Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

O00469

- PLOD2_HUMAN

UniProt

O00469 - PLOD2_HUMAN

Protein

Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2

Gene

PLOD2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 136 (01 Oct 2014)
      Sequence version 2 (26 Apr 2005)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

    Iron.By similarity
    Ascorbate.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi666 – 6661IronPROSITE-ProRule annotation
    Metal bindingi668 – 6681IronPROSITE-ProRule annotation
    Metal bindingi718 – 7181IronPROSITE-ProRule annotation
    Active sitei728 – 7281Sequence Analysis

    GO - Molecular functioni

    1. iron ion binding Source: InterPro
    2. L-ascorbic acid binding Source: UniProtKB-KW
    3. procollagen-lysine 5-dioxygenase activity Source: ProtInc

    GO - Biological processi

    1. cellular protein modification process Source: ProtInc
    2. extracellular matrix organization Source: Reactome
    3. response to hypoxia Source: UniProtKB

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Ligandi

    Iron, Metal-binding, Vitamin C

    Enzyme and pathway databases

    BRENDAi1.14.11.4. 2681.
    ReactomeiREACT_121139. 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
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:9082. PLOD2.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum Source: ProtInc
    2. endoplasmic reticulum membrane Source: Reactome
    3. extracellular vesicular exosome Source: UniProt
    4. rough endoplasmic reticulum membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    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.2 Publications
    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.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti598 – 5981R → H in BRKS2. 1 Publication
    VAR_022164
    Natural varianti601 – 6011G → V in BRKS2. 1 Publication
    VAR_022165
    Natural varianti608 – 6081T → I in BRKS2. 1 Publication
    VAR_022166
    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).1 Publication

    Keywords - Diseasei

    Disease mutation, Osteogenesis imperfecta

    Organism-specific databases

    MIMi609220. phenotype.
    Orphaneti2771. Bruck syndrome.
    PharmGKBiPA33412.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2525Sequence AnalysisAdd
    BLAST
    Chaini26 – 737712Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2PRO_0000024683Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi63 – 631N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi209 – 2091N-linked (GlcNAc...)1 Publication
    Glycosylationi297 – 2971N-linked (GlcNAc...)Sequence Analysis
    Modified residuei320 – 3201Phosphothreonine1 Publication
    Modified residuei323 – 3231Phosphotyrosine1 Publication
    Glycosylationi365 – 3651N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi522 – 5221N-linked (GlcNAc...)1 Publication
    Glycosylationi696 – 6961N-linked (GlcNAc...)Sequence Analysis
    Modified residuei704 – 7041N6-succinyllysineBy similarity
    Glycosylationi725 – 7251N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    MaxQBiO00469.
    PaxDbiO00469.
    PRIDEiO00469.

    PTM databases

    PhosphoSiteiO00469.

    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

    ArrayExpressiO00469.
    BgeeiO00469.
    CleanExiHS_PLOD2.
    GenevestigatoriO00469.

    Organism-specific databases

    HPAiCAB025898.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    BioGridi111367. 42 interactions.
    IntActiO00469. 6 interactions.
    STRINGi9606.ENSP00000282903.

    Structurei

    3D structure databases

    ProteinModelPortaliO00469.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini644 – 73794Fe2OG dioxygenasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG311199.
    HOGENOMiHOG000231099.
    HOVERGENiHBG053618.
    KOiK13645.
    OMAiLFIHNKE.
    OrthoDBiEOG79PJNP.
    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 (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. Align

    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

    MGGCTVKPQL LLLALVLHPW NPCLGADSEK PSSIPTDKLL VITVATKESD    50
    GFHRFMQSAK YFNYTVKVLG QGEEWRGGDG INSIGGGQKV RLMKEVMEHY 100
    ADQDDLVVMF TECFDVIFAG GPEEVLKKFQ KANHKVVFAA DGILWPDKRL 150
    ADKYPVVHIG KRYLNSGGFI GYAPYVNRIV QQWNLQDNDD DQLFYTKVYI 200
    DPLKREAINI TLDHKCKIFQ TLNGAVDEVV LKFENGKARA KNTFYETLPV 250
    AINGNGPTKI LLNYFGNYVP NSWTQDNGCT LCEFDTVDLS AVDVHPNVSI 300
    GVFIEQPTPF LPRFLDILLT LDYPKEALKL FIHNKEVYHE KDIKVFFDKA 350
    KHEIKTIKIV GPEENLSQAE ARNMGMDFCR QDEKCDYYFS VDADVVLTNP 400
    RTLKILIEQN RKIIAPLVTR HGKLWSNFWG ALSPDGYYAR SEDYVDIVQG 450
    NRVGVWNVPY MANVYLIKGK TLRSEMNERN YFVRDKLDPD MALCRNAREM 500
    GVFMYISNRH EFGRLLSTAN YNTSHYNNDL WQIFENPVDW KEKYINRDYS 550
    KIFTENIVEQ PCPDVFWFPI FSEKACDELV EEMEHYGKWS GGKHHDSRIS 600
    GGYENVPTDD IHMKQVDLEN VWLHFIREFI APVTLKVFAG YYTKGFALLN 650
    FVVKYSPERQ RSLRPHHDAS TFTINIALNN VGEDFQGGGC KFLRYNCSIE 700
    SPRKGWSFMH PGRLTHLHEG LPVKNGTRYI AVSFIDP 737
    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

    Sequence cautioni

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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti624 – 6241H → D in AAB58363. (PubMed:9054364)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti598 – 5981R → H in BRKS2. 1 Publication
    VAR_022164
    Natural varianti601 – 6011G → C in AR-OI; probable disease-associated mutation found in patients with osteogenesis imperfecta. 1 Publication
    VAR_069531
    Natural varianti601 – 6011G → V in BRKS2. 1 Publication
    VAR_022165
    Natural varianti608 – 6081T → I in BRKS2. 1 Publication
    VAR_022166

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei500 – 5001M → MTLQREKDSPTPETFQMLSP PK in isoform 2. 2 PublicationsVSP_013467

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    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]
    GeneIDi5352.
    KEGGihsa:5352.
    UCSCiuc003evr.1. human. [O00469-2]
    uc003evs.1. 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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS3131.1. [O00469-1 ]
    CCDS3132.1. [O00469-2 ]
    PIRi A59144.
    RefSeqi NP_000926.2. NM_000935.2. [O00469-1 ]
    NP_891988.1. NM_182943.2. [O00469-2 ]
    UniGenei Hs.477866.

    3D structure databases

    ProteinModelPortali O00469.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111367. 42 interactions.
    IntActi O00469. 6 interactions.
    STRINGi 9606.ENSP00000282903.

    Chemistry

    DrugBanki DB00126. Vitamin C.

    PTM databases

    PhosphoSitei O00469.

    Proteomic databases

    MaxQBi O00469.
    PaxDbi O00469.
    PRIDEi O00469.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000282903 ; ENSP00000282903 ; ENSG00000152952 . [O00469-2 ]
    ENST00000360060 ; ENSP00000353170 ; ENSG00000152952 . [O00469-1 ]
    GeneIDi 5352.
    KEGGi hsa:5352.
    UCSCi uc003evr.1. human. [O00469-2 ]
    uc003evs.1. human. [O00469-1 ]

    Organism-specific databases

    CTDi 5352.
    GeneCardsi GC03M145787.
    HGNCi HGNC:9082. PLOD2.
    HPAi CAB025898.
    MIMi 601865. gene.
    609220. phenotype.
    neXtProti NX_O00469.
    Orphaneti 2771. Bruck syndrome.
    PharmGKBi PA33412.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG311199.
    HOGENOMi HOG000231099.
    HOVERGENi HBG053618.
    KOi K13645.
    OMAi LFIHNKE.
    OrthoDBi EOG79PJNP.
    PhylomeDBi O00469.
    TreeFami TF313826.

    Enzyme and pathway databases

    BRENDAi 1.14.11.4. 2681.
    Reactomei REACT_121139. Collagen biosynthesis and modifying enzymes.

    Miscellaneous databases

    GenomeRNAii 5352.
    NextBioi 20746.
    PROi O00469.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O00469.
    Bgeei O00469.
    CleanExi HS_PLOD2.
    Genevestigatori O00469.

    Family and domain databases

    Gene3Di 3.90.550.10. 1 hit.
    InterProi IPR029044. Nucleotide-diphossugar_trans.
    IPR005123. Oxoglu/Fe-dep_dioxygenase.
    IPR006620. Pro_4_hyd_alph.
    IPR001006. Procol_lys_dOase.
    [Graphical view ]
    Pfami PF03171. 2OG-FeII_Oxy. 1 hit.
    [Graphical view ]
    SMARTi SM00702. P4Hc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF53448. SSF53448. 1 hit.
    PROSITEi PS51471. FE2OG_OXY. 1 hit.
    PS01325. LYS_HYDROXYLASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. 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.

    Entry informationi

    Entry nameiPLOD2_HUMAN
    AccessioniPrimary (citable) accession number: O00469
    Secondary accession number(s): Q59ED2, Q8N170
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 15, 1998
    Last sequence update: April 26, 2005
    Last modified: October 1, 2014
    This is version 136 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

    External Data

    Dasty 3