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Protein

Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2

Gene

PLOD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links.

Catalytic activityi

L-lysine-[procollagen] + 2-oxoglutarate + O2 = (2S,5R)-5-hydroxy-L-lysine-[procollagen] + succinate + CO2.

Cofactori

Protein has several cofactor binding sites:

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi666IronPROSITE-ProRule annotation1
Metal bindingi668IronPROSITE-ProRule annotation1
Metal bindingi718IronPROSITE-ProRule annotation1
Active sitei728Sequence analysis1

GO - Molecular functioni

GO - Biological processi

  • cellular protein modification process Source: ProtInc
  • response to hypoxia Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Ligandi

Iron, Metal-binding, Vitamin C

Enzyme and pathway databases

BioCyciZFISH:HS07866-MONOMER.
BRENDAi1.14.11.4. 2681.
ReactomeiR-HSA-1650814. Collagen biosynthesis and modifying enzymes.

Names & Taxonomyi

Protein namesi
Recommended name:
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (EC:1.14.11.4)
Alternative name(s):
Lysyl hydroxylase 2
Short name:
LH2
Gene namesi
Name:PLOD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:9082. PLOD2.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: ProtInc
  • endoplasmic reticulum membrane Source: Reactome
  • extracellular exosome Source: UniProtKB
  • rough endoplasmic reticulum membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Bruck syndrome 2 (BRKS2)2 Publications
The disease is caused by mutations affecting the gene represented in this entry. The molecular defect leading to Bruck syndrome is an aberrant cross-linking of bone collagen, due to underhydroxylation of lysine residues within the telopeptides of type I collagen, whereas the lysine residues in the triple helix are normal.
Disease descriptionAn autosomal recessive disease characterized by generalized osteopenia, congenital joint contractures, fragile bones with onset of fractures in infancy or early childhood, short stature, severe limb deformity, progressive scoliosis, and pterygia. It is distinguished from osteogenesis imperfecta by the absence of hearing loss and dentinogenesis imperfecta, and by the presence of clubfoot and congenital joint limitations.
See also OMIM:609220
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022164598R → H in BRKS2. 1 PublicationCorresponds to variant rs121434461dbSNPEnsembl.1
Natural variantiVAR_022165601G → V in BRKS2. 1 PublicationCorresponds to variant rs121434460dbSNPEnsembl.1
Natural variantiVAR_022166608T → I in BRKS2. 1 PublicationCorresponds to variant rs121434459dbSNPEnsembl.1

PLOD2 mutations give rise to a broad variety of phenotypes with variable degrees of severity of bone fragility and joint contractures. Disease-associated mutations have been found in patients with autosomal recessive osteogenesis imperfecta (AR-OI) (PubMed:22689593).

Keywords - Diseasei

Disease mutation, Osteogenesis imperfecta

Organism-specific databases

DisGeNETi5352.
MalaCardsiPLOD2.
MIMi609220. phenotype.
OpenTargetsiENSG00000152952.
Orphaneti2771. Bruck syndrome.
PharmGKBiPA33412.

Chemistry databases

DrugBankiDB00126. Vitamin C.

Polymorphism and mutation databases

BioMutaiPLOD2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000002468326 – 737Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2Add BLAST712

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi63N-linked (GlcNAc...)Sequence analysis1
Glycosylationi209N-linked (GlcNAc...)1 Publication1
Glycosylationi297N-linked (GlcNAc...)Sequence analysis1
Modified residuei320PhosphothreonineCombined sources1
Modified residuei323PhosphotyrosineCombined sources1
Glycosylationi365N-linked (GlcNAc...)Sequence analysis1
Glycosylationi522N-linked (GlcNAc...)1 Publication1
Glycosylationi696N-linked (GlcNAc...)Sequence analysis1
Modified residuei704N6-succinyllysineBy similarity1
Glycosylationi725N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiO00469.
MaxQBiO00469.
PaxDbiO00469.
PeptideAtlasiO00469.
PRIDEiO00469.

PTM databases

iPTMnetiO00469.
PhosphoSitePlusiO00469.
SwissPalmiO00469.
UniCarbKBiO00469.

Expressioni

Tissue specificityi

Highly expressed in pancreas and muscle. Isoform 1 and isoform 2 are expressed in the majority of the examined cell types. Isoform 2 is specifically expressed in skin, lung, dura and aorta.1 Publication

Gene expression databases

BgeeiENSG00000152952.
CleanExiHS_PLOD2.
ExpressionAtlasiO00469. baseline and differential.
GenevisibleiO00469. HS.

Organism-specific databases

HPAiCAB025898.
HPA069126.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi111367. 49 interactors.
IntActiO00469. 13 interactors.
STRINGi9606.ENSP00000282903.

Structurei

3D structure databases

ProteinModelPortaliO00469.
SMRiO00469.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini644 – 737Fe2OG dioxygenasePROSITE-ProRule annotationAdd BLAST94

Sequence similaritiesi

Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1971. Eukaryota.
ENOG410Y4QU. LUCA.
GeneTreeiENSGT00550000074427.
HOGENOMiHOG000231099.
HOVERGENiHBG053618.
InParanoidiO00469.
KOiK13645.
OMAiGLIWPDK.
OrthoDBiEOG091G02DK.
PhylomeDBiO00469.
TreeFamiTF313826.

Family and domain databases

Gene3Di3.90.550.10. 1 hit.
InterProiIPR029044. Nucleotide-diphossugar_trans.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR006620. Pro_4_hyd_alph.
IPR001006. Procol_lys_dOase.
[Graphical view]
PfamiPF03171. 2OG-FeII_Oxy. 1 hit.
[Graphical view]
SMARTiSM00702. P4Hc. 1 hit.
[Graphical view]
SUPFAMiSSF53448. SSF53448. 1 hit.
PROSITEiPS51471. FE2OG_OXY. 1 hit.
PS01325. LYS_HYDROXYLASE. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O00469-1) [UniParc]FASTAAdd to basket
Also known as: A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGGCTVKPQL LLLALVLHPW NPCLGADSEK PSSIPTDKLL VITVATKESD
60 70 80 90 100
GFHRFMQSAK YFNYTVKVLG QGEEWRGGDG INSIGGGQKV RLMKEVMEHY
110 120 130 140 150
ADQDDLVVMF TECFDVIFAG GPEEVLKKFQ KANHKVVFAA DGILWPDKRL
160 170 180 190 200
ADKYPVVHIG KRYLNSGGFI GYAPYVNRIV QQWNLQDNDD DQLFYTKVYI
210 220 230 240 250
DPLKREAINI TLDHKCKIFQ TLNGAVDEVV LKFENGKARA KNTFYETLPV
260 270 280 290 300
AINGNGPTKI LLNYFGNYVP NSWTQDNGCT LCEFDTVDLS AVDVHPNVSI
310 320 330 340 350
GVFIEQPTPF LPRFLDILLT LDYPKEALKL FIHNKEVYHE KDIKVFFDKA
360 370 380 390 400
KHEIKTIKIV GPEENLSQAE ARNMGMDFCR QDEKCDYYFS VDADVVLTNP
410 420 430 440 450
RTLKILIEQN RKIIAPLVTR HGKLWSNFWG ALSPDGYYAR SEDYVDIVQG
460 470 480 490 500
NRVGVWNVPY MANVYLIKGK TLRSEMNERN YFVRDKLDPD MALCRNAREM
510 520 530 540 550
GVFMYISNRH EFGRLLSTAN YNTSHYNNDL WQIFENPVDW KEKYINRDYS
560 570 580 590 600
KIFTENIVEQ PCPDVFWFPI FSEKACDELV EEMEHYGKWS GGKHHDSRIS
610 620 630 640 650
GGYENVPTDD IHMKQVDLEN VWLHFIREFI APVTLKVFAG YYTKGFALLN
660 670 680 690 700
FVVKYSPERQ RSLRPHHDAS TFTINIALNN VGEDFQGGGC KFLRYNCSIE
710 720 730
SPRKGWSFMH PGRLTHLHEG LPVKNGTRYI AVSFIDP
Length:737
Mass (Da):84,686
Last modified:April 26, 2005 - v2
Checksum:iC9AEA79A574D6B66
GO
Isoform 2 (identifier: O00469-2) [UniParc]FASTAAdd to basket
Also known as: B

The sequence of this isoform differs from the canonical sequence as follows:
     500-500: M → MTLQREKDSPTPETFQMLSPPK

Show »
Length:758
Mass (Da):87,098
Checksum:iED81104976B69FC7
GO
Isoform 3 (identifier: O00469-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MGGCTVKPQLLLLALVLHPWNPCLGADSEKPSSIPT → MLENHILHKRIYILTFFSQQIFILCHAHFIFFFTVR
     37-376: Missing.
     500-500: M → MTLQREKDSPTPETFQMLSPPK

Note: No experimental confirmation available.
Show »
Length:418
Mass (Da):49,142
Checksum:iA70BCF41D3E032EE
GO

Sequence cautioni

The sequence BAD93116 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti624H → D in AAB58363 (PubMed:9054364).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022164598R → H in BRKS2. 1 PublicationCorresponds to variant rs121434461dbSNPEnsembl.1
Natural variantiVAR_069531601G → C in AR-OI; probable disease-associated mutation found in patients with osteogenesis imperfecta. 1 PublicationCorresponds to variant rs762788421dbSNPEnsembl.1
Natural variantiVAR_022165601G → V in BRKS2. 1 PublicationCorresponds to variant rs121434460dbSNPEnsembl.1
Natural variantiVAR_022166608T → I in BRKS2. 1 PublicationCorresponds to variant rs121434459dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0572211 – 36MGGCT…SSIPT → MLENHILHKRIYILTFFSQQ IFILCHAHFIFFFTVR in isoform 3. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_05722237 – 376Missing in isoform 3. 1 PublicationAdd BLAST340
Alternative sequenceiVSP_013467500M → MTLQREKDSPTPETFQMLSP PK in isoform 2 and isoform 3. 3 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U84573 mRNA. Translation: AAB58363.1.
AK125700 mRNA. Translation: BAG54235.1.
AB209879 mRNA. Translation: BAD93116.1. Different initiation.
AC092982 Genomic DNA. No translation available.
AC107021 Genomic DNA. No translation available.
BC037169 mRNA. Translation: AAH37169.1.
CCDSiCCDS3131.1. [O00469-1]
CCDS3132.1. [O00469-2]
PIRiA59144.
RefSeqiNP_000926.2. NM_000935.2. [O00469-1]
NP_891988.1. NM_182943.2. [O00469-2]
UniGeneiHs.477866.

Genome annotation databases

EnsembliENST00000282903; ENSP00000282903; ENSG00000152952. [O00469-2]
ENST00000360060; ENSP00000353170; ENSG00000152952. [O00469-1]
ENST00000461497; ENSP00000419354; ENSG00000152952. [O00469-3]
GeneIDi5352.
KEGGihsa:5352.
UCSCiuc003evq.2. human. [O00469-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Osteogenesis imperfecta variant database

Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U84573 mRNA. Translation: AAB58363.1.
AK125700 mRNA. Translation: BAG54235.1.
AB209879 mRNA. Translation: BAD93116.1. Different initiation.
AC092982 Genomic DNA. No translation available.
AC107021 Genomic DNA. No translation available.
BC037169 mRNA. Translation: AAH37169.1.
CCDSiCCDS3131.1. [O00469-1]
CCDS3132.1. [O00469-2]
PIRiA59144.
RefSeqiNP_000926.2. NM_000935.2. [O00469-1]
NP_891988.1. NM_182943.2. [O00469-2]
UniGeneiHs.477866.

3D structure databases

ProteinModelPortaliO00469.
SMRiO00469.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111367. 49 interactors.
IntActiO00469. 13 interactors.
STRINGi9606.ENSP00000282903.

Chemistry databases

DrugBankiDB00126. Vitamin C.

PTM databases

iPTMnetiO00469.
PhosphoSitePlusiO00469.
SwissPalmiO00469.
UniCarbKBiO00469.

Polymorphism and mutation databases

BioMutaiPLOD2.

Proteomic databases

EPDiO00469.
MaxQBiO00469.
PaxDbiO00469.
PeptideAtlasiO00469.
PRIDEiO00469.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000282903; ENSP00000282903; ENSG00000152952. [O00469-2]
ENST00000360060; ENSP00000353170; ENSG00000152952. [O00469-1]
ENST00000461497; ENSP00000419354; ENSG00000152952. [O00469-3]
GeneIDi5352.
KEGGihsa:5352.
UCSCiuc003evq.2. human. [O00469-1]

Organism-specific databases

CTDi5352.
DisGeNETi5352.
GeneCardsiPLOD2.
HGNCiHGNC:9082. PLOD2.
HPAiCAB025898.
HPA069126.
MalaCardsiPLOD2.
MIMi601865. gene.
609220. phenotype.
neXtProtiNX_O00469.
OpenTargetsiENSG00000152952.
Orphaneti2771. Bruck syndrome.
PharmGKBiPA33412.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1971. Eukaryota.
ENOG410Y4QU. LUCA.
GeneTreeiENSGT00550000074427.
HOGENOMiHOG000231099.
HOVERGENiHBG053618.
InParanoidiO00469.
KOiK13645.
OMAiGLIWPDK.
OrthoDBiEOG091G02DK.
PhylomeDBiO00469.
TreeFamiTF313826.

Enzyme and pathway databases

BioCyciZFISH:HS07866-MONOMER.
BRENDAi1.14.11.4. 2681.
ReactomeiR-HSA-1650814. Collagen biosynthesis and modifying enzymes.

Miscellaneous databases

ChiTaRSiPLOD2. human.
GenomeRNAii5352.
PROiO00469.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000152952.
CleanExiHS_PLOD2.
ExpressionAtlasiO00469. baseline and differential.
GenevisibleiO00469. HS.

Family and domain databases

Gene3Di3.90.550.10. 1 hit.
InterProiIPR029044. Nucleotide-diphossugar_trans.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR006620. Pro_4_hyd_alph.
IPR001006. Procol_lys_dOase.
[Graphical view]
PfamiPF03171. 2OG-FeII_Oxy. 1 hit.
[Graphical view]
SMARTiSM00702. P4Hc. 1 hit.
[Graphical view]
SUPFAMiSSF53448. SSF53448. 1 hit.
PROSITEiPS51471. FE2OG_OXY. 1 hit.
PS01325. LYS_HYDROXYLASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPLOD2_HUMAN
AccessioniPrimary (citable) accession number: O00469
Secondary accession number(s): B3KWS3, Q59ED2, Q8N170
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: April 26, 2005
Last modified: November 2, 2016
This is version 159 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.