Reviewed, UniProtKB/Swiss-Prot O60568 (PLOD3_HUMAN)

Names and origin

Protein names

Recommended name:
    Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3
    EC=1.14.11.4
Alternative name(s):
    Lysyl hydroxylase 3
      Short name=LH3

Gene names

Name:

PLOD3

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	738 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	Procollagen L-lysine + 2-oxoglutarate + O2 = procollagen 5-hydroxy-L-lysine + succinate + CO2.
Cofactor	Iron. Ascorbate.
Subunit structure	Homodimer.
Subcellular location	Rough endoplasmic reticulum membrane; Peripheral membrane protein; Lumenal side.
Involvement in disease	Defects in PLOD3 are the cause of lysyl hydroxylase 3 deficiency (LH3 deficiency) [MIM:612394]; also called bone fragility with contractures arterial rupture and deafness. LH3 deficiency is a connective tissue disorder. The syndrome is characterized by congenital malformations severely affecting many tissues and organs and revealing features of several collagen disorders, most of them involving COL2A1 (type II collagen). The findings suggest that the failure of lysyl hydroxylation and hydroxylysyl carbohydrate addition, which affects many collagens, is the molecular basis of this syndrome.
Sequence similarities	Contains 1 PKHD (prolyl/lysyl hydroxylase) domain.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Ligand	Iron Metal-binding Vitamin C
Molecular function	Dioxygenase Oxidoreductase
PTM	Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW protein modification process Ref.2 Traceable author statement. Source: ProtInc
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: UniProtKB-KW 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 Ref.2 Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RHOXF2	Q9BQY4	1	EBI-741582,EBI-372094

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 738	714	Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3		PRO_0000024686
Regions
	Domain	565 – 738	174	PKHD
Sites
	Active site	729	1	Potential
	Metal binding	667	1	Iron By similarity
	Metal binding	669	1	Iron By similarity
	Metal binding	719	1	Iron By similarity
Amino acid modifications
	Glycosylation	63	1	N-linked (GlcNAc...) Potential
	Glycosylation	548	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	151	1	A → V: dbSNP rs35627324.		VAR_051708
	Natural variant	223	1	N → S in LH3 deficiency.		VAR_054913
	Natural variant	286	1	R → W: dbSNP rs1134907.		VAR_012075

Sequences

	Sequence		Length	Mass (Da)
	O60568-1 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 08424B46985941F9	FASTA	738	84,785
	10 20 30 40 50 60 MTSSGPGPRF LLLLPLLLPP AASASDRPRG RDPVNPEKLL VITVATAETE GYLRFLRSAE 70 80 90 100 110 120 FFNYTVRTLG LGEEWRGGDV ARTVGGGQKV RWLKKEMEKY ADREDMIIMF VDSYDVILAG 130 140 150 160 170 180 SPTELLKKFV QSGSRLLFSA ESFCWPEWGL AEQYPEVGTG KRFLNSGGFI GFATTIHQIV 190 200 210 220 230 240 RQWKYKDDDD DQLFYTRLYL DPGLREKLSL NLDHKSRIFQ NLNGALDEVV LKFDRNRVRI 250 260 270 280 290 300 RNVAYDTLPI VVHGNGPTKL QLNYLGNYVP NGWTPEGGCG FCNQDRRTLP GGQPPPRVFL 310 320 330 340 350 360 AVFVEQPTPF LPRFLQRLLL LDYPPDRVTL FLHNNEVFHE PHIADSWPQL QDHFSAVKLV 370 380 390 400 410 420 GPEEALSPGE ARDMAMDLCR QDPECEFYFS LDADAVLTNL QTLRILIEEN RKVIAPMLSR 430 440 450 460 470 480 HGKLWSNFWG ALSPDEYYAR SEDYVELVQR KRVGVWNVPY ISQAYVIRGD TLRMELPQRD 490 500 510 520 530 540 VFSGSDTDPD MAFCKSFRDK GIFLHLSNQH EFGRLLATSR YDTEHLHPDL WQIFDNPVDW 550 560 570 580 590 600 KEQYIHENYS RALEGEGIVE QPCPDVYWFP LLSEQMCDEL VAEMEHYGQW SGGRHEDSRL 610 620 630 640 650 660 AGGYENVPTV DIHMKQVGYE DQWLQLLRTY VGPMTESLFP GYHTKARAVM NFVVRYRPDE 670 680 690 700 710 720 QPSLRPHHDS STFTLNVALN HKGLDYEGGG CRFLRYDCVI SSPRKGWALL HPGRLTHYHE 730 GLPTTWGTRY IMVSFVDP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure, tissue distribution, and chromosomal localization of a novel isoform of lysyl hydroxylase (lysyl hydroxylase 3)." Valtavaara M., Szpirer C., Szpirer J., Myllylae R. J. Biol. Chem. 273:12881-12886(1998) [PubMed: 9582318] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning and characterization of a third human lysyl hydroxylase isoform." Passoja K., Rautavuoma K., Ala-Kokko L., Kosonen T., Kivirikko K.I. Proc. Natl. Acad. Sci. U.S.A. 95:10482-10486(1998) [PubMed: 9724729] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Complete exon-intron organization of the gene for human lysyl hydroxylase 3 (LH3)." Rautavuoma K., Passoja K., Helaakoski T., Kivirikko K.I. Matrix Biol. 19:73-79(2000) [PubMed: 10686427] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"A gene upregulated by HBVX and is similar to LH3." Lian Z., Feitelson M. Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Tissue: Pancreas.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"A connective tissue disorder caused by mutations of the lysyl hydroxylase 3 gene." Salo A.M., Cox H., Farndon P., Moss C., Grindulis H., Risteli M., Robins S.P., Myllylae R. Am. J. Hum. Genet. 83:495-503(2008) [PubMed: 18834968] [Abstract] Cited for: VARIANT LH3 DEFICIENCY SER-223.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF046889 mRNA. Translation: AAC39753.1. AF068229 mRNA. Translation: AAC34808.1. AF207069 Genomic DNA. Translation: AAF63701.1. AY220458 mRNA. Translation: AAO61775.1. AC004876 Genomic DNA. Translation: AAD45831.1. BC011674 mRNA. Translation: AAH11674.1.
IPI	IPI00030255.
RefSeq	NP_001075.1.
UniGene	Hs.153357
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O60568. 6 interactions.
PTM databases
PhosphoSite	O60568.
Proteomic databases
PeptideAtlas	O60568.
PRIDE	O60568.
Genome annotation databases
Ensembl	ENSG00000106397. Homo sapiens. [Contig view]
GeneID	8985.
KEGG	hsa:8985.
UCSC	uc003uyd.1. human.
Organism-specific databases
GeneCards	GC07M100635.
H-InvDB	HIX0006947.
HGNC	HGNC:9083. PLOD3.
MIM	603066. gene. 612394. phenotype.
PharmGKB	PA33413.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O60568.
HOVERGEN	O60568.
OMA	O60568. SAEFFNY.
Enzyme and pathway databases
BRENDA	1.14.11.4. 247.
Gene expression databases
ArrayExpress	O60568.
Bgee	O60568.
CleanEx	HS_PLOD3.
GermOnline	ENSG00000106397. Homo sapiens.
Family and domain databases
InterPro	IPR005123. Oxoglutarate/Fe-dep_Oase. IPR006620. Pro_4_hyd_alph. IPR001006. Procol_lys_dOase. [Graphical view]
Pfam	PF03171. 2OG-FeII_Oxy. 1 hit. [Graphical view]
ProDom	PD011578. ProcolLys_dioxy. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00702. P4Hc. 1 hit. [Graphical view]
PROSITE	PS01325. LYS_HYDROXYLASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00139. Succinic acid. DB00126. Vitamin C.
NextBio	33693.
SOURCE	Search...

Entry information

Entry name

PLOD3_HUMAN

Accession

Primary (citable) accession number: O60568
Secondary accession number(s): Q540C3

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	August 1, 1998
Last modified:	July 7, 2009
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)