P4HB

Protein identityUniProt · HPA

UniProt accession

P07237

Gene

P4HB

Ensembl

ENSG00000185624

Chromosome

17

Canonical length

508 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Endoplasmic reticulum

Secretome location

Intracellular and membrane

Quaternary structure

Homotetramer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

508 residues, UniProt reviewed canonical sequence.

>P07237|P4HB
     1  MLRRALLCLA VAALVRADAP EEEDHVLVLR KSNFAEALAA HKYLLVEFYA PWCGHCKALA
    61  PEYAKAAGKL KAEGSEIRLA KVDATEESDL AQQYGVRGYP TIKFFRNGDT ASPKEYTAGR
   121  EADDIVNWLK KRTGPAATTL PDGAAAESLV ESSEVAVIGF FKDVESDSAK QFLQAAEAID
   181  DIPFGITSNS DVFSKYQLDK DGVVLFKKFD EGRNNFEGEV TKENLLDFIK HNQLPLVIEF
   241  TEQTAPKIFG GEIKTHILLF LPKSVSDYDG KLSNFKTAAE SFKGKILFIF IDSDHTDNQR
   301  ILEFFGLKKE ECPAVRLITL EEEMTKYKPE SEELTAERIT EFCHRFLEGK IKPHLMSQEL
   361  PEDWDKQPVK VLVGKNFEDV AFDEKKNVFV EFYAPWCGHC KQLAPIWDKL GETYKDHENI
   421  VIAKMDSTAN EVEAVKVHSF PTLKFFPASA DRTVIDYNGE RTLDGFKKFL ESGGQDGAGD
   481  DDDLEDLEEA EEPDMEEDDD QKAVKDEL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against P4HB can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

2,108 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about P4HB.

Disease | AllUniProt

Conditions P4HB is implicated in, by any mechanism.

• Cole-Carpenter syndrome 1 (CLCRP1) MIM:112240

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 429 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cole-Carpenter syndrome 1

Disease | ImmuneIEDB

Conditions an epitope on P4HB was assayed in.

• type 1 diabetes mellitus T cell

ReferencesPubMed · IEDB

Publications for P4HB from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.22

gnomAD pLI

1

gnomAD missense Z

1.31

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to hypoxia
• cellular response to interleukin-7
• endoplasmic reticulum to Golgi vesicle-mediated transport
• insulin processing
• interleukin-12-mediated signaling pathway
• interleukin-23-mediated signaling pathway
• peptidyl-proline hydroxylation to 4-hydroxy-L-proline
• positive regulation of cell adhesion
• positive regulation of substrate adhesion-dependent cell spreading
• positive regulation of T cell migration
• positive regulation of viral entry into host cell
• protein folding
• protein folding in endoplasmic reticulum
• regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
• response to endoplasmic reticulum stress

Molecular functions

• actin binding
• enzyme binding
• integrin binding
• procollagen-proline 4-dioxygenase activity
• protein disulfide isomerase activity
• protein heterodimerization activity
• protein-disulfide reductase activity
• RNA binding
• thiol oxidase activity

Cellular components

• cytoskeleton
• cytosol
• 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
• lamellipodium
• melanosome
• procollagen-proline 4-dioxygenase complex
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• Protein disulfide-isomerase, thioredoxin-like domain
• Protein disulphide isomerase
• Thioredoxin domain
• Thioredoxin, conserved site
• Thioredoxin-like superfamily
• Thioredoxin
• Thioredoxin-like domain

KeywordsUniProt

• Acetylation
• Cell membrane
• Chaperone
• Craniosynostosis
• Disulfide bond
• Endoplasmic reticulum
• Isomerase
• Membrane
• Osteogenesis imperfecta
• Phosphoprotein
• Redox-active center
• Repeat
• Signal

InteractionsUniProt · HPA

Protein binding partners of P4HB in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ERO1B
• ILDR2
• P4HA2
• AGO2
• ERO1A
• MAPT
• NEK7