P29323 (EPHB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ephrin type-B receptor 2
EC=2.7.10.1

Alternative name(s):
Developmentally-regulated Eph-related tyrosine kinase
ELK-related tyrosine kinase
EPH tyrosine kinase 3
EPH-like kinase 5
Short name=EK5
Short name=hEK5
Renal carcinoma antigen NY-REN-47
Tyrosine-protein kinase TYRO5
Tyrosine-protein kinase receptor EPH-3

Gene names

Name:	EPHB2
Synonyms:	DRT, EPHT3, EPTH3, ERK, HEK5, TYRO5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1055 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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobs 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. Beside 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. Ref.19
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 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.
Subcellular location	Cell membrane; Single-pass type I membrane protein. Cell projection › axon By similarity. Cell projection › dendrite By similarity.
Tissue specificity	Brain, heart, lung, kidney, placenta, pancreas, liver and skeletal muscle. Preferentially expressed in fetal brain.
Involvement in disease	Defects in EPHB2 may be a cause of susceptibility to prostate cancer (PC) [MIM:176807]. It is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Note=EPHB2 mutations have been found in a prostate cancer cell line derived from a brain metastasis.
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	Neurogenesis
Cellular component	Cell membrane Cell projection Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Tumor suppressor
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB axonal fasciculation Inferred from sequence or structural similarity. Source: UniProtKB commissural neuron axon guidance Inferred from sequence or structural similarity. Source: UniProtKB corpus callosum development Inferred from sequence or structural similarity. Source: UniProtKB dendritic spine morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB inner ear morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB palate development Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of synapse assembly Inferred from sequence or structural similarity. Source: UniProtKB regulation of body fluid levels Inferred from sequence or structural similarity. Source: UniProtKB urogenital system development Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	axon Inferred from sequence or structural similarity. Source: UniProtKB dendrite Inferred from sequence or structural similarity. Source: UniProtKB integral to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW transmembrane-ephrin receptor activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P29323-1)

Also known as: EPHB2v; Long;

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: P29323-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     986-986: G → V
     987-1055: Missing.

Isoform 3 (identifier: P29323-3)

The sequence of this isoform differs from the canonical sequence as follows:
     568-568: R → RR
     986-986: G → V
     987-1055: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 1055

1037

Ephrin type-B receptor 2

PRO_0000016827

Regions

Topological domain

19 – 543

525

Extracellular Potential

Transmembrane

544 – 564

21

Helical; Potential

Topological domain

565 – 1055

491

Cytoplasmic Potential

Domain

20 – 202

183

Eph LBD

Domain

325 – 426

102

Fibronectin type-III 1

Domain

432 – 527

96

Fibronectin type-III 2

Domain

621 – 884

264

Protein kinase

Domain

913 – 977

65

SAM

Nucleotide binding

627 – 635

9

ATP By similarity

Motif

984 – 986

3

PDZ-binding (in isoform 2) Potential

Compositional bias

184 – 324

141

Cys-rich

Sites

Active site

746

1

Proton acceptor By similarity

Binding site

653

1

ATP By similarity

Amino acid modifications

Modified residue

148

1

Phosphoserine Ref.16

Modified residue

596

1

Phosphotyrosine Ref.11 Ref.13 Ref.16

Modified residue

602

1

Phosphotyrosine Ref.11 Ref.15 Ref.16

Modified residue

775

1

Phosphothreonine Ref.12 Ref.16

Modified residue

776

1

Phosphoserine Ref.14 Ref.16

Modified residue

779

1

Phosphothreonine Ref.16

Modified residue

780

1

Phosphotyrosine Ref.14 Ref.15 Ref.16

Modified residue

897

1

Phosphoserine Ref.16

Modified residue

983

1

Phosphoserine Ref.16

Glycosylation

265

1

N-linked (GlcNAc...) Potential

Glycosylation

336

1

N-linked (GlcNAc...) Potential

Glycosylation

428

1

N-linked (GlcNAc...) Potential

Glycosylation

482

1

N-linked (GlcNAc...) Potential

Disulfide bond

62 ↔ 184

Ref.18

Disulfide bond

97 ↔ 107

Ref.18

Natural variations

Alternative sequence

568

1

R → RR in isoform 3.

VSP_015713

Alternative sequence

986

1

G → V in isoform 2 and isoform 3.

VSP_003016

Alternative sequence

987 – 1055

69

Missing in isoform 2 and isoform 3.

VSP_003017

Natural variant

199

1

R → H in prostate cancer. Ref.19

VAR_032853

Natural variant

279

1

A → S in prostate cancer. Ref.19 Ref.20 Ref.21
Corresponds to variant rs35882952 [ dbSNP | Ensembl ].

VAR_032854

Natural variant

289

1

C → G. Ref.21

VAR_042172

Natural variant

361

1

I → V. Ref.21
Corresponds to variant rs56180036 [ dbSNP | Ensembl ].

VAR_042173

Natural variant

650

1

V → A in prostate cancer. Ref.20

VAR_032855

Natural variant

678

1

D → N. Ref.21
Corresponds to variant rs28936395 [ dbSNP | Ensembl ].

VAR_042174

Natural variant

679

1

H → N in prostate cancer. Ref.19

VAR_032856

Natural variant

844

1

R → W. Ref.21
Corresponds to variant rs55826626 [ dbSNP | Ensembl ].

VAR_042175

Natural variant

883

1

M → V in prostate cancer. Ref.20

VAR_032857

Natural variant

909

1

I → M in prostate cancer. Ref.19

VAR_032858

Experimental info

Sequence conflict

1 – 20

20

MALRR…LAAVE → MWVPVLALPVCTYA in BAA06506. Ref.1

Sequence conflict

154

1

G → D in BAA06506. Ref.1

Sequence conflict

476

1

K → KQ in BAA06506. Ref.1

Sequence conflict

495 – 496

2

Missing in AAA74244. Ref.5

Sequence conflict

532

1

E → D in BAA06506. Ref.1

Sequence conflict

589

1

M → I in AAA74244. Ref.5

Sequence conflict

671

1

A → R in BAA03537. Ref.7

Sequence conflict

788

1

I → F in AAA74244. Ref.5

Sequence conflict

853

1

S → A in BAA06506. Ref.1

Sequence conflict

853

1

S → A in BAA07073. Ref.6

Sequence conflict

853

1

S → A in BAA03537. Ref.7

Sequence conflict

923

1

E → K in BAA06506. Ref.1

Sequence conflict

923

1

E → K in BAA07073. Ref.6

Sequence conflict

923

1

E → K in BAA03537. Ref.7

Sequence conflict

958

1

V → L in AAA99310. Ref.2

Secondary structure

1

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1055

Helix Strand Turn

Details...

Beta strand

21 – 25

5

Helix

26 – 28

3

Beta strand

36 – 39

4

Beta strand

44 – 49

6

Beta strand

55 – 61

7

Beta strand

66 – 68

3

Beta strand

71 – 74

4

Beta strand

84 – 94

11

Helix

97 – 99

3

Beta strand

111 – 120

10

Beta strand

130 – 132

3

Beta strand

135 – 141

7

Beta strand

148 – 152

5

Beta strand

155 – 166

12

Beta strand

171 – 183

13

Beta strand

185 – 194

10

Helix

918 – 924

7

Helix

928 – 930

3

Helix

931 – 936

6

Helix

942 – 945

4

Helix

950 – 955

6

Helix

961 – 982

22

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (EPHB2v) (Long) [UniParc]. Last modified September 27, 2005. Version 5. Checksum: 4F8BFEDC45986483	FASTA	1,055	117,493
	10 20 30 40 50 60 MALRRLGAAL LLLPLLAAVE ETLMDSTTAT AELGWMVHPP SGWEEVSGYD ENMNTIRTYQ 70 80 90 100 110 120 VCNVFESSQN NWLRTKFIRR RGAHRIHVEM KFSVRDCSSI PSVPGSCKET FNLYYYEADF 130 140 150 160 170 180 DSATKTFPNW MENPWVKVDT IAADESFSQV DLGGRVMKIN TEVRSFGPVS RSGFYLAFQD 190 200 210 220 230 240 YGGCMSLIAV RVFYRKCPRI IQNGAIFQET LSGAESTSLV AARGSCIANA EEVDVPIKLY 250 260 270 280 290 300 CNGDGEWLVP IGRCMCKAGF EAVENGTVCR GCPSGTFKAN QGDEACTHCP INSRTTSEGA 310 320 330 340 350 360 TNCVCRNGYY RADLDPLDMP CTTIPSAPQA VISSVNETSL MLEWTPPRDS GGREDLVYNI 370 380 390 400 410 420 ICKSCGSGRG ACTRCGDNVQ YAPRQLGLTE PRIYISDLLA HTQYTFEIQA VNGVTDQSPF 430 440 450 460 470 480 SPQFASVNIT TNQAAPSAVS IMHQVSRTVD SITLSWSQPD QPNGVILDYE LQYYEKELSE 490 500 510 520 530 540 YNATAIKSPT NTVTVQGLKA GAIYVFQVRA RTVAGYGRYS GKMYFQTMTE AEYQTSIQEK 550 560 570 580 590 600 LPLIIGSSAA GLVFLIAVVV IAIVCNRRGF ERADSEYTDK LQHYTSGHMT PGMKIYIDPF 610 620 630 640 650 660 TYEDPNEAVR EFAKEIDISC VKIEQVIGAG EFGEVCSGHL KLPGKREIFV AIKTLKSGYT 670 680 690 700 710 720 EKQRRDFLSE ASIMGQFDHP NVIHLEGVVT KSTPVMIITE FMENGSLDSF LRQNDGQFTV 730 740 750 760 770 780 IQLVGMLRGI AAGMKYLADM NYVHRDLAAR NILVNSNLVC KVSDFGLSRF LEDDTSDPTY 790 800 810 820 830 840 TSALGGKIPI RWTAPEAIQY RKFTSASDVW SYGIVMWEVM SYGERPYWDM TNQDVINAIE 850 860 870 880 890 900 QDYRLPPPMD CPSALHQLML DCWQKDRNHR PKFGQIVNTL DKMIRNPNSL KAMAPLSSGI 910 920 930 940 950 960 NLPLLDRTIP DYTSFNTVDE WLEAIKMGQY KESFANAGFT SFDVVSQMMM EDILRVGVTL 970 980 990 1000 1010 1020 AGHQKKILNS IQVMRAQMNQ IQSVEGQPLA RRPRATGRTK RCQPRDVTKK TCNSNDGKKK 1030 1040 1050 GMGKKKTDPG RGREIQGIFF KEDSHKESND CSCGG
	Isoform 2 (Short) [UniParc]. Checksum: 4B9B532A48B754A6	FASTA	986	109,874
	10 20 30 40 50 60 MALRRLGAAL LLLPLLAAVE ETLMDSTTAT AELGWMVHPP SGWEEVSGYD ENMNTIRTYQ 70 80 90 100 110 120 VCNVFESSQN NWLRTKFIRR RGAHRIHVEM KFSVRDCSSI PSVPGSCKET FNLYYYEADF 130 140 150 160 170 180 DSATKTFPNW MENPWVKVDT IAADESFSQV DLGGRVMKIN TEVRSFGPVS RSGFYLAFQD 190 200 210 220 230 240 YGGCMSLIAV RVFYRKCPRI IQNGAIFQET LSGAESTSLV AARGSCIANA EEVDVPIKLY 250 260 270 280 290 300 CNGDGEWLVP IGRCMCKAGF EAVENGTVCR GCPSGTFKAN QGDEACTHCP INSRTTSEGA 310 320 330 340 350 360 TNCVCRNGYY RADLDPLDMP CTTIPSAPQA VISSVNETSL MLEWTPPRDS GGREDLVYNI 370 380 390 400 410 420 ICKSCGSGRG ACTRCGDNVQ YAPRQLGLTE PRIYISDLLA HTQYTFEIQA VNGVTDQSPF 430 440 450 460 470 480 SPQFASVNIT TNQAAPSAVS IMHQVSRTVD SITLSWSQPD QPNGVILDYE LQYYEKELSE 490 500 510 520 530 540 YNATAIKSPT NTVTVQGLKA GAIYVFQVRA RTVAGYGRYS GKMYFQTMTE AEYQTSIQEK 550 560 570 580 590 600 LPLIIGSSAA GLVFLIAVVV IAIVCNRRGF ERADSEYTDK LQHYTSGHMT PGMKIYIDPF 610 620 630 640 650 660 TYEDPNEAVR EFAKEIDISC VKIEQVIGAG EFGEVCSGHL KLPGKREIFV AIKTLKSGYT 670 680 690 700 710 720 EKQRRDFLSE ASIMGQFDHP NVIHLEGVVT KSTPVMIITE FMENGSLDSF LRQNDGQFTV 730 740 750 760 770 780 IQLVGMLRGI AAGMKYLADM NYVHRDLAAR NILVNSNLVC KVSDFGLSRF LEDDTSDPTY 790 800 810 820 830 840 TSALGGKIPI RWTAPEAIQY RKFTSASDVW SYGIVMWEVM SYGERPYWDM TNQDVINAIE 850 860 870 880 890 900 QDYRLPPPMD CPSALHQLML DCWQKDRNHR PKFGQIVNTL DKMIRNPNSL KAMAPLSSGI 910 920 930 940 950 960 NLPLLDRTIP DYTSFNTVDE WLEAIKMGQY KESFANAGFT SFDVVSQMMM EDILRVGVTL 970 980 AGHQKKILNS IQVMRAQMNQ IQSVEV
	Isoform 3 [UniParc]. Checksum: EF6DA7A63D894E47	FASTA	987	110,030
	10 20 30 40 50 60 MALRRLGAAL LLLPLLAAVE ETLMDSTTAT AELGWMVHPP SGWEEVSGYD ENMNTIRTYQ 70 80 90 100 110 120 VCNVFESSQN NWLRTKFIRR RGAHRIHVEM KFSVRDCSSI PSVPGSCKET FNLYYYEADF 130 140 150 160 170 180 DSATKTFPNW MENPWVKVDT IAADESFSQV DLGGRVMKIN TEVRSFGPVS RSGFYLAFQD 190 200 210 220 230 240 YGGCMSLIAV RVFYRKCPRI IQNGAIFQET LSGAESTSLV AARGSCIANA EEVDVPIKLY 250 260 270 280 290 300 CNGDGEWLVP IGRCMCKAGF EAVENGTVCR GCPSGTFKAN QGDEACTHCP INSRTTSEGA 310 320 330 340 350 360 TNCVCRNGYY RADLDPLDMP CTTIPSAPQA VISSVNETSL MLEWTPPRDS GGREDLVYNI 370 380 390 400 410 420 ICKSCGSGRG ACTRCGDNVQ YAPRQLGLTE PRIYISDLLA HTQYTFEIQA VNGVTDQSPF 430 440 450 460 470 480 SPQFASVNIT TNQAAPSAVS IMHQVSRTVD SITLSWSQPD QPNGVILDYE LQYYEKELSE 490 500 510 520 530 540 YNATAIKSPT NTVTVQGLKA GAIYVFQVRA RTVAGYGRYS GKMYFQTMTE AEYQTSIQEK 550 560 570 580 590 600 LPLIIGSSAA GLVFLIAVVV IAIVCNRRRG FERADSEYTD KLQHYTSGHM TPGMKIYIDP 610 620 630 640 650 660 FTYEDPNEAV REFAKEIDIS CVKIEQVIGA GEFGEVCSGH LKLPGKREIF VAIKTLKSGY 670 680 690 700 710 720 TEKQRRDFLS EASIMGQFDH PNVIHLEGVV TKSTPVMIIT EFMENGSLDS FLRQNDGQFT 730 740 750 760 770 780 VIQLVGMLRG IAAGMKYLAD MNYVHRDLAA RNILVNSNLV CKVSDFGLSR FLEDDTSDPT 790 800 810 820 830 840 YTSALGGKIP IRWTAPEAIQ YRKFTSASDV WSYGIVMWEV MSYGERPYWD MTNQDVINAI 850 860 870 880 890 900 EQDYRLPPPM DCPSALHQLM LDCWQKDRNH RPKFGQIVNT LDKMIRNPNS LKAMAPLSSG 910 920 930 940 950 960 INLPLLDRTI PDYTSFNTVD EWLEAIKMGQ YKESFANAGF TSFDVVSQMM MEDILRVGVT 970 980 LAGHQKKILN SIQVMRAQMN QIQSVEV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Overexpression of ERK, an EPH family receptor protein tyrosine kinase, in various human tumors." Kiyokawa E., Takai S., Tanaka M., Iwase T., Suzuki M., Xiang Y.Y., Naito Y., Yamada K., Sugimura H., Kino I. Cancer Res. 54:3645-3650(1994) [PubMed: 8033077] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"Molecular characterization and chromosomal localization of DRT (EPHT3): a developmentally regulated human protein-tyrosine kinase gene of the EPH family." Ikegaki N., Tang X.X., Liu X.-G., Biegel J.A., Allen C., Yoshioka A., Sulman E.P., Brodeur G.M., Pleasure D.E. Hum. Mol. Genet. 4:2033-2045(1995) [PubMed: 8589679] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Fetal brain.
[3]	"A variant transcript encoding an isoform of the human protein tyrosine kinase EPHB2 is generated by alternative splicing and alternative use of polyadenylation signals." Tang X.X., Pleasure D.E., Brodeur G.M., Ikegaki N. Oncogene 17:521-526(1998) [PubMed: 9696046] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal brain.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"cDNA cloning and tissue distribution of five human EPH-like receptor protein-tyrosine kinases." Fox G.M., Holst P.L., Chute H.T., Lindberg R.A., Janssen A.M., Basu R., Welcher A.A. Oncogene 10:897-905(1995) [PubMed: 7898931] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 15-986 (ISOFORM 2). Tissue: Brain.
[6]	"Identification of the human ERK gene as a putative receptor tyrosine kinase and its chromosomal localization to 1p36.1: a comparative mapping of human, mouse, and rat chromosomes." Saito T., Seki N., Matsuda Y., Kitahara M., Murata M., Kanda N., Nomura N., Yamamoto T., Hori T.-A. Genomics 26:382-384(1995) [PubMed: 7601466] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 509-986 (ISOFORM 2). Tissue: Fetal brain.
[7]	"Identification of protein-tyrosine kinase genes preferentially expressed in embryo stomach and gastric cancer." Iwase T., Tanaka M., Suzuki M., Naito Y., Sugimura H., Kino I. Biochem. Biophys. Res. Commun. 194:698-705(1993) [PubMed: 7688222] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 640-986 (ISOFORM 2). Tissue: Gastric carcinoma.
[8]	"eek and erk, new members of the eph subclass of receptor protein-tyrosine kinases." Chan J., Watt V.M. Oncogene 6:1057-1061(1991) [PubMed: 1648701] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 652-712.
[9]	"Unified nomenclature for Eph family receptors and their ligands, the ephrins." Eph nomenclature committee Cell 90:403-404(1997) [PubMed: 9267020] [Abstract] Cited for: NOMENCLATURE.
[10]	"Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed: 10508479] [Abstract] Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma.
[11]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-596 AND TYR-602, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[12]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-775, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-596, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[14]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-776 AND TYR-780, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"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-602 AND TYR-780, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[16]	"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 SER-148; TYR-596; TYR-602; THR-775; SER-776; THR-779; TYR-780; SER-897 AND SER-983, MASS SPECTROMETRY.
[17]	"Oligomeric structure of the human EphB2 receptor SAM domain." Thanos C.D., Goodwill K.E., Bowie J.U. Science 283:833-836(1999) [PubMed: 9933164] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 910-986 (ISOFORM SHORT).
[18]	"Three-dimensional structure of the EphB2 receptor in complex with an antagonistic peptide reveals a novel mode of inhibition." Chrencik J.E., Brooun A., Recht M.I., Nicola G., Davis L.K., Abagyan R., Widmer H., Pasquale E.B., Kuhn P. J. Biol. Chem. 282:36505-36513(2007) [PubMed: 17897949] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 20-195 OF HOMODIMER IN COMPLEX WITH ANTAGONISTIC PEPTIDE, DISULFIDE BOND.
[19]	"Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer." Huusko P., Ponciano-Jackson D., Wolf M., Kiefer J.A., Azorsa D.O., Tuzmen S., Weaver D., Robbins C., Moses T., Allinen M., Hautaniemi S., Chen Y., Elkahloun A., Basik M., Bova G.S., Bubendorf L., Lugli A., Sauter G. , Schleutker J., Ozcelik H., Elowe S., Pawson T., Trent J.M., Carpten J.D., Kallioniemi O.-P., Mousses S. Nat. Genet. 36:979-983(2004) [PubMed: 15300251] [Abstract] Cited for: VARIANTS PROSTATE CANCER HIS-199; SER-279; ASN-679 AND MET-909, FUNCTION AS A TUMOR SUPPRESSOR.
[20]	"A common nonsense mutation in EphB2 is associated with prostate cancer risk in African American men with a positive family history." Kittles R.A., Baffoe-Bonnie A.B., Moses T.Y., Robbins C.M., Ahaghotu C., Huusko P., Pettaway C., Vijayakumar S., Bennett J., Hoke G., Mason T., Weinrich S., Trent J.M., Collins F.S., Mousses S., Bailey-Wilson J., Furbert-Harris P., Dunston G., Powell I.J., Carpten J.D. J. Med. Genet. 43:507-511(2006) [PubMed: 16155194] [Abstract] Cited for: VARIANTS PROSTATE CANCER SER-279; ALA-650 AND VAL-883.
[21]	"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] SER-279; GLY-289; VAL-361; ASN-678 AND TRP-844.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D31661 mRNA. Translation: BAA06506.1.
L41939 mRNA. Translation: AAA99310.1.
AF025304 mRNA. Translation: AAB94602.1.
AL035704, AL158086, AL512444 Genomic DNA. Translation: CAI22645.1.
AL035704, AL158086, AL512444 Genomic DNA. Translation: CAI22646.1.
AL035704, AL158086, AL512444 Genomic DNA. Translation: CAI22647.2.
AL158086, AL035704, AL512444 Genomic DNA. Translation: CAI22897.1.
AL158086, AL512444, AL035704 Genomic DNA. Translation: CAI22898.1.
AL158086, AL035704, AL512444 Genomic DNA. Translation: CAI22899.2.
AL512444, AL035704, AL158086 Genomic DNA. Translation: CAI16428.1.
AL512444, AL035704, AL158086 Genomic DNA. Translation: CAI16429.1.
AL512444, AL035704, AL158086 Genomic DNA. Translation: CAI16430.2.
L36643 mRNA. Translation: AAA74244.1.
D37827 mRNA. Translation: BAA07073.1.
D14717 mRNA. Translation: BAA03537.1.
X59292 Genomic DNA. Translation: CAA41981.1.

IPI

IPI00021275.
IPI00219421.
IPI00252979.

PIR

A57174.
I78842.

RefSeq

NP_004433.2. NM_004442.6.
NP_059145.2. NM_017449.3.

UniGene

Hs.523329.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B4F	X-ray	1.95	A/B/C/D/E/F/G/H	910-985	[»]
1F0M	X-ray	2.20	A	910-985	[»]
2QBX	X-ray	2.30	A/B	20-196	[»]

ProteinModelPortal

P29323.

SMR

P29323. Positions 19-531, 613-985.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1162N.

MINT

MINT-5005955.

STRING

P29323.

PTM databases

PhosphoSite

P29323.

Polymorphism databases

DMDM

76803654.

Proteomic databases

PRIDE

P29323.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000400191; ENSP00000383053; ENSG00000133216.

GeneID

2048.

KEGG

hsa:2048.

UCSC

uc001bge.1. human.
uc001bgf.1. human.
uc009vqj.1. human.

Organism-specific databases

CTD

2048.

GeneCards

GC01P023037.

H-InvDB

HIX0028518.

HGNC

HGNC:3393. EPHB2.

HPA

CAB013647.

MIM

176807. phenotype.
600997. gene.
603688. phenotype.

neXtProt

NX_P29323.

Orphanet

1331. Familial prostate cancer.

PharmGKB

PA27825.

GenAtlas

Search...

Phylogenomic databases

eggNOG

maNOG13770.

HOGENOM

HBG755340.

HOVERGEN

HBG062180.

InParanoid

P29323.

OMA

ELGWIVH.

PhylomeDB

P29323.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Pathway_Interaction_DB

ephbfwdpathway. EPHB forward signaling.
ephrinbrevpathway. Ephrin B reverse signaling.
ephrinb_ephbpathway. EphrinB-EPHB pathway.
syndecan_2_pathway. Syndecan-2-mediated signaling events.

Reactome

REACT_111045. Developmental Biology.

Gene expression databases

ArrayExpress

P29323.

Bgee

P29323.

CleanEx

HS_EPHB2.

Genevestigator

P29323.

GermOnline

ENSG00000133216. Homo sapiens.

Family and domain databases

InterPro

IPR001090. Ephrin_rcpt_lig-bd.
IPR003961. Fibronectin_type3.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt.
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.
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.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 2 hits.
G3DSA:1.10.150.50. SAM_type. 1 hit.

KO

K05111.

Pfam

PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07699. GCC2_GCC3. 1 hit.
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.
SSF57184. Grow_fac_recept. 1 hit.
SSF56112. Kinase_like. 1 hit.
SSF47769. SAM_homology. 1 hit.

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.
[Graphical view]

ProtoNet

Search...

Other

NextBio

8325.

SOURCE

Search...

Entry information

Entry name

EPHB2_HUMAN

Accession

Primary (citable) accession number: P29323
Secondary accession number(s): O43477 , Q5T0U6, Q5T0U7, Q5T0U8

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	September 27, 2005
Last modified:	January 25, 2012
This is version 153 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.