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Q02809 (PLOD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 167. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1

EC=1.14.11.4
Alternative name(s):
Lysyl hydroxylase 1
Short name=LH1
Gene names
Name:PLOD1
Synonyms:LLH, PLOD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length727 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.

Ascorbate.

Subunit structure

Homodimer.

Subcellular location

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

Involvement in disease

Ehlers-Danlos syndrome 6 (EDS6) [MIM:225400]: A connective tissue disorder characterized by generalized joint hypermobility, hyperextensible skin, atrophic cutaneous scars due to tissue fragility, progressive kyphoscoliosis already present at birth, ocular manifestations, arterial rupture, easy bruising, severe neonatal muscle hypotonia and delayed motor development.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Sequence similarities

Contains 1 Fe2OG dioxygenase domain.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Ehlers-Danlos syndrome
   DomainSignal
   LigandIron
Metal-binding
Vitamin C
   Molecular functionDioxygenase
Oxidoreductase
   PTMGlycoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular protein modification process

Non-traceable author statement Ref.1. Source: UniProtKB

epidermis development

Inferred from mutant phenotype PubMed 8449506. Source: UniProtKB

extracellular matrix organization

Traceable author statement. Source: Reactome

hydroxylysine biosynthetic process

Traceable author statement Ref.1. Source: UniProtKB

oxidation-reduction process

Traceable author statement Ref.1. Source: UniProtKB

response to hypoxia

Inferred from expression pattern PubMed 15174142. Source: UniProtKB

   Cellular_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

rough endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionL-ascorbic acid binding

Inferred from electronic annotation. Source: UniProtKB-KW

iron ion binding

Inferred from electronic annotation. Source: InterPro

procollagen-lysine 5-dioxygenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein homodimerization activity

Traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Ref.1
Chain19 – 727709Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1
PRO_0000024678

Regions

Domain636 – 72792Fe2OG dioxygenase

Sites

Active site7181 Potential
Metal binding6561Iron
Metal binding6581Iron
Metal binding7081Iron

Amino acid modifications

Glycosylation1631N-linked (GlcNAc...) Potential
Glycosylation1971N-linked (GlcNAc...) Probable
Glycosylation5381N-linked (GlcNAc...) Probable
Glycosylation6861N-linked (GlcNAc...) Potential

Natural variations

Natural variant671E → D.
Corresponds to variant rs7551068 [ dbSNP | Ensembl ].
VAR_032754
Natural variant841A → T.
Corresponds to variant rs34878020 [ dbSNP | Ensembl ].
VAR_032755
Natural variant991A → T. Ref.1 Ref.4
Corresponds to variant rs7551175 [ dbSNP | Ensembl ].
VAR_014220
Natural variant1201A → S. Ref.4
Corresponds to variant rs2273285 [ dbSNP | Ensembl ].
VAR_032756
Natural variant1231Q → H in a breast cancer sample; somatic mutation. Ref.13
VAR_035479
Natural variant367 – 3715Missing in EDS6.
VAR_009269
Natural variant4461W → G in EDS6. Ref.11
VAR_023466
Natural variant5321Missing in EDS6. Ref.7
VAR_006354
Natural variant6121W → C in EDS6. Ref.8
VAR_006355
Natural variant6671A → T in EDS6. Ref.12
Corresponds to variant rs199730384 [ dbSNP | Ensembl ].
VAR_023467
Natural variant6781G → R in EDS6. Ref.7
VAR_006356
Natural variant7061H → R in EDS6. Ref.12
VAR_023468

Experimental info

Mutagenesis3691C → A: Loss of activity. Ref.9

Sequences

Sequence LengthMass (Da)Tools
Q02809 [UniParc].

Last modified October 25, 2005. Version 2.
Checksum: 6C3E0C11B15D598C

FASTA72783,550
        10         20         30         40         50         60 
MRPLLLLALL GWLLLAEAKG DAKPEDNLLV LTVATKETEG FRRFKRSAQF FNYKIQALGL 

        70         80         90        100        110        120 
GEDWNVEKGT SAGGGQKVRL LKKALEKHAD KEDLVILFAD SYDVLFASGP RELLKKFRQA 

       130        140        150        160        170        180 
RSQVVFSAEE LIYPDRRLET KYPVVSDGKR FLGSGGFIGY APNLSKLVAE WEGQDSDSDQ 

       190        200        210        220        230        240 
LFYTKIFLDP EKREQINITL DHRCRIFQNL DGALDEVVLK FEMGHVRARN LAYDTLPVLI 

       250        260        270        280        290        300 
HGNGPTKLQL NYLGNYIPRF WTFETGCTVC DEGLRSLKGI GDEALPTVLV GVFIEQPTPF 

       310        320        330        340        350        360 
VSLFFQRLLR LHYPQKHMRL FIHNHEQHHK AQVEEFLAQH GSEYQSVKLV GPEVRMANAD 

       370        380        390        400        410        420 
ARNMGADLCR QDRSCTYYFS VDADVALTEP NSLRLLIQQN KNVIAPLMTR HGRLWSNFWG 

       430        440        450        460        470        480 
ALSADGYYAR SEDYVDIVQG RRVGVWNVPY ISNIYLIKGS ALRGELQSSD LFHHSKLDPD 

       490        500        510        520        530        540 
MAFCANIRQQ DVFMFLTNRH TLGHLLSLDS YRTTHLHNDL WEVFSNPEDW KEKYIHQNYT 

       550        560        570        580        590        600 
KALAGKLVET PCPDVYWFPI FTEVACDELV EEMEHFGQWS LGNNKDNRIQ GGYENVPTID 

       610        620        630        640        650        660 
IHMNQIGFER EWHKFLLEYI APMTEKLYPG YYTRAQFDLA FVVRYKPDEQ PSLMPHHDAS 

       670        680        690        700        710        720 
TFTINIALNR VGVDYEGGGC RFLRYNCSIR APRKGWTLMH PGRLTHYHEG LPTTRGTRYI 


AVSFVDP 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of human lysyl hydroxylase: complete cDNA-derived amino acid sequence and assignment of the gene (PLOD) to chromosome 1p36.3-p36.2."
Hautala T., Byers M.G., Eddy R.L., Shows T.B., Kivirikko K.I., Myllylae R.
Genomics 13:62-69(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 19-28 AND 332-34, VARIANT THR-99.
Tissue: Placenta.
[2]"Structure and expression of the human lysyl hydroxylase gene (PLOD): introns 9 and 16 contain Alu sequences at the sites of recombination in Ehlers-Danlos syndrome type VI patients."
Heikkinen J., Hautala T., Kivirikko K.I., Myllylae R.
Genomics 24:464-471(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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], VARIANTS THR-99 AND SER-120.
Tissue: Skin.
[5]"Site-directed mutagenesis of human lysyl hydroxylase expressed in insect cells. Identification of histidine residues and an aspartic acid residue critical for catalytic activity."
Pirskanen A., Kaimio A.M., Myllylae R., Kivirikko K.I.
J. Biol. Chem. 271:9398-9402(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS.
[6]"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].
[7]"A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene."
Ha V.T., Marshall M.K., Elsas L.J., Pinnell S.R., Yeowell H.N.
J. Clin. Invest. 93:1716-1721(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDS6 GLU-532 DEL AND ARG-678.
[8]"Ehlers-Danlos syndrome type VI: lysyl hydroxylase deficiency due to a novel point mutation (W612C)."
Brinckmann J., Acil Y., Feshchenko S., Katzer E., Brenner R., Kulozik A., Kugler S.
Arch. Dermatol. Res. 290:181-186(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EDS6 CYS-612.
[9]"Deletion of cysteine 369 in lysyl hydroxylase 1 eliminates enzyme activity and causes Ehlers-Danlos syndrome type VI."
Yeowell H.N., Allen J.D., Walker L.C., Overstreet M.A., Murad S., Thai S.F.
Matrix Biol. 19:37-46(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EDS6 367-ASP--GLN-371 DEL, MUTAGENESIS OF CYS-369.
[10]"Nevo syndrome is allelic to the kyphoscoliotic type of the Ehlers-Danlos syndrome (EDS VIA)."
Giunta C., Randolph A., Al-Gazali L.I., Brunner H.G., Kraenzlin M.E., Steinmann B.
Am. J. Med. Genet. A 133:158-164(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN EDS6.
[11]"A novel mutation in the lysyl hydroxylase 1 gene causes decreased lysyl hydroxylase activity in an Ehlers-Danlos VIA patient."
Walker L.C., Overstreet M.A., Siddiqui A., De Paepe A., Ceylaner G., Malfait F., Symoens S., Atsawasuwan P., Yamauchi M., Ceylaner S., Bank R.A., Yeowell H.N.
J. Invest. Dermatol. 124:914-918(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EDS6 GLY-446.
[12]"Mutation analysis of the PLOD1 gene: an efficient multistep approach to the molecular diagnosis of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA)."
Giunta C., Randolph A., Steinmann B.
Mol. Genet. Metab. 86:269-276(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDS6 THR-667 AND ARG-706.
[13]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-123.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L06419 mRNA. Translation: AAA60116.1.
AF490527 expand/collapse EMBL AC list , AF490514, AF490515, AF490516, AF490517, AF490518, AF490519, AF490520, AF490521, AF490522, AF490523, AF490524, AF490525, AF490526 Genomic DNA. Translation: AAM12752.1.
AL096840 Genomic DNA. Translation: CAC19722.1.
BC016657 mRNA. Translation: AAH16657.1.
CCDSCCDS142.1.
PIRA38206.
RefSeqNP_000293.2. NM_000302.3.
UniGeneHs.75093.

3D structure databases

ProteinModelPortalQ02809.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111366. 29 interactions.
IntActQ02809. 14 interactions.
MINTMINT-1134973.
STRING9606.ENSP00000196061.

Chemistry

DrugBankDB00350. Minoxidil.
DB00139. Succinic acid.
DB00126. Vitamin C.

PTM databases

PhosphoSiteQ02809.

Polymorphism databases

DMDM78099790.

Proteomic databases

MaxQBQ02809.
PaxDbQ02809.
PeptideAtlasQ02809.
PRIDEQ02809.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000196061; ENSP00000196061; ENSG00000083444.
GeneID5351.
KEGGhsa:5351.
UCSCuc001atm.3. human.

Organism-specific databases

CTD5351.
GeneCardsGC01P011994.
GeneReviewsPLOD1.
HGNCHGNC:9081. PLOD1.
HPAHPA049137.
MIM153454. gene.
225400. phenotype.
neXtProtNX_Q02809.
Orphanet1900. Ehlers-Danlos syndrome, kyphoscoliotic type.
PharmGKBPA33411.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG311199.
HOGENOMHOG000231099.
HOVERGENHBG053618.
InParanoidQ02809.
KOK00473.
OrthoDBEOG79PJNP.
PhylomeDBQ02809.
TreeFamTF313826.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressQ02809.
BgeeQ02809.
CleanExHS_PLOD1.
GenevestigatorQ02809.

Family and domain databases

InterProIPR029044. Nucleotide-diphossugar_trans.
IPR005123. 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]
SUPFAMSSF53448. SSF53448. 1 hit.
PROSITEPS51471. FE2OG_OXY. 1 hit.
PS01325. LYS_HYDROXYLASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPLOD1. human.
GenomeRNAi5351.
NextBio20742.
PROQ02809.
SOURCESearch...

Entry information

Entry namePLOD1_HUMAN
AccessionPrimary (citable) accession number: Q02809
Secondary accession number(s): Q96AV9, Q9H132
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: October 25, 2005
Last modified: July 9, 2014
This is version 167 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 1

Human chromosome 1: entries, gene names and cross-references to MIM