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Protein

Ephrin type-B receptor 1

Gene

Ephb1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. In addition to 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. Involved in the maintenance of the pool of satellite cells (muscle stem cells) by promoting their self-renewal and reducing their activation and differentiation (PubMed:27446912).5 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei651ATPPROSITE-ProRule annotation1
Active sitei744Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi625 – 633ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • axon guidance receptor activity Source: MGI
  • protein-containing complex binding Source: MGI
  • transmembrane-ephrin receptor activity Source: UniProtKB

GO - Biological processi

  • angiogenesis Source: UniProtKB
  • axon guidance Source: MGI
  • camera-type eye morphogenesis Source: MGI
  • cell chemotaxis Source: UniProtKB
  • cell-substrate adhesion Source: UniProtKB
  • central nervous system projection neuron axonogenesis Source: MGI
  • cranial nerve development Source: MGI
  • dendritic spine development Source: UniProtKB
  • dendritic spine morphogenesis Source: UniProtKB
  • detection of temperature stimulus involved in sensory perception of pain Source: UniProtKB
  • ephrin receptor signaling pathway Source: MGI
  • establishment of cell polarity Source: UniProtKB
  • immunological synapse formation Source: MGI
  • negative regulation of satellite cell differentiation Source: UniProtKB
  • negative regulation of skeletal muscle satellite cell proliferation Source: UniProtKB
  • neural precursor cell proliferation Source: UniProtKB
  • neurogenesis Source: UniProtKB
  • optic nerve morphogenesis Source: MGI
  • positive regulation of synapse assembly Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • regulation of JNK cascade Source: UniProtKB
  • regulation of neuron death Source: MGI
  • retinal ganglion cell axon guidance Source: MGI
  • skeletal muscle satellite cell activation Source: UniProtKB

Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processCell adhesion, Neurogenesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-2682334 EPH-Ephrin signaling
R-MMU-3928662 EPHB-mediated forward signaling
R-MMU-3928664 Ephrin signaling
R-MMU-3928665 EPH-ephrin mediated repulsion of cells

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-B receptor 1 (EC:2.7.10.1)
Gene namesi
Name:Ephb1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1096337 Ephb1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini18 – 540ExtracellularSequence analysisAdd BLAST523
Transmembranei541 – 563HelicalSequence analysisAdd BLAST23
Topological domaini564 – 984CytoplasmicSequence analysisAdd BLAST421

Keywords - Cellular componenti

Cell membrane, Cell projection, Endosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice development is apparently normal. However, they display a dramatic reduction of ipsilateral retinal projection. Mice do not develop neuropathic algesia and physical dependence to morphine.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
ChainiPRO_000026031718 – 984Ephrin type-B receptor 1Add BLAST967

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi334N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi426N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi480N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei600PhosphotyrosineBy similarity1
Modified residuei928Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

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).By similarity
Ubiquitinated; (EFNB1)ligand-induced poly- and/or multi-ubiquitination by CBL is regulated by SRC and leads to lysosomal degradation.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8CBF3
PeptideAtlasiQ8CBF3
PRIDEiQ8CBF3

PTM databases

iPTMnetiQ8CBF3
PhosphoSitePlusiQ8CBF3

Expressioni

Tissue specificityi

Expressed in neural stem and progenitor cells in the dentate gyrus (PubMed:18057206). Expressed in myogenic progenitor cells (PubMed:27446912).2 Publications

Developmental stagei

Expressed in growth cones of ventrotemporal (uncrossed) retinal ganglion cells that give rise to ipsilateral projections (at protein level) (PubMed:12971893, PubMed:18524895). In myogenic progenitor cells, initially expressed early during myogenic development (E11.5), down-regulated during the fetal stage (lower levels at E17.5) to be re-expressed in postnatal satellite cells (PubMed:27446912).3 Publications

Gene expression databases

BgeeiENSMUSG00000032537
CleanExiMM_EPHB1
ExpressionAtlasiQ8CBF3 baseline and differential
GenevisibleiQ8CBF3 MM

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). Interacts with EPHB6; transphosphorylates EPHB6 to form an active signaling complex (By similarity). 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 similarity5 Publications

Protein-protein interaction databases

BioGridi234781, 3 interactors
IntActiQ8CBF3, 1 interactor
STRINGi10090.ENSMUSP00000035129

Structurei

3D structure databases

ProteinModelPortaliQ8CBF3
SMRiQ8CBF3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini19 – 201Eph LBDPROSITE-ProRule annotationAdd BLAST183
Domaini322 – 432Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST111
Domaini433 – 528Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST96
Domaini619 – 882Protein kinasePROSITE-ProRule annotationAdd BLAST264
Domaini911 – 975SAMPROSITE-ProRule annotationAdd BLAST65

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi982 – 984PDZ-bindingSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi183 – 319Cys-richAdd BLAST137

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0196 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118975
HOGENOMiHOG000233856
HOVERGENiHBG062180
InParanoidiQ8CBF3
KOiK05110
OMAiKACPAGM
OrthoDBiEOG091G00W0
PhylomeDBiQ8CBF3
TreeFamiTF315608

Family and domain databases

CDDicd10476 EphR_LBD_B1, 1 hit
cd00063 FN3, 2 hits
Gene3Di2.60.120.260, 1 hit
2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR027936 Eph_TM
IPR034231 EphB1_rcpt_lig-bd
IPR001090 Ephrin_rcpt_lig-bd_dom
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR008979 Galactose-bd-like_sf
IPR009030 Growth_fac_rcpt_cys_sf
IPR013783 Ig-like_fold
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001660 SAM
IPR013761 SAM/pointed_sf
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
PfamiView protein in Pfam
PF14575 EphA2_TM, 1 hit
PF01404 Ephrin_lbd, 1 hit
PF00041 fn3, 2 hits
PF07714 Pkinase_Tyr, 1 hit
PF00536 SAM_1, 1 hit
PIRSFiPIRSF000666 TyrPK_ephrin_receptor, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00615 EPH_lbd, 1 hit
SM01411 Ephrin_rec_like, 1 hit
SM00060 FN3, 2 hits
SM00454 SAM, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
SSF49265 SSF49265, 1 hit
SSF49785 SSF49785, 1 hit
SSF56112 SSF56112, 1 hit
SSF57184 SSF57184, 2 hits
PROSITEiView protein in PROSITE
PS01186 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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8CBF3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MALDCLLLFL LASAVAAMEE TLMDTRTATA ELGWTANPAS GWEEVSGYDE
60 70 80 90 100
NLNTIRTYQV CNVFEPNQNN WLLTTFINRR GAHRIYTEMR FTVRDCSSLP
110 120 130 140 150
NVPGSCKETF NLYYYETDSV IATKKSAFWS EAPYLKVDTI AADESFSQVD
160 170 180 190 200
FGGRLMKVNT EVRSFGPLTR NGFYLAFQDY GACMSLLSVR VFFKKCPSIV
210 220 230 240 250
QNFAVFPETM TGAESTSLVI ARGTCIPNAE EVDVPIKLYC NGDGEWMVPI
260 270 280 290 300
GRCTCKPGYE PENSVACKAC PAGTFKASQE AEGCSHCPSN SRSPSEASPI
310 320 330 340 350
CTCRTGYYRA DFDPPEVACT SVPSGPRNVI SIVNETSIIL EWHPPRETGG
360 370 380 390 400
RDDVTYNIIC KKCRADRRSC SRCDDNVEFV PRQLGLTECR VSISSLWAHT
410 420 430 440 450
PYTFDIQAIN GVSSKSPFPP QHVSVNITTN QAAPSTVPIM HQVSATMRSI
460 470 480 490 500
TLSWPQPEQP NGIILDYEIR YYEKEHNEFN SSMARSQTNT ARIDGLRPGM
510 520 530 540 550
VYVVQVRART VAGYGKFSGK MCFQTLTDDD YKSELREQLP LIAGSAAAGV
560 570 580 590 600
VFVVSLVAIS IVCSRKRAYS KEAAYSDKLQ HYSTGRGSPG MKIYIDPFTY
610 620 630 640 650
EDPNEAVREF AKEIDVSFVK IEEVIGAGEF GEVYKGRLKL PGKREIYVAI
660 670 680 690 700
KTLKAGYSEK QRRDFLSEAS IMGQFDHPNI IRLEGVVTKS RPVMIITEFM
710 720 730 740 750
ENGALDSFLR QNDGQFTVIQ LVGMLRGIAA GMKYLSEMNY VHRDLAARNI
760 770 780 790 800
LVNSNLVCKV SDFGLSRYLQ DDTSDPTYTS SLGGKIPVRW TAPEAIAYRK
810 820 830 840 850
FTSASDVWSY GIVMWEVMSF GERPYWDMSN QDVINAIEQD YRLPPPMDCP
860 870 880 890 900
AALHQLMLDC WQKDRNSRPR FAEIVNTLDK MIRNPASLKT VATITAVPSQ
910 920 930 940 950
PLLDRSIPDF TAFTTVDDWL SAIKMVQYRD SFLTAGFTSL QLVTQMTSED
960 970 980
LLRIGVTLAG HQKKILSSIH SMRVQMNQSP SVMA
Length:984
Mass (Da):109,881
Last modified:March 1, 2003 - v1
Checksum:iE967019C82AA400A
GO
Isoform 2 (identifier: Q8CBF3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     588-628: Missing.

Show »
Length:943
Mass (Da):105,294
Checksum:iEF28BF1D7FE097C9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti72L → Q in BAE22386 (PubMed:16141072).Curated1
Sequence conflicti187L → P in BAE22386 (PubMed:16141072).Curated1
Sequence conflicti194K → I in AAH57301 (PubMed:15489334).Curated1
Sequence conflicti641P → Q in BAC29348 (PubMed:16141072).Curated1
Sequence conflicti678P → R in AAH57301 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_021595588 – 628Missing in isoform 2. 1 PublicationAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK036148 mRNA Translation: BAC29320.1
AK036211 mRNA Translation: BAC29348.1
AK135018 mRNA Translation: BAE22386.1
CT025594
, AC109247, AC132684, AC156635 Genomic DNA Translation: CAM23741.1
BC057301 mRNA Translation: AAH57301.1
CCDSiCCDS40742.1 [Q8CBF3-1]
CCDS52901.1 [Q8CBF3-2]
RefSeqiNP_001161768.1, NM_001168296.1 [Q8CBF3-2]
NP_775623.3, NM_173447.3 [Q8CBF3-1]
UniGeneiMm.22897

Genome annotation databases

EnsembliENSMUST00000035129; ENSMUSP00000035129; ENSMUSG00000032537 [Q8CBF3-1]
ENSMUST00000085169; ENSMUSP00000082261; ENSMUSG00000032537 [Q8CBF3-2]
GeneIDi270190
KEGGimmu:270190
UCSCiuc009rfn.2 mouse [Q8CBF3-1]
uc012gzg.1 mouse [Q8CBF3-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiEPHB1_MOUSE
AccessioniPrimary (citable) accession number: Q8CBF3
Secondary accession number(s): B1B1C2
, Q3UY27, Q6PG23, Q8CBE2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: March 1, 2003
Last modified: May 23, 2018
This is version 139 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families
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