EPHA6_MOUSE
ID EPHA6_MOUSE Reviewed; 1035 AA.
AC Q62413; B9EIV2; Q8CCN2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Ephrin type-A receptor 6;
DE EC=2.7.10.1;
DE AltName: Full=EPH homology kinase 2;
DE Short=EHK-2;
DE Flags: Precursor;
GN Name=Epha6; Synonyms=Ehk-2, Ehk2;
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].
RC STRAIN=BALB/cJ;
RX PubMed=8892754; DOI=10.1089/dna.1996.15.817;
RA Lee A.M., Navaratnam D., Ichimiya S., Greene M.I., Davis J.G.;
RT "Cloning of m-ehk2 from the murine inner ear, an eph family receptor
RT tyrosine kinase expressed in the developing and adult cochlea.";
RL DNA Cell Biol. 15:817-825(1996).
RN [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 397-1035.
RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb;
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 [5] {ECO:0007744|PDB:5ZRY}
RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 957-1035 IN COMPLEX WITH ANKS1A.
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 GPI-
CC anchored 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 (By similarity). {ECO:0000250}.
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 -!- SUBUNIT: Heterotetramer upon binding of the ligand. The heterotetramer
CC is composed of an ephrin dimer and a receptor dimer. Oligomerization is
CC probably required to induce biological responses (By similarity).
CC Interacts (via SAM domain) with ANKS1A (via SAM domain)
CC (PubMed:29749928). {ECO:0000250, ECO:0000269|PubMed:29749928}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
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; U58332; AAB53836.1; -; mRNA.
DR EMBL; CH466521; EDK98232.1; -; Genomic_DNA.
DR EMBL; BC141090; AAI41091.1; -; mRNA.
DR EMBL; AK032436; BAC27868.1; -; mRNA.
DR PDB; 5ZRY; X-ray; 1.30 A; A/B=957-1035.
DR PDBsum; 5ZRY; -.
DR AlphaFoldDB; Q62413; -.
DR SMR; Q62413; -.
DR STRING; 10090.ENSMUSP00000066734; -.
DR BindingDB; Q62413; -.
DR ChEMBL; CHEMBL4739690; -.
DR GuidetoPHARMACOLOGY; 1826; -.
DR GlyGen; Q62413; 3 sites.
DR iPTMnet; Q62413; -.
DR PhosphoSitePlus; Q62413; -.
DR MaxQB; Q62413; -.
DR PaxDb; Q62413; -.
DR PRIDE; Q62413; -.
DR ProteomicsDB; 275626; -.
DR UCSC; uc012agy.1; mouse.
DR MGI; MGI:108034; Epha6.
DR eggNOG; KOG0196; Eukaryota.
DR InParanoid; Q62413; -.
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 ChiTaRS; Epha6; mouse.
DR PRO; PR:Q62413; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q62413; protein.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10484; EphR_LBD_A6; 1.
DR CDD; cd00063; FN3; 2.
DR CDD; cd09547; SAM_EPH-A6; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR042746; EPH-A6_SAM.
DR InterPro; IPR027936; Eph_TM.
DR InterPro; IPR034280; EphA6_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; IPR011641; Tyr-kin_ephrin_A/B_rcpt-like.
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; PF07699; Ephrin_rec_like; 1.
DR Pfam; PF00041; fn3; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 2.
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; 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; ATP-binding; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1035
FT /note="Ephrin type-A receptor 6"
FT /id="PRO_0000016816"
FT TOPO_DOM 23..549
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 550..570
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 571..1035
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 33..211
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 330..440
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 441..536
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 630..943
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 960..1024
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT MOTIF 1033..1035
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT ACT_SITE 797
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 636..644
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 662
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 605
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 611
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 830
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 977
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 396
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 409
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 212
FT /note="N -> S (in Ref. 1; AAB53836)"
FT /evidence="ECO:0000305"
FT CONFLICT 477
FT /note="I -> T (in Ref. 1; AAB53836)"
FT /evidence="ECO:0000305"
FT CONFLICT 905
FT /note="H -> Q (in Ref. 1; AAB53836)"
FT /evidence="ECO:0000305"
FT STRAND 958..960
FT /evidence="ECO:0007829|PDB:5ZRY"
FT HELIX 965..971
FT /evidence="ECO:0007829|PDB:5ZRY"
FT HELIX 975..977
FT /evidence="ECO:0007829|PDB:5ZRY"
FT HELIX 978..983
FT /evidence="ECO:0007829|PDB:5ZRY"
FT HELIX 989..992
FT /evidence="ECO:0007829|PDB:5ZRY"
FT HELIX 997..1002
FT /evidence="ECO:0007829|PDB:5ZRY"
FT HELIX 1008..1031
FT /evidence="ECO:0007829|PDB:5ZRY"
SQ SEQUENCE 1035 AA; 116185 MW; 9886E5A92B146E44 CRC64;
MGGCEVREFL LQFGFFLPLL TAWTGDCSHV SNQVVLLDTT TVMGELGWKT YPLNGWDAIT
EMDEHNRPIH TYQVCNVMEP NQNNWLRTNW ISRDAAQKIY VEMKFTLRDC NSIPWVLGTC
KETFNLYYIE SDESHGTKFK PSQYIKIDTI AADESFTQMD LGDRILKLNT EIREVGPIER
KGFYLAFQDI GACIALVSVR VFYKKCPFTV RNLAMFPDTI PRVDSSSLVE VRGSCVKSAE
ERDTPKLYCG ADGDWLVPLG RCICSTGYEE IEGSCHACRP GFYKAFAGNT KCSKCPPHSS
TYVEATSVCH CEKGYFRAEK DPPSMACTRP PSAPRNVAFN INETALILEW SPPSDTGGRK
DLTYSVICKK CGLDTTQCED CGGGLRFIPR HTGLINNSVV VLDFVSHVNY TFEIEAMNGV
SELSISPKPF TAITVTTDHD APSLIGMMRK DWASQNSLAL SWQAPAFSNG AILDYEIKYY
EKEHEQLTYS STRSKAPSVI VTGLKPATTY IFHIRVRTAT GYSGYSQKFE FETGDETSDM
AAEQGQILVI ATAAVGGFTL LVILTLFFLI TGRCQWYIKA KMKSEEKRRT HLQNGHLRFP
GIKTYIDPDT YEDPSLAVHE FAKEIDPSRI RIERVIGAGE FGEVCSGRLK TPGKREIPVA
IKTLKGGHMD RQRRDFLREA SIMGQFDHPN IIRLEGVVTK RSFPAIGVEA FCPSFLRAGF
LNGIQAPHPV TAGGSLPPRI PAGRPVMIVV EYMENGSLDS FLRKHDGHFT VIQLVGMLRG
IASGMKYLSD MGYVHRDLAA RNILVNSNLV CKVSDFGLSR VLEDDPEAAY TTTGGKIPIR
WTAPEAIAYR KFSSASDAWS YGIVMWEVMS YGERPYWEMS NQDVILSIEE GYRLPAPMGC
PPSLHQLMLH CWQKERNHRP KFTDIVSFLD KLIRNPSALH TLVEDILVMP ESPGDVPEYP
LFVTVGDWLD SIKMGQYKSN FMAAGFTTFD LISRMSIDDI RRIGVILIGH QRRIVSSIQT
LRLHMMHIQE KGFHV
