PTN2_HUMAN » Tyrosine-protein phosphatase non-receptor type 2

PTN2_HUMAN » Tyrosine-protein phosphatase non-receptor type 2
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Topology in Endoplasmic reticulum membrane
Topologylumenal side
cytoplasmic side
PTN2_HUMAN » Tyrosine-protein phosphatase non-receptor type 2 » T-cell protein-tyrosine phosphatase;TCPTP;
Hydrophobic Thickness 35.2 ± 3.6 Å
Tilt Angle 0 ± 0°
ΔGtransfer -32.2 kcal/mol
ΔGfold -13.4 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome, HMDB
Topology In
TM Segments 385-411 (385-414)
Pathways

Immune System (Reactome)

PDB 1l8k (1-314)
OPM none
Complexes none
Interactions

EGFR, Complex: PTN2:EGFR, PubMed

GHR, Complex: GHR:PTN2, PubMed

GOGB1, Complex: GOGB1:PTN2, PubMed

INSR, Complex: INSR:PTN2, PubMed

ITA1, Complex: PTN2:ITA1, PubMed

ITB1, Complex: ITA1:ITB1:PTN2, PubMed

LMAN1, Complex: PTN2:LMAN1, PubMed

PGFRB, Complex: PGFRB:PTN2, PubMed

TMED9, Complex: PTN2:TMED9, PubMed

TMEDA, Complex: PTN2:TMEDA, PubMed

Domains

AA: 42-274, PDBID: 1L8K, Subunit A, Seq Identity:100%, Protein-tyrosine phosphatase

UniProt annotation for PTN2_HUMAN » Tyrosine-protein phosphatase non-receptor type 2
FUNCTION: 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, STAT5A, STAT5B 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. Finally, it negatively regulates prolactin-mediated signaling pathway through dephosphorylation of STAT5A and STAT5B. May also bind DNA.

CATALYTIC ACTIVITY: Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.

SUBUNIT: Interacts with RMDN3. Isoform 1 interacts with TMED9. Isoform 1 interacts with STX17; dephosphorylates STX17. Interacts with ITGA1 (via cytoplasmic domain); activates the phosphatase activity towards EGFR. Interacts with TRAF2; probably involved in tumor necrosis factor-mediated signaling. Interacts with MET.

TISSUE SPECIFICITY: Ubiquitously expressed. Isoform 2 is probably the major isoform. Isoform 1 is expressed in T-cells and in placenta.

INDUCTION: Up-regulated by IL4/interleukin-4 (at protein level).

UniProt features for PTN2_HUMAN » Tyrosine-protein phosphatase non-receptor type 2
CHAIN 1 415 Tyrosine-protein phosphatase non-receptor type 2.
DOMAIN 5 275 Tyrosine-protein phosphatase.
REGION 216 222 Substrate binding (By similarity).
ACT_SITE 216 216 Phosphocysteine intermediate (By similarity).
Amino Acid Sequence for PTN2_HUMAN » Tyrosine-protein phosphatase non-receptor type 2
MPTTIEREFE ELDTQRRWQP LYLEIRNESH DYPHRVAKFP ENRNRNRYRD VSPYDHSRVK LQNAENDYIN ASLVDIEEAQ RSYILTQGPL PNTCCHFWLM VWQQKTKAVV MLNRIVEKES VKCAQYWPTD DQEMLFKETG FSVKLLSEDV KSYYTVHLLQ LENINSGETR TISHFHYTTW PDFGVPESPA SFLNFLFKVR ESGSLNPDHG PAVIHCSAGI GRSGTFSLVD TCLVLMEKGD DINIKQVLLN MRKYRMGLIQ TPDQLRFSYM AIIEGAKCIK GDSSIQKRWK ELSKEDLSPA FDHSPNKIMT EKYNGNRIGL EEEKLTGDRC TGLSSKMQDT MEENSESALR KRIREDRKAT TAQKVQQMKQ RLNENERKRK RWLYWQPILT KMGFMSVILV GAFVGWTLFF QQNAL