dbPTM

EPHA2_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	EPHA2_MOUSE
UniProt AC	Q03145
Protein Name	Ephrin type-A receptor 2
Gene Name	Epha2
Organism	Mus musculus (Mouse).
Sequence Length	977
Subcellular Localization	Cell membrane Single-pass type I membrane protein . Cell projection, ruffle membrane Single-pass type I membrane protein . Cell projection, lamellipodium membrane Single-pass type I membrane protein . Cell junction, focal adhesion . Present at
Protein Description	Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A 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. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis..
Protein Sequence	MELRAVGFCLALLWGCALAAAAAQGKEVVLLDFAAMKGELGWLTHPYGKGWDLMQNIMDDMPIYMYSVCNVVSGDQDNWLRTNWVYREEAERIFIELKFTVRDCNSFPGGASSCKETFNLYYAESDVDYGTNFQKRQFTKIDTIAPDEITVSSDFEARNVKLNVEERMVGPLTRKGFYLAFQDIGACVALLSVRVYYKKCPEMLQSLARFPETIAVAVSDTQPLATVAGTCVDHAVVPYGGEGPLMHCTVDGEWLVPIGQCLCQEGYEKVEDACRACSPGFFKSEASESPCLECPEHTLPSTEGATSCQCEEGYFRAPEDPLSMSCTRPPSAPNYLTAIGMGAKVELRWTAPKDTGGRQDIVYSVTCEQCWPESGECGPCEASVRYSEPPHALTRTSVTVSDLEPHMNYTFAVEARNGVSGLVTSRSFRTASVSINQTEPPKVRLEDRSTTSLSVTWSIPVSQQSRVWKYEVTYRKKGDANSYNVRRTEGFSVTLDDLAPDTTYLVQVQALTQEGQGAGSKVHEFQTLSTEGSANMAVIGGVAVGVVLLLVLAGVGLFIHRRRRNLRARQSSEDVRFSKSEQLKPLKTYVDPHTYEDPNQAVLKFTTEIHPSCVARQKVIGAGEFGEVYKGTLKASSGKKEIPVAIKTLKAGYTEKQRVDFLSEASIMGQFSHHNIIRLEGVVSKYKPMMIITEYMENGALDKFLREKDGEFSVLQLVGMLRGIASGMKYLANMNYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDPEATYTTSGGKIPIRWTAPEAISYRKFTSASDVWSYGIVMWEVMTYGERPYWELSNHEVMKAINDGFRLPTPMDCPSAIYQLMMQCWQQERSRRPKFADIVSILDKLIRAPDSLKTLADFDPRVSIRLPSTSGSEGVPFRTVSEWLESIKMQQYTEHFMVAGYTAIEKVVQMSNEDIKRIGVRLPGHQKRIAYSLLGLKDQVNTVGIPI

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
106	Phosphorylation	FTVRDCNSFPGGASS EEEEECCCCCCCHHC	38.87	28576409
112	Phosphorylation	NSFPGGASSCKETFN CCCCCCHHCCHHHEE	39.27	22817900
113	Phosphorylation	SFPGGASSCKETFNL CCCCCHHCCHHHEEE	28.77	22817900
152	Phosphorylation	APDEITVSSDFEARN CCCEEEECCCCHHCC	18.62	26824392
305	Ubiquitination	TLPSTEGATSCQCEE CCCCCCCCCCCCCCC	7.07	27667366
364	Phosphorylation	GRQDIVYSVTCEQCW CCCEEEEEEEECCCC	10.47	23984901
366	Phosphorylation	QDIVYSVTCEQCWPE CEEEEEEEECCCCCC	12.37	23984901
374	Phosphorylation	CEQCWPESGECGPCE ECCCCCCCCCCCCCE	35.49	27087446
383	Phosphorylation	ECGPCEASVRYSEPP CCCCCEEEEECCCCC	5.71	23984901
408	N-linked_Glycosylation	SDLEPHMNYTFAVEA HHCCCCCCEEEEEEE	29.65	19656770
436	N-linked_Glycosylation	RTASVSINQTEPPKV EEEEEEECCCCCCEE	34.90	19656770
571	Phosphorylation	RNLRARQSSEDVRFS HHHHHHCCCCCCCCC	30.09	27087446
572	Phosphorylation	NLRARQSSEDVRFSK HHHHHCCCCCCCCCH	29.49	24453211
578	Phosphorylation	SSEDVRFSKSEQLKP CCCCCCCCHHHCCCC	25.38	26824392
579	Ubiquitination	SEDVRFSKSEQLKPL CCCCCCCHHHCCCCC	56.13	22790023
580	Phosphorylation	EDVRFSKSEQLKPLK CCCCCCHHHCCCCCC	29.40	22499769
584	Ubiquitination	FSKSEQLKPLKTYVD CCHHHCCCCCCEECC	48.26	22790023
588	Phosphorylation	EQLKPLKTYVDPHTY HCCCCCCEECCCCCC	36.14	22499769
589	Phosphorylation	QLKPLKTYVDPHTYE CCCCCCEECCCCCCC	10.98	25521595
594	Phosphorylation	KTYVDPHTYEDPNQA CEECCCCCCCCCCCH	33.71	22499769
595	Phosphorylation	TYVDPHTYEDPNQAV EECCCCCCCCCCCHH	18.46	25521595
604	Ubiquitination	DPNQAVLKFTTEIHP CCCCHHHEEECEECH	33.78	22790023
609	Ubiquitination	VLKFTTEIHPSCVAR HHEEECEECHHHHHH	5.63	27667366
618	Ubiquitination	PSCVARQKVIGAGEF HHHHHHCEEECCCCC	30.21	22790023
629	Phosphorylation	AGEFGEVYKGTLKAS CCCCCEEEEEEEECC	10.21	29514104
632	Phosphorylation	FGEVYKGTLKASSGK CCEEEEEEEECCCCC	22.42	17242355
648	Phosphorylation	EIPVAIKTLKAGYTE CCCEEEEEECCCCCH	27.64	-
736	Phosphorylation	KYLANMNYVHRDLAA HHHHCCCCCCHHHHH	6.20	18387945
762	Phosphorylation	KVSDFGLSRVLEDDP EECHHCCCHHCCCCC	22.26	20415495
772	Phosphorylation	LEDDPEATYTTSGGK CCCCCCCEEECCCCE	21.53	26239621
773	Phosphorylation	EDDPEATYTTSGGKI CCCCCCEEECCCCEE	18.31	25521595
774	Phosphorylation	DDPEATYTTSGGKIP CCCCCEEECCCCEEE	15.32	22499769
775	Phosphorylation	DPEATYTTSGGKIPI CCCCEEECCCCEEEE	18.24	22499769
776	Phosphorylation	PEATYTTSGGKIPIR CCCEEECCCCEEEEE	37.44	22499769
791	Phosphorylation	WTAPEAISYRKFTSA EECCCCCCCCCCCCH	26.40	25263469
870	Phosphorylation	PKFADIVSILDKLIR CCHHHHHHHHHHHHC	20.12	-
874	Ubiquitination	DIVSILDKLIRAPDS HHHHHHHHHHCCCCH	42.22	-
883	Ubiquitination	IRAPDSLKTLADFDP HCCCCHHHCCCCCCC	45.50	22790023
893	Phosphorylation	ADFDPRVSIRLPSTS CCCCCCEEEECCCCC	11.85	26824392
898	Phosphorylation	RVSIRLPSTSGSEGV CEEEECCCCCCCCCC	39.53	27087446
899	Phosphorylation	VSIRLPSTSGSEGVP EEEECCCCCCCCCCC	34.86	27087446
900	Phosphorylation	SIRLPSTSGSEGVPF EEECCCCCCCCCCCC	44.66	26824392
902	Phosphorylation	RLPSTSGSEGVPFRT ECCCCCCCCCCCCEE	30.83	27087446
922	Phosphorylation	ESIKMQQYTEHFMVA HHHHHHHCHHHHHHH	9.37	22499769
923	Phosphorylation	SIKMQQYTEHFMVAG HHHHHHCHHHHHHHH	20.74	22499769
931	Phosphorylation	EHFMVAGYTAIEKVV HHHHHHHHHHHHHHH	5.35	22499769
932	Phosphorylation	HFMVAGYTAIEKVVQ HHHHHHHHHHHHHHH	21.90	22499769
941	Phosphorylation	IEKVVQMSNEDIKRI HHHHHHCCHHHHHHH	21.70	26824392
961	Phosphorylation	GHQKRIAYSLLGLKD CHHHHHHHHHCCCCC	9.47	17242355

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
595	Y	Phosphorylation	Kinase	EPHA2	Q03145	GPS
736	Y	Phosphorylation	Kinase	EPHA2	Q03145	GPS
773	Y	Phosphorylation	Kinase	EPHA2	Q03145	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
898	S	Phosphorylation	18387945
Phosphorylated at Ser-898 by PKA; blocks cell retraction induced by EPHA2 kinase activity.
898	S	Phosphorylation	18387945
Phosphorylated at Ser-898 by PKB; serum-induced phosphorylation which targets EPHA2 to the cell leading edge and stimulates cell migration.
898	S	Phosphorylation	18387945
Phosphorylated at Ser-898 in response to TNF by RPS6KA1 and RPS6KA3; RPS6KA-EPHA2 signaling pathway controls cell migration.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of EPHA2_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions

Drug and Disease Associations

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

Regulatory Network of EPHA2_MOUSE

Related Literatures of Post-Translational Modification

N-linked Glycosylation
Reference	PubMed
"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."; Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,Schiess R., Aebersold R., Watts J.D.; Nat. Biotechnol. 27:378-386(2009). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-408 AND ASN-436, AND MASSSPECTROMETRY.	19349973 [Abstract]
"The mouse C2C12 myoblast cell surface N-linked glycoproteome:identification, glycosite occupancy, and membrane orientation."; Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I.,Bausch-Fluck D., Elliott S.T., Boheler K.R., Van Eyk J.E.,Wollscheid B.; Mol. Cell. Proteomics 8:2555-2569(2009). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-408 AND ASN-436, AND MASSSPECTROMETRY.	19656770 [Abstract]
Phosphorylation
Reference	PubMed
"Large scale localization of protein phosphorylation by use ofelectron capture dissociation mass spectrometry."; Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; Mol. Cell. Proteomics 8:904-912(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-595 AND TYR-773, ANDMASS SPECTROMETRY.	19131326 [Abstract]
"Identification and functional analysis of phosphorylated tyrosineresidues within EphA2 receptor tyrosine kinase."; Fang W.B., Brantley-Sieders D.M., Hwang Y., Ham A.-J.L., Chen J.; J. Biol. Chem. 283:16017-16026(2008). Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH VAV2;VAV3 AND PI3-KINASE P85 SUBUNIT, PHOSPHORYLATION AT TYR-589; TYR-595;TYR-736 AND TYR-773, AND MUTAGENESIS OF TYR-589; TYR-595; TYR-736;TYR-773 AND TYR-931.	18387945 [Abstract]

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