P4HA1

Protein identityUniProt · HPA

UniProt accession

P13674

Gene

P4HA1

Ensembl

ENSG00000122884

Chromosome

10

Canonical length

534 aa

Protein class

Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Endoplasmic reticulum,Vesicles,Mitochondria

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

534 residues, UniProt reviewed canonical sequence.

>P13674|P4HA1
     1  MIWYILIIGI LLPQSLAHPG FFTSIGQMTD LIHTEKDLVT SLKDYIKAEE DKLEQIKKWA
    61  EKLDRLTSTA TKDPEGFVGH PVNAFKLMKR LNTEWSELEN LVLKDMSDGF ISNLTIQRQY
   121  FPNDEDQVGA AKALLRLQDT YNLDTDTISK GNLPGVKHKS FLTAEDCFEL GKVAYTEADY
   181  YHTELWMEQA LRQLDEGEIS TIDKVSVLDY LSYAVYQQGD LDKALLLTKK LLELDPEHQR
   241  ANGNLKYFEY IMAKEKDVNK SASDDQSDQK TTPKKKGVAV DYLPERQKYE MLCRGEGIKM
   301  TPRRQKKLFC RYHDGNRNPK FILAPAKQED EWDKPRIIRF HDIISDAEIE IVKDLAKPRL
   361  RRATISNPIT GDLETVHYRI SKSAWLSGYE NPVVSRINMR IQDLTGLDVS TAEELQVANY
   421  GVGGQYEPHF DFARKDEPDA FKELGTGNRI ATWLFYMSDV SAGGATVFPE VGASVWPKKG
   481  TAVFWYNLFA SGEGDYSTRH AACPVLVGNK WVSNKWLHER GQEFRRPCTL SELE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against P4HA1 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

105 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about P4HA1.

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 86 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital disorder of connective tissue
• P4HA1-related disorder

Disease | ImmuneIEDB

Conditions an epitope on P4HA1 was assayed in.

• narcolepsy B cell
• multiple sclerosis B cell
• peripheral nervous system disease B cell

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)

0.34

gnomAD pLI

0.93

gnomAD missense Z

2.01

DepMap mean gene effect

-0.06

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

Biological processes

• collagen fibril organization

Molecular functions

• identical protein binding
• iron ion binding
• L-ascorbic acid binding
• procollagen-proline 4-dioxygenase activity

Cellular components

• endoplasmic reticulum
• endoplasmic reticulum lumen
• membrane
• mitochondrion
• procollagen-proline 4-dioxygenase complex

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 P4HA1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AGO2
• CPSF6