O00469 (PLOD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	737 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Defects in PLOD2 are the cause of Bruck syndrome type 2 (BRKS2) [MIM:609220]. Bruck syndrome, 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.9 Ref.10
Sequence similarities	Contains 1 Fe2OG dioxygenase domain.
Sequence caution	The sequence BAD93116.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Osteogenesis imperfecta
Domain	Signal
Ligand	Iron Metal-binding Vitamin C
Molecular function	Dioxygenase Oxidoreductase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	protein modification process Traceable author statement. Source: ProtInc response to hypoxia Inferred from expression pattern. Source: UniProtKB
Cellular component	rough endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	L-ascorbic acid binding Inferred from electronic annotation. Source: UniProtKB-KW iron ion binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW procollagen-lysine 5-dioxygenase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Chain	26 – 737	712	Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2		PRO_0000024683
Regions
	Domain	644 – 737	94	Fe2OG dioxygenase
Sites
	Active site	728	1	Potential
	Metal binding	666	1	Iron By similarity
	Metal binding	668	1	Iron By similarity
	Metal binding	718	1	Iron By similarity
Amino acid modifications
	Modified residue	320	1	Phosphothreonine Ref.6
	Modified residue	323	1	Phosphotyrosine Ref.6
	Glycosylation	63	1	N-linked (GlcNAc...) Potential
	Glycosylation	209	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	297	1	N-linked (GlcNAc...) Potential
	Glycosylation	365	1	N-linked (GlcNAc...) Potential
	Glycosylation	522	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	696	1	N-linked (GlcNAc...) Potential
	Glycosylation	725	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	500	1	M → MTLQREKDSPTPETFQMLSP PK in isoform 2.		VSP_013467
	Natural variant	598	1	R → H in BRKS2. Ref.10		VAR_022164
	Natural variant	601	1	G → V in BRKS2. Ref.9		VAR_022165
	Natural variant	608	1	T → I in BRKS2. Ref.9		VAR_022166
Experimental info
	Sequence conflict	624	1	H → D in AAB58363. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (A) [UniParc]. Last modified April 26, 2005. Version 2. Checksum: C9AEA79A574D6B66	FASTA	737	84,686
	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
	Isoform 2 (B) [UniParc]. Checksum: ED81104976B69FC7	FASTA	758	87,098
	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 TLQREKDSPT PETFQMLSPP KGVFMYISNR HEFGRLLSTA 550 560 570 580 590 600 NYNTSHYNND LWQIFENPVD WKEKYINRDY SKIFTENIVE QPCPDVFWFP IFSEKACDEL 610 620 630 640 650 660 VEEMEHYGKW SGGKHHDSRI SGGYENVPTD DIHMKQVDLE NVWLHFIREF IAPVTLKVFA 670 680 690 700 710 720 GYYTKGFALL NFVVKYSPER QRSLRPHHDA STFTINIALN NVGEDFQGGG CKFLRYNCSI 730 740 750 ESPRKGWSFM HPGRLTHLHE GLPVKNGTRY IAVSFIDP

References

	« Hide 'large scale' referencesShow '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]	"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: 16641997] [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: 10372558] [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: 15489334] [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: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-320 AND TYR-323, MASS SPECTROMETRY. 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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-209 AND ASN-522, MASS SPECTROMETRY. 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: 21269460] [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: 12881513] [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: 15523624] [Abstract] Cited for: VARIANT BRKS2 HIS-598.
+	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.
IPI	IPI00337495. IPI00472165.
PIR	A59144.
RefSeq	NP_000926.2. NM_000935.2. NP_891988.1. NM_182943.2.
UniGene	Hs.477866.
3D structure databases
ProteinModelPortal	O00469.
SMR	O00469. Positions 562-736.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00469. 4 interactions.
STRING	O00469.
PTM databases
PhosphoSite	O00469.
Proteomic databases
PRIDE	O00469.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000360060; ENSP00000353170; ENSG00000152952.
GeneID	5352.
KEGG	hsa:5352.
UCSC	uc003evr.1. human. uc003evs.1. human.
Organism-specific databases
CTD	5352.
GeneCards	GC03M145787.
HGNC	HGNC:9082. PLOD2.
HPA	CAB025898.
MIM	601865. gene. 609220. phenotype.
neXtProt	NX_O00469.
Orphanet	2771. Bruck syndrome.
PharmGKB	PA33412.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG06587.
HOVERGEN	HBG053618.
OMA	LFIHNKE.
Enzyme and pathway databases
BRENDA	1.14.11.4. 2681.
Gene expression databases
ArrayExpress	O00469.
Bgee	O00469.
CleanEx	HS_PLOD2.
Genevestigator	O00469.
GermOnline	ENSG00000152952. Homo sapiens.
Family and domain databases
InterPro	IPR005123. Oxoglutarate/Fe-dep_oxygenase. IPR006620. Pro_4_hyd_alph. IPR001006. Procol_lys_dOase. [Graphical view]
KO	K13645.
Pfam	PF03171. 2OG-FeII_Oxy. 1 hit. [Graphical view]
SMART	SM00702. P4Hc. 1 hit. [Graphical view]
PROSITE	PS51471. FE2OG_OXY. 1 hit. PS01325. LYS_HYDROXYLASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00126. Vitamin C.
NextBio	20746.
SOURCE	Search...

Entry information

Entry name

PLOD2_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.