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Reviewed, UniProtKB/Swiss-Prot O00469 (PLOD2_HUMAN)

Last modified July 7, 2009. Version 87. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2
    EC=1.14.11.4
Alternative name(s):
    Lysyl hydroxylase 2
      Short name=LH2
Gene names
Name: PLOD2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length737 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

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 activity

Procollagen L-lysine + 2-oxoglutarate + O2 = procollagen 5-hydroxy-L-lysine + succinate + CO2.

Cofactor

Iron By similarity.

Ascorbate By similarity.

Subunit structure

Homodimer By similarity.

Subcellular location

Rough endoplasmic reticulum membrane; Peripheral membrane protein; Lumenal side.

Tissue specificity

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. Ref.2

Involvement in disease

Defects in PLOD2 are the cause of Bruck syndrome 2 (BRKS2) [MIM:609220]. Bruck syndrome [MIM:259450], also known as osteogenesis imperfecta with congenital joint contractures, is an autosomal recessive disease characterized by generalized osteopenia, joint contractures at birth, fragile bones and short stature. It can be distinguished from osteogenesis imperfecta by the absence of hearing loss and dentinogenesis imperfecta, and by the presence of clubfoot and congenital joint limitations. The molecular defect 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. Ref.7 Ref.8

Sequence similarities

Contains 1 PKHD (prolyl/lysyl hydroxylase) domain.

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

RUVBL2Q9Y2301EBI-1047459,EBI-352939

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O00469-1)

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.
Isoform 2 (identifier: O00469-2)

Also known as: A;

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

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 737712Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2
PRO_0000024683

Regions

Domain563 – 737175PKHD

Sites

Active site7281 Potential
Metal binding6661Iron By similarity
Metal binding6681Iron By similarity
Metal binding7181Iron By similarity

Amino acid modifications

Modified residue3201Phosphothreonine Ref.4
Modified residue3231Phosphotyrosine Ref.4
Glycosylation631N-linked (GlcNAc...) Potential
Glycosylation2091N-linked (GlcNAc...)
Glycosylation2971N-linked (GlcNAc...) Potential
Glycosylation3651N-linked (GlcNAc...) Potential
Glycosylation5221N-linked (GlcNAc...)
Glycosylation6961N-linked (GlcNAc...) Potential
Glycosylation7251N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence5001M → MTLQREKDSPTPETFQMLSP PK in isoform 2.
VSP_013467
Natural variant5981R → H in BRKS2. Ref.8
VAR_022164
Natural variant6011G → V in BRKS2. Ref.7
VAR_022165
Natural variant6081T → I in BRKS2. Ref.7
VAR_022166

Experimental info

Sequence conflict6241H → D in AAB58363. Ref.1

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 26, 2005. Version 2.
Checksum: C9AEA79A574D6B66

FASTA73784,686
        10         20         30         40         50         60 
MGGCTVKPQL LLLALVLHPW NPCLGADSEK PSSIPTDKLL VITVATKESD GFHRFMQSAK 

        70         80         90        100        110        120 
YFNYTVKVLG QGEEWRGGDG INSIGGGQKV RLMKEVMEHY ADQDDLVVMF TECFDVIFAG 

       130        140        150        160        170        180 
GPEEVLKKFQ KANHKVVFAA DGILWPDKRL ADKYPVVHIG KRYLNSGGFI GYAPYVNRIV 

       190        200        210        220        230        240 
QQWNLQDNDD DQLFYTKVYI DPLKREAINI TLDHKCKIFQ TLNGAVDEVV LKFENGKARA 

       250        260        270        280        290        300 
KNTFYETLPV AINGNGPTKI LLNYFGNYVP NSWTQDNGCT LCEFDTVDLS AVDVHPNVSI 

       310        320        330        340        350        360 
GVFIEQPTPF LPRFLDILLT LDYPKEALKL FIHNKEVYHE KDIKVFFDKA KHEIKTIKIV 

       370        380        390        400        410        420 
GPEENLSQAE ARNMGMDFCR QDEKCDYYFS VDADVVLTNP RTLKILIEQN RKIIAPLVTR 

       430        440        450        460        470        480 
HGKLWSNFWG ALSPDGYYAR SEDYVDIVQG NRVGVWNVPY MANVYLIKGK TLRSEMNERN 

       490        500        510        520        530        540 
YFVRDKLDPD MALCRNAREM GVFMYISNRH EFGRLLSTAN YNTSHYNNDL WQIFENPVDW 

       550        560        570        580        590        600 
KEKYINRDYS KIFTENIVEQ PCPDVFWFPI FSEKACDELV EEMEHYGKWS GGKHHDSRIS 

       610        620        630        640        650        660 
GGYENVPTDD IHMKQVDLEN VWLHFIREFI APVTLKVFAG YYTKGFALLN FVVKYSPERQ 

       670        680        690        700        710        720 
RSLRPHHDAS TFTINIALNN VGEDFQGGGC KFLRYNCSIE SPRKGWSFMH PGRLTHLHEG 

       730 
LPVKNGTRYI AVSFIDP

« Hide

Isoform 2 (A).

Checksum: ED81104976B69FC7
Show »

FASTA75887,098

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References

« Hide 'large scale' references
[1]"Cloning and characterization of a novel human lysyl hydroxylase isoform highly expressed in pancreas and muscle."
Valtavaara M., Papponen H., Pirttila A.M., Hiltunen K., Helander H., Myllylae R.
J. Biol. Chem. 272:6831-6834(1997) [PubMed: 9054364] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Kidney.
[2]"Tissue specificity of a new splice form of the human lysyl hydroxylase 2 gene."
Yeowell H.N., Walker L.C.
Matrix Biol. 18:179-187(1999) [PubMed: 10372558] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
Tissue: Skin fibroblast.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Placenta.
[4]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-320 AND TYR-323, MASS SPECTROMETRY.
Tissue: Platelet.
[5]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[6]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-209 AND ASN-522, MASS SPECTROMETRY.
Tissue: Liver.
[7]"Identification of PLOD2 as telopeptide lysyl hydroxylase, an important enzyme in fibrosis."
van der Slot A.J., Zuurmond A.-M., Bardoel A.F.J., Wijmenga C., Pruijs H.E.H., Sillence D.O., Brinckmann J., Abraham D.J., Black C.M., Verzijl N., DeGroot J., Hanemaaijer R., TeKoppele J.M., Huizinga T.W.J., Bank R.A.
J. Biol. Chem. 278:40967-40972(2003) [PubMed: 12881513] [Abstract]
Cited for: VARIANTS BRKS2 VAL-601 AND ILE-608.
[8]"Phenotypic and molecular characterization of Bruck syndrome (osteogenesis imperfecta with contractures of the large joints) caused by a recessive mutation in PLOD2."
Ha-Vinh R., Alanay Y., Bank R.A., Campos-Xavier A.B., Zankl A., Superti-Furga A., Bonafe L.
Am. J. Med. Genet. A 131:115-120(2004) [PubMed: 15523624] [Abstract]
Cited for: VARIANT BRKS2 HIS-598.
+Additional computationally mapped references.

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Cross-references

Sequence databases

U84573 mRNA. Translation: AAB58363.1.
BC037169 mRNA. Translation: AAH37169.1.
IPIIPI00337495.
IPI00472165.
PIRA59144.
RefSeqNP_000926.2.
NP_891988.1.
UniGeneHs.477866

3D structure databases

ModBaseSearch...

Protein-protein interaction databases

IntActO00469. 1 interaction.

PTM databases

PhosphoSiteO00469.

Proteomic databases

PRIDEO00469.

Genome annotation databases

EnsemblENSG00000152952. Homo sapiens. [Contig view]
GeneID5352.
KEGGhsa:5352.
UCSCuc003evr.1. human.
uc003evs.1. human.

Organism-specific databases

GeneCardsGC03M147269.
HGNCHGNC:9082. PLOD2.
MIM601865. gene.
609220. phenotype.
Orphanet2771. Bruck syndrome.
PharmGKBPA33412.
GenAtlasSearch...

Phylogenomic databases

HOVERGENO00469.
OMAO00469. LNNVGED.

Enzyme and pathway databases

BRENDA1.14.11.4. 247.

Gene expression databases

ArrayExpressO00469.
BgeeO00469.
CleanExHS_PLOD2.
GermOnlineENSG00000152952. Homo sapiens.

Family and domain databases

InterProIPR005123. Oxoglutarate/Fe-dep_Oase.
IPR006620. Pro_4_hyd_alph.
IPR001006. Procol_lys_dOase.
[Graphical view]
PfamPF03171. 2OG-FeII_Oxy. 1 hit.
[Graphical view]
ProDomPD011578. ProcolLys_dioxy. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00702. P4Hc. 1 hit.
[Graphical view]
PROSITEPS01325. LYS_HYDROXYLASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00126. Vitamin C.
NextBio20746.
SOURCESearch...

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Entry information

Entry namePLOD2_HUMAN
AccessionPrimary (citable) accession number: O00469
Secondary accession number(s): Q8N170
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: April 26, 2005
Last modified: July 7, 2009
This is version 87 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents