss of the
FT collagen-independent constitutive activation; when
FT associated with Q-211."
FT /evidence="ECO:0000269|PubMed:24509848"
FT MUTAGEN 707
FT /note="G->A: Confers over 20-fold resistance to the ability
FT of an inhibitor to inhibit autophosphorylation."
FT /evidence="ECO:0000269|PubMed:23899692"
FT MUTAGEN 740
FT /note="Y->F: Abolishes interaction with PTPN11."
FT /evidence="ECO:0000269|PubMed:16337946"
FT CONFLICT 94
FT /note="L -> V (in Ref. 2; AAA02866 and 5; AAC50917)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="R -> H (in Ref. 14; AAH70070)"
FT /evidence="ECO:0000305"
FT CONFLICT 285..286
FT /note="VH -> MW (in Ref. 8; ACF47649)"
FT /evidence="ECO:0000305"
FT CONFLICT 741
FT /note="P -> Q (in Ref. 14; AAH70070)"
FT /evidence="ECO:0000305"
FT CONFLICT 847..867
FT /note="QLTDEQVIENAGEFFRDQGRQ -> SAHRRAGHRERGGVLPGPGPA (in
FT Ref. 6; CAA66871)"
FT /evidence="ECO:0000305"
FT TURN 37..39
FT /evidence="ECO:0007829|PDB:4AG4"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 47..50
FT /evidence="ECO:0007829|PDB:4AG4"
FT HELIX 55..57
FT /evidence="ECO:0007829|PDB:4AG4"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:4AG4"
FT TURN 68..70
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 87..103
FT /evidence="ECO:0007829|PDB:4AG4"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 116..127
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 151..169
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 178..186
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 191..197
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 217..220
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 223..226
FT /evidence="ECO:0007829|PDB:4AG4"
FT HELIX 230..232
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 245..248
FT /evidence="ECO:0007829|PDB:4AG4"
FT TURN 251..254
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:4AG4"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 266..287
FT /evidence="ECO:0007829|PDB:4AG4"
FT HELIX 291..293
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 299..306
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 308..312
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 318..321
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 332..351
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 353..367
FT /evidence="ECO:0007829|PDB:4AG4"
FT STRAND 582..584
FT /evidence="ECO:0007829|PDB:6Y23"
FT HELIX 607..609
FT /evidence="ECO:0007829|PDB:6FEX"
FT STRAND 610..618
FT /evidence="ECO:0007829|PDB:6FEX"
FT STRAND 620..631
FT /evidence="ECO:0007829|PDB:6FEX"
FT HELIX 632..634
FT /evidence="ECO:0007829|PDB:6FEX"
FT STRAND 637..639
FT /evidence="ECO:0007829|PDB:4BKJ"
FT STRAND 646..648
FT /evidence="ECO:0007829|PDB:7BE6"
FT STRAND 651..657
FT /evidence="ECO:0007829|PDB:6FEX"
FT HELIX 663..676
FT /evidence="ECO:0007829|PDB:6FEX"
FT STRAND 687..691
FT /evidence="ECO:0007829|PDB:6FEX"
FT STRAND 693..696
FT /evidence="ECO:0007829|PDB:6FEX"
FT STRAND 698..702
FT /evidence="ECO:0007829|PDB:6FEX"
FT HELIX 709..714
FT /evidence="ECO:0007829|PDB:6FEX"
FT STRAND 717..720
FT /evidence="ECO:0007829|PDB:6FIO"
FT STRAND 736..738
FT /evidence="ECO:0007829|PDB:6FIL"
FT HELIX 740..759
FT /evidence="ECO:0007829|PDB:6FEX"
FT HELIX 769..771
FT /evidence="ECO:0007829|PDB:6FEX"
FT STRAND 772..774
FT /evidence="ECO:0007829|PDB:6FEX"
FT HELIX 776..778
FT /evidence="ECO:0007829|PDB:6FEX"
FT STRAND 780..782
FT /evidence="ECO:0007829|PDB:6FEX"
FT HELIX 786..788
FT /evidence="ECO:0007829|PDB:6Y23"
FT HELIX 790..795
FT /evidence="ECO:0007829|PDB:6FEX"
FT STRAND 796..799
FT /evidence="ECO:0007829|PDB:6FIQ"
FT STRAND 802..805
FT /evidence="ECO:0007829|PDB:6FIQ"
FT HELIX 807..809
FT /evidence="ECO:0007829|PDB:6FEX"
FT HELIX 812..817
FT /evidence="ECO:0007829|PDB:6FEX"
FT HELIX 822..837
FT /evidence="ECO:0007829|PDB:6FEX"
FT TURN 838..840
FT /evidence="ECO:0007829|PDB:6FEX"
FT TURN 844..847
FT /evidence="ECO:0007829|PDB:6FEX"
FT HELIX 850..862
FT /evidence="ECO:0007829|PDB:6FEX"
FT HELIX 878..887
FT /evidence="ECO:0007829|PDB:6FEX"
FT HELIX 892..894
FT /evidence="ECO:0007829|PDB:6FEX"
FT HELIX 898..907
FT /evidence="ECO:0007829|PDB:6FEX"
FT HELIX 910..912
FT /evidence="ECO:0007829|PDB:4BKJ"
SQ SEQUENCE 913 AA; 101128 MW; C96913EA906C481E CRC64;
MGPEALSSLL LLLLVASGDA DMKGHFDPAK CRYALGMQDR TIPDSDISAS SSWSDSTAAR
HSRLESSDGD GAWCPAGSVF PKEEEYLQVD LQRLHLVALV GTQGRHAGGL GKEFSRSYRL
RYSRDGRRWM GWKDRWGQEV ISGNEDPEGV VLKDLGPPMV ARLVRFYPRA DRVMSVCLRV
ELYGCLWRDG LLSYTAPVGQ TMYLSEAVYL NDSTYDGHTV GGLQYGGLGQ LADGVVGLDD
FRKSQELRVW PGYDYVGWSN HSFSSGYVEM EFEFDRLRAF QAMQVHCNNM HTLGARLPGG
VECRFRRGPA MAWEGEPMRH NLGGNLGDPR ARAVSVPLGG RVARFLQCRF LFAGPWLLFS
EISFISDVVN NSSPALGGTF PPAPWWPPGP PPTNFSSLEL EPRGQQPVAK AEGSPTAILI
GCLVAIILLL LLIIALMLWR LHWRRLLSKA ERRVLEEELT VHLSVPGDTI LINNRPGPRE
PPPYQEPRPR GNPPHSAPCV PNGSALLLSN PAYRLLLATY ARPPRGPGPP TPAWAKPTNT
QAYSGDYMEP EKPGAPLLPP PPQNSVPHYA EADIVTLQGV TGGNTYAVPA LPPGAVGDGP
PRVDFPRSRL RFKEKLGEGQ FGEVHLCEVD SPQDLVSLDF PLNVRKGHPL LVAVKILRPD
ATKNARNDFL KEVKIMSRLK DPNIIRLLGV CVQDDPLCMI TDYMENGDLN QFLSAHQLED
KAAEGAPGDG QAAQGPTISY PMLLHVAAQI ASGMRYLATL NFVHRDLATR NCLVGENFTI
KIADFGMSRN LYAGDYYRVQ GRAVLPIRWM AWECILMGKF TTASDVWAFG VTLWEVLMLC
RAQPFGQLTD EQVIENAGEF FRDQGRQVYL SRPPACPQGL YELMLRCWSR ESEQRPPFSQ
LHRFLAEDAL NTV
