Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Tyrosine-protein phosphatase non-receptor type 1  

UniProtKB / Swiss-Prot ID :  PTN1_HUMAN

Gene Name (Synonyms) : 
PTPN1, PTP1B  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Note=Interacts with EPHA3 at the cell membrane. 

Protein Function :  Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. 

Protein Sequence MEMEKEFEQIDKSGSWAAIYQDIRHEASDFPCRVAKLPKNKNRNRYRDVSPFDHSRIKLHQEDNDYINAS...
Predicted Secondary Structure CCHHHHHHHHHHCCCHHHHHHHHHHCCCCCCEEECCCCCCCCCCCCCCCCCCCCCEEEECCCCCCEEEEE...
Protein Variant
LocationDescription
381G -> S (in dbSNP:rs16995304). VAR_022013
387P -> L (associated with low glucosetolerance; dbSNP:rs16995309).
- top -

Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
- top -

Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
1N-acetylmethionine----MEMEK
----CCHHH
11.32HPRD
Link
1N-acetylmethionine.----MEMEK
----CCHHH
11.32UniProtKB
Link
20PhosphotyrosineWAAIYQDIR
HHHHHHHHH
8.73HPRD
Link
20PhosphotyrosineWAAIYQDIR
HHHHHHHHH
8.73PhosphoELM
Link
20PhosphotyrosineWAAIYQDIR
HHHHHHHHH
8.73Phosphositeplus
Link
20Phosphotyrosine.WAAIYQDIR
HHHHHHHHH
8.73UniProtKB
Link
32S-nitrosocysteineSDFPCRVAK
CCCCEEECC
5.73dbSNO
Link
46PhosphotyrosineNRNRYRDVS
CCCCCCCCC
18.08Phosphositeplus
Link
50PhosphoserineYRDVSPFDH
CCCCCCCCC
24.92Phosphositeplus
Link
50PhosphoserineYRDVSPFDH
CCCCCCCCC
24.92SysPTM
Link
50Phosphoserine (AKT1)YRDVSPFDH
CCCCCCCCC
24.92HPRD
Link
50Phosphoserine (CLK1)YRDVSPFDH
CCCCCCCCC
24.92HPRD
Link
50Phosphoserine (CLK2)YRDVSPFDH
CCCCCCCCC
24.92HPRD
Link
50Phosphoserine (PKB_group;CLK1)YRDVSPFDH
CCCCCCCCC
24.92PhosphoELM
Link
50Phosphoserine; by PKB/AKT1, CLK1 andCLK2.YRDVSPFDH
CCCCCCCCC
24.92UniProtKB
Link
66PhosphotyrosineEDNDYINAS
CCCCEEEEE
11.43Phosphositeplus
Link
66Phosphotyrosine (EGFR)EDNDYINAS
CCCCEEEEE
11.43HPRD
Link
66Phosphotyrosine (EGFR)EDNDYINAS
CCCCEEEEE
11.43PhosphoELM
Link
66Phosphotyrosine (INSR)EDNDYINAS
CCCCEEEEE
11.43HPRD
Link
66Phosphotyrosine; by EGFR.EDNDYINAS
CCCCEEEEE
11.43UniProtKB
Link
92S-nitrosocysteineLPNTCGHFW
CHHHHHHHH
5.18dbSNO
Link
152PhosphotyrosineDIKSYYTVR
EECCCEEEE
9.73Phosphositeplus
Link
152Phosphotyrosine (INSR)DIKSYYTVR
EECCCEEEE
9.73HPRD
Link
152Phosphotyrosine (INSR)DIKSYYTVR
EECCCEEEE
9.73PhosphoELM
Link
153PhosphotyrosineIKSYYTVRQ
ECCCEEEEE
13.07Phosphositeplus
Link
153Phosphotyrosine (INSR)IKSYYTVRQ
ECCCEEEEE
13.07HPRD
Link
153Phosphotyrosine (INSR)IKSYYTVRQ
ECCCEEEEE
13.07PhosphoELM
Link
215Cysteine persulfide.VVVHCSAGI
EEEECCCCC
1.69UniProtKB
Link
215N,N-(cysteine-1,S-diyl)serine (Cys-Ser); in inhibited form.VVVHCSAGI
EEEECCCCC
1.69UniProtKB
Link
215S-glutathionyl cysteineVVVHCSAGI
EEEECCCCC
1.69HPRD
Link
215S-nitrosocysteineVVVHCSAGI
EEEECCCCC
1.69dbSNO
Link
215S-nitrosocysteine; in reversiblyinhibited form.VVVHCSAGI
EEEECCCCC
1.69UniProtKB
Link
242PhosphoserineRKDPSSVDI
CCCCCCCCH
53.80Phosphositeplus
Link
242Phosphoserine (CLK1)RKDPSSVDI
CCCCCCCCH
53.80HPRD
Link
242Phosphoserine (CLK2)RKDPSSVDI
CCCCCCCCH
53.80HPRD
Link
242Phosphoserine; by CLK1 and CLK2.RKDPSSVDI
CCCCCCCCH
53.80UniProtKB
Link
243PhosphoserineKDPSSVDIK
CCCCCCCHH
29.24Phosphositeplus
Link
243Phosphoserine (CLK1)KDPSSVDIK
CCCCCCCHH
29.24HPRD
Link
243Phosphoserine (CLK2)KDPSSVDIK
CCCCCCCHH
29.24HPRD
Link
243Phosphoserine; by CLK1 and CLK2.KDPSSVDIK
CCCCCCCHH
29.24UniProtKB
Link
271PhosphotyrosineLRFSYLAVI
HHHHHHHHH
8.93Phosphositeplus
Link
295PhosphoserineWKELSHEDL
CCCHHHHCC
26.39HPRD
Link-
295PhosphoserineWKELSHEDL
CCCHHHHCC
26.39Phosphositeplus
Link-
295PhosphoserineWKELSHEDL
CCCHHHHCC
26.39SysPTM
Link-
295Phosphoserine.WKELSHEDL
CCCHHHHCC
26.39UniProtKB
Link-
335Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)HQWVKEETQ
HHHHHHHHH
47.04Phosphositeplus
Link-
347Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)DCPIKEEKG
CCCCCHHHC
44.99Phosphositeplus
Link-
350Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)IKEEKGSPL
CCHHHCCCC
66.82Phosphositeplus
Link-
352PhosphoserineEEKGSPLNA
HHHCCCCCC
36.96PhosphoELM
Link-
352PhosphoserineEEKGSPLNA
HHHCCCCCC
36.96Phosphositeplus
Link-
352PhosphoserineEEKGSPLNA
HHHCCCCCC
36.96SysPTM
Link-
352Phosphoserine (CSNK2A1)EEKGSPLNA
HHHCCCCCC
36.96HPRD
Link-
352Phosphoserine (CSNK2A2)EEKGSPLNA
HHHCCCCCC
36.96HPRD
Link-
352Phosphoserine.EEKGSPLNA
HHHCCCCCC
36.96UniProtKB
Link-
365PhosphoserineIESMSQDTE
CCCCCCHHH
33.90Phosphositeplus
Link-
378PhosphoserineVVGGSLRGA
HHHCCCCHH
14.68Phosphositeplus
Link-
378Phosphoserine (CSNK2A1)VVGGSLRGA
HHHCCCCHH
14.68HPRD
Link-
378Phosphoserine (CSNK2A2)VVGGSLRGA
HHHCCCCHH
14.68HPRD
Link-
378Phosphoserine (PKC_group;PKC_alpha)VVGGSLRGA
HHHCCCCHH
14.68PhosphoELM
Link-
378Phosphoserine; by PKC.VVGGSLRGA
HHHCCCCHH
14.68UniProtKB
Link-
386PhosphoserineAQAASPAKG
HHHCCCCCC
28.53Phosphositeplus
Link-
386Phosphoserine (CDK1)AQAASPAKG
HHHCCCCCC
28.53HPRD
Link-
386Phosphoserine (CDK_group;CDK1)AQAASPAKG
HHHCCCCCC
28.53PhosphoELM
Link-
386Phosphoserine (CSNK2A1)AQAASPAKG
HHHCCCCCC
28.53HPRD
Link-
386Phosphoserine (CSNK2A2)AQAASPAKG
HHHCCCCCC
28.53HPRD
Link-
386Phosphoserine; by CDK1.AQAASPAKG
HHHCCCCCC
28.53UniProtKB
Link-
- top -

Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
PPIP1_HUMANphysical interactionMINT-51115MINT9857189
INSR_HUMANphysical interactionMINT-1894192MINT16582879
INSR_HUMANdirect interactionMINT-1894168MINT16582879
CADH2_HUMANphysical interactionMINT-73489MINT11106648
CADH2_HUMANphysical interactionMINT-73488MINT11106648
GHR_HUMANdirect interaction
dephosphorylation
physical interaction
physical interaction
physical interaction
EBI-1265790
EBI-1265906
EBI-1
intact12907755
12907755
12907755
12907755
12907755
ACTN1_HUMANdephosphorylationEBI-968815
intact16291744
GRB2_HUMANin vivoHPRD:01477HPRD12388170
10660596
CADH2_HUMANin vitroHPRD:01477HPRD12377785
CTNB1_HUMANin vivoHPRD:01477HPRD12377785
ESR1_HUMANin vitroHPRD:01477HPRD7539106
IRS1_HUMANin vivoHPRD:01477HPRD10660596
INSR_HUMANin vitro
in vivo
HPRD:01477HPRD8826975
12237455
11506178
9355745
JAK2_HUMANin vivoHPRD:01477HPRD11694501
IGF1R_HUMANin vivoHPRD:01477HPRD8999839
PGFRB_HUMANin vivoHPRD:01477HPRD7545675
BCR_HUMANin vitro
in vivo
HPRD:01477HPRD9566916
LTK_HUMANin vitroHPRD:01477HPRD12237455
MK01_HUMANin vitroHPRD:01477HPRD12082107
SRC_HUMANin vitro
in vivo
HPRD:01477HPRD12468645
8647855
9261115
11007774
STA5A_HUMANin vitroHPRD:01477HPRD12237455
STA5B_HUMANin vitroHPRD:01477HPRD12237455
IKBA_HUMANin vivoHPRD:01477HPRD8940099
CAN2_HUMANin vitroHPRD:01477HPRD9407132
TRPV6_HUMANin vivoHPRD:01477HPRD15894168
LAT_HUMANin vitroHPRD:01477HPRD12857726
- top -

Disease Reference
Kegg disease
There are no disease associations of PTM sites.
Drug Reference
Kegg drug
D04050 Ertiprotafib (USAN/INN)
DrugBank
DB01133Tiludronate
- top -
Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"Human placenta protein-tyrosine-phosphatase: amino acid sequence andrelationship to a family of receptor-like proteins.";
Charbonneau H., Tonks N.K., Kumar S., Diltz C.D., Harrylock M.,Cool D.E., Krebs E.G., Fischer E.H., Walsh K.A.;
Proc. Natl. Acad. Sci. U.S.A. 86:5252-5256(1989).
Cited for: PROTEIN SEQUENCE OF 1-321.
Phosphorylation
ReferencePubMed
"The CLK family kinases, CLK1 and CLK2, phosphorylate and activate thetyrosine phosphatase, PTP-1B.";
Moeslein F.M., Myers M.P., Landreth G.E.;
J. Biol. Chem. 274:26697-26704(1999).
Cited for: PHOSPHORYLATION AT SER-50; SER-242 AND SER-243, AND MUTAGENESIS OFSER-50.
"Phosphorylation of PTP1B at Ser(50) by Akt impairs its ability todephosphorylate the insulin receptor.";
Ravichandran L.V., Chen H., Li Y., Quon M.J.;
Mol. Endocrinol. 15:1768-1780(2001).
Cited for: PHOSPHORYLATION AT SER-50, AND MUTAGENESIS OF SER-50.
"Immunoaffinity profiling of tyrosine phosphorylation in cancercells.";
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,Zha X.-M., Polakiewicz R.D., Comb M.J.;
Nat. Biotechnol. 23:94-101(2005).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-20, AND MASSSPECTROMETRY.
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks.";
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.;
Cell 127:635-648(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50 AND SER-295, AND MASSSPECTROMETRY.
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle.";
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.;
Mol. Cell 31:438-448(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50 AND SER-352, AND MASSSPECTROMETRY.
"Multi-site phosphorylation of the protein tyrosine phosphatase,PTP1B: identification of cell cycle regulated and phorbol esterstimulated sites of phosphorylation.";
Flint A.J., Gebbink M.F.G.B., Franza B.R. Jr., Hill D.E., Tonks N.K.;
EMBO J. 12:1937-1946(1993).
Cited for: PHOSPHORYLATION AT SER-352; SER-378 AND SER-386.
"Protein tyrosine phosphatase 1B interacts with and is tyrosinephosphorylated by the epidermal growth factor receptor.";
Liu F., Chernoff J.;
Biochem. J. 327:139-145(1997).
Cited for: PHOSPHORYLATION AT TYR-66.
S-nitrosylation
ReferencePubMed
"H2s-induced sulfhydration of the phosphatase PTP1B and its role inthe endoplasmic reticulum stress response.";
Krishnan N., Fu C., Pappin D.J., Tonks N.K.;
Sci. Signal. 4:RA86-RA86(2011).
Cited for: FUNCTION, SULFHYDRATION AT CYS-215, S-NITROSYLATION AT CYS-215,MUTAGENESIS OF CYS-215, AND MUTAGENESIS OF ASP-181 AND CYS-215.
- top -
Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures