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Reviewed, UniProtKB/Swiss-Prot P54762 (EPHB1_HUMAN)

Last modified July 7, 2009. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Ephrin type-B receptor 1
    EC=2.7.10.1
Alternative name(s):
    Tyrosine-protein kinase receptor EPH-2
      Short name=NET
    HEK6
    ELK
Gene names
Name: EPHB1
Synonyms: EPHT2, NET
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length984 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Receptor for members of the ephrin-B family. Binds to ephrin-B1, -B2 and -B3. May be involved in cell-cell interactions in the nervous system.

Catalytic activity

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

Subunit structure

The ligand-activated form interacts with GRB2, GRB10 and NCK through their respective SH2 domains. The GRB10 SH2 domain binds EPHB1 through Tyr-928, while GRB2 binds residues within the catalytic domain. Interacts with EPHB6. The NCK SH2 domain binds EPHB1 through Tyr-594. Interacts with PRKCABP By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Preferentially expressed in brain.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.

Contains 2 fibronectin type-III domains.

Contains 1 protein kinase domain.

Contains 1 SAM (sterile alpha motif) domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GRB10Q133221EBI-80252,EBI-80275
GRB2P629931EBI-80252,EBI-401755

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P54762-1)

Also known as: EPHB1A;

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.
Isoform 2 (identifier: P54762-2)

Also known as: EPH1B1B;

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: MALDYLLLLLLASAVAAMEETLMDTRT → METRERKKSRAEFGTR
Isoform 3 (identifier: P54762-3)

Also known as: EPHB1C;

The sequence of this isoform differs from the canonical sequence as follows:
     642-682: Missing.
Isoform 4 (identifier: P54762-4)

Also known as: EPHB1D;

The sequence of this isoform differs from the canonical sequence as follows:
     617-984: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Ref.3
Chain18 – 984967Ephrin type-B receptor 1
PRO_0000016824

Regions

Topological domain18 – 540523Extracellular Potential
Transmembrane541 – 56323 Potential
Topological domain564 – 984421Cytoplasmic Potential
Domain323 – 424102Fibronectin type-III 1
Domain430 – 52596Fibronectin type-III 2
Domain619 – 882264Protein kinase
Domain911 – 97565SAM
Nucleotide binding625 – 6339ATP By similarity
Motif982 – 9843PDZ-binding Potential
Compositional bias183 – 319137Cys-rich

Sites

Active site7441Proton acceptor By similarity
Binding site6511ATP By similarity

Amino acid modifications

Modified residue9281Phosphotyrosine Ref.4
Modified residue9681Phosphoserine Ref.6
Glycosylation3341N-linked (GlcNAc...) Potential
Glycosylation4261N-linked (GlcNAc...) Potential
Glycosylation4801N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 2727MALDY…MDTRT → METRERKKSRAEFGTR in isoform 2.
VSP_003013
Alternative sequence617 – 984368Missing in isoform 4.
VSP_003014
Alternative sequence642 – 68241Missing in isoform 3.
VSP_003015
Natural variant181M → V Ref.8
VAR_042165
Natural variant871T → S: dbSNP rs1042794.
VAR_011801
Natural variant1521G → R: dbSNP rs1042793.
VAR_011802
Natural variant3671R → G: dbSNP rs1042789.
VAR_011803
Natural variant3871T → M Ref.8
VAR_042166
Natural variant4851R → S: dbSNP rs1042788.
VAR_011804
Natural variant7071S → T in an ovarian undifferentiated carcinoma sample; somatic mutation. Ref.8
VAR_042167
Natural variant7191I → V in a gastric adenocarcinoma sample; somatic mutation. Ref.8
VAR_042168
Natural variant7431R → Q in a gastric adenocarcinoma sample; somatic mutation. Ref.8
VAR_042169
Natural variant8471M → T: dbSNP rs1042785.
VAR_011805
Natural variant9121A → T Ref.8
VAR_042170
Natural variant9811T → M Ref.8
VAR_042171

Experimental info

Mutagenesis9281Y → F: Disrupts binding with the GRB10 SH2 domain, providing evidence for phosphorylation. Ref.4
Sequence conflict121A → E in AAD02030. Ref.2
Sequence conflict121A → E in AAB94627. Ref.2
Sequence conflict121A → E in AAB94628. Ref.2
Sequence conflict1851S → I in AAD02030. Ref.2
Sequence conflict1851S → I in AAD02031. Ref.2
Sequence conflict1851S → I in AAB94627. Ref.2
Sequence conflict1851S → I in AAB94628. Ref.2
Sequence conflict2741T → R in AAD02030. Ref.2
Sequence conflict2741T → R in AAD02031. Ref.2
Sequence conflict2741T → R in AAB94627. Ref.2
Sequence conflict2741T → R in AAB94628. Ref.2
Sequence conflict3361T → S in AAD02030. Ref.2
Sequence conflict3361T → S in AAD02031. Ref.2
Sequence conflict3361T → S in AAB94627. Ref.2
Sequence conflict3361T → S in AAB94628. Ref.2
Sequence conflict8131V → H in AAD02030. Ref.2
Sequence conflict8131V → H in AAB94627. Ref.2
Sequence conflict8191S → Y in AAD02030. Ref.2
Sequence conflict8191S → Y in AAB94627. Ref.2
Sequence conflict9731R → W in AAD02030. Ref.2
Sequence conflict9731R → W in AAD02031. Ref.2
Sequence conflict9731R → W in AAB94627. Ref.2

Secondary structure

........................... 984
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (EPHB1A) [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 8044160E24E93A92

FASTA984109,885
        10         20         30         40         50         60 
MALDYLLLLL 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 GRCTCKPGYE PENSVACKAC PAGTFKASQE AEGCSHCPSN SRSPAEASPI 

       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 GMKYLAEMNY 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 LLRIGITLAG 

       970        980 
HQKKILNSIH SMRVQISQSP TAMA 

« Hide

Isoform 2 (EPH1B1B).

Checksum: AD6BBC76C9487EC9
Show »

FASTA973108,898
Isoform 3 (EPHB1C).

Checksum: 153B7903D9A7D48C
Show »

FASTA943105,136
Isoform 4 (EPHB1D).

Checksum: 681E7EBB892759E7
Show »

FASTA61668,432

References

« Hide 'large scale' references
[1]"cDNA cloning, molecular characterization, and chromosomal localization of NET(EPHT2), a human EPH-related receptor protein-tyrosine kinase gene preferentially expressed in brain."
Tang X.X., Biegel J.A., Nycum L.M., Yoshioka A., Brodeur G.M., Pleasure D.E., Ikegaki N.
Genomics 29:426-437(1995) [PubMed: 8666391] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal brain.
[2]Stein E., Schoecklmann H.O., Daniel T.O.
Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
Tissue: Kidney.
[3]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract]
Cited for: PROTEIN SEQUENCE OF 18-32.
[4]"Ligand activation of ELK receptor tyrosine kinase promotes its association with Grb10 and Grb2 in vascular endothelial cells."
Stein E., Cerretti D.P., Daniel T.O.
J. Biol. Chem. 271:23588-23593(1996) [PubMed: 8798570] [Abstract]
Cited for: INTERACTION WITH GRB2 AND GRB10, MUTAGENESIS OF TYR-928, PHOSPHORYLATION AT TYR-928.
[5]"The kinase-null EphB6 receptor undergoes transphosphorylation in a complex with EphB1."
Freywald A., Sharfe N., Roifman C.M.
J. Biol. Chem. 277:3823-3828(2002) [PubMed: 11713248] [Abstract]
Cited for: INTERACTION WITH EPHB6.
[6]"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column."
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.
Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-968, MASS SPECTROMETRY.
[7]"Solution structure of the C-terminal SAM-domain of mouse ephrin type-B receptor 1 precursor (EC 2.7.1.112)."
RIKEN structural genomics initiative (RSGI)
Submitted (JUL-2007) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 899-984.
[8]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed: 17344846] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-18; MET-387; THR-707; VAL-719; GLN-743; THR-912 AND MET-981.
+Additional computationally mapped references.

Cross-references

Sequence databases

L40636 mRNA. Translation: AAB08520.1.
AF037331 mRNA. Translation: AAD02030.1.
AF037332 mRNA. Translation: AAD02031.1.
AF037333 mRNA. Translation: AAB94627.1.
AF037334 mRNA. Translation: AAB94628.1.
IPIIPI00008315.
IPI00219244.
IPI00219245.
IPI00334334.
RefSeqNP_004432.1.
UniGeneHs.116092

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
2DJSNMR-A434-528[»]
2EAONMR-A899-984[»]
SMRP54762. Positions 18-197, 592-889.
ModBaseSearch...

Protein-protein interaction databases

IntActP54762. 7 interactions.

PTM databases

PhosphoSiteP54762.

Proteomic databases

PRIDEP54762.

Genome annotation databases

EnsemblENSG00000154928. Homo sapiens. [Contig view]
GeneID2047.
KEGGhsa:2047.
UCSCuc003eqt.1. human.

Organism-specific databases

GeneCardsGC03P135996.
H-InvDBHIX0021414.
HIX0043235.
HGNCHGNC:3392. EPHB1.
MIM600600. gene.
PharmGKBPA27824.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP54762.

Enzyme and pathway databases

BRENDA2.7.10.1. 247.
Pathway_Interaction_DBephbfwdpathway. EPHB forward signaling.
ephrinbrevpathway. Ephrin B reverse signaling.
ephrinb_ephbpathway. EphrinB-EPHB pathway.

Gene expression databases

ArrayExpressP54762.
BgeeP54762.
CleanExHS_EPHB1.

Family and domain databases

InterProIPR013032. EGF-like_reg_CS.
IPR001090. Ephrin_rcpt_lig-bd.
IPR008957. Fibronectin_typ-III-like_fold.
IPR003961. FN_III.
IPR003962. FnIII_subd.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM_type.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
IPR016257. TyrPK_ephrin_receptor.
IPR001426. YKase_receptorV_CS.
[Graphical view]
Gene3DG3DSA:2.60.40.30. FN_III-like. 2 hits.
G3DSA:1.10.150.50. SAM_type. 1 hit.
PfamPF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PIRSFPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSPR00014. FNTYPEIII.
PR00109. TYRKINASE.
ProDomPD001495. Ephrin_receptor. 1 hit.
PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
PROSITEPS01186. EGF_2. 1 hit. Uncertain.
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]
ProtoNetSearch...

Other Resources

NextBio8321.
PMAP-CutDBP54762.
SOURCESearch...

Entry information

Entry nameEPHB1_HUMAN
AccessionPrimary (citable) accession number: P54762
Secondary accession number(s): O43569, O95142, O95143
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 7, 2009
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents