ERBB4_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: ERBB4_MOUSE
• UniProt AC: Q61527
• Protein Name: Receptor tyrosine-protein kinase erbB-4
• Gene Name: Erbb4
• Organism: Mus musculus (Mouse).
• Sequence Length: 1308
• Subcellular Localization: Cell membrane ; Single-pass type I membrane protein . In response to NRG1 treatment, the activated receptor is internalized.; ERBB4 intracellular domain: Nucleus. Mitochondrion. Following proteolytical processing E4ICD (E4ICD1 or E4ICD2 generate
• Protein Description: Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis..
• Protein Sequence: MKLATGLWVWGSLLMAAGTVQPSASQSVCAGTENKLSSLSDLEQQYRALRKYYENCEVVMGNLEITSIEHNRDLSFLRSIREVTGYVLVALNQFRYLPLENLRIIRGTKLYEDRYALAIFLNYRKDGNFGLQELGLKNLTEILNGGVYVDQNKFLCYADTIHWQDIVRNPWPSNMTLVSTNGSSGCGRCHKSCTGRCWGPTENHCQTLTRTVCAEQCDGRCYGPYVSDCCHRECAGGCSGPKDTDCFACMNFNDSGACVTQCPQTFVYNPTTFQLEHNFNAKYTYGAFCVKKCPHNFVVDSSSCVRACPSSKMEVEENGIKMCKPCTDICPKACDGIGTGSLMSAQTVDSSNIDKFINCTKINGNLIFLVTGIHGDPYNAIDAIDPEKLNVFRTVREITGFLNIQSWPPNMTDFSVFSNLVTIGGRVLYSGLSLLILKQQGITSLQFQSLKEISAGNIYITDNSNLCYYHTINWTTLFSTINQRIVIRDNRRAENCTAEGMVCNHLCSNDGCWGPGPDQCLSCRRFSRGKICIESCNLYDGEFREFENGSICVECDSQCEKMEDGLLTCHGPGPDNCTKCSHFKDGPNCVEKCPDGLQGANSFIFKYADQDRECHPCHPNCTQGCNGPTSHDCIYYPWTGHSTLPQHARTPLIAAGVIGGLFILVIMALTFAVYVRRKSIKKKRALRRFLETELVEPLTPSGTAPNQAQLRILKETELKRVKVLGSGAFGTVYKGIWVPEGETVKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLSPTIQLVTQLMPHGCLLDYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEGDEKEYNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDVYMVMVKCWMIDADSRPKFKELAAEFSRMARDPQRYLVIQGDDRMKLPSPNDSKFFQNLLDEEDLEDMMDAEEYLVPQAFNIPPPIYTSRTRIDSNRSEIGHSPPPAYTPMSGNQFVYQDGGFATQQGMPMPYRATTSTIPEAPVAQGATAEMFDDSCCNGTLRKPVAPHVQEDSSTQRYSADPTVFAPERNPRGELDEEGYMTPMHDKPKQEYLNPVEENPFVSRRKNGDLQALDNPEYHSASSGPPKAEDEYVNEPLYLNTFANALGSAEYMKNSVLSVPEKAKKAFDNPDYWNHSLPPRSTLQHPDYLQEYSTKYFYKQNGRIRPIVAENPEYLSEFSLKPGTMLPPPPYRHRNTVV

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
138	N-linked_Glycosylation	LQELGLKNLTEILNG CHHHCCCCHHHHHCC	58.18	-
174	N-linked_Glycosylation	VRNPWPSNMTLVSTN HCCCCCCCCEEEEEC	24.31	-
181	N-linked_Glycosylation	NMTLVSTNGSSGCGR CCEEEEECCCCCCCC	40.62	-
253	N-linked_Glycosylation	CFACMNFNDSGACVT CEEECCCCCCCCEEE	37.22	-
410	N-linked_Glycosylation	NIQSWPPNMTDFSVF CCCCCCCCCCCCCHH	41.74	-
473	N-linked_Glycosylation	LCYYHTINWTTLFST EEEEEECCHHHHCEE	31.06	-
495	N-linked_Glycosylation	RDNRRAENCTAEGMV CCCCCCCCCCCCCCC	27.70	-
548	N-linked_Glycosylation	GEFREFENGSICVEC CCCEEECCCCEEEEE	55.63	-
576	N-linked_Glycosylation	CHGPGPDNCTKCSHF ECCCCCCCCCCCCCC	38.19	-
620	N-linked_Glycosylation	ECHPCHPNCTQGCNG CCCCCCCCCCCCCCC	20.15	-
692	Phosphorylation	ALRRFLETELVEPLT HHHHHHHHHEECCCC	36.44	20415495
699	Phosphorylation	TELVEPLTPSGTAPN HHEECCCCCCCCCCC	26.56	26745281
701	Phosphorylation	LVEPLTPSGTAPNQA EECCCCCCCCCCCHH	43.47	20415495
703	Phosphorylation	EPLTPSGTAPNQAQL CCCCCCCCCCCHHHH	43.19	20415495
704	Ubiquitination	PLTPSGTAPNQAQLR CCCCCCCCCCHHHHH	12.45	27667366
714	Ubiquitination	QAQLRILKETELKRV HHHHHHHHHHCCCEE	61.28	27667366
726	Phosphorylation	KRVKVLGSGAFGTVY CEEEEECCCCCCCEE	23.84	29514104
731	Phosphorylation	LGSGAFGTVYKGIWV ECCCCCCCEECEEEE	17.76	20469934
733	Phosphorylation	SGAFGTVYKGIWVPE CCCCCCEECEEEECC	11.88	29514104
735	Ubiquitination	AFGTVYKGIWVPEGE CCCCEECEEEECCCC	10.99	27667366
745	Ubiquitination	VPEGETVKIPVAIKI ECCCCEEECEEEEEE	49.03	22790023
875	Phosphorylation	LEGDEKEYNADGGKM HCCCCCEECCCCCCC	27.07	-
935	Ubiquitination	EIPDLLEKGERLPQP CCHHHHHCCCCCCCC	67.07	-
997	Phosphorylation	DDRMKLPSPNDSKFF CCCCCCCCCCCHHHH	46.93	22324799
1035	Phosphorylation	FNIPPPIYTSRTRID HCCCCCCCCCCCEEC	12.39	-
1056	Phosphorylation	GHSPPPAYTPMSGNQ CCCCCCCCCCCCCCE	19.70	-
1150	Phosphorylation	GELDEEGYMTPMHDK CCCCCCCCCCCCCCC	10.90	20469934
1152	Phosphorylation	LDEEGYMTPMHDKPK CCCCCCCCCCCCCCC	14.69	20469934
1162	Phosphorylation	HDKPKQEYLNPVEEN CCCCCHHHCCCCCCC	14.86	-
1188	Phosphorylation	QALDNPEYHSASSGP CCCCCCCCCCCCCCC	11.44	-
1202	Phosphorylation	PPKAEDEYVNEPLYL CCCCCHHCCCCCCHH	22.39	-
1242	Phosphorylation	KAFDNPDYWNHSLPP HHHCCCCCCCCCCCC	14.90	-
1258	Phosphorylation	STLQHPDYLQEYSTK CCCCCCHHHHHHHHH	18.09	-
1284	Phosphorylation	IVAENPEYLSEFSLK EEECCHHHHHCCCCC	19.45	-

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
-	K	Ubiquitination	E3 ubiquitin ligase	Itch	Q8C863	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Wwp1	Q8BZZ3	PMID:22199232

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of ERBB4_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 ERBB4_MOUSE !!

Protein-Protein Interaction

Oops, there are no PPI records of ERBB4_MOUSE !!

Drug and Disease Associations

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