EPHA2_MOUSE
ID EPHA2_MOUSE Reviewed; 977 AA.
AC Q03145; Q3UNI2; Q60633; Q62212;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Ephrin type-A receptor 2;
DE EC=2.7.10.1;
DE AltName: Full=Epithelial cell kinase;
DE AltName: Full=Tyrosine-protein kinase receptor ECK;
DE AltName: Full=Tyrosine-protein kinase receptor MPK-5;
DE AltName: Full=Tyrosine-protein kinase receptor SEK-2;
DE Flags: Precursor;
GN Name=Epha2; Synonyms=Eck, Myk2, Sek2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], GLYCOSYLATION, CATALYTIC ACTIVITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=8183555;
RA Ganju P., Shigemoto K., Brennan J., Entwistle A., Reith A.D.;
RT "The Eck receptor tyrosine kinase is implicated in pattern formation during
RT gastrulation, hindbrain segmentation and limb development.";
RL Oncogene 9:1613-1624(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=7918100; DOI=10.1016/0925-4773(94)90078-7;
RA Ruiz J.C., Robertson E.J.;
RT "The expression of the receptor-protein tyrosine kinase gene, eck, is
RT highly restricted during early mouse development.";
RL Mech. Dev. 46:87-100(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Vagina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 552-977, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=7947319; DOI=10.1016/0925-4773(94)90091-4;
RA Becker N., Seitanidou T., Murphy P., Mattei M.-G., Topilko P., Nieto A.,
RA Wilkinson D.G., Charnay P., Gilardi P.;
RT "Several receptor tyrosine kinase genes of the Eph family are segmentally
RT expressed in the developing hindbrain.";
RL Mech. Dev. 47:3-17(1994).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 742-799.
RC TISSUE=Embryonic brain;
RX PubMed=1281307;
RA Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A.,
RA Wilkinson D.G., Charnay P.;
RT "An Eph-related receptor protein tyrosine kinase gene segmentally expressed
RT in the developing mouse hindbrain.";
RL Oncogene 7:2499-2506(1992).
RN [9]
RP INTERACTION WITH SLA.
RC TISSUE=Embryonic brain;
RX PubMed=7543898; DOI=10.1074/jbc.270.33.19201;
RA Pandey A., Duan H., Dixit V.M.;
RT "Characterization of a novel Src-like adapter protein that associates with
RT the Eck receptor tyrosine kinase.";
RL J. Biol. Chem. 270:19201-19204(1995).
RN [10]
RP DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=11287184; DOI=10.1016/s0925-4773(01)00290-8;
RA Naruse-Nakajima C., Asano M., Iwakura Y.;
RT "Involvement of EphA2 in the formation of the tail notochord via
RT interaction with ephrinA1.";
RL Mech. Dev. 102:95-105(2001).
RN [11]
RP FUNCTION IN ANGIOGENESIS, AND DISRUPTION PHENOTYPE.
RX PubMed=15054110; DOI=10.1242/jcs.01061;
RA Brantley-Sieders D.M., Caughron J., Hicks D., Pozzi A., Ruiz J.C., Chen J.;
RT "EphA2 receptor tyrosine kinase regulates endothelial cell migration and
RT vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase
RT activation.";
RL J. Cell Sci. 117:2037-2049(2004).
RN [12]
RP FUNCTION IN CELL PROLIFERATION, AND DISRUPTION PHENOTYPE.
RX PubMed=16849550; DOI=10.1158/0008-5472.can-06-0004;
RA Guo H., Miao H., Gerber L., Singh J., Denning M.F., Gilliam A.C., Wang B.;
RT "Disruption of EphA2 receptor tyrosine kinase leads to increased
RT susceptibility to carcinogenesis in mouse skin.";
RL Cancer Res. 66:7050-7058(2006).
RN [13]
RP FUNCTION IN ANGIOGENESIS, INTERACTION WITH VAV2 AND VAV3, AND MUTAGENESIS
RP OF TYR-589; TYR-595 AND ASP-740.
RX PubMed=16782872; DOI=10.1128/mcb.02215-05;
RA Hunter S.G., Zhuang G., Brantley-Sieders D.M., Swat W., Cowan C.W.,
RA Chen J.;
RT "Essential role of Vav family guanine nucleotide exchange factors in EphA
RT receptor-mediated angiogenesis.";
RL Mol. Cell. Biol. 26:4830-4842(2006).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH VAV2; VAV3
RP AND PI3-KINASE P85 SUBUNIT, PHOSPHORYLATION AT TYR-589; TYR-595; TYR-736
RP AND TYR-773, AND MUTAGENESIS OF TYR-589; TYR-595; TYR-736; TYR-773 AND
RP TYR-931.
RX PubMed=18387945; DOI=10.1074/jbc.m709934200;
RA Fang W.B., Brantley-Sieders D.M., Hwang Y., Ham A.-J.L., Chen J.;
RT "Identification and functional analysis of phosphorylated tyrosine residues
RT within EphA2 receptor tyrosine kinase.";
RL J. Biol. Chem. 283:16017-16026(2008).
RN [15]
RP FUNCTION IN LENS FIBER CELLS MORPHOGENESIS.
RX PubMed=18948590; DOI=10.1073/pnas.0808987105;
RA Cooper M.A., Son A.I., Komlos D., Sun Y., Kleiman N.J., Zhou R.;
RT "Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to
RT cataract.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:16620-16625(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-595 AND TYR-773, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Liver, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [18]
RP FUNCTION IN BONE IN REMODELING.
RX PubMed=19299512; DOI=10.1074/jbc.m807598200;
RA Irie N., Takada Y., Watanabe Y., Matsuzaki Y., Naruse C., Asano M.,
RA Iwakura Y., Suda T., Matsuo K.;
RT "Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis
RT and suppresses osteoblastogenesis.";
RL J. Biol. Chem. 284:14637-14644(2009).
RN [19]
RP FUNCTION IN MAMMARY GLAND DEVELOPMENT.
RX PubMed=19321667; DOI=10.1091/mbc.e08-04-0378;
RA Vaught D., Chen J., Brantley-Sieders D.M.;
RT "Regulation of mammary gland branching morphogenesis by EphA2 receptor
RT tyrosine kinase.";
RL Mol. Biol. Cell 20:2572-2581(2009).
RN [20]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-408 AND ASN-436.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [21]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-408 AND ASN-436.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [22]
RP UBIQUITINATION, AND INTERACTION WITH ANKS1A.
RX PubMed=20100865; DOI=10.1128/mcb.01605-09;
RA Kim J., Lee H., Kim Y., Yoo S., Park E., Park S.;
RT "The SAM domains of Anks family proteins are critically involved in
RT modulating the degradation of EphA receptors.";
RL Mol. Cell. Biol. 30:1582-1592(2010).
RN [23]
RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=27446912; DOI=10.3389/fcell.2016.00058;
RA Alonso-Martin S., Rochat A., Mademtzoglou D., Morais J., de Reynies A.,
RA Aurade F., Chang T.H., Zammit P.S., Relaix F.;
RT "Gene expression profiling of muscle stem cells identifies novel regulators
RT of postnatal myogenesis.";
RL Front. Cell Dev. Biol. 4:58-58(2016).
RN [24] {ECO:0007744|PDB:5ZRX}
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 900-977 IN COMPLEX WITH INPPL1,
RP FUNCTION, AND MUTAGENESIS OF LYS-918; LYS-957 AND ARG-958.
RX PubMed=29749928; DOI=10.7554/elife.35677;
RA Wang Y., Shang Y., Li J., Chen W., Li G., Wan J., Liu W., Zhang M.;
RT "Specific Eph receptor-cytoplasmic effector signaling mediated by SAM-SAM
RT domain interactions.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Receptor tyrosine kinase which binds promiscuously membrane-
CC bound ephrin-A family ligands residing on adjacent cells, leading to
CC contact-dependent bidirectional signaling into neighboring cells. The
CC signaling pathway downstream of the receptor is referred to as forward
CC signaling while the signaling pathway downstream of the ephrin ligand
CC is referred to as reverse signaling. Activated by the ligand ephrin-
CC A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation
CC and differentiation of cells (PubMed:29749928). Regulates cell adhesion
CC and differentiation through DSG1/desmoglein-1 and inhibition of the
CC ERK1/ERK2 signaling pathway. May also participate in UV radiation-
CC induced apoptosis and have a ligand-independent stimulatory effect on
CC chemotactic cell migration. During development, may function in
CC distinctive aspects of pattern formation and subsequently in
CC development of several fetal tissues. Involved for instance in
CC angiogenesis, in early hindbrain development and epithelial
CC proliferation and branching morphogenesis during mammary gland
CC development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens
CC fiber cells shape and interactions and be important for lens
CC transparency development and maintenance. With ephrin-A2/EFNA2 may play
CC a role in bone remodeling through regulation of osteoclastogenesis and
CC osteoblastogenesis. {ECO:0000269|PubMed:15054110,
CC ECO:0000269|PubMed:16782872, ECO:0000269|PubMed:16849550,
CC ECO:0000269|PubMed:18387945, ECO:0000269|PubMed:18948590,
CC ECO:0000269|PubMed:19299512, ECO:0000269|PubMed:19321667,
CC ECO:0000269|PubMed:29749928}.
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:8183555};
CC -!- SUBUNIT: Homodimer. Interacts with INPPL1; regulates activated EPHA2
CC endocytosis and degradation (PubMed:29749928). Interacts (inactivated
CC form) with PTK2/FAK1 and interacts (EFNA1 ligand-activated form) with
CC PTPN11; regulates integrin-mediated adhesion. Interacts with ARHGEF16,
CC DOCK4 and ELMO2; mediates ligand-independent activation of RAC1 which
CC stimulates cell migration. Interacts with CLDN4; phosphorylates CLDN4
CC and may regulate tight junctions. Interacts with ACP1. Interacts with
CC CEMIP. Interacts with NCK1; may regulate EPHA2 activity in cell
CC migration and adhesion. Interacts with SLA. Interacts (phosphorylated
CC form) with VAV2, VAV3 and PI3-kinase p85 subunit (PIK3R1, PIK3R2 or
CC PIK3R3); critical for the EFNA1-induced activation of RAC1 which
CC stimulates cell migration. Interacts with ANKS1A. Interacts with TIMD4
CC (By similarity). {ECO:0000250|UniProtKB:P29317,
CC ECO:0000269|PubMed:16782872, ECO:0000269|PubMed:18387945,
CC ECO:0000269|PubMed:20100865, ECO:0000269|PubMed:29749928,
CC ECO:0000269|PubMed:7543898}.
CC -!- INTERACTION:
CC Q03145; Q03137: Epha4; NbExp=3; IntAct=EBI-529701, EBI-1539152;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P29317};
CC Single-pass type I membrane protein {ECO:0000255}. Cell projection,
CC ruffle membrane {ECO:0000250|UniProtKB:P29317}; Single-pass type I
CC membrane protein {ECO:0000255}. Cell projection, lamellipodium membrane
CC {ECO:0000250|UniProtKB:P29317}; Single-pass type I membrane protein
CC {ECO:0000255}. Cell junction, focal adhesion
CC {ECO:0000250|UniProtKB:P29317}. Note=Present at regions of cell-cell
CC contacts but also at the leading edge of migrating cells. Relocates
CC from the plasma membrane to the cytoplasmic and perinuclear regions in
CC cancer cells. {ECO:0000250|UniProtKB:P29317}.
CC -!- TISSUE SPECIFICITY: Expressed in the lung, intestine and liver
CC (PubMed:11287184). Expressed in myogenic progenitor cells
CC (PubMed:27446912). {ECO:0000269|PubMed:11287184,
CC ECO:0000269|PubMed:27446912}.
CC -!- DEVELOPMENTAL STAGE: First detected in gastrulation stage embryos (6.5-
CC 7.5 dpc) in ectodermal cells adjacent to the distal region of the
CC primitive streak. By the neural plate stage (approximately 7.5 dpc),
CC EPHA2 expression becomes restricted to the extreme distal end or node
CC of the primitive streak. After the beginning of somitogenesis
CC (approximately 8.0 dpc), expression persists in the node as this
CC structure regresses toward the caudal end of the embryo. In addition,
CC beginning at the mid head fold stage (approximately 7.75 dpc), we
CC observe that EPHA2 exhibits a dynamic and spatially restricted
CC expression pattern in the prospective hindbrain region. EPHA2
CC transcripts are initially detected in a 5-cell wide strip of mesodermal
CC cells underlying prospective rhombomere 4 (R4). Subsequently at the
CC beginning of somitogenesis, expression is observed in prospective R4.
CC At the 4-8-somite stage, EPHA2 transcripts are observed in R4,
CC mesenchymal cells underlying R4, and surface ectoderm in the vicinity
CC of the developing second branchial arch. By the 10-somite stage,
CC expression in these cells is down-regulated. Additionally, at the 5-8-
CC somite stage, EPHA2 transcripts are detected initially in the lateral
CC mesenchyme immediately underlying the surface ectoderm adjacent to R5
CC and R6, and subsequently in surface ectoderm overlying the developing
CC third branchial arch. In myogenic progenitor cells, expressed during
CC the acquisition of muscle stem cell properties, from 18.5 dpc to
CC adulthood (PubMed:27446912). {ECO:0000269|PubMed:11287184,
CC ECO:0000269|PubMed:27446912, ECO:0000269|PubMed:7918100,
CC ECO:0000269|PubMed:7947319, ECO:0000269|PubMed:8183555}.
CC -!- PTM: Autophosphorylates. Phosphorylated at Ser-898 by PKB; serum-
CC induced phosphorylation which targets EPHA2 to the cell leading edge
CC and stimulates cell migration. Phosphorylation by PKB is inhibited by
CC EFNA1-activated EPHA2 which regulates PKB activity via a reciprocal
CC regulatory loop. Phosphorylated on tyrosine upon binding and activation
CC by EFNA1. Phosphorylated residues Tyr-589 and Tyr-595 are required for
CC binding VAV2 and VAV3 while phosphorylated residues Tyr-736 and Tyr-931
CC are required for binding PI3-kinase p85 subunit (PIK3R1, PIK3R2 or
CC PIK3R3). These phosphorylated residues are critical for recruitment of
CC VAV2 and VAV3 and PI3-kinase p85 subunit which transduce downstream
CC signaling to activate RAC1 GTPase and cell migration. Dephosphorylation
CC of Tyr-931 by PTPRF prevents the interaction of EPHA2 with NCK1.
CC Phosphorylated at Ser-898 in response to TNF by RPS6KA1 and RPS6KA3;
CC RPS6KA-EPHA2 signaling pathway controls cell migration. Phosphorylated
CC at Ser-898 by PKA; blocks cell retraction induced by EPHA2 kinase
CC activity. Dephosphorylated by ACP1. {ECO:0000250|UniProtKB:P29317,
CC ECO:0000269|PubMed:18387945}.
CC -!- PTM: Ubiquitinated by CHIP/STUB1. Ubiquitination is regulated by the
CC HSP90 chaperone and regulates the receptor stability and activity
CC through proteasomal degradation. ANKS1A prevents ubiquitination and
CC degradation. {ECO:0000269|PubMed:20100865}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable, fertile but exhibit aberrant
CC development of tail vertebra and susceptibility to carcinogenesis.
CC {ECO:0000269|PubMed:11287184, ECO:0000269|PubMed:15054110,
CC ECO:0000269|PubMed:16849550}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; X78339; CAA55135.1; -; mRNA.
DR EMBL; U07634; AAA82113.1; -; mRNA.
DR EMBL; AK137704; BAE23470.1; -; mRNA.
DR EMBL; AK144202; BAE25765.1; -; mRNA.
DR EMBL; AL607087; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL670285; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466615; EDL13361.1; -; Genomic_DNA.
DR EMBL; BC140960; AAI40961.1; -; mRNA.
DR EMBL; X76010; CAA53597.1; -; mRNA.
DR EMBL; X57243; CAA40519.1; -; mRNA.
DR CCDS; CCDS18869.1; -.
DR PIR; I48759; I48759.
DR PIR; I48974; I48974.
DR PIR; S49004; S49004.
DR RefSeq; NP_034269.2; NM_010139.3.
DR PDB; 5ZRX; X-ray; 1.50 A; A/B=900-977.
DR PDBsum; 5ZRX; -.
DR AlphaFoldDB; Q03145; -.
DR SMR; Q03145; -.
DR BioGRID; 199469; 3.
DR CORUM; Q03145; -.
DR DIP; DIP-829N; -.
DR IntAct; Q03145; 4.
DR MINT; Q03145; -.
DR STRING; 10090.ENSMUSP00000006614; -.
DR BindingDB; Q03145; -.
DR ChEMBL; CHEMBL4105859; -.
DR GuidetoPHARMACOLOGY; 1822; -.
DR GlyGen; Q03145; 2 sites.
DR iPTMnet; Q03145; -.
DR PhosphoSitePlus; Q03145; -.
DR EPD; Q03145; -.
DR MaxQB; Q03145; -.
DR PaxDb; Q03145; -.
DR PeptideAtlas; Q03145; -.
DR PRIDE; Q03145; -.
DR ProteomicsDB; 275752; -.
DR ABCD; Q03145; 35 sequenced antibodies.
DR Antibodypedia; 4183; 1285 antibodies from 46 providers.
DR DNASU; 13836; -.
DR Ensembl; ENSMUST00000006614; ENSMUSP00000006614; ENSMUSG00000006445.
DR GeneID; 13836; -.
DR KEGG; mmu:13836; -.
DR UCSC; uc008voc.2; mouse.
DR CTD; 1969; -.
DR MGI; MGI:95278; Epha2.
DR VEuPathDB; HostDB:ENSMUSG00000006445; -.
DR eggNOG; KOG0196; Eukaryota.
DR GeneTree; ENSGT00940000160786; -.
DR HOGENOM; CLU_000288_141_0_1; -.
DR InParanoid; Q03145; -.
DR OMA; MPIYMYT; -.
DR OrthoDB; 933071at2759; -.
DR PhylomeDB; Q03145; -.
DR TreeFam; TF315608; -.
DR BRENDA; 2.7.10.1; 3474.
DR Reactome; R-MMU-2682334; EPH-Ephrin signaling.
DR Reactome; R-MMU-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-MMU-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR Reactome; R-MMU-9013420; RHOU GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR Reactome; R-MMU-9013424; RHOV GTPase cycle.
DR Reactome; R-MMU-9696264; RND3 GTPase cycle.
DR Reactome; R-MMU-9696270; RND2 GTPase cycle.
DR Reactome; R-MMU-9696273; RND1 GTPase cycle.
DR BioGRID-ORCS; 13836; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Epha2; mouse.
DR PRO; PR:Q03145; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q03145; protein.
DR Bgee; ENSMUSG00000006445; Expressed in neural plate and 151 other tissues.
DR Genevisible; Q03145; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005925; C:focal adhesion; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031256; C:leading edge membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070160; C:tight junction; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019838; F:growth factor binding; ISO:MGI.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IBA:GO_Central.
DR GO; GO:0090630; P:activation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0048320; P:axial mesoderm formation; IMP:MGI.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0001568; P:blood vessel development; IMP:MGI.
DR GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IMP:MGI.
DR GO; GO:0048514; P:blood vessel morphogenesis; IMP:MGI.
DR GO; GO:0046849; P:bone remodeling; IMP:UniProtKB.
DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IMP:UniProtKB.
DR GO; GO:0046058; P:cAMP metabolic process; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0060326; P:cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0048870; P:cell motility; ISS:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:MGI.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:MGI.
DR GO; GO:0030216; P:keratinocyte differentiation; ISO:MGI.
DR GO; GO:0070309; P:lens fiber cell morphogenesis; IDA:UniProtKB.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:MGI.
DR GO; GO:0032682; P:negative regulation of chemokine production; IMP:MGI.
DR GO; GO:0001818; P:negative regulation of cytokine production; IMP:MGI.
DR GO; GO:1901491; P:negative regulation of lymphangiogenesis; IMP:MGI.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0021915; P:neural tube development; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; IDA:MGI.
DR GO; GO:0060035; P:notochord cell development; IMP:MGI.
DR GO; GO:0014028; P:notochord formation; IMP:MGI.
DR GO; GO:0048570; P:notochord morphogenesis; IMP:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IMP:UniProtKB.
DR GO; GO:0030316; P:osteoclast differentiation; IDA:UniProtKB.
DR GO; GO:1904238; P:pericyte cell differentiation; IMP:MGI.
DR GO; GO:1903348; P:positive regulation of bicellular tight junction assembly; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0036342; P:post-anal tail morphogenesis; IMP:MGI.
DR GO; GO:0043491; P:protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0045765; P:regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0043535; P:regulation of blood vessel endothelial cell migration; IDA:UniProtKB.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0010591; P:regulation of lamellipodium assembly; ISS:UniProtKB.
DR GO; GO:0070848; P:response to growth factor; ISS:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IMP:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0001570; P:vasculogenesis; IMP:MGI.
DR CDD; cd10480; EphR_LBD_A2; 1.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR027936; Eph_TM.
DR InterPro; IPR034263; EphA2_rcpt_lig-bd.
DR InterPro; IPR001090; Ephrin_rcpt_lig-bd_dom.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016257; Tyr_kinase_ephrin_rcpt.
DR InterPro; IPR001426; Tyr_kinase_rcpt_V_CS.
DR Pfam; PF14575; EphA2_TM; 1.
DR Pfam; PF01404; Ephrin_lbd; 1.
DR Pfam; PF00041; fn3; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00536; SAM_1; 1.
DR PIRSF; PIRSF000666; TyrPK_ephrin_receptor; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00615; EPH_lbd; 1.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS51550; EPH_LBD; 1.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00790; RECEPTOR_TYR_KIN_V_1; 1.
DR PROSITE; PS00791; RECEPTOR_TYR_KIN_V_2; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Angiogenesis; Apoptosis; ATP-binding; Cell adhesion;
KW Cell junction; Cell membrane; Cell projection; Differentiation;
KW Disulfide bond; Glycoprotein; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..977
FT /note="Ephrin type-A receptor 2"
FT /id="PRO_0000016801"
FT TOPO_DOM 26..538
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 539..559
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 560..977
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..205
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 329..433
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 439..530
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 614..876
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 905..969
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..205
FT /note="Mediates interaction with CLDN4"
FT /evidence="ECO:0000250"
FT REGION 607..907
FT /note="Mediates interaction with ARHGEF16"
FT /evidence="ECO:0000250"
FT REGION 887..977
FT /note="Negatively regulates interaction with ARHGEF16"
FT /evidence="ECO:0000250"
FT MOTIF 975..977
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT ACT_SITE 740
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 620..628
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 647
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 571
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29317"
FT MOD_RES 580
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29317"
FT MOD_RES 589
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 595
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:18387945,
FT ECO:0007744|PubMed:19131326"
FT MOD_RES 629
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29317"
FT MOD_RES 648
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P29317"
FT MOD_RES 736
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:18387945"
FT MOD_RES 773
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:18387945,
FT ECO:0007744|PubMed:19131326"
FT MOD_RES 870
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29317"
FT MOD_RES 893
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29317"
FT MOD_RES 898
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29317"
FT MOD_RES 902
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29317"
FT MOD_RES 922
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 931
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29317"
FT CARBOHYD 408
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770"
FT CARBOHYD 436
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770"
FT DISULFID 69..187
FT /evidence="ECO:0000250"
FT DISULFID 104..114
FT /evidence="ECO:0000250"
FT MUTAGEN 589
FT /note="Y->E: No significant effect on kinase activity and
FT loss of binding to VAV2 and VAV3. Inhibits EFNA1-induced
FT vascular assembly and RAC1 activation in endothelial cells,
FT no significant effect on kinase activity, significant
FT reduction in phosphorylation and binding to VAV3; when
FT associated with E-595."
FT /evidence="ECO:0000269|PubMed:16782872,
FT ECO:0000269|PubMed:18387945"
FT MUTAGEN 589
FT /note="Y->F: Inhibits EFNA1-induced vascular assembly and
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:16782872,
FT ECO:0000269|PubMed:18387945"
FT MUTAGEN 595
FT /note="Y->E: No significant effect on kinase activity and
FT loss of binding to VAV2 and VAV3. Inhibits EFNA1-induced
FT vascular assembly and RAC1 activation in endothelial cells,
FT no significant effect on kinase activity, significant
FT reduction in phosphorylation and binding to VAV3; when
FT associated with E-589."
FT /evidence="ECO:0000269|PubMed:16782872,
FT ECO:0000269|PubMed:18387945"
FT MUTAGEN 595
FT /note="Y->F: Inhibits EFNA1-induced vascular assembly and
FT abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:16782872,
FT ECO:0000269|PubMed:18387945"
FT MUTAGEN 736
FT /note="Y->F: Inhibits EFNA1-induced vascular assembly and
FT RAC1 activation in endothelial cells. No significant effect
FT on kinase activity. Loss of binding to PI3-kinase p85
FT subunit."
FT /evidence="ECO:0000269|PubMed:18387945"
FT MUTAGEN 740
FT /note="D->N: Loss of kinase activity and binding to VAV3."
FT /evidence="ECO:0000269|PubMed:16782872"
FT MUTAGEN 773
FT /note="Y->F: No significant effect on kinase activity.
FT Significant reduction in phosphorylation."
FT /evidence="ECO:0000269|PubMed:18387945"
FT MUTAGEN 918
FT /note="K->A: Strongly reduced binding affinity for INPPL1
FT SAM domain."
FT /evidence="ECO:0000269|PubMed:29749928"
FT MUTAGEN 931
FT /note="Y->F: Inhibits EFNA1-induced vascular assembly and
FT RAC1 activation in endothelial cells. Inhibits kinase
FT activity. Loss of binding to VAV3 and PI3-kinase p85
FT subunit."
FT /evidence="ECO:0000269|PubMed:18387945"
FT MUTAGEN 957
FT /note="K->A: Strongly reduced binding affinity for INPPL1
FT SAM domain."
FT /evidence="ECO:0000269|PubMed:29749928"
FT MUTAGEN 958
FT /note="R->C,K: Abolishes interaction with INPPL1 SAM
FT domain."
FT /evidence="ECO:0000269|PubMed:29749928"
FT CONFLICT 5
FT /note="A -> T (in Ref. 1; CAA55135)"
FT /evidence="ECO:0000305"
FT CONFLICT 112..113
FT /note="SS -> HA (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="A -> R (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 209
FT /note="R -> C (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 244
FT /note="P -> A (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 258..260
FT /note="IGQ -> SE (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 291
FT /note="C -> S (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 339..340
FT /note="IG -> C (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 371..372
FT /note="WP -> CA (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 383
FT /note="S -> T (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 457
FT /note="W -> R (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 485
FT /note="V -> G (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 511
FT /note="L -> W (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 534
FT /note="A -> R (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 678
FT /note="R -> P (in Ref. 1; CAA55135)"
FT /evidence="ECO:0000305"
FT CONFLICT 681
FT /note="G -> A (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 819..820
FT /note="YW -> LL (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 878
FT /note="A -> R (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT CONFLICT 919..920
FT /note="MQ -> IE (in Ref. 2; AAA82113)"
FT /evidence="ECO:0000305"
FT HELIX 910..916
FT /evidence="ECO:0007829|PDB:5ZRX"
FT HELIX 920..922
FT /evidence="ECO:0007829|PDB:5ZRX"
FT HELIX 923..928
FT /evidence="ECO:0007829|PDB:5ZRX"
FT HELIX 934..937
FT /evidence="ECO:0007829|PDB:5ZRX"
FT HELIX 942..947
FT /evidence="ECO:0007829|PDB:5ZRX"
FT HELIX 953..969
FT /evidence="ECO:0007829|PDB:5ZRX"
SQ SEQUENCE 977 AA; 108852 MW; 66338CE7EF2DEE02 CRC64;
MELRAVGFCL ALLWGCALAA AAAQGKEVVL LDFAAMKGEL GWLTHPYGKG WDLMQNIMDD
MPIYMYSVCN VVSGDQDNWL RTNWVYREEA ERIFIELKFT VRDCNSFPGG ASSCKETFNL
YYAESDVDYG TNFQKRQFTK IDTIAPDEIT VSSDFEARNV KLNVEERMVG PLTRKGFYLA
FQDIGACVAL LSVRVYYKKC PEMLQSLARF PETIAVAVSD TQPLATVAGT CVDHAVVPYG
GEGPLMHCTV DGEWLVPIGQ CLCQEGYEKV EDACRACSPG FFKSEASESP CLECPEHTLP
STEGATSCQC EEGYFRAPED PLSMSCTRPP SAPNYLTAIG MGAKVELRWT APKDTGGRQD
IVYSVTCEQC WPESGECGPC EASVRYSEPP HALTRTSVTV SDLEPHMNYT FAVEARNGVS
GLVTSRSFRT ASVSINQTEP PKVRLEDRST TSLSVTWSIP VSQQSRVWKY EVTYRKKGDA
NSYNVRRTEG FSVTLDDLAP DTTYLVQVQA LTQEGQGAGS KVHEFQTLST EGSANMAVIG
GVAVGVVLLL VLAGVGLFIH RRRRNLRARQ SSEDVRFSKS EQLKPLKTYV DPHTYEDPNQ
AVLKFTTEIH PSCVARQKVI GAGEFGEVYK GTLKASSGKK EIPVAIKTLK AGYTEKQRVD
FLSEASIMGQ FSHHNIIRLE GVVSKYKPMM IITEYMENGA LDKFLREKDG EFSVLQLVGM
LRGIASGMKY LANMNYVHRD LAARNILVNS NLVCKVSDFG LSRVLEDDPE ATYTTSGGKI
PIRWTAPEAI SYRKFTSASD VWSYGIVMWE VMTYGERPYW ELSNHEVMKA INDGFRLPTP
MDCPSAIYQL MMQCWQQERS RRPKFADIVS ILDKLIRAPD SLKTLADFDP RVSIRLPSTS
GSEGVPFRTV SEWLESIKMQ QYTEHFMVAG YTAIEKVVQM SNEDIKRIGV RLPGHQKRIA
YSLLGLKDQV NTVGIPI
