EPHA4_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: EPHA4_MOUSE
• UniProt AC: Q03137
• Protein Name: Ephrin type-A receptor 4
• Gene Name: Epha4
• Organism: Mus musculus (Mouse).
• Sequence Length: 986
• Subcellular Localization: Cell membrane ; Single-pass type I membrane protein . Cell projection, axon . Cell projection, dendrite . Cell junction, synapse, postsynaptic cell membrane, postsynaptic density. Early endosome . Clustered upon activation and targeted to early endos
• Protein Description: 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. In addition to 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..
• Protein Sequence: MAGIFYFILFSFLFGICDAVTGSRVYPANEVTLLDSRSVQGELGWIASPLEGGWEEVSIMDEKNTPIRTYQVCNVMEASQNNWLRTDWITREGAQRVYIEIKFTLRDCNSLPGVMGTCKETFNLYYYESDNDKERFIRESQFGKIDTIAADESFTQVDIGDRIMKLNTEIRDVGPLSKKGFYLAFQDVGACIALVSVRVFYKKCPLTVRNLAQFPDTITGADTSSLVEVRGSCVNNSEEKDVPKMYCGADGEWLVPIGNCLCNAGHEEQNGECQACKIGYYKALSTDASCAKCPPHSYSVWEGATSCTCDRGFFRADNDAASMPCTRPPSAPLNLISNVNETSVNLEWSSPQNTGGRQDISYNVVCKKCGAGDPSKCRPCGSGVHYTPQQNGLKTTRVSITDLLAHTNYTFEIWAVNGVSKYNPSPDQSVSVTVTTNQAAPSSIALVQAKEVTRYSVALAWLEPDRPNGVILEYEVKYYEKDQNERSYRIVRTAARNTDIKGLNPLTSYVFHVRARTAAGYGDFSEPLEVTTNTVPSRIIGDGANSTVLLVSVSGSVVLVVILIAAFVISRRRSKYSKAKQEADEEKHLNQGVRTYVDPFTYEDPNQAVREFAKEIDASCIKIEKVIGVGEFGEVCSGRLKVPGKREICVAIKTLKAGYTDKQRRDFLSEASIMGQFDHPNIIHLEGVVTKCKPVMIITEYMENGSLDAFLRKNDGRFTVIQLVGMLRGIGSGMKYLSDMSYVHRDLAARNILVNSNLVCKVSDFGMSRVLEDDPEAAYTTRGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVIKAIEEGYRLPPPMDCPIALHQLMLDCWQKERSDRPKFGQIVNMLDKLIRNPNSLKRTGSESSRPNTALLDPSSPEFSAVVSVGDWLQAIKMDRYKDNFTAAGYTTLEAVVHMSQDDLARIGITAITHQNKILSSVQAMRTQMQQMHGRMVPV

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
140	Phosphorylation	KERFIRESQFGKIDT HHHEEEHHHCCCCCE	22.44	29899451
153	Phosphorylation	DTIAADESFTQVDIG CEEECCCCCEECCHH	33.85	29899451
177	Phosphorylation	IRDVGPLSKKGFYLA EEECCCCCCCCEEEE	35.14	23737553
235	N-linked_Glycosylation	EVRGSCVNNSEEKDV EEECCCCCCCCCCCC	51.11	-
340	N-linked_Glycosylation	LNLISNVNETSVNLE CEEEECCCCCEEEEE	51.59	-
408	N-linked_Glycosylation	TDLLAHTNYTFEIWA HHHHHHCCCEEEEEE	24.79	-
587	Ubiquitination	KQEADEEKHLNQGVR HHHHHHHHHHHHHHH	51.88	22790023
595	Phosphorylation	HLNQGVRTYVDPFTY HHHHHHHHCCCCCCC	26.03	22817900
596	Phosphorylation	LNQGVRTYVDPFTYE HHHHHHHCCCCCCCC	7.71	8622893
601	Phosphorylation	RTYVDPFTYEDPNQA HHCCCCCCCCCHHHH	31.24	-
602	Phosphorylation	TYVDPFTYEDPNQAV HCCCCCCCCCHHHHH	20.79	8622893
654	Phosphorylation	EICVAIKTLKAGYTD HEEEEEEEHHCCCCH	27.64	18846507
659	Phosphorylation	IKTLKAGYTDKQRRD EEEHHCCCCHHHHHH	19.34	18846507
660	Phosphorylation	KTLKAGYTDKQRRDF EEHHCCCCHHHHHHH	35.48	22817900
735	Ubiquitination	RGIGSGMKYLSDMSY HCCCCCCHHHHCCCH	46.71	22790023
761	Acetylation	VNSNLVCKVSDFGMS ECCCEEEEECCCCCC	36.98	6569755
779	Phosphorylation	EDDPEAAYTTRGGKI CCCCCHHCCCCCCCC	18.72	22499769
780	Phosphorylation	DDPEAAYTTRGGKIP CCCCHHCCCCCCCCC	12.80	22499769
781	Phosphorylation	DPEAAYTTRGGKIPI CCCHHCCCCCCCCCC	18.03	22499769
887	Phosphorylation	KLIRNPNSLKRTGSE HHHHCCCHHCCCCCC	36.20	26824392
893	Phosphorylation	NSLKRTGSESSRPNT CHHCCCCCCCCCCCC	33.42	25338131
900	Phosphorylation	SESSRPNTALLDPSS CCCCCCCCCCCCCCC	22.74	25177544
906	Phosphorylation	NTALLDPSSPEFSAV CCCCCCCCCCCCCEE	59.18	29899451
928	Phosphorylation	QAIKMDRYKDNFTAA HHHCHHHCCCCCCCC	20.59	22817900
947	Phosphorylation	LEAVVHMSQDDLARI HHHEEECCHHHHHHH	18.64	29899451

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
596	Y	Phosphorylation	Kinase	EPHA4	Q03137	GPS
602	Y	Phosphorylation	Kinase	EPHA4	Q03137	GPS
779	Y	Phosphorylation	Kinase	EPHA4	Q03137	PSP
928	Y	Phosphorylation	Kinase	EPHA4	Q03137	PSP

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of EPHA4_MOUSE !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of EPHA4_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
VAPB_HUMAN	VAPB	physical	18555774

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"Large-scale identification and evolution indexing of tyrosinephosphorylation sites from murine brain.";
Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
J. Proteome Res. 7:311-318(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-596 AND TYR-602, ANDMASS SPECTROMETRY.
PubMed: 18034455

"A juxtamembrane autophosphorylation site in the Eph family receptortyrosine kinase, Sek, mediates high affinity interaction withp59fyn.";
Ellis C., Kasmi F., Ganju P., Walls E., Panayotou G., Reith A.D.;
Oncogene 12:1727-1736(1996).
Cited for: PHOSPHORYLATION AT TYR-596 AND TYR-602, AND INTERACTION WITH FYN.
PubMed: 8622893