Human Gene P4HB (ENST00000331483.9) Description and Page Index
  Description: Homo sapiens prolyl 4-hydroxylase subunit beta (P4HB), mRNA. (from RefSeq NM_000918)
RefSeq Summary (NM_000918): This gene encodes the beta subunit of prolyl 4-hydroxylase, a highly abundant multifunctional enzyme that belongs to the protein disulfide isomerase family. When present as a tetramer consisting of two alpha and two beta subunits, this enzyme is involved in hydroxylation of prolyl residues in preprocollagen. This enzyme is also a disulfide isomerase containing two thioredoxin domains that catalyze the formation, breakage and rearrangement of disulfide bonds. Other known functions include its ability to act as a chaperone that inhibits aggregation of misfolded proteins in a concentration-dependent manner, its ability to bind thyroid hormone, its role in both the influx and efflux of S-nitrosothiol-bound nitric oxide, and its function as a subunit of the microsomal triglyceride transfer protein complex. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1803611.5600.1, HM005572.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1968540, SAMEA1968832 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000331483.9/ ENSP00000327801.4 RefSeq Select criteria :: based on conservation, expression ##RefSeq-Attributes-END##
Gencode Transcript: ENST00000331483.9
Gencode Gene: ENSG00000185624.15
Transcript (Including UTRs)
   Position: hg38 chr17:81,843,166-81,860,535 Size: 17,370 Total Exon Count: 11 Strand: -
Coding Region
   Position: hg38 chr17:81,844,012-81,860,471 Size: 16,460 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:81,843,166-81,860,535)mRNA (may differ from genome)Protein (508 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: PDIA1_HUMAN
DESCRIPTION: RecName: Full=Protein disulfide-isomerase; Short=PDI; EC=5.3.4.1; AltName: Full=Cellular thyroid hormone-binding protein; AltName: Full=Prolyl 4-hydroxylase subunit beta; AltName: Full=p55; Flags: Precursor;
FUNCTION: 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.
CATALYTIC ACTIVITY: Catalyzes the rearrangement of -S-S- bonds in proteins.
SUBUNIT: 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. Binds to CD4, and upon HIV-1 binding to the cell membrane, is part of a P4HB/PDI-CD4-CXCR4-gp120 complex.
INTERACTION: Q03518:TAP1; NbExp=4; IntAct=EBI-395883, EBI-747259;
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen. Melanosome. Cell membrane; Peripheral membrane protein (Potential). Note=Highly abundant. In some cell types, seems to be also secreted or associated with the plasma membrane, where it undergoes constant shedding and replacement from intracellular sources (Probable). Localizes near CD4-enriched regions on lymphoid cell surfaces. Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
MISCELLANEOUS: Reduces and may activate fusogenic properties of HIV-1 gp120 surface protein, thereby enabling HIV-1 entry into the cell.
SIMILARITY: Belongs to the protein disulfide isomerase family.
SIMILARITY: Contains 2 thioredoxin domains.

-  MalaCards Disease Associations
  MalaCards Gene Search: P4HB
Diseases sorted by gene-association score: cole-carpenter syndrome 1* (1329), cole-carpenter syndrome* (395), abetalipoproteinemia (19), carpenter syndrome (19), multiple sulfatase deficiency (6), autosomal dominant nonsyndromic deafness 20 (5)
* = Manually curated disease association

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

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 764.07 RPKM in Pancreas
Total median expression: 8160.53 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 -19.8064-0.309 Picture PostScript Text
3' UTR -323.80846-0.383 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
IPR005788 - Disulphide_isomerase
IPR005792 - Prot_disulphide_isomerase
IPR005746 - Thioredoxin
IPR012336 - Thioredoxin-like_fold
IPR017937 - Thioredoxin_CS
IPR013766 - Thioredoxin_domain

Pfam Domains:
PF00085 - Thioredoxin

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

1BJX
- NMR MuPIT

1MEK
- NMR MuPIT

1X5C
- NMR MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2BJX - NMR MuPIT 2K18 - NMR MuPIT 3BJ5 - X-ray MuPIT
3UEM - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P07237
FrontTopSide
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
Genome BrowserGenome BrowserNo orthologGenome BrowserNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsemblEnsembl  
Protein SequenceProtein Sequence Protein Sequence  
AlignmentAlignment Alignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003723 RNA binding
GO:0003756 protein disulfide isomerase activity
GO:0004656 procollagen-proline 4-dioxygenase activity
GO:0005178 integrin binding
GO:0005515 protein binding
GO:0015037 peptide disulfide oxidoreductase activity
GO:0016853 isomerase activity
GO:0019899 enzyme binding
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0006457 protein folding
GO:0018401 peptidyl-proline hydroxylation to 4-hydroxy-L-proline
GO:0034378 chylomicron assembly
GO:0034379 very-low-density lipoprotein particle assembly
GO:0034976 response to endoplasmic reticulum stress
GO:0035722 interleukin-12-mediated signaling pathway
GO:0038155 interleukin-23-mediated signaling pathway
GO:0043687 post-translational protein modification
GO:0044267 cellular protein metabolic process
GO:0045454 cell redox homeostasis
GO:0046598 positive regulation of viral entry into host cell
GO:0055114 oxidation-reduction process
GO:0071456 cellular response to hypoxia
GO:1902175 regulation of oxidative stress-induced intrinsic apoptotic signaling pathway

Cellular Component:
GO:0005576 extracellular region
GO:0005783 endoplasmic reticulum
GO:0005788 endoplasmic reticulum lumen
GO:0005793 endoplasmic reticulum-Golgi intermediate compartment
GO:0005886 plasma membrane
GO:0005925 focal adhesion
GO:0009897 external side of plasma membrane
GO:0016020 membrane
GO:0016222 procollagen-proline 4-dioxygenase complex
GO:0034663 endoplasmic reticulum chaperone complex
GO:0042470 melanosome
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  HM005572 - Homo sapiens clone HTL-S-32 testicular secretory protein Li 32 mRNA, complete cds.
LF384827 - JP 2014500723-A/192330: Polycomb-Associated Non-Coding RNAs.
MA620404 - JP 2018138019-A/192330: Polycomb-Associated Non-Coding RNAs.
BC018801 - Homo sapiens prolyl 4-hydroxylase, beta polypeptide, mRNA (cDNA clone IMAGE:3607959).
AK128783 - Homo sapiens cDNA FLJ45462 fis, clone BRSTN2011961, highly similar to Protein disulfide-isomerase precursor (EC 5.3.4.1).
E02164 - Human protein disulfideisomerase gene.
E03087 - cDNA encoding human protein disulfide isomerase(PDI).
BC010859 - Homo sapiens prolyl 4-hydroxylase, beta polypeptide, mRNA (cDNA clone MGC:9192 IMAGE:3879411), complete cds.
BC029617 - Homo sapiens prolyl 4-hydroxylase, beta polypeptide, mRNA (cDNA clone MGC:9695 IMAGE:3848651), complete cds.
J02783 - Human thyroid hormone binding protein (p55) mRNA, complete cds.
AK095938 - Homo sapiens cDNA FLJ38619 fis, clone HEART2007696, highly similar to Protein disulfide-isomerase precursor (EC 5.3.4.1).
E06719 - cDNA encoding human protein disulfide isomerase.
BC014504 - Homo sapiens prolyl 4-hydroxylase, beta polypeptide, mRNA (cDNA clone IMAGE:4861217), partial cds.
BC071892 - Homo sapiens prolyl 4-hydroxylase, beta polypeptide, mRNA (cDNA clone MGC:88571 IMAGE:5443660), complete cds.
AB062434 - Homo sapiens mRNA for OK/SW-CL.24, complete cds.
AK075503 - Homo sapiens cDNA PSEC0201 fis, clone HEMBA1002107, highly similar to PROTEIN DISULFIDE ISOMERASE PRECURSOR (PDI) (EC 5.3.4.1).
X07077 - Human mRNA for glutathione-insulin transhydrogenase (EC 5.3.4.1 / 1.8.4.2).
LF328590 - JP 2014500723-A/136093: Polycomb-Associated Non-Coding RNAs.
MA564167 - JP 2018138019-A/136093: Polycomb-Associated Non-Coding RNAs.
JD409227 - Sequence 390251 from Patent EP1572962.
JD497444 - Sequence 478468 from Patent EP1572962.
AL357203 - Homo sapiens EST from clone 375854, 5' end.
JD310053 - Sequence 291077 from Patent EP1572962.
JD361373 - Sequence 342397 from Patent EP1572962.
JD466835 - Sequence 447859 from Patent EP1572962.
JD354336 - Sequence 335360 from Patent EP1572962.
AK297081 - Homo sapiens cDNA FLJ59033 complete cds, highly similar to Protein disulfide-isomerase precursor (EC 5.3.4.1).
LF328591 - JP 2014500723-A/136094: Polycomb-Associated Non-Coding RNAs.
MA564168 - JP 2018138019-A/136094: Polycomb-Associated Non-Coding RNAs.
JD174606 - Sequence 155630 from Patent EP1572962.
AK297967 - Homo sapiens cDNA FLJ59361 complete cds, highly similar to Protein disulfide-isomerase precursor (EC 5.3.4.1).
X05130 - Human mRNA for prolyl 4-hydoxylase beta subunit (EC 1.14.11.2) (procollagen-L-proline, 2-oxoglutarate:oxygen oxidoreductase, 4-hydroxylating).
LF328592 - JP 2014500723-A/136095: Polycomb-Associated Non-Coding RNAs.
MA564169 - JP 2018138019-A/136095: Polycomb-Associated Non-Coding RNAs.
LF328593 - JP 2014500723-A/136096: Polycomb-Associated Non-Coding RNAs.
MA564170 - JP 2018138019-A/136096: Polycomb-Associated Non-Coding RNAs.
JD434393 - Sequence 415417 from Patent EP1572962.
JD142487 - Sequence 123511 from Patent EP1572962.
JD138030 - Sequence 119054 from Patent EP1572962.
AK300561 - Homo sapiens cDNA FLJ59430 complete cds, highly similar to Protein disulfide-isomerase precursor (EC 5.3.4.1).
AK315631 - Homo sapiens cDNA, FLJ96716, Homo sapiens procollagen-proline, 2-oxoglutarate 4-dioxygenase(proline 4-hydroxylase), beta polypeptide (protein disulfideisomerase; thyroid hormone binding protein p55) (P4HB), mRNA.
CU677027 - Synthetic construct Homo sapiens gateway clone IMAGE:100017989 5' read P4HB mRNA.
JF432204 - Synthetic construct Homo sapiens clone IMAGE:100073368 prolyl 4-hydroxylase, beta polypeptide (P4HB) gene, encodes complete protein.
KJ891744 - Synthetic construct Homo sapiens clone ccsbBroadEn_01138 P4HB gene, encodes complete protein.
KJ905847 - Synthetic construct Homo sapiens clone ccsbBroadEn_15517 P4HB gene, encodes complete protein.
E06720 - cDNA encoding hybrid protein which contains prepro fragment of human serum albumin and protein disulfide isomerase.
AB527806 - Synthetic construct DNA, clone: pF1KB5939, Homo sapiens P4HB gene for prolyl 4-hydroxylase, beta polypeptide, without stop codon, in Flexi system.
LF328594 - JP 2014500723-A/136097: Polycomb-Associated Non-Coding RNAs.
MA564171 - JP 2018138019-A/136097: Polycomb-Associated Non-Coding RNAs.
LP895361 - Sequence 225 from Patent EP3253886.
LF328595 - JP 2014500723-A/136098: Polycomb-Associated Non-Coding RNAs.
MA564172 - JP 2018138019-A/136098: Polycomb-Associated Non-Coding RNAs.
LF328596 - JP 2014500723-A/136099: Polycomb-Associated Non-Coding RNAs.
MA564173 - JP 2018138019-A/136099: Polycomb-Associated Non-Coding RNAs.
LF328597 - JP 2014500723-A/136100: Polycomb-Associated Non-Coding RNAs.
MA564174 - JP 2018138019-A/136100: Polycomb-Associated Non-Coding RNAs.
LF328598 - JP 2014500723-A/136101: Polycomb-Associated Non-Coding RNAs.
MA564175 - JP 2018138019-A/136101: Polycomb-Associated Non-Coding RNAs.
AK298005 - Homo sapiens cDNA FLJ59939 complete cds, highly similar to Protein disulfide-isomerase precursor (EC 5.3.4.1).
AK308600 - Homo sapiens cDNA, FLJ98641.
LF328599 - JP 2014500723-A/136102: Polycomb-Associated Non-Coding RNAs.
MA564176 - JP 2018138019-A/136102: Polycomb-Associated Non-Coding RNAs.
CU688720 - Synthetic construct Homo sapiens gateway clone IMAGE:100019722 5' read P4HB mRNA.
LF328600 - JP 2014500723-A/136103: Polycomb-Associated Non-Coding RNAs.
MA564177 - JP 2018138019-A/136103: Polycomb-Associated Non-Coding RNAs.
LF328601 - JP 2014500723-A/136104: Polycomb-Associated Non-Coding RNAs.
MA564178 - JP 2018138019-A/136104: Polycomb-Associated Non-Coding RNAs.
AK296206 - Homo sapiens cDNA FLJ56766 complete cds, highly similar to Protein disulfide-isomerase precursor (EC5.3.4.1).
LF328602 - JP 2014500723-A/136105: Polycomb-Associated Non-Coding RNAs.
MA564179 - JP 2018138019-A/136105: Polycomb-Associated Non-Coding RNAs.
LF328603 - JP 2014500723-A/136106: Polycomb-Associated Non-Coding RNAs.
MA564180 - JP 2018138019-A/136106: Polycomb-Associated Non-Coding RNAs.
LF328604 - JP 2014500723-A/136107: Polycomb-Associated Non-Coding RNAs.
MA564181 - JP 2018138019-A/136107: Polycomb-Associated Non-Coding RNAs.
LF328606 - JP 2014500723-A/136109: Polycomb-Associated Non-Coding RNAs.
MA564183 - JP 2018138019-A/136109: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_hifPathway - Hypoxia-Inducible Factor in the Cardiovascular System
h_vitCBPathway - Vitamin C in the Brain

Reactome (by CSHL, EBI, and GO)

Protein P07237 (Reactome details) participates in the following event(s):

R-HSA-2002460 P4HB binds Collagen chains
R-HSA-3341296 GPX7,8 catalyze peroxidation of P4HB (PDI)
R-HSA-5358336 P4HB forms mixed disulphides with Hh precursors
R-HSA-5358340 Autoproteolytic cleavage of Hh precursors
R-HSA-1650808 Prolyl 4-hydroxylase converts collagen prolines to 4-hydroxyprolines
R-HSA-8950183 IL12B binds IL23A
R-HSA-8950456 IL12B dimerizes
R-HSA-174786 ApoB-48 + 40 triacylglycerol + 60 phospholipid => ApoB-48:TG:PL complex
R-HSA-8866329 MTTP lipidates APOB-100, forming a pre-VLDL
R-HSA-8952289 FAM20C phosphorylates FAM20C substrates
R-HSA-1650814 Collagen biosynthesis and modifying enzymes
R-HSA-3299685 Detoxification of Reactive Oxygen Species
R-HSA-5358346 Hedgehog ligand biogenesis
R-HSA-1474290 Collagen formation
R-HSA-2262752 Cellular responses to stress
R-HSA-5358351 Signaling by Hedgehog
R-HSA-9020591 Interleukin-12 signaling
R-HSA-9020933 Interleukin-23 signaling
R-HSA-8963888 Chylomicron assembly
R-HSA-8866423 VLDL assembly
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-1474244 Extracellular matrix organization
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-162582 Signal Transduction
R-HSA-447115 Interleukin-12 family signaling
R-HSA-8963898 Plasma lipoprotein assembly
R-HSA-392499 Metabolism of proteins
R-HSA-597592 Post-translational protein modification
R-HSA-449147 Signaling by Interleukins
R-HSA-174824 Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-382551 Transport of small molecules
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: B2RDQ2, ERBA2L, NM_000918, P07237, P30037, P32079, PDI, PDIA1, PDIA1_HUMAN, PO4DB, Q15205, Q6LDE5, uc002kbn.1, uc002kbn.2, uc002kbn.3
UCSC ID: uc002kbn.3
RefSeq Accession: NM_000918
Protein: P07237 (aka PDIA1_HUMAN)
CCDS: CCDS11787.1

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