PLOD2

Protein identityUniProt · HPA

UniProt accession

O00469

Gene

PLOD2

Ensembl

ENSG00000152952

Chromosome

3

Canonical length

737 aa

Protein class

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

Subcellular location

Nucleoli,Cytosol

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is a membrane-bound homodimeric enzyme that is localized to the cisternae of the rough endoplasmic reticulum. The enzyme (cofactors iron and ascorbate) catalyzes the hydroxylation of lysyl residues in collagen-like peptides. The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks. Some patients with Ehlers-Danlos syndrome type VIB have deficiencies in lysyl hydroxylase activity. Mutations in the coding region of this gene are associated with Bruck syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

737 residues, UniProt reviewed canonical sequence.

>O00469|PLOD2
     1  MGGCTVKPQL LLLALVLHPW NPCLGADSEK PSSIPTDKLL VITVATKESD GFHRFMQSAK
    61  YFNYTVKVLG QGEEWRGGDG INSIGGGQKV RLMKEVMEHY ADQDDLVVMF TECFDVIFAG
   121  GPEEVLKKFQ KANHKVVFAA DGILWPDKRL ADKYPVVHIG KRYLNSGGFI GYAPYVNRIV
   181  QQWNLQDNDD DQLFYTKVYI DPLKREAINI TLDHKCKIFQ TLNGAVDEVV LKFENGKARA
   241  KNTFYETLPV AINGNGPTKI LLNYFGNYVP NSWTQDNGCT LCEFDTVDLS AVDVHPNVSI
   301  GVFIEQPTPF LPRFLDILLT LDYPKEALKL FIHNKEVYHE KDIKVFFDKA KHEIKTIKIV
   361  GPEENLSQAE ARNMGMDFCR QDEKCDYYFS VDADVVLTNP RTLKILIEQN RKIIAPLVTR
   421  HGKLWSNFWG ALSPDGYYAR SEDYVDIVQG NRVGVWNVPY MANVYLIKGK TLRSEMNERN
   481  YFVRDKLDPD MALCRNAREM GVFMYISNRH EFGRLLSTAN YNTSHYNNDL WQIFENPVDW
   541  KEKYINRDYS KIFTENIVEQ PCPDVFWFPI FSEKACDELV EEMEHYGKWS GGKHHDSRIS
   601  GGYENVPTDD IHMKQVDLEN VWLHFIREFI APVTLKVFAG YYTKGFALLN FVVKYSPERQ
   661  RSLRPHHDAS TFTINIALNN VGEDFQGGGC KFLRYNCSIE SPRKGWSFMH PGRLTHLHEG
   721  LPVKNGTRYI AVSFIDP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PLOD2 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

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

76 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PLOD2.

Disease | AllUniProt

Conditions PLOD2 is implicated in, by any mechanism.

• Bruck syndrome 2 (BRKS2) MIM:609220

Disease | GeneticClinVar

39 pathogenic / likely-pathogenic of 547 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Bruck syndrome 2
• Osteogenesis imperfecta
• 9 conditions
• PLOD2-related disorder

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)

0.64

gnomAD pLI

0

gnomAD missense Z

0.56

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• collagen biosynthetic process
• collagen fibril organization
• hydroxylysine biosynthetic process
• response to hypoxia

Molecular functions

• iron ion binding
• L-ascorbic acid binding
• procollagen-lysine 5-dioxygenase activity

Cellular components

• cytoplasm
• endoplasmic reticulum
• endoplasmic reticulum membrane
• extracellular exosome
• extracellular space
• Golgi apparatus
• rough endoplasmic reticulum membrane

Protein domainsUniProt · Pfam · InterPro

• Procollagen-lysine 5-dioxygenase, conserved site
• Oxoglutarate/iron-dependent dioxygenase domain
• Prolyl 4-hydroxylase, alpha subunit
• Nucleotide-diphospho-sugar transferases
• Isopenicillin N synthase-like, Fe(2+) 2OG dioxygenase domain
• Collagen-modifying Glycosyltransferase 25
• PLOD1-3-like, GT domain
• 2OG-Fe(II) oxygenase superfamily
• PLOD GT domain

KeywordsUniProt

• Cytoplasm
• Dioxygenase
• Endoplasmic reticulum
• Glycoprotein
• Iron
• Membrane
• Metal-binding
• Osteogenesis imperfecta
• Oxidoreductase
• Phosphoprotein
• Signal
• Vitamin C

InteractionsUniProt · HPA

Protein binding partners of PLOD2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RUVBL2