NTRK2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: NTRK2_HUMAN
• UniProt AC: Q16620
• Protein Name: BDNF/NT-3 growth factors receptor
• Gene Name: NTRK2
• Organism: Homo sapiens (Human).
• Sequence Length: 822
• 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 and mediate communication between neurons and glia..
• Protein Sequence: MSSWIRWHGPAMARLWGFCWLVVGFWRAAFACPTSCKCSASRIWCSDPSPGIVAFPRLEPNSVDPENITEIFIANQKRLEIINEDDVEAYVGLRNLTIVDSGLKFVAHKAFLKNSNLQHINFTRNKLTSLSRKHFRHLDLSELILVGNPFTCSCDIMWIKTLQEAKSSPDTQDLYCLNESSKNIPLANLQIPNCGLPSANLAAPNLTVEEGKSITLSCSVAGDPVPNMYWDVGNLVSKHMNETSHTQGSLRITNISSDDSGKQISCVAENLVGEDQDSVNLTVHFAPTITFLESPTSDHHWCIPFTVKGNPKPALQWFYNGAILNESKYICTKIHVTNHTEYHGCLQLDNPTHMNNGDYTLIAKNEYGKDEKQISAHFMGWPGIDDGANPNYPDVIYEDYGTAANDIGDTTNRSNEIPSTDVTDKTGREHLSVYAVVVIASVVGFCLLVMLFLLKLARHSKFGMKGPASVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKPDTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMAEGNPPTELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQEVYELMLGCWQREPHMRKNIKGIHTLLQNLAKASPVYLDILG

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	PNSVDPENITEIFIA CCCCCCCCCCEEEEE	52.44	16335952
95	N-linked_Glycosylation	EAYVGLRNLTIVDSG HHHEECCCCEEECCC	46.72	7574684
97	O-linked_Glycosylation	YVGLRNLTIVDSGLK HEECCCCEEECCCCH	23.62	28657654
121	N-linked_Glycosylation	NSNLQHINFTRNKLT CCCCCCEEECHHHHH	30.06	16335952
131	Phosphorylation	RNKLTSLSRKHFRHL HHHHHHHCHHHHCCC	38.76	24260401
141	Phosphorylation	HFRHLDLSELILVGN HHCCCCHHHHEECCC	29.98	-
151	Phosphorylation	ILVGNPFTCSCDIMW EECCCCEEECCEEEE	12.55	-
153	Phosphorylation	VGNPFTCSCDIMWIK CCCCEEECCEEEEEH	16.27	-
161	Phosphorylation	CDIMWIKTLQEAKSS CEEEEEHHHHHHHCC	25.25	-
178	N-linked_Glycosylation	TQDLYCLNESSKNIP HHCEEEECCCCCCCC	43.47	7574684
205	N-linked_Glycosylation	SANLAAPNLTVEEGK CCCCCCCCEEEECCC	43.55	7574684
241	N-linked_Glycosylation	NLVSKHMNETSHTQG HHHHHHCCCCCCCCC	49.46	7574684
253	Phosphorylation	TQGSLRITNISSDDS CCCCEEEEECCCCCC	21.77	-
254	N-linked_Glycosylation	QGSLRITNISSDDSG CCCEEEEECCCCCCC	29.76	16335952
256	Phosphorylation	SLRITNISSDDSGKQ CEEEEECCCCCCCCE	29.77	-
257	Phosphorylation	LRITNISSDDSGKQI EEEEECCCCCCCCEE	41.46	-
260	Phosphorylation	TNISSDDSGKQISCV EECCCCCCCCEEEEE	53.53	-
280	N-linked_Glycosylation	GEDQDSVNLTVHFAP CCCCCCCEEEEEECC	33.67	7574684
325	N-linked_Glycosylation	FYNGAILNESKYICT HHCCCCCCCCCEEEE	45.44	UniProtKB CARBOHYD
338	N-linked_Glycosylation	CTKIHVTNHTEYHGC EEEEEECCCCCCCEE	38.71	7574684
412	N-linked_Glycosylation	NDIGDTTNRSNEIPS HHCCCCCCCCCCCCC	47.69	7574684
414	Phosphorylation	IGDTTNRSNEIPSTD CCCCCCCCCCCCCCC	40.67	29083192
419	Phosphorylation	NRSNEIPSTDVTDKT CCCCCCCCCCCCCCC	42.79	29083192
420	Phosphorylation	RSNEIPSTDVTDKTG CCCCCCCCCCCCCCC	29.18	29083192
461	Acetylation	LKLARHSKFGMKGPA HHHHHHHCCCCCCCC	39.55	30593105
506	Phosphorylation	DAVIIGMTKIPVIEN CCEEEECEECCEECC	22.17	-
516	Phosphorylation	PVIENPQYFGITNSQ CEECCCCCCCCCCCC	12.67	10533983
558	Phosphorylation	KVFLAECYNLCPEQD HHHHHHHHHHCCCCC	11.59	25884760
573	Phosphorylation	KILVAVKTLKDASDN EEEEEEEEHHHCCHH	32.23	22964224
698	Phosphorylation	KIGDFGMSRDVYSTD EECCCCCCCCCEECC	26.21	-
702	Phosphorylation	FGMSRDVYSTDYYRV CCCCCCCEECCCEEE	15.33	10533983
706	Phosphorylation	RDVYSTDYYRVGGHT CCCEECCCEEECCEE	8.02	15494731
707	Phosphorylation	DVYSTDYYRVGGHTM CCEECCCEEECCEEE	11.13	10533983
713	Phosphorylation	YYRVGGHTMLPIRWM CEEECCEEEEEEECC	24.55	30177828
724	Phosphorylation	IRWMPPESIMYRKFT EECCCCHHHCCEEEC	20.59	30177828
727	Phosphorylation	MPPESIMYRKFTTES CCCHHHCCEEECCHH	14.69	30177828
817	Phosphorylation	LAKASPVYLDILG-- HHHHCCEEHHCCC--	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
516	Y	Phosphorylation	Kinase	NTRK2	Q16620	GPS
702	Y	Phosphorylation	Kinase	NTRK2	Q16620	GPS
706	Y	Phosphorylation	Kinase	NTRK2	Q16620	GPS
707	Y	Phosphorylation	Kinase	NTRK2	Q16620	GPS
817	Y	Phosphorylation	Kinase	NTRK2	Q16620	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	NEDD4L	Q96PU5	PMID:16701206

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of NTRK2_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 NTRK2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
FYN_HUMAN	FYN	physical	9648856
GIPC1_HUMAN	GIPC1	physical	11251075
SQSTM_HUMAN	SQSTM1	physical	12471037
SHC3_HUMAN	SHC3	physical	12074588
PLCG1_HUMAN	PLCG1	physical	12074588
P85A_HUMAN	PIK3R1	physical	12074588
SH2B1_HUMAN	SH2B1	physical	12074588
NCK2_HUMAN	NCK2	physical	12074588
TRAF6_HUMAN	TRAF6	physical	18457658
SQSTM_HUMAN	SQSTM1	physical	18457658
RPB7_HUMAN	POLR2G	physical	21988832
RANB9_HUMAN	RANBP9	physical	20403074
ACK1_HUMAN	TNK2	physical	23598414
NTF4_HUMAN	NTF4	physical	25241761

Drug and Disease Associations

• Kegg Disease
• H00043: Neuroblastoma
• OMIM Disease
• 613886: Obesity, hyperphagia, and developmental delay (OBHD)
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

N-linked Glycosylation

"Human plasma N-glycoproteome analysis by immunoaffinity subtraction,hydrazide chemistry, and mass spectrometry.";
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,Moore R.J., Smith R.D.;
J. Proteome Res. 4:2070-2080(2005).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-67; ASN-121 AND ASN-254,AND MASS SPECTROMETRY.
PubMed: 16335952

"Extracellular domain of neurotrophin receptor trkB: disulfidestructure, N-glycosylation sites, and ligand binding.";
Haniu M., Talvenheimo J., Le J., Katta V., Welcher A., Rohde M.F.;
Arch. Biochem. Biophys. 322:256-264(1995).
Cited for: DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-67; ASN-95; ASN-121;ASN-178; ASN-205; ASN-241; ASN-254; ASN-280; ASN-338 AND ASN-412.
PubMed: 7574684