EPHA4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: EPHA4_HUMAN
• UniProt AC: P54764
• Protein Name: Ephrin type-A receptor 4
• Gene Name: EPHA4
• Organism: Homo sapiens (Human).
• 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 endosome..
• 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: MAGIFYFALFSCLFGICDAVTGSRVYPANEVTLLDSRSVQGELGWIASPLEGGWEEVSIMDEKNTPIRTYQVCNVMEPSQNNWLRTDWITREGAQRVYIEIKFTLRDCNSLPGVMGTCKETFNLYYYESDNDKERFIRENQFVKIDTIAADESFTQVDIGDRIMKLNTEIRDVGPLSKKGFYLAFQDVGACIALVSVRVFYKKCPLTVRNLAQFPDTITGADTSSLVEVRGSCVNNSEEKDVPKMYCGADGEWLVPIGNCLCNAGHEERSGECQACKIGYYKALSTDATCAKCPPHSYSVWEGATSCTCDRGFFRADNDAASMPCTRPPSAPLNLISNVNETSVNLEWSSPQNTGGRQDISYNVVCKKCGAGDPSKCRPCGSGVHYTPQQNGLKTTKVSITDLLAHTNYTFEIWAVNGVSKYNPNPDQSVSVTVTTNQAAPSSIALVQAKEVTRYSVALAWLEPDRPNGVILEYEVKYYEKDQNERSYRIVRTAARNTDIKGLNPLTSYVFHVRARTAAGYGDFSEPLEVTTNTVPSRIIGDGANSTVLLVSVSGSVVLVVILIAAFVISRRRSKYSKAKQEADEEKHLNQGVRTYVDPFTYEDPNQAVREFAKEIDASCIKIEKVIGVGEFGEVCSGRLKVPGKREICVAIKTLKAGYTDKQRRDFLSEASIMGQFDHPNIIHLEGVVTKCKPVMIITEYMENGSLDAFLRKNDGRFTVIQLVGMLRGIGSGMKYLSDMSYVHRDLAARNILVNSNLVCKVSDFGMSRVLEDDPEAAYTTRGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVIKAIEEGYRLPPPMDCPIALHQLMLDCWQKERSDRPKFGQIVNMLDKLIRNPNSLKRTGTESSRPNTALLDPSSPEFSAVVSVGDWLQAIKMDRYKDNFTAAGYTTLEAVVHVNQEDLARIGITAITHQNKILSSVQAMRTQMQQMHGRMVPV

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
6	Phosphorylation	--MAGIFYFALFSCL --CCHHHHHHHHHHH	5.99	21406692
11	Phosphorylation	IFYFALFSCLFGICD HHHHHHHHHHHHHHH	15.68	21406692
21	Phosphorylation	FGICDAVTGSRVYPA HHHHHHHCCCCEECC	31.03	21406692
23	Phosphorylation	ICDAVTGSRVYPANE HHHHHCCCCEECCCE	14.81	21406692
104	Phosphorylation	VYIEIKFTLRDCNSL EEEEEEEEECCCCCC	18.84	24719451
117	Phosphorylation	SLPGVMGTCKETFNL CCCCCEEEEECEEEE	11.43	-
168	Phosphorylation	DRIMKLNTEIRDVGP HHHHHHCCCEEECCC	43.13	-
196	Phosphorylation	GACIALVSVRVFYKK HHHHHEEEHHHHHHH	12.69	24719451
235	N-linked_Glycosylation	EVRGSCVNNSEEKDV EEECCCCCCCCCCCC	51.11	UniProtKB CARBOHYD
340	N-linked_Glycosylation	LNLISNVNETSVNLE CEEEECCCCCEEEEE	51.59	UniProtKB CARBOHYD
349	Phosphorylation	TSVNLEWSSPQNTGG CEEEEEECCCCCCCC	23.82	-
350	Phosphorylation	SVNLEWSSPQNTGGR EEEEEECCCCCCCCC	31.42	-
354	Phosphorylation	EWSSPQNTGGRQDIS EECCCCCCCCCCEEE	35.45	-
399	Phosphorylation	GLKTTKVSITDLLAH CCCCEEEEHHHHHHC	22.71	24719451
408	N-linked_Glycosylation	TDLLAHTNYTFEIWA HHHHHCCCCEEEEEE	24.79	UniProtKB CARBOHYD
409	Phosphorylation	DLLAHTNYTFEIWAV HHHHCCCCEEEEEEE	17.60	24719451
545	N-linked_Glycosylation	RIIGDGANSTVLLVS EEECCCCCCEEEEEE	43.68	UniProtKB CARBOHYD
576	Phosphorylation	ISRRRSKYSKAKQEA HHHHHHHHHHHHHHH	19.36	29083192
577	Phosphorylation	SRRRSKYSKAKQEAD HHHHHHHHHHHHHHH	29.85	29083192
595	Phosphorylation	HLNQGVRTYVDPFTY HHHHHHHHCCCCCCC	26.03	25849741
596	Phosphorylation	LNQGVRTYVDPFTYE HHHHHHHCCCCCCCC	7.71	20007894
601	Phosphorylation	RTYVDPFTYEDPNQA HHCCCCCCCCCHHHH	31.24	25849741
602	Phosphorylation	TYVDPFTYEDPNQAV HCCCCCCCCCHHHHH	20.79	20007894
637	Phosphorylation	GEFGEVCSGRLKVPG CCCCCCCCCCCCCCC	31.93	-
684	Ubiquitination	FDHPNIIHLEGVVTK CCCCCEEEEEEEECC	17.65	-
693	Acetylation	EGVVTKCKPVMIITE EEEECCCEEEEEEEE	42.05	30588515
701	Phosphorylation	PVMIITEYMENGSLD EEEEEEEEECCCCHH	10.90	29978859
706	Phosphorylation	TEYMENGSLDAFLRK EEEECCCCHHHHHHC	34.36	29978859
732	Phosphorylation	GMLRGIGSGMKYLSD HHHHCCCCCCHHHHC	33.52	22210691
735	Ubiquitination	RGIGSGMKYLSDMSY HCCCCCCHHHHCCCH	46.71	21890473
735	Ubiquitination	RGIGSGMKYLSDMSY HCCCCCCHHHHCCCH	46.71	21890473
735	Ubiquitination	RGIGSGMKYLSDMSY HCCCCCCHHHHCCCH	46.71	21890473
735	Ubiquitination	RGIGSGMKYLSDMSY HCCCCCCHHHHCCCH	46.71	21890473
741	Phosphorylation	MKYLSDMSYVHRDLA CHHHHCCCHHCHHHH	29.06	-
756	Phosphorylation	ARNILVNSNLVCKVS HHCEEECCCEEEEEC	24.86	-
779	Phosphorylation	EDDPEAAYTTRGGKI CCCCCHHCCCCCCCC	18.72	27273156
780	Phosphorylation	DDPEAAYTTRGGKIP CCCCHHCCCCCCCCC	12.80	21082442
781	Phosphorylation	DPEAAYTTRGGKIPI CCCHHCCCCCCCCCC	18.03	21082442
798	Phosphorylation	TAPEAIAYRKFTSAS ECCHHHHCCCCCCHH	14.28	-
809	Phosphorylation	TSASDVWSYGIVMWE CCHHHHHHHHEEEEE	17.21	22210691
810	Phosphorylation	SASDVWSYGIVMWEV CHHHHHHHHEEEEEE	8.65	22210691
841	Phosphorylation	IKAIEEGYRLPPPMD HHHHHCCCCCCCCCC	16.56	22210691
887	Phosphorylation	KLIRNPNSLKRTGTE HHHHCCCHHCCCCCC	36.20	29514088
928	Phosphorylation	QAIKMDRYKDNFTAA HHHCHHHCCCCCCCC	20.59	27642862
937	Phosphorylation	DNFTAAGYTTLEAVV CCCCCCCCEEEEEEE	7.57	27642862
957	Phosphorylation	DLARIGITAITHQNK HHHHHCEEEEEHHHH	13.54	21406692
960	Phosphorylation	RIGITAITHQNKILS HHCEEEEEHHHHHHH	18.23	21406692
967	Phosphorylation	THQNKILSSVQAMRT EHHHHHHHHHHHHHH	31.75	27174698
968	Phosphorylation	HQNKILSSVQAMRTQ HHHHHHHHHHHHHHH	18.14	27174698
974	Phosphorylation	SSVQAMRTQMQQMHG HHHHHHHHHHHHHHC	18.46	27174698

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	P54764	PSP
602	Y	Phosphorylation	Kinase	EPHA4	P54764	PSP
779	Y	Phosphorylation	Kinase	EPHA4	P54764	PSP

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of EPHA4_HUMAN !!

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_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
EFNB3_HUMAN	EFNB3	physical	9484836
ANC2_HUMAN	ANAPC2	physical	21186356
FZR1_HUMAN	FZR1	physical	21186356
FGFR1_HUMAN	FGFR1	physical	18790757
FABPL_HUMAN	FABP1	physical	28514442
TENS3_HUMAN	TNS3	physical	28065597

Drug and Disease Associations

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