P4HA2

Protein identityUniProt · HPA

UniProt accession

O15460

Gene

P4HA2

Ensembl

ENSG00000072682

Chromosome

5

Canonical length

535 aa

Protein class

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

Subcellular location

Endoplasmic reticulum,Vesicles

Secretome location

Intracellular and membrane

OverviewNCBI Gene

This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

535 residues, UniProt reviewed canonical sequence.

>O15460|P4HA2
     1  MKLWVSALLM AWFGVLSCVQ AEFFTSIGHM TDLIYAEKEL VQSLKEYILV EEAKLSKIKS
    61  WANKMEALTS KSAADAEGYL AHPVNAYKLV KRLNTDWPAL EDLVLQDSAA GFIANLSVQR
   121  QFFPTDEDEI GAAKALMRLQ DTYRLDPGTI SRGELPGTKY QAMLSVDDCF GMGRSAYNEG
   181  DYYHTVLWME QVLKQLDAGE EATTTKSQVL DYLSYAVFQL GDLHRALELT RRLLSLDPSH
   241  ERAGGNLRYF EQLLEEEREK TLTNQTEAEL ATPEGIYERP VDYLPERDVY ESLCRGEGVK
   301  LTPRRQKRLF CRYHHGNRAP QLLIAPFKEE DEWDSPHIVR YYDVMSDEEI ERIKEIAKPK
   361  LARATVRDPK TGVLTVASYR VSKSSWLEED DDPVVARVNR RMQHITGLTV KTAELLQVAN
   421  YGVGGQYEPH FDFSRNDERD TFKHLGTGNR VATFLNYMSD VEAGGATVFP DLGAAIWPKK
   481  GTAVFWYNLL RSGEGDYRTR HAACPVLVGC KWVSNKWFHE RGQEFLRPCG STEVD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against P4HA2 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

75 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about P4HA2.

Disease | AllUniProt

Conditions P4HA2 is implicated in, by any mechanism.

• Myopia 25, autosomal dominant (MYP25) MIM:617238

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 139 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Myopia 25, autosomal dominant
• High myopia, early-onset

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)

0.66

gnomAD pLI

0

gnomAD missense Z

0.82

DepMap mean gene effect

-0.14

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Molecular functions

• electron transfer activity
• iron ion binding
• L-ascorbic acid binding
• procollagen-proline 4-dioxygenase activity

Cellular components

• cytosol
• endoplasmic reticulum
• endoplasmic reticulum lumen
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• Oxoglutarate/iron-dependent dioxygenase domain
• Prolyl 4-hydroxylase, alpha subunit
• Tetratricopeptide-like helical domain superfamily
• Prolyl 4-hydroxylase, N-terminal
• Tetratricopeptide repeat
• Prolyl 4-hydroxylase alpha subunit, Fe(2+) 2OG dioxygenase domain
• Prolyl 4-hydroxylase
• Prolyl 4-hydroxylase, peptide-substrate-binding domain
• Prolyl 4-Hydroxylase alpha-subunit, N-terminal region
• 2OG-Fe(II) oxygenase superfamily
• Prolyl 4-hydroxylase peptide-substrate-binding domain

KeywordsUniProt

• Dioxygenase
• Endoplasmic reticulum
• Glycoprotein
• Iron
• Metal-binding
• Oxidoreductase
• Signal
• TPR repeat
• Vitamin C

InteractionsUniProt · HPA

Protein binding partners of P4HA2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• P4HB
• KIF7
• NEK7