Q03137 (EPHA4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ephrin type-A receptor 4
EC=2.7.10.1

Alternative name(s):
Tyrosine-protein kinase receptor MPK-3
Tyrosine-protein kinase receptor SEK-1

Gene names

Name:	Epha4
Synonyms:	Sek, Sek1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	986 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 membrane-bound ephrin 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. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. Beside its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, plays also a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium. Ref.7 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18
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. Interacts (phosphorylated at position Tyr-602) with FYN. Interacts (via PDZ motif) with SIPA1L1 (via PDZ domain); controls neuronal morphology through regulation of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B or RAP2C) GTPases. Interacts with CDK5, CDK5R1 and NGEF; upon activation by EFNA1 induces NGEF phosphorylation by the kinase CDK5. Interacts with CHN1; effector of EPHA4 in axon guidance linking EPHA4 activation to RAC1 regulation. Ref.6 Ref.8 Ref.13 Ref.14 Ref.15 Ref.16
Subcellular location	Cell membrane; Single-pass type I membrane protein. Cell projection › axon. Cell projection › dendrite. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density By similarity. Early endosome. Note: Clustered upon activation and targeted to early endosome. Ref.15
Tissue specificity	Highest expression in the adult brain and retina and also detectable in kidney, lung, skeletal muscle and thymus. Not detected in heart and liver.
Developmental stage	Found in both the 10-day embryonic brain and body tissues. In the embryonic brain, expressed in the developing cortex of the telencephalon and major cortical tracts. Also expressed in the hippocampus, fornix and striatal cells and tracts. In the diencephalon, strongly expressed in thalamus, hypothalamus and thalamo-cortical projection. Also expressed in red nuclei of the mesencephalon and in the cerebellum. In the spinal cord, persistent expression occurs in the dorsal funiculus and ventral gray matter. Ref.9
Domain	The protein kinase domain mediates interaction with NGEF.
Disruption phenotype	Mice are viable and fertile but display a loss of coordination of limb movement associated with disruptions of cortico-spinal tract. They also display altered development of the thymic epithelium which leads to a defective T-cells development. Ref.7 Ref.10 Ref.12
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	Cell adhesion Neurogenesis
Cellular component	Cell junction Cell membrane Cell projection Endosome Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adult walking behavior Inferred from mutant phenotype PubMed 12649481. Source: MGI cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW corticospinal tract morphogenesis Inferred from mutant phenotype Ref.7. Source: UniProtKB fasciculation of motor neuron axon Inferred from mutant phenotype Ref.18. Source: UniProtKB fasciculation of sensory neuron axon Inferred from mutant phenotype Ref.18. Source: UniProtKB glial cell migration Inferred from electronic annotation. Source: Compara motor neuron axon guidance Inferred from mutant phenotype Ref.16. Source: UniProtKB negative regulation of axon regeneration Inferred from mutant phenotype Ref.10. Source: UniProtKB peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of JUN kinase activity Inferred from direct assay PubMed 10523642. Source: BHF-UCL positive regulation of Rho guanyl-nucleotide exchange factor activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of dendrite morphogenesis Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of Rac GTPase activity Inferred from direct assay Ref.13. Source: UniProtKB regulation of Rap GTPase activity Inferred from mutant phenotype Ref.14. Source: UniProtKB regulation of astrocyte differentiation Inferred from mutant phenotype Ref.10. Source: UniProtKB regulation of dendritic spine morphogenesis Inferred from mutant phenotype Ref.15. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara axon Inferred from direct assay Ref.15. Source: UniProtKB axon terminus Inferred from electronic annotation. Source: Compara axonal growth cone Inferred from electronic annotation. Source: Compara cell junction Inferred from electronic annotation. Source: UniProtKB-KW cell surface Inferred from electronic annotation. Source: Compara dendrite Inferred from direct assay Ref.15. Source: UniProtKB early endosome membrane Inferred from direct assay Ref.15. Source: UniProtKB endoplasmic reticulum Inferred from electronic annotation. Source: Compara filopodium Inferred from electronic annotation. Source: Compara integral to plasma membrane Inferred from direct assay Ref.15. Source: UniProtKB mitochondrial outer membrane Inferred from electronic annotation. Source: Compara neuromuscular junction Inferred from electronic annotation. Source: Compara perikaryon Inferred from electronic annotation. Source: Compara postsynaptic density Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DH domain binding Inferred from sequence or structural similarity. Source: UniProtKB GPI-linked ephrin receptor activity Inferred from mutant phenotype Ref.15Ref.14. Source: UniProtKB transmembrane-ephrin receptor activity Inferred from direct assay Ref.13. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Chn1	Q91V57-1	2	EBI-1539152,EBI-1539203
Efnb2	P52800	2	EBI-1539152,EBI-1032676
VAPB	O95292	2	EBI-1539152,EBI-1188298	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: Q03137-1)

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 Short (identifier: Q03137-2)

The sequence of this isoform differs from the canonical sequence as follows:
     783-832: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Potential

Chain

20 – 986

967

Ephrin type-A receptor 4

PRO_0000016808

Regions

Topological domain

20 – 547

528

Extracellular Potential

Transmembrane

548 – 569

22

Helical; Potential

Topological domain

570 – 986

417

Cytoplasmic Potential

Domain

30 – 209

180

Eph LBD

Domain

328 – 431

104

Fibronectin type-III 1

Domain

441 – 532

92

Fibronectin type-III 2

Domain

621 – 882

262

Protein kinase

Domain

911 – 975

65

SAM

Nucleotide binding

627 – 635

9

ATP By similarity

Motif

984 – 986

3

PDZ-binding Potential

Compositional bias

191 – 325

135

Cys-rich

Sites

Active site

746

1

Proton acceptor By similarity

Binding site

653

1

ATP By similarity

Amino acid modifications

Modified residue

596

1

Phosphotyrosine; by autocatalysis Ref.6 Ref.17

Modified residue

602

1

Phosphotyrosine; by autocatalysis Ref.6 Ref.17

Modified residue

779

1

Phosphotyrosine; by autocatalysis Potential

Modified residue

928

1

Phosphotyrosine; by autocatalysis Potential

Glycosylation

235

1

N-linked (GlcNAc...) Potential

Glycosylation

340

1

N-linked (GlcNAc...) Potential

Glycosylation

408

1

N-linked (GlcNAc...) Potential

Glycosylation

423

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

783 – 832

50

Missing in isoform Short.

VSP_002998

Experimental info

Mutagenesis

635

1

V → M: Kinase dead; loss of autophosphorylation and loss of CHN1 phosphorylation. No effect on interaction with NGEF. Ref.8 Ref.16

Sequence conflict

145

1

I → T in CAA46268. Ref.1

Sequence conflict

145

1

I → T in AAB25836. Ref.1

Secondary structure

1

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986

Helix Strand Turn

Details...

Helix

618 – 620

3

Beta strand

621 – 629

9

Beta strand

631 – 640

10

Beta strand

648 – 655

8

Helix

661 – 674

14

Beta strand

685 – 689

5

Beta strand

691 – 694

4

Beta strand

696 – 700

5

Helix

707 – 712

6

Turn

713 – 716

4

Helix

720 – 739

20

Helix

749 – 751

3

Beta strand

752 – 754

3

Beta strand

760 – 762

3

Helix

788 – 790

3

Helix

793 – 798

6

Helix

803 – 818

16

Turn

824 – 827

4

Helix

830 – 838

9

Helix

851 – 860

10

Helix

865 – 867

3

Helix

871 – 883

13

Helix

885 – 888

4

Helix

916 – 922

7

Helix

926 – 928

3

Helix

929 – 934

6

Helix

940 – 943

4

Helix

948 – 954

7

Helix

959 – 977

19

Helix

978 – 980

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 89BEB2C7CDB54A55	FASTA	986	109,814
	10 20 30 40 50 60 MAGIFYFILF SFLFGICDAV TGSRVYPANE VTLLDSRSVQ GELGWIASPL EGGWEEVSIM 70 80 90 100 110 120 DEKNTPIRTY QVCNVMEASQ NNWLRTDWIT REGAQRVYIE IKFTLRDCNS LPGVMGTCKE 130 140 150 160 170 180 TFNLYYYESD NDKERFIRES QFGKIDTIAA DESFTQVDIG DRIMKLNTEI RDVGPLSKKG 190 200 210 220 230 240 FYLAFQDVGA CIALVSVRVF YKKCPLTVRN LAQFPDTITG ADTSSLVEVR GSCVNNSEEK 250 260 270 280 290 300 DVPKMYCGAD GEWLVPIGNC LCNAGHEEQN GECQACKIGY YKALSTDASC AKCPPHSYSV 310 320 330 340 350 360 WEGATSCTCD RGFFRADNDA ASMPCTRPPS APLNLISNVN ETSVNLEWSS PQNTGGRQDI 370 380 390 400 410 420 SYNVVCKKCG AGDPSKCRPC GSGVHYTPQQ NGLKTTRVSI TDLLAHTNYT FEIWAVNGVS 430 440 450 460 470 480 KYNPSPDQSV SVTVTTNQAA PSSIALVQAK EVTRYSVALA WLEPDRPNGV ILEYEVKYYE 490 500 510 520 530 540 KDQNERSYRI VRTAARNTDI KGLNPLTSYV FHVRARTAAG YGDFSEPLEV TTNTVPSRII 550 560 570 580 590 600 GDGANSTVLL VSVSGSVVLV VILIAAFVIS RRRSKYSKAK QEADEEKHLN QGVRTYVDPF 610 620 630 640 650 660 TYEDPNQAVR EFAKEIDASC IKIEKVIGVG EFGEVCSGRL KVPGKREICV AIKTLKAGYT 670 680 690 700 710 720 DKQRRDFLSE ASIMGQFDHP NIIHLEGVVT KCKPVMIITE YMENGSLDAF LRKNDGRFTV 730 740 750 760 770 780 IQLVGMLRGI GSGMKYLSDM SYVHRDLAAR NILVNSNLVC KVSDFGMSRV LEDDPEAAYT 790 800 810 820 830 840 TRGGKIPIRW TAPEAIAYRK FTSASDVWSY GIVMWEVMSY GERPYWDMSN QDVIKAIEEG 850 860 870 880 890 900 YRLPPPMDCP IALHQLMLDC WQKERSDRPK FGQIVNMLDK LIRNPNSLKR TGSESSRPNT 910 920 930 940 950 960 ALLDPSSPEF SAVVSVGDWL QAIKMDRYKD NFTAAGYTTL EAVVHMSQDD LARIGITAIT 970 980 HQNKILSSVQ AMRTQMQQMH GRMVPV
	Isoform Short [UniParc]. Checksum: 3C3EFE4620316DB2	FASTA	936	103,984
	10 20 30 40 50 60 MAGIFYFILF SFLFGICDAV TGSRVYPANE VTLLDSRSVQ GELGWIASPL EGGWEEVSIM 70 80 90 100 110 120 DEKNTPIRTY QVCNVMEASQ NNWLRTDWIT REGAQRVYIE IKFTLRDCNS LPGVMGTCKE 130 140 150 160 170 180 TFNLYYYESD NDKERFIRES QFGKIDTIAA DESFTQVDIG DRIMKLNTEI RDVGPLSKKG 190 200 210 220 230 240 FYLAFQDVGA CIALVSVRVF YKKCPLTVRN LAQFPDTITG ADTSSLVEVR GSCVNNSEEK 250 260 270 280 290 300 DVPKMYCGAD GEWLVPIGNC LCNAGHEEQN GECQACKIGY YKALSTDASC AKCPPHSYSV 310 320 330 340 350 360 WEGATSCTCD RGFFRADNDA ASMPCTRPPS APLNLISNVN ETSVNLEWSS PQNTGGRQDI 370 380 390 400 410 420 SYNVVCKKCG AGDPSKCRPC GSGVHYTPQQ NGLKTTRVSI TDLLAHTNYT FEIWAVNGVS 430 440 450 460 470 480 KYNPSPDQSV SVTVTTNQAA PSSIALVQAK EVTRYSVALA WLEPDRPNGV ILEYEVKYYE 490 500 510 520 530 540 KDQNERSYRI VRTAARNTDI KGLNPLTSYV FHVRARTAAG YGDFSEPLEV TTNTVPSRII 550 560 570 580 590 600 GDGANSTVLL VSVSGSVVLV VILIAAFVIS RRRSKYSKAK QEADEEKHLN QGVRTYVDPF 610 620 630 640 650 660 TYEDPNQAVR EFAKEIDASC IKIEKVIGVG EFGEVCSGRL KVPGKREICV AIKTLKAGYT 670 680 690 700 710 720 DKQRRDFLSE ASIMGQFDHP NIIHLEGVVT KCKPVMIITE YMENGSLDAF LRKNDGRFTV 730 740 750 760 770 780 IQLVGMLRGI GSGMKYLSDM SYVHRDLAAR NILVNSNLVC KVSDFGMSRV LEDDPEAAYT 790 800 810 820 830 840 TRVIKAIEEG YRLPPPMDCP IALHQLMLDC WQKERSDRPK FGQIVNMLDK LIRNPNSLKR 850 860 870 880 890 900 TGSESSRPNT ALLDPSSPEF SAVVSVGDWL QAIKMDRYKD NFTAAGYTTL EAVVHMSQDD 910 920 930 LARIGITAIT HQNKILSSVQ AMRTQMQQMH GRMVPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"An Eph-related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain." Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A., Wilkinson D.G., Charnay P. Oncogene 7:2499-2506(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Strain: C57BL/6. Tissue: Embryonic brain.
[2]	Erratum Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A., Wilkinson D.G., Charnay P. Oncogene 8:1103-1103(1993) [PubMed] [Europe PMC] [Abstract]
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). Strain: C57BL/6J.
[4]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). Tissue: Limb.
[6]	"A juxtamembrane autophosphorylation site in the Eph family receptor tyrosine kinase, Sek, mediates high affinity interaction with p59fyn." Ellis C., Kasmi F., Ganju P., Walls E., Panayotou G., Reith A.D. Oncogene 12:1727-1736(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-596 AND TYR-602, INTERACTION WITH FYN.
[7]	"EphA4 (Sek1) receptor tyrosine kinase is required for the development of the corticospinal tract." Dottori M., Hartley L., Galea M., Paxinos G., Polizzotto M., Kilpatrick T., Bartlett P.F., Murphy M., Koentgen F., Boyd A.W. Proc. Natl. Acad. Sci. U.S.A. 95:13248-13253(1998) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION IN AXON GUIDANCE.
[8]	"EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin." Shamah S.M., Lin M.Z., Goldberg J.L., Estrach S., Sahin M., Hu L., Bazalakova M., Neve R.L., Corfas G., Debant A., Greenberg M.E. Cell 105:233-244(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NGEF, MUTAGENESIS OF VAL-635.
[9]	"Developmental expression of EphA4-tyrosine kinase receptor in the mouse brain and spinal cord." Greferath U., Canty A.J., Messenger J., Murphy M. Mech. Dev. 119:S231-S238(2002) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[10]	"Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient mice." Goldshmit Y., Galea M.P., Wise G., Bartlett P.F., Turnley A.M. J. Neurosci. 24:10064-10073(2004) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION IN AXONAL REGENERATION.
[11]	"EphA4 regulates central nervous system vascular formation." Goldshmit Y., Galea M.P., Bartlett P.F., Turnley A.M. J. Comp. Neurol. 497:864-875(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ANGIOGENESIS.
[12]	"Thymic alterations in EphA4-deficient mice." Munoz J.J., Alfaro D., Garcia-Ceca J., Alonso-C L.M., Jimenez E., Zapata A. J. Immunol. 177:804-813(2006) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION IN THYMUS DEVELOPMENT.
[13]	"Rac-GAP alpha-chimerin regulates motor-circuit formation as a key mediator of EphrinB3/EphA4 forward signaling." Iwasato T., Katoh H., Nishimaru H., Ishikawa Y., Inoue H., Saito Y.M., Ando R., Iwama M., Takahashi R., Negishi M., Itohara S. Cell 130:742-753(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN RAC1 REGULATION, FUNCTION IN AXON GUIDANCE, INTERACTION WITH CHN1.
[14]	"The EphA4 receptor regulates neuronal morphology through SPAR-mediated inactivation of Rap GTPases." Richter M., Murai K.K., Bourgin C., Pak D.T., Pasquale E.B. J. Neurosci. 27:14205-14215(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN NEURON MORPHOLOGY, INTERACTION WITH SIPA1L1.
[15]	"Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism." Fu W.Y., Chen Y., Sahin M., Zhao X.S., Shi L., Bikoff J.B., Lai K.O., Yung W.H., Fu A.K., Greenberg M.E., Ip N.Y. Nat. Neurosci. 10:67-76(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DENDRITIC SPINE MORPHOGENESIS, TOPOLOGY, SUBCELLULAR LOCATION, INTERACTION WITH NGEF.
[16]	"alpha2-Chimaerin is an essential EphA4 effector in the assembly of neuronal locomotor circuits." Beg A.A., Sommer J.E., Martin J.H., Scheiffele P. Neuron 55:768-778(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN AXON GUIDANCE, INTERACTION WITH CHN1, MUTAGENESIS OF VAL-635.
[17]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-596 AND TYR-602, MASS SPECTROMETRY. Tissue: Brain.
[18]	"Segregation of axial motor and sensory pathways via heterotypic trans-axonal signaling." Gallarda B.W., Bonanomi D., Mueller D., Brown A., Alaynick W.A., Andrews S.E., Lemke G., Pfaff S.L., Marquardt T. Science 320:233-236(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MOTOR AND SENSORY AXONS SEGREGATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X65138 mRNA. Translation: CAA46268.1.
X57241 mRNA. Translation: CAA40517.1.
S57168 mRNA. Translation: AAB25836.1.
AK147698 mRNA. Translation: BAE28081.1.
CH466548 Genomic DNA. Translation: EDL00429.1.
BC052164 mRNA. Translation: AAH52164.1.

IPI

IPI00129198.
IPI00230383.

PIR

S78059.

RefSeq

NP_031962.2. NM_007936.3.

UniGene

Mm.400747.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B0X	X-ray	2.00	A	890-981	[»]
2HEL	X-ray	2.35	A	591-896	[»]
2I8J	model	-	@	594-888	[»]
2XYU	X-ray	2.12	A	612-896	[»]
2Y6M	X-ray	1.70	A	606-896	[»]
2Y6O	X-ray	1.54	A	606-896	[»]

ProteinModelPortal

Q03137.

SMR

Q03137. Positions 30-981.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1019N.

IntAct

Q03137. 4 interactions.

MINT

MINT-3381444.

PTM databases

PhosphoSite

Q03137.

Proteomic databases

PaxDb

Q03137.

PRIDE

Q03137.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000027451; ENSMUSP00000027451; ENSMUSG00000026235.

GeneID

13838.

KEGG

mmu:13838.

UCSC

uc007bpz.1. mouse.

Organism-specific databases

CTD

2043.

MGI

MGI:98277. Epha4.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00670000097666.

HOGENOM

HOG000233856.

HOVERGEN

HBG062180.

InParanoid

Q80VZ2.

KO

K05105.

OMA

ITAVTHQ.

OrthoDB

EOG48SGS9.

Enzyme and pathway databases

BRENDA

2.7.10.1. 3474.

Gene expression databases

ArrayExpress

Q03137.

Bgee

Q03137.

CleanEx

MM_EPHA4.

Genevestigator

Q03137.

GermOnline

ENSMUSG00000026235. Mus musculus.

Family and domain databases

Gene3D

1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.

InterPro

IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. Fibronectin_type3.
IPR008979. Galactose-bd-like.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016257. Tyr_kinase_ephrin_rcpt.
IPR001426. Tyr_kinase_rcpt_V_CS.
[Graphical view]

Pfam

PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF07647. SAM_2. 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.
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

BindingDB

Q03137.

ChEMBL

CHEMBL1293259.

EvolutionaryTrace

Q03137.

NextBio

284664.

SOURCE

Search...

Entry information

Entry name

EPHA4_MOUSE

Accession

Primary (citable) accession number: Q03137
Secondary accession number(s): Q80VZ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	July 27, 2011
Last modified:	May 29, 2013
This is version 150 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program