UFO_HUMAN
ID UFO_HUMAN Reviewed; 894 AA.
AC P30530; Q8N5L2; Q9UD27;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 4.
DT 03-AUG-2022, entry version 224.
DE RecName: Full=Tyrosine-protein kinase receptor UFO;
DE EC=2.7.10.1 {ECO:0000269|PubMed:28076778};
DE AltName: Full=AXL oncogene;
DE Flags: Precursor;
GN Name=AXL; Synonyms=UFO;
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].
RX PubMed=2247464; DOI=10.1073/pnas.87.22.8913;
RA Partanen J., Maekelae T.P., Alitalo R., Lehvaeslaiho H., Alitalo K.;
RT "Putative tyrosine kinases expressed in K-562 human leukemia cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:8913-8917(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), AND ROLE IN MYELOID LEUKEMIA.
RC TISSUE=Fibroblast;
RX PubMed=1656220; DOI=10.1128/mcb.11.10.5016-5031.1991;
RA O'Bryan J.P., Frye R.A., Cogswell P.C., Neubauer A., Kitch B., Prokop C.,
RA Espinosa R., le Beau M.M., Earp H., Liu E.T.;
RT "AXL, a transforming gene isolated from primary human myeloid leukemia
RT cells, encodes a novel receptor tyrosine kinase.";
RL Mol. Cell. Biol. 11:5016-5031(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RX PubMed=1834974;
RA Janssen J.W.G., Schulz A.S., Steenvoorden A.C.M., Schmidberger M.,
RA Strehl S., Ambros P., Bartram C.R.;
RT "A novel putative tyrosine kinase receptor with oncogenic potential.";
RL Oncogene 6:2113-2120(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
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 NUCLEOTIDE SEQUENCE [MRNA] OF 674-730.
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 677-730, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Colon tumor;
RX PubMed=7896447; DOI=10.1002/ijc.2910600611;
RA Craven R.J., Xu L.H., Weiner T.M., Fridell Y.-W., Dent G.A., Srivastava S.,
RA Varnum B., Liu E.T., Cance W.G.;
RT "Receptor tyrosine kinases expressed in metastatic colon cancer.";
RL Int. J. Cancer 60:791-797(1995).
RN [8]
RP INTERACTION WITH LIGAND GAS6.
RX PubMed=7854420; DOI=10.1038/373623a0;
RA Varnum B.C., Young C., Elliott G., Garcia A., Bartley T.D., Fridell Y.W.,
RA Hunt R.W., Trail G., Clogston C., Toso R.J., Yanagihara D., Bennett L.,
RA Silber M., Merewether L.A., Tseng A., Escobar E., Liu E.T., Yamane H.K.;
RT "Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein
RT encoded by growth-arrest-specific gene 6.";
RL Nature 373:623-626(1995).
RN [9]
RP INTERACTION WITH GAS6, AND ACTIVITY REGULATION.
RX PubMed=8621659; DOI=10.1074/jbc.271.16.9785;
RA Mark M.R., Chen J., Hammonds R.G., Sadick M., Godowski P.J.;
RT "Characterization of Gas6, a member of the superfamily of G domain-
RT containing proteins, as a ligand for Rse and Axl.";
RL J. Biol. Chem. 271:9785-9789(1996).
RN [10]
RP PHOSPHORYLATION AT TYR-779; TYR-821 AND TYR-866, AND INTERACTION WITH GRB2;
RP LCK; PIK3R1; PIK3R2 AND PLCG1.
RX PubMed=9178760; DOI=10.1038/sj.onc.1201123;
RA Braunger J., Schleithoff L., Schulz A.S., Kessler H., Lammers R.,
RA Ullrich A., Bartram C.R., Janssen J.W.;
RT "Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is
RT mediated mainly by a multi-substrate docking-site.";
RL Oncogene 14:2619-2631(1997).
RN [11]
RP ROLE IN PROSTATIC CARCINOMA.
RX PubMed=10403904; DOI=10.1046/j.1525-1500.1999.99034.x;
RA Jacob A.N., Kalapurakal J., Davidson W.R., Kandpal G., Dunson N.,
RA Prashar Y., Kandpal R.P.;
RT "A receptor tyrosine kinase, UFO/Axl, and other genes isolated by a
RT modified differential display PCR are overexpressed in metastatic prostatic
RT carcinoma cell line DU145.";
RL Cancer Detect. Prev. 23:325-332(1999).
RN [12]
RP ROLE IN BREAST CANCER.
RX PubMed=11484958; DOI=10.1023/a:1011126330233;
RA Berclaz G., Altermatt H.J., Rohrbach V., Kieffer I., Dreher E.,
RA Andres A.C.;
RT "Estrogen dependent expression of the receptor tyrosine kinase axl in
RT normal and malignant human breast.";
RL Ann. Oncol. 12:819-824(2001).
RN [13]
RP INTERACTION WITH NCK2; PIK3R3; SOCS1 AND TNS2.
RX PubMed=12470648; DOI=10.1016/s0006-291x(02)02718-3;
RA Hafizi S., Alindri F., Karlsson R., Dahlbaeck B.;
RT "Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1
RT domain-containing protein with homology to tensin.";
RL Biochem. Biophys. Res. Commun. 299:793-800(2002).
RN [14]
RP FUNCTION OF THE GAS6/AXL SIGNALING PATHWAY.
RX PubMed=12364394; DOI=10.1161/01.res.0000036753.50601.e9;
RA D'Arcangelo D., Gaetano C., Capogrossi M.C.;
RT "Acidification prevents endothelial cell apoptosis by Axl activation.";
RL Circ. Res. 91:E4-12(2002).
RN [15]
RP ROLE IN THYROID CARCINOMAS.
RX PubMed=12490074; DOI=10.1089/105072502320908303;
RA Ito M., Nakashima M., Nakayama T., Ohtsuru A., Nagayama Y., Takamura N.,
RA Demedchik E.P., Sekine I., Yamashita S.;
RT "Expression of receptor-type tyrosine kinase, Axl, and its ligand, Gas6, in
RT pediatric thyroid carcinomas around Chernobyl.";
RL Thyroid 12:971-975(2002).
RN [16]
RP INTERACTION WITH CBL AND GAS6, AND UBIQUITINATION.
RX PubMed=15958209; DOI=10.1016/j.bbrc.2005.05.086;
RA Valverde P.;
RT "Effects of Gas6 and hydrogen peroxide in Axl ubiquitination and
RT downregulation.";
RL Biochem. Biophys. Res. Commun. 333:180-185(2005).
RN [17]
RP ACTIVITY REGULATION, AND FUNCTION.
RX PubMed=15507525; DOI=10.1182/blood-2004-04-1469;
RA Gallicchio M., Mitola S., Valdembri D., Fantozzi R., Varnum B.,
RA Avanzi G.C., Bussolino F.;
RT "Inhibition of vascular endothelial growth factor receptor 2-mediated
RT endothelial cell activation by Axl tyrosine kinase receptor.";
RL Blood 105:1970-1976(2005).
RN [18]
RP FUNCTION IN PLATELET ACTIVATION AND THROMBOTIC RESPONSE REGULATION.
RX PubMed=15733062; DOI=10.1111/j.1538-7836.2005.01186.x;
RA Gould W.R., Baxi S.M., Schroeder R., Peng Y.W., Leadley R.J.,
RA Peterson J.T., Perrin L.A.;
RT "Gas6 receptors Axl, Sky and Mer enhance platelet activation and regulate
RT thrombotic responses.";
RL J. Thromb. Haemost. 3:733-741(2005).
RN [19]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=17005688; DOI=10.1128/jvi.01157-06;
RA Shimojima M., Takada A., Ebihara H., Neumann G., Fujioka K., Irimura T.,
RA Jones S., Feldmann H., Kawaoka Y.;
RT "Tyro3 family-mediated cell entry of Ebola and Marburg viruses.";
RL J. Virol. 80:10109-10116(2006).
RN [20]
RP INTERACTION WITH GRB2; PIK3R1 AND PIK3R2, AND PHOSPHORYLATION AT TYR-779;
RP TYR-821 AND TYR-866.
RX PubMed=18346204; DOI=10.1111/j.1471-4159.2008.05343.x;
RA Weinger J.G., Gohari P., Yan Y., Backer J.M., Varnum B., Shafit-Zagardo B.;
RT "In brain, Axl recruits Grb2 and the p85 regulatory subunit of PI3 kinase;
RT in vitro mutagenesis defines the requisite binding sites for downstream Akt
RT activation.";
RL J. Neurochem. 106:134-146(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-884, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [22]
RP FUNCTION OF THE GAS6/AXL SIGNALING PATHWAY.
RX PubMed=18840707; DOI=10.1182/blood-2008-05-157073;
RA Park I.K., Giovenzana C., Hughes T.L., Yu J., Trotta R., Caligiuri M.A.;
RT "The Axl/Gas6 pathway is required for optimal cytokine signaling during
RT human natural killer cell development.";
RL Blood 113:2470-2477(2009).
RN [23]
RP INTERACTION WITH GRB2 AND TNK2.
RX PubMed=19815557; DOI=10.1074/jbc.m109.072660;
RA Pao-Chun L., Chan P.M., Chan W., Manser E.;
RT "Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is
RT mediated by Grb2: an analysis of ACK1 effects on Axl signaling.";
RL J. Biol. Chem. 284:34954-34963(2009).
RN [24]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=21501828; DOI=10.1016/j.chom.2011.03.012;
RA Morizono K., Xie Y., Olafsen T., Lee B., Dasgupta A., Wu A.M., Chen I.S.;
RT "The soluble serum protein Gas6 bridges virion envelope phosphatidylserine
RT to the TAM receptor tyrosine kinase Axl to mediate viral entry.";
RL Cell Host Microbe 9:286-298(2011).
RN [25]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=22156524; DOI=10.1128/jvi.06451-11;
RA Shimojima M., Stroher U., Ebihara H., Feldmann H., Kawaoka Y.;
RT "Identification of cell surface molecules involved in dystroglycan-
RT independent Lassa virus cell entry.";
RL J. Virol. 86:2067-2078(2012).
RN [26]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=22673088; DOI=10.1292/jvms.12-0176;
RA Shimojima M., Kawaoka Y.;
RT "Cell surface molecules involved in infection mediated by lymphocytic
RT choriomeningitis virus glycoprotein.";
RL J. Vet. Med. Sci. 74:1363-1366(2012).
RN [27]
RP FUNCTION (MICROBIAL INFECTION), AND REVIEW.
RX PubMed=25277499; DOI=10.1016/j.virol.2014.09.009;
RA Moller-Tank S., Maury W.;
RT "Phosphatidylserine receptors: enhancers of enveloped virus entry and
RT infection.";
RL Virology 468:565-580(2014).
RN [28]
RP FUNCTION (MICROBIAL INFECTION), MUTAGENESIS OF LYS-567, CATALYTIC ACTIVITY,
RP AND SUBCELLULAR LOCATION.
RX PubMed=28076778; DOI=10.1016/j.celrep.2016.12.045;
RA Meertens L., Labeau A., Dejarnac O., Cipriani S., Sinigaglia L.,
RA Bonnet-Madin L., Le Charpentier T., Hafirassou M.L., Zamborlini A.,
RA Cao-Lormeau V.M., Coulpier M., Misse D., Jouvenet N., Tabibiazar R.,
RA Gressens P., Schwartz O., Amara A.;
RT "Axl Mediates ZIKA Virus Entry in Human Glial Cells and Modulates Innate
RT Immune Responses.";
RL Cell Rep. 18:324-333(2017).
RN [29]
RP FUNCTION (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=29379210; DOI=10.1038/s41564-017-0092-4;
RA Chen J., Yang Y.F., Yang Y., Zou P., Chen J., He Y., Shui S.L., Cui Y.R.,
RA Bai R., Liang Y.J., Hu Y., Jiang B., Lu L., Zhang X., Liu J., Xu J.;
RT "AXL promotes Zika virus infection in astrocytes by antagonizing type I
RT interferon signalling.";
RL Nat. Microbiol. 3:302-309(2018).
RN [30]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=31311882; DOI=10.1128/mbio.01372-19;
RA Strange D.P., Jiyarom B., Pourhabibi Zarandi N., Xie X., Baker C.,
RA Sadri-Ardekani H., Shi P.Y., Verma S.;
RT "Axl Promotes Zika Virus Entry and Modulates the Antiviral State of Human
RT Sertoli Cells.";
RL MBio 10:0-0(2019).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 33-227 IN COMPLEX WITH GAS6,
RP MUTAGENESIS OF GLU-63; GLU-66 AND THR-84, AND SUBUNIT.
RX PubMed=16362042; DOI=10.1038/sj.emboj.7600912;
RA Sasaki T., Knyazev P.G., Clout N.J., Cheburkin Y., Goehring W., Ullrich A.,
RA Timpl R., Hohenester E.;
RT "Structural basis for Gas6-Axl signalling.";
RL EMBO J. 25:80-87(2006).
RN [32]
RP VARIANTS [LARGE SCALE ANALYSIS] MET-112; TRP-295; CYS-499 AND GLY-515.
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: Receptor tyrosine kinase that transduces signals from the
CC extracellular matrix into the cytoplasm by binding growth factor GAS6
CC and which is thus regulating many physiological processes including
CC cell survival, cell proliferation, migration and differentiation.
CC Ligand binding at the cell surface induces dimerization and
CC autophosphorylation of AXL. Following activation by ligand, AXL binds
CC and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1,
CC PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other
CC downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2.
CC Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory
CC subunits by AXL leads to the downstream activation of the AKT kinase.
CC GAS6/AXL signaling plays a role in various processes such as
CC endothelial cell survival during acidification by preventing apoptosis,
CC optimal cytokine signaling during human natural killer cell
CC development, hepatic regeneration, gonadotropin-releasing hormone
CC neuron survival and migration, platelet activation, or regulation of
CC thrombotic responses. Also plays an important role in inhibition of
CC Toll-like receptors (TLRs)-mediated innate immune response.
CC {ECO:0000269|PubMed:10403904, ECO:0000269|PubMed:11484958,
CC ECO:0000269|PubMed:12364394, ECO:0000269|PubMed:12490074,
CC ECO:0000269|PubMed:15507525, ECO:0000269|PubMed:15733062,
CC ECO:0000269|PubMed:1656220, ECO:0000269|PubMed:18840707}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for lassa virus and
CC lymphocytic choriomeningitis virus, possibly through GAS6 binding to
CC phosphatidyl-serine at the surface of virion envelope.
CC {ECO:0000269|PubMed:17005688, ECO:0000269|PubMed:21501828,
CC ECO:0000269|PubMed:22156524, ECO:0000269|PubMed:25277499}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for Ebolavirus,
CC possibly through GAS6 binding to phosphatidyl-serine at the surface of
CC virion envelope. {ECO:0000269|PubMed:22673088}.
CC -!- FUNCTION: (Microbial infection) Promotes Zika virus entry in glial
CC cells, Sertoli cells and astrocytes (PubMed:28076778, PubMed:29379210,
CC PubMed:31311882). Additionally, Zika virus potentiates AXL kinase
CC activity to antagonize type I interferon signaling and thereby promotes
CC infection (PubMed:28076778). Interferon signaling inhibition occurs via
CC an SOCS1-dependent mechanism (PubMed:29379210).
CC {ECO:0000269|PubMed:28076778, ECO:0000269|PubMed:29379210,
CC ECO:0000269|PubMed:31311882}.
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:28076778};
CC -!- ACTIVITY REGULATION: Activated by GAS6-binding and subsequent
CC autophosphorylation. {ECO:0000269|PubMed:15507525,
CC ECO:0000269|PubMed:8621659}.
CC -!- SUBUNIT: Heterodimer and heterotetramer with ligand GAS6. Interacts
CC with CBL, GRB2, LCK, NCK2, PIK3R1, PIK3R2, PIK3R3, PLCG1, SOCS1 and
CC TNS2. Part of a complex including AXL, TNK2 and GRB2, in which GRB2
CC promotes AXL recruitment by TNK2. {ECO:0000269|PubMed:12470648,
CC ECO:0000269|PubMed:15958209, ECO:0000269|PubMed:16362042,
CC ECO:0000269|PubMed:18346204, ECO:0000269|PubMed:19815557,
CC ECO:0000269|PubMed:7854420, ECO:0000269|PubMed:8621659,
CC ECO:0000269|PubMed:9178760}.
CC -!- INTERACTION:
CC P30530; P00533: EGFR; NbExp=4; IntAct=EBI-2850927, EBI-297353;
CC P30530; Q14393-1: GAS6; NbExp=8; IntAct=EBI-2850927, EBI-20753849;
CC P30530; P62993: GRB2; NbExp=3; IntAct=EBI-2850927, EBI-401755;
CC P30530; P08238: HSP90AB1; NbExp=3; IntAct=EBI-2850927, EBI-352572;
CC P30530; P0DTC2: S; Xeno; NbExp=9; IntAct=EBI-2850927, EBI-25474821;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28076778,
CC ECO:0000269|PubMed:29379210, ECO:0000269|PubMed:7896447}; Single-pass
CC type I membrane protein {ECO:0000269|PubMed:7896447}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P30530-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P30530-2; Sequence=VSP_005017;
CC -!- TISSUE SPECIFICITY: Highly expressed in metastatic colon tumors.
CC Expressed in primary colon tumors. Weakly expressed in normal colon
CC tissue. {ECO:0000269|PubMed:7896447}.
CC -!- PTM: Monoubiquitinated upon GAS6-binding. A very small proportion of
CC the receptor could be subjected to polyubiquitination in a very
CC transient fashion. {ECO:0000269|PubMed:15958209}.
CC -!- PTM: Phosphorylated at tyrosine residues by autocatalysis, which
CC activates kinase activity. {ECO:0000269|PubMed:18346204,
CC ECO:0000269|PubMed:9178760}.
CC -!- DISEASE: Note=AXL and its ligand GAS6 are highly expressed in thyroid
CC carcinoma tissues, and might thus be involved in thyroid tumorigenesis.
CC Overexpression of AXL and its ligand was also detected in many other
CC cancers such as myeloproliferative disorders, prostatic carcinoma
CC cells, or breast cancer.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. AXL/UFO subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/AXLID733ch19q13.html";
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DR EMBL; M76125; AAA61243.1; -; mRNA.
DR EMBL; S65125; AAB20305.1; -; mRNA.
DR EMBL; X57019; CAA40338.1; -; mRNA.
DR EMBL; AC011510; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032229; AAH32229.1; -; mRNA.
DR CCDS; CCDS12574.1; -. [P30530-2]
DR CCDS; CCDS12575.1; -. [P30530-1]
DR PIR; A41527; A41527.
DR RefSeq; NP_001690.2; NM_001699.5. [P30530-2]
DR RefSeq; NP_068713.2; NM_021913.4. [P30530-1]
DR PDB; 2C5D; X-ray; 3.30 A; C/D=33-227.
DR PDB; 4RA0; X-ray; 3.07 A; C/D=33-227.
DR PDB; 5U6B; X-ray; 2.84 A; A/B/C/D=514-818.
DR PDB; 5VXZ; X-ray; 2.30 A; C/D=34-135.
DR PDBsum; 2C5D; -.
DR PDBsum; 4RA0; -.
DR PDBsum; 5U6B; -.
DR PDBsum; 5VXZ; -.
DR AlphaFoldDB; P30530; -.
DR SMR; P30530; -.
DR BioGRID; 107036; 202.
DR CORUM; P30530; -.
DR IntAct; P30530; 61.
DR MINT; P30530; -.
DR STRING; 9606.ENSP00000301178; -.
DR BindingDB; P30530; -.
DR ChEMBL; CHEMBL4895; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB12141; Gilteritinib.
DR DrugCentral; P30530; -.
DR GuidetoPHARMACOLOGY; 1835; -.
DR GlyConnect; 1983; 12 N-Linked glycans (4 sites).
DR GlyGen; P30530; 7 sites, 9 N-linked glycans (3 sites).
DR iPTMnet; P30530; -.
DR PhosphoSitePlus; P30530; -.
DR BioMuta; AXL; -.
DR DMDM; 239938818; -.
DR CPTAC; CPTAC-1766; -.
DR CPTAC; CPTAC-2791; -.
DR EPD; P30530; -.
DR jPOST; P30530; -.
DR MassIVE; P30530; -.
DR MaxQB; P30530; -.
DR PaxDb; P30530; -.
DR PeptideAtlas; P30530; -.
DR PRIDE; P30530; -.
DR ProteomicsDB; 54712; -. [P30530-1]
DR ProteomicsDB; 54713; -. [P30530-2]
DR ABCD; P30530; 23 sequenced antibodies.
DR Antibodypedia; 30709; 1043 antibodies from 43 providers.
DR CPTC; P30530; 2 antibodies.
DR DNASU; 558; -.
DR Ensembl; ENST00000301178.9; ENSP00000301178.3; ENSG00000167601.12. [P30530-1]
DR Ensembl; ENST00000359092.7; ENSP00000351995.2; ENSG00000167601.12. [P30530-2]
DR GeneID; 558; -.
DR KEGG; hsa:558; -.
DR MANE-Select; ENST00000301178.9; ENSP00000301178.3; NM_021913.5; NP_068713.2.
DR UCSC; uc010ehj.5; human. [P30530-1]
DR CTD; 558; -.
DR DisGeNET; 558; -.
DR GeneCards; AXL; -.
DR GeneReviews; AXL; -.
DR HGNC; HGNC:905; AXL.
DR HPA; ENSG00000167601; Low tissue specificity.
DR MalaCards; AXL; -.
DR MIM; 109135; gene.
DR neXtProt; NX_P30530; -.
DR OpenTargets; ENSG00000167601; -.
DR PharmGKB; PA25197; -.
DR VEuPathDB; HostDB:ENSG00000167601; -.
DR eggNOG; ENOG502QQQ3; Eukaryota.
DR GeneTree; ENSGT00940000160232; -.
DR InParanoid; P30530; -.
DR OMA; IIRCSVQ; -.
DR OrthoDB; 263089at2759; -.
DR PhylomeDB; P30530; -.
DR TreeFam; TF317402; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; P30530; -.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR SignaLink; P30530; -.
DR SIGNOR; P30530; -.
DR BioGRID-ORCS; 558; 16 hits in 1111 CRISPR screens.
DR ChiTaRS; AXL; human.
DR EvolutionaryTrace; P30530; -.
DR GeneWiki; AXL_receptor_tyrosine_kinase; -.
DR GenomeRNAi; 558; -.
DR Pharos; P30530; Tchem.
DR PRO; PR:P30530; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P30530; protein.
DR Bgee; ENSG00000167601; Expressed in synovial joint and 204 other tissues.
DR ExpressionAtlas; P30530; baseline and differential.
DR Genevisible; P30530; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0044228; C:host cell surface; IDA:CACAO.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
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:0032036; F:myosin heavy chain binding; IEA:Ensembl.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IEA:Ensembl.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; EXP:Reactome.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0001618; F:virus receptor activity; IDA:FlyBase.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR GO; GO:0048469; P:cell maturation; IEP:UniProtKB.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IEA:Ensembl.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0035457; P:cellular response to interferon-alpha; IDA:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0097028; P:dendritic cell differentiation; IEP:UniProtKB.
DR GO; GO:0034101; P:erythrocyte homeostasis; IEA:Ensembl.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0021885; P:forebrain cell migration; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0001779; P:natural killer cell differentiation; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:2000669; P:negative regulation of dendritic cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IDA:UniProtKB.
DR GO; GO:0051250; P:negative regulation of lymphocyte activation; IEA:Ensembl.
DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR GO; GO:0097350; P:neutrophil clearance; IEA:Ensembl.
DR GO; GO:0042698; P:ovulation cycle; IEA:Ensembl.
DR GO; GO:0006909; P:phagocytosis; IDA:UniProtKB.
DR GO; GO:0030168; P:platelet activation; IBA:GO_Central.
DR GO; GO:0001961; P:positive regulation of cytokine-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0032825; P:positive regulation of natural killer cell differentiation; IDA:UniProtKB.
DR GO; GO:0048549; P:positive regulation of pinocytosis; IMP:CACAO.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IBA:GO_Central.
DR GO; GO:1903902; P:positive regulation of viral life cycle; IMP:FlyBase.
DR GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0032940; P:secretion by cell; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IEA:Ensembl.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0060068; P:vagina development; IEA:Ensembl.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0046718; P:viral entry into host cell; IMP:CACAO.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF00041; fn3; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00409; IG; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS50835; IG_LIKE; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Differentiation; Disulfide bond; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction; Immunity;
KW Immunoglobulin domain; Innate immunity; Kinase; Membrane;
KW Nucleotide-binding; Oncogene; Phosphoprotein; Proto-oncogene; Receptor;
KW Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..894
FT /note="Tyrosine-protein kinase receptor UFO"
FT /id="PRO_0000024481"
FT TOPO_DOM 26..451
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 452..472
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 473..894
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..128
FT /note="Ig-like C2-type 1"
FT DOMAIN 139..222
FT /note="Ig-like C2-type 2"
FT DOMAIN 227..331
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 336..428
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 536..807
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 26..92
FT /note="Interaction with GAS6"
FT REGION 823..853
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 866..894
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 672
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 542..550
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 567
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 703
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 779
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:18346204,
FT ECO:0000269|PubMed:9178760"
FT MOD_RES 821
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:18346204,
FT ECO:0000269|PubMed:9178760"
FT MOD_RES 866
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:18346204,
FT ECO:0000269|PubMed:9178760"
FT MOD_RES 884
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT CARBOHYD 43
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 339
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 345
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 401
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 56..117
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 160..205
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 429..437
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:1656220"
FT /id="VSP_005017"
FT VARIANT 112
FT /note="T -> M (in dbSNP:rs35202236)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_045596"
FT VARIANT 266
FT /note="D -> N (in dbSNP:rs7249222)"
FT /id="VAR_057990"
FT VARIANT 295
FT /note="R -> W (in a lung neuroendocrine carcinoma sample;
FT somatic mutation; dbSNP:rs751738506)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_045597"
FT VARIANT 499
FT /note="R -> C (in a gastric adenocarcinoma sample; somatic
FT mutation; dbSNP:rs747576071)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041877"
FT VARIANT 515
FT /note="S -> G (in dbSNP:rs1240393707)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041878"
FT MUTAGEN 63
FT /note="E->R: Slightly reduced affinity for GAS6."
FT /evidence="ECO:0000269|PubMed:16362042"
FT MUTAGEN 66
FT /note="E->R: Reduced affinity for GAS6."
FT /evidence="ECO:0000269|PubMed:16362042"
FT MUTAGEN 84
FT /note="T->R: Reduced affinity for GAS6."
FT /evidence="ECO:0000269|PubMed:16362042"
FT MUTAGEN 567
FT /note="K->M: Catalytically inactive mutant."
FT /evidence="ECO:0000269|PubMed:28076778"
FT CONFLICT 303
FT /note="T -> P (in Ref. 3; AAB20305/CAA40338)"
FT /evidence="ECO:0000305"
FT CONFLICT 338
FT /note="E -> K (in Ref. 2; AAA61243)"
FT /evidence="ECO:0000305"
FT CONFLICT 430
FT /note="Q -> E (in Ref. 3; AAB20305/CAA40338)"
FT /evidence="ECO:0000305"
FT CONFLICT 639
FT /note="D -> G (in Ref. 3; AAB20305/CAA40338)"
FT /evidence="ECO:0000305"
FT CONFLICT 696
FT /note="K -> I (in Ref. 7; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 764
FT /note="Q -> R (in Ref. 5; AAH32229)"
FT /evidence="ECO:0000305"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:5VXZ"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:4RA0"
FT STRAND 52..63
FT /evidence="ECO:0007829|PDB:5VXZ"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:5VXZ"
FT STRAND 80..87
FT /evidence="ECO:0007829|PDB:5VXZ"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:5VXZ"
FT STRAND 94..106
FT /evidence="ECO:0007829|PDB:5VXZ"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:5VXZ"
FT STRAND 113..121
FT /evidence="ECO:0007829|PDB:5VXZ"
FT STRAND 124..127
FT /evidence="ECO:0007829|PDB:5VXZ"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:5VXZ"
FT STRAND 140..143
FT /evidence="ECO:0007829|PDB:4RA0"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:4RA0"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:4RA0"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:4RA0"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:4RA0"
FT STRAND 170..175
FT /evidence="ECO:0007829|PDB:4RA0"
FT STRAND 178..187
FT /evidence="ECO:0007829|PDB:4RA0"
FT STRAND 190..194
FT /evidence="ECO:0007829|PDB:4RA0"
FT STRAND 201..209
FT /evidence="ECO:0007829|PDB:4RA0"
FT STRAND 212..215
FT /evidence="ECO:0007829|PDB:4RA0"
FT STRAND 219..223
FT /evidence="ECO:0007829|PDB:4RA0"
FT STRAND 515..517
FT /evidence="ECO:0007829|PDB:5U6B"
FT HELIX 524..529
FT /evidence="ECO:0007829|PDB:5U6B"
FT HELIX 533..535
FT /evidence="ECO:0007829|PDB:5U6B"
FT STRAND 536..544
FT /evidence="ECO:0007829|PDB:5U6B"
FT STRAND 546..556
FT /evidence="ECO:0007829|PDB:5U6B"
FT STRAND 558..571
FT /evidence="ECO:0007829|PDB:5U6B"
FT HELIX 576..590
FT /evidence="ECO:0007829|PDB:5U6B"
FT STRAND 602..605
FT /evidence="ECO:0007829|PDB:5U6B"
FT STRAND 616..621
FT /evidence="ECO:0007829|PDB:5U6B"
FT HELIX 628..637
FT /evidence="ECO:0007829|PDB:5U6B"
FT STRAND 638..640
FT /evidence="ECO:0007829|PDB:5U6B"
FT HELIX 646..665
FT /evidence="ECO:0007829|PDB:5U6B"
FT HELIX 675..677
FT /evidence="ECO:0007829|PDB:5U6B"
FT STRAND 678..680
FT /evidence="ECO:0007829|PDB:5U6B"
FT STRAND 686..688
FT /evidence="ECO:0007829|PDB:5U6B"
FT STRAND 698..700
FT /evidence="ECO:0007829|PDB:5U6B"
FT HELIX 713..715
FT /evidence="ECO:0007829|PDB:5U6B"
FT HELIX 718..723
FT /evidence="ECO:0007829|PDB:5U6B"
FT HELIX 728..743
FT /evidence="ECO:0007829|PDB:5U6B"
FT HELIX 755..763
FT /evidence="ECO:0007829|PDB:5U6B"
FT HELIX 776..785
FT /evidence="ECO:0007829|PDB:5U6B"
FT HELIX 790..792
FT /evidence="ECO:0007829|PDB:5U6B"
FT HELIX 796..809
FT /evidence="ECO:0007829|PDB:5U6B"
SQ SEQUENCE 894 AA; 98337 MW; 262D3659218E3202 CRC64;
MAWRCPRMGR VPLAWCLALC GWACMAPRGT QAEESPFVGN PGNITGARGL TGTLRCQLQV
QGEPPEVHWL RDGQILELAD STQTQVPLGE DEQDDWIVVS QLRITSLQLS DTGQYQCLVF
LGHQTFVSQP GYVGLEGLPY FLEEPEDRTV AANTPFNLSC QAQGPPEPVD LLWLQDAVPL
ATAPGHGPQR SLHVPGLNKT SSFSCEAHNA KGVTTSRTAT ITVLPQQPRN LHLVSRQPTE
LEVAWTPGLS GIYPLTHCTL QAVLSDDGMG IQAGEPDPPE EPLTSQASVP PHQLRLGSLH
PHTPYHIRVA CTSSQGPSSW THWLPVETPE GVPLGPPENI SATRNGSQAF VHWQEPRAPL
QGTLLGYRLA YQGQDTPEVL MDIGLRQEVT LELQGDGSVS NLTVCVAAYT AAGDGPWSLP
VPLEAWRPGQ AQPVHQLVKE PSTPAFSWPW WYVLLGAVVA AACVLILALF LVHRRKKETR
YGEVFEPTVE RGELVVRYRV RKSYSRRTTE ATLNSLGISE ELKEKLRDVM VDRHKVALGK
TLGEGEFGAV MEGQLNQDDS ILKVAVKTMK IAICTRSELE DFLSEAVCMK EFDHPNVMRL
IGVCFQGSER ESFPAPVVIL PFMKHGDLHS FLLYSRLGDQ PVYLPTQMLV KFMADIASGM
EYLSTKRFIH RDLAARNCML NENMSVCVAD FGLSKKIYNG DYYRQGRIAK MPVKWIAIES
LADRVYTSKS DVWSFGVTMW EIATRGQTPY PGVENSEIYD YLRQGNRLKQ PADCLDGLYA
LMSRCWELNP QDRPSFTELR EDLENTLKAL PPAQEPDEIL YVNMDEGGGY PEPPGAAGGA
DPPTQPDPKD SCSCLTAAEV HPAGRYVLCP STTPSPAQPA DRGSPAAPGQ EDGA
