dbPTM

PTN2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	PTN2_HUMAN
UniProt AC	P17706
Protein Name	Tyrosine-protein phosphatase non-receptor type 2
Gene Name	PTPN2
Organism	Homo sapiens (Human).
Sequence Length	415
Subcellular Localization	Isoform 1: Endoplasmic reticulum . Endoplasmic reticulum-Golgi intermediate compartment . Targeted to the endoplasmic reticulum by its C-terminal hydrophobic region. Isoform 2: Nucleus. Cytoplasm. Cell membrane. Predominantly localizes to chrom
Protein Description	Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3 and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the development of the immune system. Functions in T-cell receptor signaling through dephosphorylation of FYN and LCK to control T-cells differentiation and activation. Dephosphorylates CSF1R, negatively regulating its downstream signaling and macrophage differentiation. Negatively regulates cytokine (IL2/interleukin-2 and interferon)-mediated signaling through dephosphorylation of the cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that propagate signaling downstream of the cytokine receptors. Also regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine signaling through dephosphorylation of STAT3 and STAT6 respectively. In addition to the immune system, it is involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth. Activated by the integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates EGF signaling. Dephosphorylates PDGFRB and negatively regulates platelet-derived growth factor receptor-beta signaling pathway and therefore cell proliferation. Negatively regulates tumor necrosis factor-mediated signaling downstream via MAPK through SRC dephosphorylation. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of the hepatocyte growth factor receptor MET. Plays also an important role in glucose homeostasis. For instance, negatively regulates the insulin receptor signaling pathway through the dephosphorylation of INSR and control gluconeogenesis and liver glucose production through negative regulation of the IL6 signaling pathways. May also bind DNA..
Protein Sequence	MPTTIEREFEELDTQRRWQPLYLEIRNESHDYPHRVAKFPENRNRNRYRDVSPYDHSRVKLQNAENDYINASLVDIEEAQRSYILTQGPLPNTCCHFWLMVWQQKTKAVVMLNRIVEKESVKCAQYWPTDDQEMLFKETGFSVKLLSEDVKSYYTVHLLQLENINSGETRTISHFHYTTWPDFGVPESPASFLNFLFKVRESGSLNPDHGPAVIHCSAGIGRSGTFSLVDTCLVLMEKGDDINIKQVLLNMRKYRMGLIQTPDQLRFSYMAIIEGAKCIKGDSSIQKRWKELSKEDLSPAFDHSPNKIMTEKYNGNRIGLEEEKLTGDRCTGLSSKMQDTMEENSESALRKRIREDRKATTAQKVQQMKQRLNENERKRKRWLYWQPILTKMGFMSVILVGAFVGWTLFFQQNAL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
3	Phosphorylation	-----MPTTIEREFE -----CCCCHHHHHH	38.82	29116813
4	Phosphorylation	----MPTTIEREFEE ----CCCCHHHHHHH	18.25	29116813
14	Phosphorylation	REFEELDTQRRWQPL HHHHHHHHHHCCEEE	36.28	29116813
22	Phosphorylation	QRRWQPLYLEIRNES HHCCEEEEEEECCCC	14.69	28796482
29	Phosphorylation	YLEIRNESHDYPHRV EEEECCCCCCCCCCC	25.80	28152594
32	Phosphorylation	IRNESHDYPHRVAKF ECCCCCCCCCCCCCC	8.77	28152594
38	Ubiquitination	DYPHRVAKFPENRNR CCCCCCCCCCCCCCC	59.60	-
38	Ubiquitination	DYPHRVAKFPENRNR CCCCCCCCCCCCCCC	59.60	19608861
38	Acetylation	DYPHRVAKFPENRNR CCCCCCCCCCCCCCC	59.60	25953088
48	Phosphorylation	ENRNRNRYRDVSPYD CCCCCCCCCCCCCCC	18.08	28796482
52	Phosphorylation	RNRYRDVSPYDHSRV CCCCCCCCCCCCCHH	23.25	28796482
54	Phosphorylation	RYRDVSPYDHSRVKL CCCCCCCCCCCHHCC	20.84	28796482
57	Phosphorylation	DVSPYDHSRVKLQNA CCCCCCCCHHCCCCC	35.55	28796482
60	Ubiquitination	PYDHSRVKLQNAEND CCCCCHHCCCCCCCC	43.15	-
60	Ubiquitination	PYDHSRVKLQNAEND CCCCCHHCCCCCCCC	43.15	-
68	Phosphorylation	LQNAENDYINASLVD CCCCCCCCCCEEEEE	13.99	28796482
72	Phosphorylation	ENDYINASLVDIEEA CCCCCCEEEEEHHHH	25.16	26552605
106	Phosphorylation	LMVWQQKTKAVVMLN HHHHHHHHCHHHHHC	21.65	20068231
118	Acetylation	MLNRIVEKESVKCAQ HHCCHHHHCCCCCCC	44.38	25953088
122	Ubiquitination	IVEKESVKCAQYWPT HHHHCCCCCCCCCCC	32.88	-
137	Ubiquitination	DDQEMLFKETGFSVK CCHHHHHHHHCCEEE	50.86	-
144	Ubiquitination	KETGFSVKLLSEDVK HHHCCEEEECCHHHH	42.38	-
179	O-linked_Glycosylation	ISHFHYTTWPDFGVP EEEEEEECCCCCCCC	28.03	29351928
216	S-nitrosylation	HGPAVIHCSAGIGRS CCCEEEEECCCCCCC	1.73	-
245	Ubiquitination	KGDDINIKQVLLNMR CCCCCCHHHHHHHCH	29.84	2190698
245 (in isoform 2)	Ubiquitination	-	29.84	21906983
245 (in isoform 1)	Ubiquitination	-	29.84	21906983
254	Phosphorylation	VLLNMRKYRMGLIQT HHHHCHHHHCCCCCC	8.75	24043423
261	Phosphorylation	YRMGLIQTPDQLRFS HHCCCCCCCCHHHHE	23.10	24043423
268	Phosphorylation	TPDQLRFSYMAIIEG CCCHHHHEEEHHHHC	13.94	30631047
268	Ubiquitination	TPDQLRFSYMAIIEG CCCHHHHEEEHHHHC	13.94	-
269	Phosphorylation	PDQLRFSYMAIIEGA CCHHHHEEEHHHHCC	6.45	30631047
280	Ubiquitination	IEGAKCIKGDSSIQK HHCCCCCCCCHHHHH	67.16	-
287	Ubiquitination	KGDSSIQKRWKELSK CCCHHHHHHHHHHCH	59.56	-
293	Phosphorylation	QKRWKELSKEDLSPA HHHHHHHCHHHCCHH	34.78	23401153
294	Ubiquitination	KRWKELSKEDLSPAF HHHHHHCHHHCCHHC	68.80	-
298	Phosphorylation	ELSKEDLSPAFDHSP HHCHHHCCHHCCCCC	26.89	29255136
304	Phosphorylation	LSPAFDHSPNKIMTE CCHHCCCCCCCEEEE	31.82	29255136
304 (in isoform 2)	Phosphorylation	-	31.82	7593185
307	Ubiquitination	AFDHSPNKIMTEKYN HCCCCCCCEEEECCC	36.92	-
307	Acetylation	AFDHSPNKIMTEKYN HCCCCCCCEEEECCC	36.92	25953088
310	Phosphorylation	HSPNKIMTEKYNGNR CCCCCEEEECCCCCC	32.57	26074081
312	Ubiquitination	PNKIMTEKYNGNRIG CCCEEEECCCCCCCC	34.54	19608861
312	Acetylation	PNKIMTEKYNGNRIG CCCEEEECCCCCCCC	34.54	19608861
313	Phosphorylation	NKIMTEKYNGNRIGL CCEEEECCCCCCCCC	23.28	26074081
324	Ubiquitination	RIGLEEEKLTGDRCT CCCCCCCCCCCCCCC	55.41	-
326	Phosphorylation	GLEEEKLTGDRCTGL CCCCCCCCCCCCCHH	48.37	26074081
335	Acetylation	DRCTGLSSKMQDTME CCCCHHCHHHHHHHH	36.87	19608861
336	Ubiquitination	RCTGLSSKMQDTMEE CCCHHCHHHHHHHHH	36.89	-
336	Acetylation	RCTGLSSKMQDTMEE CCCHHCHHHHHHHHH	36.89	25953088
337	Sulfoxidation	CTGLSSKMQDTMEEN CCHHCHHHHHHHHHC	4.75	21406390
340	Phosphorylation	LSSKMQDTMEENSES HCHHHHHHHHHCCHH	15.02	28555341
345	Phosphorylation	QDTMEENSESALRKR HHHHHHCCHHHHHHH	35.89	28555341
347	Phosphorylation	TMEENSESALRKRIR HHHHCCHHHHHHHHH	32.21	21815630
364	Ubiquitination	RKATTAQKVQQMKQR HHCHHHHHHHHHHHH	39.28	-
384	Phosphorylation	RKRKRWLYWQPILTK HHHHHHHHHHHHHHH	8.61	-

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
304	S	Phosphorylation	Kinase	CDK1	P06493	PSP
304	S	Phosphorylation	Kinase	CDK2	P24941	PSP
304	S	Phosphorylation	Kinase	CDK-FAMILY	-	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of PTN2_HUMAN !!

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 PTN2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
STAT1_HUMAN	STAT1	physical	19171783
TRAF2_HUMAN	TRAF2	physical	15696169
SRC_HUMAN	SRC	physical	15696169
STAT6_HUMAN	STAT6	physical	17210636
CO5A1_HUMAN	COL5A1	physical	26186194
SYVC_HUMAN	VARS	physical	26344197
APLP2_HUMAN	APLP2	physical	27880917
A4_HUMAN	APP	physical	27880917
CALU_HUMAN	CALU	physical	27880917
CASC4_HUMAN	CASC4	physical	27880917
CSPG5_HUMAN	CSPG5	physical	27880917
GOLI4_HUMAN	GOLIM4	physical	27880917
ECHA_HUMAN	HADHA	physical	27880917
SYHC_HUMAN	HARS	physical	27880917
HMGN5_HUMAN	HMGN5	physical	27880917
IMA5_HUMAN	KPNA1	physical	27880917
IMA7_HUMAN	KPNA6	physical	27880917
NUP50_HUMAN	NUP50	physical	27880917
PRS4_HUMAN	PSMC1	physical	27880917
PRS7_HUMAN	PSMC2	physical	27880917
PRS6B_HUMAN	PSMC4	physical	27880917
PRS8_HUMAN	PSMC5	physical	27880917
PRS10_HUMAN	PSMC6	physical	27880917
PSMD1_HUMAN	PSMD1	physical	27880917
PSD10_HUMAN	PSMD10	physical	27880917
PSMD2_HUMAN	PSMD2	physical	27880917
PSMD4_HUMAN	PSMD4	physical	27880917
PSMD6_HUMAN	PSMD6	physical	27880917
SETD7_HUMAN	SETD7	physical	27880917
OCLN_HUMAN	OCLN	physical	26090670
CO5A1_HUMAN	COL5A1	physical	28514442
PTN20_HUMAN	PTPN20B	physical	27432908
IMA6_HUMAN	KPNA5	physical	27432908
AN32C_HUMAN	ANP32C	physical	27432908
IMA5_HUMAN	KPNA1	physical	27432908
AN32B_HUMAN	ANP32B	physical	27432908
TXND5_HUMAN	TXNDC5	physical	27432908
NMNA1_HUMAN	NMNAT1	physical	27432908
AN32E_HUMAN	ANP32E	physical	27432908
TR61B_HUMAN	TRMT61B	physical	27432908
RCL1_HUMAN	RCL1	physical	27432908
BRX1_HUMAN	BRIX1	physical	27432908
IMA7_HUMAN	KPNA6	physical	27432908
GAR1_HUMAN	GAR1	physical	27432908
PNO1_HUMAN	PNO1	physical	27432908
G45IP_HUMAN	GADD45GIP1	physical	27432908
ZCCHL_HUMAN	ZC3HAV1L	physical	27432908
DIM1_HUMAN	DIMT1	physical	27432908
NSUN5_HUMAN	NSUN5	physical	27432908
DJC10_HUMAN	DNAJC10	physical	27432908
CH033_HUMAN	C8orf33	physical	27432908
MRM3_HUMAN	RNMTL1	physical	27432908
G3BP1_HUMAN	G3BP1	physical	27432908
SPB1_HUMAN	FTSJ3	physical	27432908
IF2A_HUMAN	EIF2S1	physical	27432908
BYST_HUMAN	BYSL	physical	27432908
PSD13_HUMAN	PSMD13	physical	27432908
RBM34_HUMAN	RBM34	physical	27432908
CSKI1_HUMAN	CASKIN1	physical	27432908
HOP2_HUMAN	PSMC3IP	physical	27432908
GTPBA_HUMAN	GTPBP10	physical	27432908
PSMD8_HUMAN	PSMD8	physical	27432908
RL3L_HUMAN	RPL3L	physical	27432908
TFB1M_HUMAN	TFB1M	physical	27432908
RPP30_HUMAN	RPP30	physical	27432908
DUS10_HUMAN	DUSP10	physical	27432908
EXOS4_HUMAN	EXOSC4	physical	27432908
GRSF1_HUMAN	GRSF1	physical	27432908
EGFR_HUMAN	EGFR	physical	11514572

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.

Regulatory Network of PTN2_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-38 AND LYS-312, AND MASSSPECTROMETRY.	19608861 [Abstract]
Phosphorylation
Reference	PubMed
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298 AND SER-304, ANDMASS SPECTROMETRY.	19413330 [Abstract]
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298 AND SER-304, ANDMASS SPECTROMETRY.	18669648 [Abstract]