Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

P4HB (P07237) - Overview - Molecular Target Synopsis

Protein


P4HB, Protein disulfide-isomerase
Enzyme Classification 5.3.4.1
UniProt P07237

Also Known as PDIA1_HUMAN, P4HB, ERBA2L, PDI, PDIA1, PO4DB

This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations, functions as a chaperone that inhibits aggregation of misfolded proteins. At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). Heterodimer; heterodimerizes with the protein microsomal triglyceride transfer MTTP (PubMed:23475612, PubMed:26224785). Homodimer. Monomers and homotetramers may also occur. Also constitutes the structural subunit of prolyl 4-hydroxylase and of the microsomal triacylglycerol transfer protein MTTP in mammalian cells. Stabilizes both enzymes and retain them in the ER without contributing to the catalytic activity (By similarity). Binds UBQLN1 (PubMed:12095988). Interacts with ERO1B (PubMed:11707400). Binds to CD4, and upon HIV-1 binding to the cell membrane, is part of a P4HB/PDI-CD4-CXCR4-gp120 complex.

4JU5
CRYSTAL STRUCTURE OF THE DIMERIC FORM OF THE BB' DOMAINS OF HUMAN PROTEIN DISULFIDE ISOMERASE
RCSB/PDB
Inspect Structure
See all 3D Structures for P4HB

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: P4HB is active in the following subcellular-locations: cell membrane, endoplasmic reticulum, endoplasmic reticulum lumen, melanosome.
GO terms: P4HB is active in the following subcellular-locations: endoplasmic reticulum, endoplasmic reticulum chaperone complex, endoplasmic reticulum lumen, endoplasmic reticulum-Golgi intermediate compartment, external side of plasma membrane, extracellular exosome, extracellular region, focal adhesion, melanosome, procollagen-proline 4-dioxygenase complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project P4HB has gain in 1 cell-lines, loss in 1 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: CAKI_1, MCF7, HS578T

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: G84, A3/KAW, SF539

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: IMR-90, SK-N-SH, BJ

(see details)

3D Structures


For P4HB there are:
10 structures (12 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


P4HB has been screened with 43 compounds (45 bioactivities), 3 compounds have bioactivities that show binding affinity of <= 500nM (3 bioactivities). (see details)