Reviewed, UniProtKB/Swiss-Prot P54753 (EPHB3_HUMAN)

Names and origin

Protein names

Recommended name:
    Ephrin type-B receptor 3
    EC=2.7.10.1
Alternative name(s):
    EPH-like kinase 2
      Short name=EK2
      Short name=hEK2
    Tyrosine-protein kinase TYRO6

Gene names

Name:	EPHB3
Synonyms:	ETK2, HEK2, TYRO6

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	998 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 for members of the ephrin-B family. Binds to ephrin-B1 and -B2.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Ubiquitous.
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.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro transmembrane receptor protein tyrosine kinase signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ephrin receptor activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 33	33	Potential
	Chain	34 – 998	965	Ephrin type-B receptor 3		PRO_0000016831
Regions
	Topological domain	34 – 559	526	Extracellular Potential
	Transmembrane	560 – 580	21	Potential
	Topological domain	581 – 998	418	Cytoplasmic Potential
	Domain	340 – 443	104	Fibronectin type-III 1
	Domain	453 – 544	92	Fibronectin type-III 2
	Domain	633 – 896	264	Protein kinase
	Domain	925 – 989	65	SAM
	Nucleotide binding	639 – 647	9	ATP By similarity
	Motif	996 – 998	3	PDZ-binding Potential
	Compositional bias	199 – 336	138	Cys-rich
Sites
	Active site	758	1	Proton acceptor By similarity
	Binding site	665	1	ATP By similarity
Amino acid modifications
	Modified residue	600	1	Phosphotyrosine Ref.3
	Modified residue	608	1	Phosphotyrosine
	Modified residue	614	1	Phosphotyrosine
	Modified residue	792	1	Phosphotyrosine Ref.4
	Modified residue	971	1	Phosphothreonine
	Glycosylation	351	1	N-linked (GlcNAc...) Potential
	Glycosylation	445	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	168	1	R → L in a lung small cell carcinoma sample; somatic mutation. Ref.6		VAR_042176
	Natural variant	440	1	R → C: dbSNP rs56029711. Ref.6		VAR_042177
	Natural variant	579	1	I → V: dbSNP rs56103851. Ref.6		VAR_042178
	Natural variant	601	1	I → L: dbSNP rs56129875. Ref.6		VAR_042179
	Natural variant	724	1	R → W in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.6		VAR_042180
Experimental info
	Sequence conflict	367	1	G → V in CAA53021. Ref.1
	Sequence conflict	406 – 408	3	TER → SEP in CAA53021. Ref.1
	Sequence conflict	412	1	I → T in CAA53021. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P54753-1 [UniParc]. Last modified September 27, 2005. Version 2. Checksum: 9B65A4EF58B27407	FASTA	998	110,330
	10 20 30 40 50 60 MARARPPPPP SPPPGLLPLL PPLLLLPLLL LPAGCRALEE TLMDTKWVTS ELAWTSHPES 70 80 90 100 110 120 GWEEVSGYDE AMNPIRTYQV CNVRESSQNN WLRTGFIWRR DVQRVYVELK FTVRDCNSIP 130 140 150 160 170 180 NIPGSCKETF NLFYYEADSD VASASSPFWM ENPYVKVDTI APDESFSRLD AGRVNTKVRS 190 200 210 220 230 240 FGPLSKAGFY LAFQDQGACM SLISVRAFYK KCASTTAGFA LFPETLTGAE PTSLVIAPGT 250 260 270 280 290 300 CIPNAVEVSV PLKLYCNGDG EWMVPVGACT CATGHEPAAK ESQCRPCPPG SYKAKQGEGP 310 320 330 340 350 360 CLPCPPNSRT TSPAASICTC HNNFYRADSD SADSACTTVP SPPRGVISNV NETSLILEWS 370 380 390 400 410 420 EPRDLGGRDD LLYNVICKKC HGAGGASACS RCDDNVEFVP RQLGLTERRV HISHLLAHTR 430 440 450 460 470 480 YTFEVQAVNG VSGKSPLPPR YAAVNITTNQ AAPSEVPTLR LHSSSGSSLT LSWAPPERPN 490 500 510 520 530 540 GVILDYEMKY FEKSEGIAST VTSQMNSVQL DGLRPDARYV VQVRARTVAG YGQYSRPAEF 550 560 570 580 590 600 ETTSERGSGA QQLQEQLPLI VGSATAGLVF VVAVVVIAIV CLRKQRHGSD SEYTEKLQQY 610 620 630 640 650 660 IAPGMKVYID PFTYEDPNEA VREFAKEIDV SCVKIEEVIG AGEFGEVCRG RLKQPGRREV 670 680 690 700 710 720 FVAIKTLKVG YTERQRRDFL SEASIMGQFD HPNIIRLEGV VTKSRPVMIL TEFMENCALD 730 740 750 760 770 780 SFLRLNDGQF TVIQLVGMLR GIAAGMKYLS EMNYVHRDLA ARNILVNSNL VCKVSDFGLS 790 800 810 820 830 840 RFLEDDPSDP TYTSSLGGKI PIRWTAPEAI AYRKFTSASD VWSYGIVMWE VMSYGERPYW 850 860 870 880 890 900 DMSNQDVINA VEQDYRLPPP MDCPTALHQL MLDCWVRDRN LRPKFSQIVN TLDKLIRNAA 910 920 930 940 950 960 SLKVIASAQS GMSQPLLDRT VPDYTTFTTV GDWLDAIKMG RYKESFVSAG FASFDLVAQM 970 980 990 TAEDLLRIGV TLAGHQKKIL SSIQDMRLQM NQTLPVQV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PCR mediated detection of a new human receptor-tyrosine-kinase, HEK 2." Boehme B., Holtrich U., Wolf G., Luzius H., Grzeschik K.-H., Strebhardt K., Ruebsamen-Waigmann H. Oncogene 8:2857-2862(1993) [PubMed: 8397371] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Embryo.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Uterus.
[3]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-600, MASS SPECTROMETRY.
[4]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-792, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[5]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-608; TYR-614; TYR-792 AND THR-971, MASS SPECTROMETRY.
[6]	"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. , 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] LEU-168; CYS-440; VAL-579; LEU-601 AND TRP-724.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X75208 mRNA. Translation: CAA53021.1. BC052968 mRNA. Translation: AAH52968.1.
IPI	IPI00289329.
PIR	S37627.
RefSeq	NP_004434.2.
UniGene	Hs.2913
3D structure databases
SMR	P54753. Positions 38-212, 335-449, 450-546, 606-903, 914-993.
ModBase	Search...
Protein-protein interaction databases
STRING	P54753.
PTM databases
PhosphoSite	P54753.
Proteomic databases
PRIDE	P54753.
Genome annotation databases
Ensembl	ENST00000330394; ENSP00000332118; ENSG00000182580; Homo sapiens. [Genome view]
GeneID	2049.
KEGG	hsa:2049.
UCSC	uc003foz.1. human.
Organism-specific databases
CTD	2049.
GeneCards	GC03P185762.
H-InvDB	HIX0024492.
HGNC	HGNC:3394. EPHB3.
HPA	HPA007698. HPA008184.
MIM	601839. gene.
PharmGKB	PA27826.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18794.
HOGENOM	HBG755340.
HOVERGEN	P54753.
InParanoid	P54753.
OMA	FASFDLV.
OrthoDB	EOG9HB15Q.
PhylomeDB	P54753.
Enzyme and pathway databases
BRENDA	2.7.10.1. 247.
Pathway_Interaction_DB	ephbfwdpathway. EPHB forward signaling. ephrinb_ephbpathway. EphrinB-EPHB pathway.
Gene expression databases
ArrayExpress	P54753.
Bgee	P54753.
CleanEx	HS_EPHB3.
Genevestigator	P54753.
GermOnline	ENSG00000182580. Homo sapiens.
Family and domain databases
InterPro	IPR001090. Ephrin_rcpt_lig-bd. IPR008957. Fibronectin_typ-III-like_fold. IPR003961. FN_III. IPR003962. FnIII_subd. IPR008979. Galactose-bd-like. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001660. SAM. IPR010993. SAM_homology. IPR013761. SAM_type. IPR021129. SAM_type1. IPR020635. Tyr_Pkinase_cat_dom. IPR020685. Tyr_prot_kinase. IPR008266. Tyr_prot_kinase_AS. IPR016257. Tyr_prot_kinase_ephrin_rcpt. IPR001426. Tyr_prot_kinase_rcpt_V_CS. [Graphical view]
Gene3D	G3DSA:2.60.40.30. FN_III-like. 2 hits. G3DSA:1.10.150.50. SAM_type. 1 hit.
PANTHER	PTHR23256. Tyr_prot_kinase. 1 hit.
Pfam	PF01404. Ephrin_lbd. 1 hit. PF00041. fn3. 2 hits. PF00536. SAM_1. 1 hit. [Graphical view]
PIRSF	PIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTS	PR00014. FNTYPEIII.
SMART	SM00615. EPH_lbd. 1 hit. SM00060. FN3. 2 hits. SM00454. SAM. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
PROSITE	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 Resources
NextBio	8331.
SOURCE	Search...

Entry information

Entry name

EPHB3_HUMAN

Accession

Primary (citable) accession number: P54753
Secondary accession number(s): Q7Z740

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	September 27, 2005
Last modified:	February 9, 2010
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.