Human Gene PTPN1 (uc002xvl.3) Description and Page Index
  Description: Homo sapiens protein tyrosine phosphatase, non-receptor type 1 (PTPN1), mRNA.
RefSeq Summary (NM_002827): The protein encoded by this gene is the founding member of the protein tyrosine phosphatase (PTP) family, which was isolated and identified based on its enzymatic activity and amino acid sequence. PTPs catalyze the hydrolysis of the phosphate monoesters specifically on tyrosine residues. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP has been shown to act as a negative regulator of insulin signaling by dephosphorylating the phosphotryosine residues of insulin receptor kinase. This PTP was also reported to dephosphorylate epidermal growth factor receptor kinase, as well as JAK2 and TYK2 kinases, which implicated the role of this PTP in cell growth control, and cell response to interferon stimulation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013].
Transcript (Including UTRs)
   Position: hg19 chr20:49,126,891-49,201,086 Size: 74,196 Total Exon Count: 10 Strand: +
Coding Region
   Position: hg19 chr20:49,127,065-49,199,252 Size: 72,188 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr20:49,126,891-49,201,086)mRNA (may differ from genome)Protein (435 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsGeneNetwork
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Tyrosine-protein phosphatase non-receptor type 1; EC=; AltName: Full=Protein-tyrosine phosphatase 1B; Short=PTP-1B;
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.
CATALYTIC ACTIVITY: Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.
SUBUNIT: Interacts with EPHA3 (phosphorylated); dephosphorylates EPHA3 and may regulate its trafficking and function.
INTERACTION: P15116:Cdh2 (xeno); NbExp=3; IntAct=EBI-968788, EBI-397974; P10912:GHR; NbExp=5; IntAct=EBI-968788, EBI-286316; P63166:Sumo1 (xeno); NbExp=2; IntAct=EBI-968788, EBI-80152;
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Note=Interacts with EPHA3 at the cell membrane.
PTM: Oxidized on Cys-215; the Cys-SOH formed in response to redox signaling reacts with the alpha-amido of the following residue to form a sulfenamide cross-link, triggering a conformational change that inhibits substrate binding and activity. The active site can be restored by reduction.
PTM: Ser-50 is the major site of phosphorylation as compared to Ser-242 and Ser-243. Activated by phosphorylation at Ser-50.
PTM: S-nitrosylation of Cys-215 inactivates the enzyme activity.
PTM: Sulfhydration at Cys-215 following endoplasmic reticulum stress inactivates the enzyme activity, promoting EIF2AK3/PERK activity.
SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily.
SIMILARITY: Contains 1 tyrosine-protein phosphatase domain.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PTPN1
CDC HuGE Published Literature: PTPN1
Positive Disease Associations: anthropometric parameters diabetes, type 2 insulin , atherosclerosis, diabetic , diabetes or impaired glucose tolerance , diabetes, type 2 , diabetes, type 2 glucose insulin obesity , diabetes, type 2; glucose tolerance , glucose tolerance; insulin; body fat , obesity , type 1 diabetes
Related Studies:
  1. anthropometric parameters diabetes, type 2 insulin
    Meshkani, R. et al. 2007, 1484insG Polymorphism of the PTPN1 Gene Is Associated with Insulin Resistance in an Iranian Population, Arch Med Res 2007 38(5) 556-562. [PubMed 17560463]
    Our results from a sample of Iranian type 2 diabetes cases and controls provide evidence that the 1484insG genotype of the PTPN1 gene may be associated with insulin resistance and other cardiovascular risk factors in non-diabetic male subjects.
  2. atherosclerosis, diabetic
    Burdon, K. P. et al. 2006, Association of protein tyrosine phosphatase-n1 polymorphisms with coronary calcified plaque in the diabetes heart study, Diabetes 2006 55(3) 651-8. [PubMed 16505227]
  3. diabetes or impaired glucose tolerance
    Mok A et al. 2002, A single nucleotide polymorphism in protein tyrosine phosphatase PTP-1B is associated with protection from diabetes or impaired glucose tolerance in Oji-Cree., The Journal of clinical endocrinology and metabolism. 2002 Feb;87(2):724-7. [PubMed 11836311]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: PTPN1
Diseases sorted by gene-association score: diabetes mellitus, noninsulin-dependent* (112), bubonic plague (23), carbuncle (7), leopard syndrome (5), fructose intolerance, hereditary (4), obesity (2), overnutrition (1), glucose metabolism disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 55.61 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 972.17 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -83.00174-0.477 Picture PostScript Text
3' UTR -632.341834-0.345 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000387 - Tyr/Dual-specificity_Pase
IPR016130 - Tyr_Pase_AS
IPR012265 - Tyr_Pase_non-rcpt_typ-1/2
IPR000242 - Tyr_Pase_rcpt/non-rcpt

Pfam Domains:
PF00102 - Protein-tyrosine phosphatase

SCOP Domains:
52799 - (Phosphotyrosine protein) phosphatases II

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT

- X-ray MuPIT

- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
1BZH - X-ray MuPIT 1BZJ - X-ray MuPIT 1C83 - X-ray MuPIT
1C84 - X-ray MuPIT 1C85 - X-ray MuPIT 1C86 - X-ray MuPIT
1C87 - X-ray MuPIT 1C88 - X-ray MuPIT 1ECV - X-ray MuPIT
1EEN - X-ray MuPIT 1EEO - X-ray MuPIT 1G1F - X-ray MuPIT
1G1G - X-ray MuPIT 1G1H - X-ray MuPIT 1G7F - X-ray MuPIT
1G7G - X-ray MuPIT 1GFY - X-ray MuPIT 1I57 - X-ray MuPIT
1JF7 - X-ray MuPIT 1KAK - X-ray MuPIT 1KAV - X-ray MuPIT
1L8G - X-ray MuPIT 1LQF - X-ray MuPIT 1NL9 - X-ray MuPIT
1NNY - X-ray MuPIT 1NO6 - X-ray MuPIT 1NWE - X-ray MuPIT
1NWL - X-ray MuPIT 1NZ7 - X-ray MuPIT 1OEM - X-ray MuPIT
1OEO - X-ray MuPIT 1OES - X-ray MuPIT 1OET - X-ray MuPIT
1OEU - X-ray MuPIT 1OEV - X-ray MuPIT 1ONY - X-ray MuPIT
1ONZ - X-ray MuPIT 1PA1 - X-ray MuPIT 1PH0 - X-ray MuPIT
1PTT - X-ray MuPIT 1PTU - X-ray MuPIT 1PTV - X-ray MuPIT
1PTY - X-ray MuPIT 1PXH - X-ray MuPIT 1PYN - X-ray MuPIT
1Q1M - X-ray MuPIT 1Q6J - X-ray MuPIT 1Q6M - X-ray MuPIT
1Q6N - X-ray MuPIT 1Q6P - X-ray MuPIT 1Q6S - X-ray MuPIT
1Q6T - X-ray MuPIT 1QXK - X-ray MuPIT 1SUG - X-ray MuPIT
1T48 - X-ray MuPIT 1T49 - X-ray MuPIT 1T4J - X-ray MuPIT
1WAX - X-ray MuPIT 1XBO - X-ray MuPIT 2AZR - X-ray MuPIT
2B07 - X-ray MuPIT 2B4S - X-ray MuPIT 2BGD - X-ray MuPIT
2BGE - X-ray MuPIT 2CM2 - X-ray MuPIT 2CM3 - X-ray MuPIT
2CM7 - X-ray MuPIT 2CM8 - X-ray MuPIT 2CMA - X-ray MuPIT
2CMB - X-ray MuPIT 2CMC - X-ray MuPIT 2CNE - X-ray MuPIT
2CNF - X-ray MuPIT 2CNG - X-ray MuPIT 2CNH - X-ray MuPIT
2CNI - X-ray MuPIT 2F6F - X-ray MuPIT 2F6T - X-ray MuPIT
2F6V - X-ray MuPIT 2F6W - X-ray MuPIT 2F6Y - X-ray MuPIT
2F6Z - X-ray MuPIT 2F70 - X-ray MuPIT 2F71 - X-ray MuPIT
2FJM - X-ray MuPIT 2FJN - X-ray MuPIT 2H4G - X-ray MuPIT
2H4K - X-ray MuPIT 2HB1 - X-ray MuPIT 2HNP - X-ray MuPIT
2HNQ - X-ray MuPIT 2NT7 - X-ray MuPIT 2NTA - X-ray MuPIT
2QBP - X-ray MuPIT 2QBQ - X-ray MuPIT 2QBR - X-ray MuPIT
2QBS - X-ray MuPIT 2VEU - X-ray MuPIT 2VEV - X-ray MuPIT
2VEW - X-ray MuPIT 2VEX - X-ray MuPIT 2VEY - X-ray MuPIT
2ZMM - X-ray MuPIT 2ZN7 - X-ray MuPIT 3A5J - X-ray MuPIT
3A5K - X-ray MuPIT 3CWE - X-ray MuPIT 3D9C - X-ray MuPIT
3EAX - X-ray MuPIT 3EB1 - X-ray MuPIT 3EU0 - X-ray MuPIT
3I7Z - X-ray MuPIT 3I80 - X-ray MuPIT 3QKP - X-ray MuPIT
3QKQ - X-ray MuPIT 3SME - X-ray MuPIT 3ZV2 - X-ray

ModBase Predicted Comparative 3D Structure on P18031
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserGenome BrowserNo orthologNo ortholog
Gene DetailsGene Details Gene Details  
Gene SorterGene Sorter Gene Sorter  
 Protein SequenceProtein SequenceProtein Sequence  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003723 RNA binding
GO:0004721 phosphoprotein phosphatase activity
GO:0004725 protein tyrosine phosphatase activity
GO:0005158 insulin receptor binding
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0016787 hydrolase activity
GO:0016791 phosphatase activity
GO:0019899 enzyme binding
GO:0019901 protein kinase binding
GO:0030971 receptor tyrosine kinase binding
GO:0045296 cadherin binding
GO:0046875 ephrin receptor binding
GO:0051721 protein phosphatase 2A binding

Biological Process:
GO:0006470 protein dephosphorylation
GO:0006987 activation of signaling protein activity involved in unfolded protein response
GO:0007257 activation of JUN kinase activity
GO:0008286 insulin receptor signaling pathway
GO:0009966 regulation of signal transduction
GO:0009968 negative regulation of signal transduction
GO:0016311 dephosphorylation
GO:0030100 regulation of endocytosis
GO:0030948 negative regulation of vascular endothelial growth factor receptor signaling pathway
GO:0030968 endoplasmic reticulum unfolded protein response
GO:0031532 actin cytoskeleton reorganization
GO:0033157 regulation of intracellular protein transport
GO:0034976 response to endoplasmic reticulum stress
GO:0035335 peptidyl-tyrosine dephosphorylation
GO:0035791 platelet-derived growth factor receptor-beta signaling pathway
GO:0036498 IRE1-mediated unfolded protein response
GO:0043407 negative regulation of MAP kinase activity
GO:0046626 regulation of insulin receptor signaling pathway
GO:0046627 negative regulation of insulin receptor signaling pathway
GO:0060338 regulation of type I interferon-mediated signaling pathway
GO:0060397 JAK-STAT cascade involved in growth hormone signaling pathway
GO:0061098 positive regulation of protein tyrosine kinase activity
GO:0070373 negative regulation of ERK1 and ERK2 cascade
GO:1902202 regulation of hepatocyte growth factor receptor signaling pathway
GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
GO:1903896 positive regulation of IRE1-mediated unfolded protein response
GO:1903898 negative regulation of PERK-mediated unfolded protein response
GO:1990264 peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity
GO:2000646 positive regulation of receptor catabolic process

Cellular Component:
GO:0005737 cytoplasm
GO:0005769 early endosome
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005829 cytosol
GO:0016020 membrane
GO:0031410 cytoplasmic vesicle
GO:0097443 sorting endosome
GO:0098554 cytoplasmic side of endoplasmic reticulum membrane
GO:0005886 plasma membrane

-  Descriptions from all associated GenBank mRNAs
  LF206034 - JP 2014500723-A/13537: Polycomb-Associated Non-Coding RNAs.
AK290638 - Homo sapiens cDNA FLJ75657 complete cds, highly similar to Homo sapiens protein tyrosine phosphatase, non-receptor type 1 (PTPN1), mRNA.
AK316563 - Homo sapiens cDNA, FLJ92897, Homo sapiens protein tyrosine phosphatase, non-receptor type 1 (PTPN1), mRNA.
AK299830 - Homo sapiens cDNA FLJ50851 complete cds, highly similar to Tyrosine-protein phosphatase non-receptor type1 (EC
BC015660 - Homo sapiens protein tyrosine phosphatase, non-receptor type 1, mRNA (cDNA clone MGC:23121 IMAGE:4844022), complete cds.
BC018164 - Homo sapiens protein tyrosine phosphatase, non-receptor type 1, mRNA (cDNA clone MGC:17207 IMAGE:4338750), complete cds.
M31724 - Human phosphotyrosyl-protein phosphatase (PTP-1B) mRNA, complete cds.
M33689 - Human (clone lambda-16-1) non-receptor tyrosine phosphatase 1 (PTPN1) mRNA, complete cds.
AB385151 - Synthetic construct DNA, clone: pF1KB5674, Homo sapiens PTPN1 gene for protein tyrosine phosphatase, non-receptor type 1, complete cds, without stop codon, in Flexi system.
BT006752 - Homo sapiens protein tyrosine phosphatase, non-receptor type 1 mRNA, complete cds.
MA441611 - JP 2018138019-A/13537: Polycomb-Associated Non-Coding RNAs.
JD536347 - Sequence 517371 from Patent EP1572962.
LF350708 - JP 2014500723-A/158211: Polycomb-Associated Non-Coding RNAs.
JD338694 - Sequence 319718 from Patent EP1572962.
JD173577 - Sequence 154601 from Patent EP1572962.
LF350709 - JP 2014500723-A/158212: Polycomb-Associated Non-Coding RNAs.
JD493004 - Sequence 474028 from Patent EP1572962.
MA586285 - JP 2018138019-A/158211: Polycomb-Associated Non-Coding RNAs.
MA586286 - JP 2018138019-A/158212: Polycomb-Associated Non-Coding RNAs.
LF350721 - JP 2014500723-A/158224: Polycomb-Associated Non-Coding RNAs.
LF350728 - JP 2014500723-A/158231: Polycomb-Associated Non-Coding RNAs.
LF350730 - JP 2014500723-A/158233: Polycomb-Associated Non-Coding RNAs.
DQ594466 - Homo sapiens piRNA piR-60578, complete sequence.
LF350731 - JP 2014500723-A/158234: Polycomb-Associated Non-Coding RNAs.
JD148932 - Sequence 129956 from Patent EP1572962.
DQ601174 - Homo sapiens piRNA piR-39240, complete sequence.
JD351413 - Sequence 332437 from Patent EP1572962.
JD119062 - Sequence 100086 from Patent EP1572962.
JD389654 - Sequence 370678 from Patent EP1572962.
JD356889 - Sequence 337913 from Patent EP1572962.
JD467893 - Sequence 448917 from Patent EP1572962.
JD398140 - Sequence 379164 from Patent EP1572962.
JD090400 - Sequence 71424 from Patent EP1572962.
JD199016 - Sequence 180040 from Patent EP1572962.
JD263794 - Sequence 244818 from Patent EP1572962.
JD533241 - Sequence 514265 from Patent EP1572962.
JD504971 - Sequence 485995 from Patent EP1572962.
JD246104 - Sequence 227128 from Patent EP1572962.
JD434348 - Sequence 415372 from Patent EP1572962.
JD114902 - Sequence 95926 from Patent EP1572962.
JD316401 - Sequence 297425 from Patent EP1572962.
JD129205 - Sequence 110229 from Patent EP1572962.
JD396668 - Sequence 377692 from Patent EP1572962.
JD442174 - Sequence 423198 from Patent EP1572962.
JD493914 - Sequence 474938 from Patent EP1572962.
LF350734 - JP 2014500723-A/158237: Polycomb-Associated Non-Coding RNAs.
JD466954 - Sequence 447978 from Patent EP1572962.
JD391675 - Sequence 372699 from Patent EP1572962.
JD337214 - Sequence 318238 from Patent EP1572962.
JD292989 - Sequence 274013 from Patent EP1572962.
JD366015 - Sequence 347039 from Patent EP1572962.
JD079026 - Sequence 60050 from Patent EP1572962.
JD383966 - Sequence 364990 from Patent EP1572962.
JD342513 - Sequence 323537 from Patent EP1572962.
JD466908 - Sequence 447932 from Patent EP1572962.
LF350735 - JP 2014500723-A/158238: Polycomb-Associated Non-Coding RNAs.
JD159813 - Sequence 140837 from Patent EP1572962.
JD090777 - Sequence 71801 from Patent EP1572962.
JD299369 - Sequence 280393 from Patent EP1572962.
LF350736 - JP 2014500723-A/158239: Polycomb-Associated Non-Coding RNAs.
MA586298 - JP 2018138019-A/158224: Polycomb-Associated Non-Coding RNAs.
MA586305 - JP 2018138019-A/158231: Polycomb-Associated Non-Coding RNAs.
MA586307 - JP 2018138019-A/158233: Polycomb-Associated Non-Coding RNAs.
MA586308 - JP 2018138019-A/158234: Polycomb-Associated Non-Coding RNAs.
MA586311 - JP 2018138019-A/158237: Polycomb-Associated Non-Coding RNAs.
MA586312 - JP 2018138019-A/158238: Polycomb-Associated Non-Coding RNAs.
MA586313 - JP 2018138019-A/158239: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04520 - Adherens junction
hsa04910 - Insulin signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein P18031 (Reactome details) participates in the following event(s):

R-HSA-1168445 PTP1B binds the GH receptor complex
R-HSA-8849428 PTPN1 binds PTK6
R-HSA-8849435 PTPN1 dephosphorylates PTK6
R-HSA-1169210 PTP1B dephosphorylates JAK2
R-HSA-1169192 PTP1B dephosphorylates GHR
R-HSA-377643 Dephosphorylation of inactive SRC by PTPB1
R-HSA-997311 Dephosphorylation of TYK2 by PTP1B
R-HSA-877308 Dephosphorylation of JAKs by PTPs
R-HSA-6807027 PTPN1 and PTPN2 dephosphorylate MET
R-HSA-982772 Growth hormone receptor signaling
R-HSA-8849472 PTK6 Down-Regulation
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-8848021 Signaling by PTK6
R-HSA-354192 Integrin alphaIIb beta3 signaling
R-HSA-912694 Regulation of IFNA signaling
R-HSA-877312 Regulation of IFNG signaling
R-HSA-6807004 Negative regulation of MET activity
R-HSA-168256 Immune System
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases
R-HSA-76009 Platelet Aggregation (Plug Formation)
R-HSA-9006921 Integrin signaling
R-HSA-909733 Interferon alpha/beta signaling
R-HSA-877300 Interferon gamma signaling
R-HSA-6806834 Signaling by MET
R-HSA-162582 Signal Transduction
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-913531 Interferon Signaling
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-109582 Hemostasis

-  Other Names for This Gene
  Alternate Gene Symbols: NM_002827, NP_002818, P18031, PTN1_HUMAN, PTP1B, Q5TGD8, Q9BQV9, Q9NQQ4
UCSC ID: uc002xvl.3
RefSeq Accession: NM_002827
Protein: P18031 (aka PTN1_HUMAN)
CCDS: CCDS13430.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_002827.2
exon count: 10CDS single in 3' UTR: no RNA size: 3318
ORF size: 1308CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2757.00frame shift in genome: no % Coverage: 99.94
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.