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Protein

Ephrin type-A receptor 3

Gene

epha3

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially efna5. Upon activation by efna5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation probably through activation by efna1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development (By similarity).By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei658 – 6581ATPPROSITE-ProRule annotation
Active sitei751 – 7511Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi633 – 6386ATPPROSITE-ProRule annotation
Nucleotide bindingi705 – 7117ATPPROSITE-ProRule annotation
Nucleotide bindingi755 – 7562ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 928.

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-A receptor 3 (EC:2.7.10.1)
Alternative name(s):
EPH-like kinase 1
Tyrosine-protein kinase receptor ZEK1
Gene namesi
Name:epha3
Synonyms:ek1, zek1
OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)
Taxonomic identifieri7955 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
Proteomesi
  • UP000000437 Componenti: Unplaced

Organism-specific databases

ZFINiZDB-GENE-990415-58. ek1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini21 – 545525ExtracellularSequence analysisAdd
BLAST
Transmembranei546 – 56621HelicalSequence analysisAdd
BLAST
Topological domaini567 – 981415CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020By similarityAdd
BLAST
Chaini21 – 981961Ephrin type-A receptor 3PRO_0000016806Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi340 – 3401N-linked (GlcNAc...)Sequence analysis
Glycosylationi410 – 4101N-linked (GlcNAc...)Sequence analysis
Glycosylationi435 – 4351N-linked (GlcNAc...)Sequence analysis
Glycosylationi485 – 4851N-linked (GlcNAc...)Sequence analysis
Modified residuei601 – 6011Phosphotyrosine; by autocatalysisBy similarity
Modified residuei607 – 6071Phosphotyrosine; by autocatalysisBy similarity
Modified residuei706 – 7061Phosphotyrosine; by autocatalysisBy similarity
Modified residuei784 – 7841Phosphotyrosine; by autocatalysisSequence analysis
Modified residuei927 – 9271Phosphotyrosine; by autocatalysisSequence analysis

Post-translational modificationi

Autophosphorylates upon activation by efna5.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO13146.

Expressioni

Tissue specificityi

Widely expressed in the developing zebrafish nervous system.

Interactioni

Subunit structurei

Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity).By similarity

Protein-protein interaction databases

STRINGi7955.ENSDARP00000096552.

Structurei

3D structure databases

ProteinModelPortaliO13146.
SMRiO13146. Positions 29-207, 600-904.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 210182Eph LBDPROSITE-ProRule annotationAdd
BLAST
Domaini328 – 441114Fibronectin type-III 1PROSITE-ProRule annotationAdd
BLAST
Domaini442 – 53392Fibronectin type-III 2PROSITE-ProRule annotationAdd
BLAST
Domaini626 – 887262Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini910 – 97465SAMPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi979 – 9813PDZ-bindingSequence analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi192 – 325134Cys-richAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.PROSITE-ProRule annotation
Contains 1 Eph LBD (Eph ligand-binding) domain.PROSITE-ProRule annotation
Contains 2 fibronectin type-III domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0196. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000233856.
HOVERGENiHBG062180.
InParanoidiO13146.
KOiK05105.
PhylomeDBiO13146.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR027936. Eph_TM.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. FN3_dom.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016257. Tyr_kinase_ephrin_rcpt.
IPR001426. Tyr_kinase_rcpt_V_CS.
[Graphical view]
PfamiPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00615. EPH_lbd. 1 hit.
SM01411. Ephrin_rec_like. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEiPS01186. EGF_2. 1 hit.
PS51550. EPH_LBD. 1 hit.
PS50853. FN3. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00790. RECEPTOR_TYR_KIN_V_1. 1 hit.
PS00791. RECEPTOR_TYR_KIN_V_2. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O13146-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALFRIYSFL APFHILVLCQ ALRNYPDNEV TLLDSMSAPG DLGWEAYPSE
60 70 80 90 100
GWEEISVMDE RNIPMRTYQV CNVMEANQNN WLRTGLIQRE GAQRVYVEIK
110 120 130 140 150
FTLRDCNSLP GVPGTCKETF NVYYHESNNA VAAPLRHIRE SQYIKIDTIA
160 170 180 190 200
ADESFTQTDV GDRVMKLNTE VRDISGLSKR GLYLAFQDLG ACIALVSVRV
210 220 230 240 250
FYKRCPLAVL NLARFPDTVT GGDSALVEVR GTCVEDAEEL EGPRMFCSAD
260 270 280 290 300
GGWLVPIGRC VCRPGFEEVD GHCQPCRSGF YKASAMDAYC VKCPPHSYSH
310 320 330 340 350
QDKASECVCE RGFYRAESDP RSMACTRPPS APGNPISMVN ETAVTLEWSP
360 370 380 390 400
PRDSGGRGDV SYSVHCRKCS GETGASERCV PCGSGAHFNP RQFGLTHPRV
410 420 430 440 450
LVTELQPHTN YTFSVEALNG VSDLSPSPRQ LVSVNVTTSQ TVSVILKERK
460 470 480 490 500
GTDSVTLAWQ GPEPVDGTVV EYEVTYYEKN QQDQNYTVLK TKSNSMTVDG
510 520 530 540 550
LKPGTTYIFR VRARTDGGYG NYKGEIELET SHEDMLAVGD PNQQTILAIS
560 570 580 590 600
VAGGAVLLVL LVACFIVSGR RCGYIKAKQD PEEEKMQFQH GRVKLPETRT
610 620 630 640 650
YIHPHTYEDP NQAVRDFAKE IEVSNIRIER VIGAGEFGEV CSGRLRLPSK
660 670 680 690 700
REIQVAIKSL KAGYSEHQRR DFLSEASIMG QFDHPNIIRL EGVVTRCKPV
710 720 730 740 750
MIVTEYMENG SLDTFLKKHD GQFTVIQLLG MLRGIAAGMQ YLSEMNYVHR
760 770 780 790 800
DLAARNILVN RNLVCKVSDF GLSRVLEDDP EAAYTTRGGK IPIRWTAPEA
810 820 830 840 850
ITYRKFTSAS DVWSYGIVMW EVISYGERPY WEMSNQDVIK AVDEGYRLPA
860 870 880 890 900
PMDCPVVLHQ LMLDCWEKNR SDRPKFGQIV NTLDRLIRNP SSLKQLANSA
910 920 930 940 950
VWEDPVTPEA AVNTVEDWLD LIKMGQYKEH FSSAGYVTLD SVLYVSSSEL
960 970 980
DKMGVELAGH QKKILSSIQC LQAHHGTQVQ V
Length:981
Mass (Da):109,655
Last modified:July 1, 1997 - v1
Checksum:iF0B3F5218965E2C6
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti141 – 1411S → N.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U89295 mRNA. Translation: AAC60220.1.
RefSeqiNP_571170.1. NM_131095.1.
UniGeneiDr.75760.

Genome annotation databases

GeneIDi30311.
KEGGidre:30311.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U89295 mRNA. Translation: AAC60220.1.
RefSeqiNP_571170.1. NM_131095.1.
UniGeneiDr.75760.

3D structure databases

ProteinModelPortaliO13146.
SMRiO13146. Positions 29-207, 600-904.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi7955.ENSDARP00000096552.

Proteomic databases

PaxDbiO13146.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi30311.
KEGGidre:30311.

Organism-specific databases

CTDi30311.
ZFINiZDB-GENE-990415-58. ek1.

Phylogenomic databases

eggNOGiKOG0196. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000233856.
HOVERGENiHBG062180.
InParanoidiO13146.
KOiK05105.
PhylomeDBiO13146.

Enzyme and pathway databases

BRENDAi2.7.10.1. 928.

Miscellaneous databases

NextBioi20806751.
PROiO13146.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR027936. Eph_TM.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. FN3_dom.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016257. Tyr_kinase_ephrin_rcpt.
IPR001426. Tyr_kinase_rcpt_V_CS.
[Graphical view]
PfamiPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00615. EPH_lbd. 1 hit.
SM01411. Ephrin_rec_like. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEiPS01186. EGF_2. 1 hit.
PS51550. EPH_LBD. 1 hit.
PS50853. FN3. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00790. RECEPTOR_TYR_KIN_V_1. 1 hit.
PS00791. RECEPTOR_TYR_KIN_V_2. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Novel Eph-family receptor tyrosine kinase is widely expressed in the developing zebrafish nervous system."
    Bovenkamp D.E., Greer P.
    Dev. Dyn. 209:166-181(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiEPHA3_DANRE
AccessioniPrimary (citable) accession number: O13146
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 1, 1997
Last modified: May 11, 2016
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.