P09759 (EPHB1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ephrin type-B receptor 1
EC=2.7.10.1

Alternative name(s):
ELK
Tyrosine-protein kinase receptor EPH-2

Gene names

Name:	Ephb1
Synonyms:	Elk, Epth2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	984 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. Beside its role in axon guidance plays also an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively By similarity.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	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. Interacts with EPHB6; transphosphorylates EPHB6 to form an active signaling complex. Interacts with PICK1. Interacts (through Tyr-594) with NCK1 (via SH2 domain); activates the JUN cascade to regulate cell adhesion. The ligand-activated form interacts (through Tyr-928) with GRB7 and GRB10 (via SH2 domains). The ligand-activated form interacts (residues within the catalytic domain) with GRB2 (via SH2 domain). Interacts with GRB2, SHC1 and SRC; activates the MAPK/ERK cascade to regulate cell migration. Interacts with CBL; regulates receptor degradation through ubiquitination. Interacts with ACP1 By similarity.
Subcellular location	Cell membrane By similarity; Single-pass type I membrane protein. Early endosome membrane By similarity. Cell projection › dendrite By similarity.
Tissue specificity	Restricted to brain and testes. Ref.1
Post-translational modification	Phosphorylated. Autophosphorylation is stimulated by the ligand EFNB1. Required for interaction with SH2 domain-containing interactors, for activation of the MAPK/ERK and JUN signaling cascades and for ubiquitination by CBL By similarity. Ref.1 Ubiquitinated; (EFNB1)ligand-induced poly- and/or multi-ubiquitination by CBL is regulated by SRC and leads to lysosomal degradation By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily. Contains 1 Eph LBD (Eph ligand-binding) domain. Contains 2 fibronectin type-III domains. Contains 1 protein kinase domain. Contains 1 SAM (sterile alpha motif) domain.

Ontologies

Keywords
Biological process	Cell adhesion Neurogenesis
Cellular component	Cell membrane Cell projection Endosome Membrane
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB camera-type eye morphogenesis Inferred from electronic annotation. Source: Compara cell chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB cell-substrate adhesion Inferred from sequence or structural similarity. Source: UniProtKB central nervous system projection neuron axonogenesis Inferred from sequence or structural similarity. Source: UniProtKB dendritic spine morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB detection of temperature stimulus involved in sensory perception of pain Inferred from sequence or structural similarity. Source: UniProtKB establishment of cell polarity Inferred from sequence or structural similarity. Source: UniProtKB neural precursor cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB optic nerve morphogenesis Inferred from electronic annotation. Source: Compara positive regulation of synapse assembly Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.1. Source: RGD regulation of ERK1 and ERK2 cascade Inferred from sequence or structural similarity. Source: UniProtKB regulation of JNK cascade Inferred from sequence or structural similarity. Source: UniProtKB retinal ganglion cell axon guidance Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	axon Inferred from electronic annotation. Source: Compara dendrite Inferred from electronic annotation. Source: UniProtKB-SubCell early endosome membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB membrane raft Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW axon guidance receptor activity Inferred from electronic annotation. Source: Compara transmembrane-ephrin receptor activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 17	17	Potential
	Chain	18 – 984	967	Ephrin type-B receptor 1		PRO_0000016825
Regions
	Topological domain	18 – 540	523	Extracellular Potential
	Transmembrane	541 – 563	23	Helical; Potential
	Topological domain	564 – 984	421	Cytoplasmic Potential
	Domain	19 – 201	183	Eph LBD
	Domain	323 – 424	102	Fibronectin type-III 1
	Domain	430 – 525	96	Fibronectin type-III 2
	Domain	619 – 882	264	Protein kinase
	Domain	911 – 975	65	SAM
	Nucleotide binding	625 – 633	9	ATP By similarity
	Motif	982 – 984	3	PDZ-binding Potential
	Compositional bias	183 – 319	137	Cys-rich
Sites
	Active site	744	1	Proton acceptor By similarity
	Binding site	651	1	ATP By similarity
Amino acid modifications
	Modified residue	928	1	Phosphotyrosine; by autocatalysis By similarity
	Glycosylation	334	1	N-linked (GlcNAc...) Potential
	Glycosylation	426	1	N-linked (GlcNAc...) Potential
	Glycosylation	480	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	P09759 [UniParc]. Last modified December 1, 1992. Version 2. Checksum: 521EAC240D8FB91A	FASTA	984	109,883
	10 20 30 40 50 60 MALDCLLLFL LASAVAAMEE TLMDTRTATA ELGWTANPAS GWEEVSGYDE NLNTIRTYQV 70 80 90 100 110 120 CNVFEPNQNN WLLTTFINRR GAHRIYTEMR FTVRDCSSLP NVPGSCKETF NLYYYETDSV 130 140 150 160 170 180 IATKKSAFWS EAPYLKVDTI AADESFSQVD FGGRLMKVNT EVRSFGPLTR NGFYLAFQDY 190 200 210 220 230 240 GACMSLLSVR VFFKKCPSIV QNFAVFPETM TGAESTSLVI ARGTCIPNAE EVDVPIKLYC 250 260 270 280 290 300 NGDGEWMVPI GRCTCKAGYE PENSVACKAC PAGTFKASQE AEGCSHCPSN SRSPSEASPI 310 320 330 340 350 360 CTCRTGYYRA DFDPPEVACT SVPSGPRNVI SIVNETSIIL EWHPPRETGG RDDVTYNIIC 370 380 390 400 410 420 KKCRADRRSC SRCDDNVEFV PRQLGLTECR VSISSLWAHT PYTFDIQAIN GVSSKSPFPP 430 440 450 460 470 480 QHVSVNITTN QAAPSTVPIM HQVSATMRSI TLSWPQPEQP NGIILDYEIR YYEKEHNEFN 490 500 510 520 530 540 SSMARSQTNT ARIDGLRPGM VYVVQVRART VAGYGKFSGK MCFQTLTDDD YKSELREQLP 550 560 570 580 590 600 LIAGSAAAGV VFVVSLVAIS IVCSRKRAYS KEAVYSDKLQ HYSTGRGSPG MKIYIDPFTY 610 620 630 640 650 660 EDPNEAVREF AKEIDVSFVK IEEVIGAGEF GEVYKGRLKL PGKREIYVAI KTLKAGYSEK 670 680 690 700 710 720 QRRDFLSEAS IMGQFDHPNI IRLEGVVTKS RPVMIITEFM ENGALDSFLR QNDGQFTVIQ 730 740 750 760 770 780 LVGMLRGIAA GMKYLSEMNY VHRDLAARNI LVNSNLVCKV SDFGLSRYLQ DDTSDPTYTS 790 800 810 820 830 840 SLGGKIPVRW TAPEAIAYRK FTSASDVWSY GIVMWEVMSF GERPYWDMSN QDVINAIEQD 850 860 870 880 890 900 YRLPPPMDCP AALHQLMLDC WQKDRNSRPR FAEIVNTLDK MIRNPASLKT VATITAVPSQ 910 920 930 940 950 960 PLLDRSIPDF TAFTTVDDWL SAIKMVQYRD SFLTAGFTSL QLVTQMTSED LLRIGVTLAG 970 980 HQKKILSSIH SMRVQMNQSP SVMA

References

[1]	"Characterization of elk, a brain-specific receptor tyrosine kinase." Lhotak V., Greer P., Letwin K., Pawson T. Mol. Cell. Biol. 11:2496-2502(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], AUTOPHOSPHORYLATION, TISSUE SPECIFICITY. Strain: Wistar. Tissue: Brain.
[2]	"Novel protein-tyrosine kinase cDNAs related to fps/fes and eph cloned using anti-phosphotyrosine antibody." Letwin K., Yee S.P., Pawson T. Oncogene 3:621-627(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 605-984. Strain: Wistar. Tissue: Brain.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M59814 mRNA. No translation available. X13411 mRNA. Translation: CAA31777.1.
IPI	IPI00189428.
PIR	A39753.
RefSeq	NP_001097998.1. NM_001104528.1.
UniGene	Rn.46606.
3D structure databases
ProteinModelPortal	P09759.
SMR	P09759. Positions 18-197, 436-528, 592-889, 900-984.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-138N.
STRING	10116.ENSRNOP00000010634.
PTM databases
PhosphoSite	P09759.
Proteomic databases
PaxDb	P09759.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	24338.
KEGG	rno:24338.
UCSC	RGD:2556. rat.
Organism-specific databases
CTD	2047.
RGD	2556. Ephb1.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233856.
HOVERGEN	HBG062180.
InParanoid	P09759.
KO	K05110.
OrthoDB	EOG4W9J35.
Enzyme and pathway databases
BRENDA	2.7.10.1. 5301.
Gene expression databases
ArrayExpress	P09759.
Genevestigator	P09759.
GermOnline	ENSRNOG00000007865. Rattus norvegicus.
Family and domain databases
Gene3D	1.10.150.50. 1 hit. 2.60.40.10. 2 hits.
InterPro	IPR001090. Ephrin_rcpt_lig-bd_dom. IPR003961. Fibronectin_type3. IPR008979. Galactose-bd-like. IPR013783. Ig-like_fold. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001660. SAM. IPR013761. SAM/pointed. IPR021129. SAM_type1. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR016257. Tyr_kinase_ephrin_rcpt. IPR001426. Tyr_kinase_rcpt_V_CS. [Graphical view]
Pfam	PF01404. Ephrin_lbd. 1 hit. PF00041. fn3. 2 hits. PF07714. Pkinase_Tyr. 1 hit. PF00536. SAM_1. 1 hit. [Graphical view]
PIRSF	PIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTS	PR00109. TYRKINASE.
SMART	SM00615. EPH_lbd. 1 hit. SM00060. FN3. 2 hits. SM00454. SAM. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 2 hits. SSF49785. Gal_bind_like. 1 hit. SSF56112. Kinase_like. 1 hit. SSF47769. SAM_homology. 1 hit.
PROSITE	PS01186. EGF_2. 1 hit. Uncertain. 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]
ProtoNet	Search...
Other
NextBio	603035.

Entry information

Entry name

EPHB1_RAT

Accession

Primary (citable) accession number: P09759

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	December 1, 1992
Last modified:	April 3, 2013
This is version 144 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program