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Protein

Ephrin type-B receptor 2

Gene

Ephb2

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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor.7 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei653ATPPROSITE-ProRule annotation1
Active sitei746Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi627 – 635ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processNeurogenesis
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 2Curated (EC:2.7.10.1)
Alternative name(s):
Neural kinase
Nuk receptor tyrosine kinase
Tyrosine-protein kinase receptor EPH-3
Tyrosine-protein kinase receptor SEK-3
Gene namesi
Name:Ephb2Imported
Synonyms:Epth3, Nuk1 Publication, Sek3Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:99611 Ephb2

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 domaini19 – 543ExtracellularSequence analysisAdd BLAST525
Transmembranei544 – 564HelicalSequence analysisAdd BLAST21
Topological domaini565 – 986CytoplasmicSequence analysisAdd BLAST422

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice are long-lived and fertile. They display strain-specific circling behavior, are hyperactive and exhibit rapid head bobbing and twirled excessively when picked-up by the tail. This is probably due to abnormal vestibular function.2 Publications

Chemistry databases

ChEMBLiCHEMBL5961
GuidetoPHARMACOLOGYi1831

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000001682819 – 986Ephrin type-B receptor 2Sequence analysisAdd BLAST968

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi62 ↔ 1841 Publication
Disulfide bondi97 ↔ 1071 Publication
Glycosylationi265N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi336N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi428N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi482N-linked (GlcNAc...) asparagine1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP54763
PaxDbiP54763
PRIDEiP54763

PTM databases

iPTMnetiP54763
PhosphoSitePlusiP54763
SwissPalmiP54763

Expressioni

Tissue specificityi

Expressed in the epithelial dark cells of the inner ear. Expressed in the region of the proximal tubules of the kidney nephron. Expressed in myogenic progenitor cells (PubMed:27446912).2 Publications

Developmental stagei

Highly expressed in ventral cells of the neural tube and within axons of the peripheral nervous system during development. Expressed in the vestibulo-acoustic system and hindbrain as early as E11.5. Detected in the spinal cord at E12. Expressed in cells of the developing outer retina. Also expressed in mesenchyme adjacent to vessels. In myogenic progenitor cells, highly expressed during early development (E11.5) and progressively repressed as developments proceeds (PubMed:27446912).5 Publications

Gene expression databases

BgeeiENSMUSG00000028664 Expressed in 302 organ(s), highest expression level in floor plate of midbrain
CleanExiMM_EPHB2
ExpressionAtlasiP54763 baseline and differential

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 (via PDZ-binding motif) with GRIP1 and PICK1 (via PDZ domain) (By similarity). Interacts with ARHGEF15; mediates ARHGEF15 phosphorylation, ubiquitination and degradation by the proteasome. Interacts with AQP1; involved in endolymph production in the inner ear.By similarity5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

CORUMiP54763
DIPiDIP-34917N
IntActiP54763, 13 interactors
MINTiP54763
STRINGi10090.ENSMUSP00000101471

Chemistry databases

BindingDBiP54763

Structurei

Secondary structure

1986
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP54763
SMRiP54763
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP54763

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 202Eph LBDPROSITE-ProRule annotationAdd BLAST183
Domaini324 – 434Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST111
Domaini435 – 530Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST96
Domaini621 – 884Protein kinasePROSITE-ProRule annotationAdd BLAST264
Domaini913 – 977SAMPROSITE-ProRule annotationAdd BLAST65

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi984 – 986PDZ-binding3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi184 – 321Cys-richAdd BLAST138

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
GeneTreeiENSGT00930000150909
HOGENOMiHOG000233856
HOVERGENiHBG062180
InParanoidiP54763
KOiK05111
OMAiVNNLDKM
OrthoDBiEOG091G00W0
TreeFamiTF315608

Family and domain databases

CDDicd10477 EphR_LBD_B2, 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
IPR034238 EphB2_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
PF07699 Ephrin_rec_like, 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, 1 hit
PROSITEiView protein in PROSITE
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 (3+)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 3Curated (identifier: P54763-3) [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
MAVRRLGAAL LLLPLLAAVE ETLMDSTTAT AELGWMVHPP SGWEEVSGYD
60 70 80 90 100
ENMNTIRTYQ VCNVFESSQN NWLRTKFIRR RGAHRIHVEM KFSVRDCSSI
110 120 130 140 150
PSVPGSCKET FNLYYYEADF DLATKTFPNW MENPWVKVDT IAADESFSQV
160 170 180 190 200
DLGGRVMKIN TEVRSFGPVS RNGFYLAFQD YGGCMSLIAV RVFYRKCPRI
210 220 230 240 250
IQNGAIFQET LSGAESTSLV AARGSCIANA EEVDVPIKLY CNGDGEWLVP
260 270 280 290 300
IGRCMCKAGF EAVENGTVCR GCPSGTFKAN QGDEACTHCP INSRTTSEGA
310 320 330 340 350
TNCVCRNGYY RADLDPLDMP CTTIPSAPQA VISSVNETSL MLEWTPPRDS
360 370 380 390 400
GGREDLVYNI ICKSCGSGRG ACTRCGDNVQ YAPRQLGLTE PRIYISDLLA
410 420 430 440 450
HTQYTFEIQA VNGVTDQSPF SPQFASVNIT TNQAAPSAVS IMHQVSRTVD
460 470 480 490 500
SITLSWSQPD QPNGVILDYE LQYYEKELSE YNATAIKSPT NTVTVQGLKA
510 520 530 540 550
GAIYVFQVRA RTVAGYGRYS GKMYFQTMTE AEYQTSIKEK LPLIVGSSAA
560 570 580 590 600
GLVFLIAVVV IAIVCNRRGF ERADSEYTDK LQHYTSGHMT PGMKIYIDPF
610 620 630 640 650
TYEDPNEAVR EFAKEIDISC VKIEQVIGAG EFGEVCSGHL KLPGKREIFV
660 670 680 690 700
AIKTLKSGYT EKQRRDFLSE ASIMGQFDHP NVIHLEGVVT KSTPVMIITE
710 720 730 740 750
FMENGSLDSF LRQNDGQFTV IQLVGMLRGI AAGMKYLADM NYVHRDLAAR
760 770 780 790 800
NILVNSNLVC KVSDFGLSRF LEDDTSDPTY TSALGGKIPI RWTAPEAIQY
810 820 830 840 850
RKFTSASDVW SYGIVMWEVM SYGERPYWDM TNQDVINAIE QDYRLPPPMD
860 870 880 890 900
CPSALHQLML DCWQKDRNHR PKFGQIVNTL DKMIRNPNSL KAMAPLSSGI
910 920 930 940 950
NLPLLDRTIP DYTSFNTVDE WLEAIKMGQY KESFANAGFT SFDVVSQMMM
960 970 980
EDILRVGVTL AGHQKKILNS IQVMRAQMNQ IQSVEV
Length:986
Mass (Da):109,899
Last modified:October 14, 2015 - v3
Checksum:i92DB5234F18758A7
GO
Isoform 2Curated (identifier: P54763-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     566-566: N → NR

Note: No experimental confirmation available.
Show »
Length:987
Mass (Da):110,055
Checksum:iEE04E7A723307E4B
GO
Isoform 4Curated (identifier: P54763-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     476-476: K → KQ

Note: No experimental confirmation available.
Show »
Length:987
Mass (Da):110,027
Checksum:i586D4C475F42641F
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F6Q4H2F6Q4H2_MOUSE
Ephrin type-B receptor 2
Ephb2
276Annotation score:

Sequence cautioni

The sequence AAA72411 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH62924 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_057932476K → KQ in isoform 4. Curated1
Alternative sequenceiVSP_057933566N → NR in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL627214 Genomic DNA No translation available.
AL627345 Genomic DNA No translation available.
AL671173 Genomic DNA No translation available.
BC043088 mRNA Translation: AAH43088.2
BC062924 mRNA Translation: AAH62924.1 Different initiation.
L25890 mRNA Translation: AAA72411.1 Different initiation.
X76011 mRNA Translation: CAA53598.1
RefSeqiNP_001277682.1, NM_001290753.2 [P54763-4]
NP_034272.1, NM_010142.4 [P54763-3]
XP_006538594.1, XM_006538531.3 [P54763-2]
UniGeneiMm.250981

Genome annotation databases

EnsembliENSMUST00000059287; ENSMUSP00000058135; ENSMUSG00000028664 [P54763-4]
ENSMUST00000105845; ENSMUSP00000101471; ENSMUSG00000028664 [P54763-3]
ENSMUST00000105846; ENSMUSP00000101472; ENSMUSG00000028664 [P54763-2]
GeneIDi13844
KEGGimmu:13844
UCSCiuc008vim.2 mouse
uc008vin.2 mouse

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL627214 Genomic DNA No translation available.
AL627345 Genomic DNA No translation available.
AL671173 Genomic DNA No translation available.
BC043088 mRNA Translation: AAH43088.2
BC062924 mRNA Translation: AAH62924.1 Different initiation.
L25890 mRNA Translation: AAA72411.1 Different initiation.
X76011 mRNA Translation: CAA53598.1
RefSeqiNP_001277682.1, NM_001290753.2 [P54763-4]
NP_034272.1, NM_010142.4 [P54763-3]
XP_006538594.1, XM_006538531.3 [P54763-2]
UniGeneiMm.250981

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JPAX-ray1.91A/B587-898[»]
1KGYX-ray2.70A/B/C/D20-199[»]
1NUKX-ray2.90A20-202[»]
1SHWX-ray2.20B19-199[»]
2HENX-ray2.60A/B/C/D614-898[»]
3ETPX-ray2.00A20-199[»]
ProteinModelPortaliP54763
SMRiP54763
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

CORUMiP54763
DIPiDIP-34917N
IntActiP54763, 13 interactors
MINTiP54763
STRINGi10090.ENSMUSP00000101471

Chemistry databases

BindingDBiP54763
ChEMBLiCHEMBL5961
GuidetoPHARMACOLOGYi1831

PTM databases

iPTMnetiP54763
PhosphoSitePlusiP54763
SwissPalmiP54763

Proteomic databases

MaxQBiP54763
PaxDbiP54763
PRIDEiP54763

Protocols and materials databases

DNASUi13844
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000059287; ENSMUSP00000058135; ENSMUSG00000028664 [P54763-4]
ENSMUST00000105845; ENSMUSP00000101471; ENSMUSG00000028664 [P54763-3]
ENSMUST00000105846; ENSMUSP00000101472; ENSMUSG00000028664 [P54763-2]
GeneIDi13844
KEGGimmu:13844
UCSCiuc008vim.2 mouse
uc008vin.2 mouse

Organism-specific databases

CTDi2048
MGIiMGI:99611 Ephb2

Phylogenomic databases

eggNOGiKOG0196 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00930000150909
HOGENOMiHOG000233856
HOVERGENiHBG062180
InParanoidiP54763
KOiK05111
OMAiVNNLDKM
OrthoDBiEOG091G00W0
TreeFamiTF315608

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

Miscellaneous databases

ChiTaRSiEphb2 mouse
EvolutionaryTraceiP54763
PROiPR:P54763
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028664 Expressed in 302 organ(s), highest expression level in floor plate of midbrain
CleanExiMM_EPHB2
ExpressionAtlasiP54763 baseline and differential

Family and domain databases

CDDicd10477 EphR_LBD_B2, 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
IPR034238 EphB2_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
PF07699 Ephrin_rec_like, 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, 1 hit
PROSITEiView protein in PROSITE
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
ProtoNetiSearch...

Entry informationi

Entry nameiEPHB2_MOUSE
AccessioniPrimary (citable) accession number: P54763
Secondary accession number(s): A3KG00
, A3KG01, A3KG02, A3KG89, A3KG90, Q62213, Q6GTQ7, Q6P5F1, Q9QVY4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 14, 2015
Last modified: November 7, 2018
This is version 194 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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