Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O00469 (PLOD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

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) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

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

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

L-lysine-[procollagen] + 2-oxoglutarate + O2 = (2S,5R)-5-hydroxy-L-lysine-[procollagen] + 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.4

Involvement in disease

Bruck syndrome 2 (BRKS2) [MIM:609220]: An 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.
Note: 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. Ref.9 Ref.10

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) (Ref.11).

Sequence similarities

Contains 1 Fe2OG dioxygenase domain.

Sequence caution

The sequence BAD93116.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

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

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.
Isoform 2 (identifier: O00469-2)

Also known as: B;

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

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

Domain644 – 73794Fe2OG dioxygenase

Sites

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

Amino acid modifications

Modified residue3201Phosphothreonine Ref.6
Modified residue3231Phosphotyrosine Ref.6
Modified residue7041N6-succinyllysine By similarity
Glycosylation631N-linked (GlcNAc...) Potential
Glycosylation2091N-linked (GlcNAc...) Ref.7
Glycosylation2971N-linked (GlcNAc...) Potential
Glycosylation3651N-linked (GlcNAc...) Potential
Glycosylation5221N-linked (GlcNAc...) Ref.7
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.10
VAR_022164
Natural variant6011G → C in AR-OI; probable disease-associated mutation found in patients with osteogenesis imperfecta. Ref.11
VAR_069531
Natural variant6011G → V in BRKS2. Ref.9
VAR_022165
Natural variant6081T → I in BRKS2. Ref.9
VAR_022166

Experimental info

Sequence conflict6241H → D in AAB58363. Ref.1

Sequences

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

Checksum: ED81104976B69FC7
Show »

FASTA75887,098

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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Kidney.
[2]"Homo sapiens protein coding cDNA."
Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Aortic endothelium.
[3]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
Tissue: Skin fibroblast.
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Placenta.
[6]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-320 AND TYR-323, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[7]"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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-209 AND ASN-522.
Tissue: Liver.
[8]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS BRKS2 VAL-601 AND ILE-608.
[10]"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] [Europe PMC] [Abstract]
Cited for: VARIANT BRKS2 HIS-598.
[11]"Mutations in PLOD2 cause autosomal-recessive connective tissue disorders within the Bruck syndrome--osteogenesis imperfecta phenotypic spectrum."
Puig-Hervas M.T., Temtamy S., Aglan M., Valencia M., Martinez-Glez V., Ballesta-Martinez M.J., Lopez-Gonzalez V., Ashour A.M., Amr K., Pulido V., Guillen-Navarro E., Lapunzina P., Caparros-Martin J.A., Ruiz-Perez V.L.
Hum. Mutat. 33:1444-1449(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AR-OI CYS-601.
+Additional computationally mapped references.

Web resources

Osteogenesis imperfecta variant database

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

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U84573 mRNA. Translation: AAB58363.1.
AB209879 mRNA. Translation: BAD93116.1. Different initiation.
AC092982 Genomic DNA. No translation available.
AC107021 Genomic DNA. No translation available.
BC037169 mRNA. Translation: AAH37169.1.
PIRA59144.
RefSeqNP_000926.2. NM_000935.2.
NP_891988.1. NM_182943.2.
UniGeneHs.477866.

3D structure databases

ProteinModelPortalO00469.
SMRO00469. Positions 562-735.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111367. 42 interactions.
IntActO00469. 5 interactions.
STRING9606.ENSP00000282903.

Chemistry

DrugBankDB00126. Vitamin C.

PTM databases

PhosphoSiteO00469.

Proteomic databases

PaxDbO00469.
PRIDEO00469.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000282903; ENSP00000282903; ENSG00000152952. [O00469-2]
ENST00000360060; ENSP00000353170; ENSG00000152952. [O00469-1]
GeneID5352.
KEGGhsa:5352.
UCSCuc003evr.1. human. [O00469-2]
uc003evs.1. human. [O00469-1]

Organism-specific databases

CTD5352.
GeneCardsGC03M145787.
HGNCHGNC:9082. PLOD2.
HPACAB025898.
MIM601865. gene.
609220. phenotype.
neXtProtNX_O00469.
Orphanet2771. Bruck syndrome.
PharmGKBPA33412.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG311199.
HOGENOMHOG000231099.
HOVERGENHBG053618.
KOK13645.
OMALFIHNKE.
OrthoDBEOG79PJNP.
PhylomeDBO00469.
TreeFamTF313826.

Enzyme and pathway databases

BRENDA1.14.11.4. 2681.
ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressO00469.
BgeeO00469.
CleanExHS_PLOD2.
GenevestigatorO00469.

Family and domain databases

InterProIPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR006620. Pro_4_hyd_alph.
IPR001006. Procol_lys_dOase.
[Graphical view]
PfamPF03171. 2OG-FeII_Oxy. 1 hit.
[Graphical view]
SMARTSM00702. P4Hc. 1 hit.
[Graphical view]
PROSITEPS51471. FE2OG_OXY. 1 hit.
PS01325. LYS_HYDROXYLASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi5352.
NextBio20746.
PROO00469.
SOURCESearch...

Entry information

Entry namePLOD2_HUMAN
AccessionPrimary (citable) accession number: O00469
Secondary accession number(s): Q59ED2, Q8N170
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: April 26, 2005
Last modified: April 16, 2014
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

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