NTRK2_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: NTRK2_RAT
• UniProt AC: Q63604
• Protein Name: BDNF/NT-3 growth factors receptor
• Gene Name: Ntrk2
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 821
• Subcellular Localization: Cell membrane ; Single-pass type I membrane protein . Endosome membrane ; Single-pass type I membrane protein . Early endosome membrane . Internalized to endosomes upon ligand-binding.
• Protein Description: Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2. Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells..
• Protein Sequence: MSPWPRWHGPAMARLWGLCLLVLGFWRASLACPMSCKCSTTRIWCTEPSPGIVAFPRLEPNSIDPENITEILIANQKRLEIINEDDVEAYVGLKNLTIVDSGLKFVAYKAFLKNGNLRHINFTRNKLTSLSRRHFRHLDLSDLILTGNPFTCSCDIMWLKTLQETKSSPDTQDLYCLNESSKNTPLANLQIPNCGLPSARLAAPNLTVEEGKSVTISCSVGGDPLPTLYWDVGNLVSKHMNETSHTQGSLRITNISSDDSGKQISCVAENLVGEDQDSVNLTVHFAPTITFLESPTSDHHWCIPFTVRGNPKPALQWFYNGAILNESKYICTKIHVTNHTEYHGCLQLDNPTHMNNGDYTLMAKNEYGKDERQISAHFMGRPGVDYETNPNYPEVLYEDWTTPTDIGDTTNKSNEIPSTDVADQTNREHLSVYAVVVIASVVGFCLLVMLLLLKLARHSKFGMKGPASVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKPDTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMAEGNPPTELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQEVYELMLGCWQREPHTRKNIKNIHTLLQNLAKASPVYLDILG

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
67	N-linked_Glycosylation	PNSIDPENITEILIA CCCCCCCCHHHHEEE	52.44	-
95	N-linked_Glycosylation	EAYVGLKNLTIVDSG HHHHCCCCCEEECCC	47.67	24090084
121	N-linked_Glycosylation	NGNLRHINFTRNKLT CCCCCCEEEEHHHHH	26.55	-
178	N-linked_Glycosylation	TQDLYCLNESSKNTP CCCEEEECCCCCCCC	43.47	-
205	N-linked_Glycosylation	SARLAAPNLTVEEGK HHHEECCCEEEECCC	43.55	-
241	N-linked_Glycosylation	NLVSKHMNETSHTQG HHHHHHCCCCCCCCC	49.46	24090084
254	N-linked_Glycosylation	QGSLRITNISSDDSG CCCEEEEECCCCCCC	29.76	-
280	N-linked_Glycosylation	GEDQDSVNLTVHFAP CCCCCCCEEEEEECC	33.67	-
325	N-linked_Glycosylation	FYNGAILNESKYICT HHCCCCCCCCCEEEE	45.44	-
338	N-linked_Glycosylation	CTKIHVTNHTEYHGC EEEEEECCCCCCCEE	38.71	-
350	N-linked_Glycosylation	HGCLQLDNPTHMNNG CEEEECCCCCCCCCC	52.54	-
411	N-linked_Glycosylation	TDIGDTTNKSNEIPS CCCCCCCCCCCCCCC	48.10	-
468	Phosphorylation	FGMKGPASVISNDDD CCCCCCCEEECCCCC	24.10	30240740
471	Phosphorylation	KGPASVISNDDDSAS CCCCEEECCCCCCCC	31.86	30240740
476	Phosphorylation	VISNDDDSASPLHHI EECCCCCCCCCCCCC	37.33	30240740
478	Phosphorylation	SNDDDSASPLHHISN CCCCCCCCCCCCCCC	31.76	30240740
487	Phosphorylation	LHHISNGSNTPSSSE CCCCCCCCCCCCCCC	41.61	30240740
492	Phosphorylation	NGSNTPSSSEGGPDA CCCCCCCCCCCCCCC	33.34	30240740
515	Phosphorylation	PVIENPQYFGITNSQ CEECCCCCCCCCCCC	12.67	17337442
524	Ubiquitination	GITNSQLKPDTFVQH CCCCCCCCCCCHHHH	32.96	-
557	Phosphorylation	KVFLAECYNLCPEQD HHHHHHHHHHCCCCC	11.59	-
690	Ubiquitination	VGENLLVKIGDFGMS CCCCEEEEECCCCCC	40.72	-
701	Phosphorylation	FGMSRDVYSTDYYRV CCCCCCCEECCEEEE	15.33	10533983
703	Phosphorylation	MSRDVYSTDYYRVGG CCCCCEECCEEEECC	15.44	-
705	Phosphorylation	RDVYSTDYYRVGGHT CCCEECCEEEECCEE	8.02	10533983
706	Phosphorylation	DVYSTDYYRVGGHTM CCEECCEEEECCEEE	11.13	10533983
782	Phosphorylation	RTCPQEVYELMLGCW CCCCHHHHHHHHHHH	11.55	-
811	Ubiquitination	TLLQNLAKASPVYLD HHHHHHHHHCCCCHH	53.19	-
813	Phosphorylation	LQNLAKASPVYLDIL HHHHHHHCCCCHHCC	17.75	22673903
816	Phosphorylation	LAKASPVYLDILG-- HHHHCCCCHHCCC--	11.31	10533983

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
478	S	Phosphorylation	Kinase	CDK5	P49615	PSP
515	Y	Phosphorylation	Kinase	NTRK2	Q63604	GPS
701	Y	Phosphorylation	Kinase	NTRK2	Q63604	GPS
705	Y	Phosphorylation	Kinase	NTRK2	Q63604	GPS
705	Y	Phosphorylation	Kinase	SRC	P12931	PSP
706	Y	Phosphorylation	Kinase	NTRK2	Q63604	GPS
706	Y	Phosphorylation	Kinase	SRC	P12931	PSP
816	Y	Phosphorylation	Kinase	NTRK2	Q63604	GPS

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of NTRK2_RAT !!

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of NTRK2_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
GIPC1_RAT	Gipc1	physical	11251075
BDNF_HUMAN	BDNF	physical	1645620
NTF3_HUMAN	NTF3	physical	1645620
TNR16_RAT	Ngfr	physical	19549834
UCHL1_RAT	Uchl1	physical	28500221

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Identification of TrkB autophosphorylation sites and evidence thatphospholipase C-gamma 1 is a substrate of the TrkB receptor.";
Middlemas D.S., Meisenhelder J., Hunter T.;
J. Biol. Chem. 269:5458-5466(1994).
Cited for: PHOSPHORYLATION AT TYR-701; TYR-705; TYR-706 AND TYR-816.
PubMed: 8106527