O60568 · PLOD3_HUMAN
- ProteinMultifunctional procollagen lysine hydroxylase and glycosyltransferase LH3
- GenePLOD3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids738 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Multifunctional enzyme that catalyzes a series of essential post-translational modifications on Lys residues in procollagen (PubMed:11956192, PubMed:12475640, PubMed:18298658, PubMed:18834968, PubMed:30089812).
Plays a redundant role in catalyzing the formation of hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens (PubMed:11956192, PubMed:12475640, PubMed:18298658, PubMed:18834968, PubMed:30089812, PubMed:9582318, PubMed:9724729).
Plays a redundant role in catalyzing the transfer of galactose onto hydroxylysine groups, giving rise to galactosyl 5-hydroxylysine (PubMed:12475640, PubMed:18298658, PubMed:18834968, PubMed:30089812).
Has an essential role by catalyzing the subsequent transfer of glucose moieties, giving rise to 1,2-glucosylgalactosyl-5-hydroxylysine residues (PubMed:10934207, PubMed:11896059, PubMed:11956192, PubMed:12475640, PubMed:18298658, PubMed:18834968, PubMed:30089812).
Catalyzes hydroxylation and glycosylation of Lys residues in the MBL1 collagen-like domain, giving rise to hydroxylysine and 1,2-glucosylgalactosyl-5-hydroxylysine residues (PubMed:25419660).
Essential for normal biosynthesis and secretion of type IV collagens (Probable) (PubMed:18834968).
Essential for normal formation of basement membranes (By similarity).
Plays a redundant role in catalyzing the formation of hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens (PubMed:11956192, PubMed:12475640, PubMed:18298658, PubMed:18834968, PubMed:30089812, PubMed:9582318, PubMed:9724729).
Plays a redundant role in catalyzing the transfer of galactose onto hydroxylysine groups, giving rise to galactosyl 5-hydroxylysine (PubMed:12475640, PubMed:18298658, PubMed:18834968, PubMed:30089812).
Has an essential role by catalyzing the subsequent transfer of glucose moieties, giving rise to 1,2-glucosylgalactosyl-5-hydroxylysine residues (PubMed:10934207, PubMed:11896059, PubMed:11956192, PubMed:12475640, PubMed:18298658, PubMed:18834968, PubMed:30089812).
Catalyzes hydroxylation and glycosylation of Lys residues in the MBL1 collagen-like domain, giving rise to hydroxylysine and 1,2-glucosylgalactosyl-5-hydroxylysine residues (PubMed:25419660).
Essential for normal biosynthesis and secretion of type IV collagens (Probable) (PubMed:18834968).
Essential for normal formation of basement membranes (By similarity).
Catalytic activity
- 2-oxoglutarate + L-lysyl-[collagen] + O2 = (5R)-5-hydroxy-L-lysyl-[collagen] + CO2 + succinate
Cofactor
Protein has several cofactor binding sites:
Activity regulation
Lysyl hydroxylase activity is strongly inhibited by imidazole.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
35 μM | UDP-galactose | |||||
17 μM | UDP-glucose | |||||
100 μM | 2-oxoglutarate | |||||
300 μM | ascorbate | |||||
350 μM | ascorbate |
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 44-46 | UDP (UniProtKB | ChEBI) | ||||
Sequence: VAT | ||||||
Binding site | 112 | Mn2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 112-114 | UDP (UniProtKB | ChEBI) | ||||
Sequence: DSY | ||||||
Binding site | 115 | Mn2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 253 | Mn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 256-259 | UDP (UniProtKB | ChEBI) | ||||
Sequence: GPTK | ||||||
Binding site | 599 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 656 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 667 | Fe cation (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 669 | Fe cation (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 676 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 719 | Fe cation (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 729 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: R |
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameMultifunctional procollagen lysine hydroxylase and glycosyltransferase LH3
Including 2 domains:
- Recommended nameProcollagen-lysine,2-oxoglutarate 5-dioxygenase 3
- EC number
- Alternative names
- Recommended nameProcollagen glycosyltransferase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO60568
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Peripheral membrane protein
Note: The majority of the secreted protein is associated with the extracellular matrix.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Bone fragility with contractures, arterial rupture, and deafness (BCARD)
- Note
- DescriptionAn autosomal recessive connective tissue disorder, secondary to lysyl hydroxylase 3 deficiency. It is characterized by congenital malformations severely affecting multiple tissues and organs. Clinical features include growth retardation, craniofacial dysmorphism, popliteal and cerebral aneurysm, cerebral arterial hemorrhage, skin blistering and easy bruisability, and osteopenia.
- See alsoMIM:612394
Natural variants in BCARD
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_054913 | 223 | N>S | in BCARD; generates a new glycosylation site; decreases protein stability; strongly decreases lysyl hydroxylase activity and nearly abolishes glycosyltransferase activity; dbSNP:rs121434414 | |
VAR_082150 | 452-738 | missing | in BCARD; uncertain significance |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 75 | Decreased lysyl hydroxylase activity and loss of glycosyltransferase activity. | ||||
Sequence: W → A | ||||||
Mutagenesis | 114 | Decreased lysyl hydroxylase and glycosyltransferase activity. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 144 | Strongly reduced glucosyltransferase activity. Strongly reduced galactosyltransferase activity. | ||||
Sequence: C → I | ||||||
Natural variant | VAR_051708 | 151 | in dbSNP:rs35627324 | |||
Sequence: A → V | ||||||
Mutagenesis | 187-189 | Nearly abolishes glucosyltransferase activity. Nearly abolishes galactosyltransferase activity. | ||||
Sequence: DDD → ADA | ||||||
Mutagenesis | 187-191 | Loss of glucosyltransferase activity. Loss of galactosyltransferase activity. | ||||
Sequence: DDDDD → ADAAA | ||||||
Mutagenesis | 208 | Reduced glucosyltransferase activity. | ||||
Sequence: L → I | ||||||
Natural variant | VAR_054913 | 223 | in BCARD; generates a new glycosylation site; decreases protein stability; strongly decreases lysyl hydroxylase activity and nearly abolishes glycosyltransferase activity; dbSNP:rs121434414 | |||
Sequence: N → S | ||||||
Natural variant | VAR_012075 | 286 | in dbSNP:rs1134907 | |||
Sequence: R → W | ||||||
Natural variant | VAR_082150 | 452-738 | in BCARD; uncertain significance | |||
Sequence: Missing | ||||||
Mutagenesis | 669 | Strongly decreased lysyl hydroxylase activity. No effect on glycosyltransferase activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 672 | Loss of dimerization. Loss of lysyl hydroxylase activity and decreased glycosyltransferase activity. | ||||
Sequence: T → N | ||||||
Mutagenesis | 714 | Loss of dimerization. Loss of lysyl hydroxylase activity and no effect on glycosyltransferase activity. | ||||
Sequence: R → N | ||||||
Mutagenesis | 715 | No effect on dimerization, lysyl hydroxylase and glycosyltransferase activity. | ||||
Sequence: L → D | ||||||
Mutagenesis | 715 | Loss of lysyl hydroxylase activity and decreased glycosyltransferase activity. | ||||
Sequence: L → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 952 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Signal | 1-24 | UniProt | |||||
Sequence: MTSSGPGPRFLLLLPLLLPPAASA | |||||||
Chain | PRO_0000024686 | 25-738 | UniProt | Multifunctional procollagen lysine hydroxylase and glycosyltransferase LH3 | |||
Sequence: SDRPRGRDPVNPEKLLVITVATAETEGYLRFLRSAEFFNYTVRTLGLGEEWRGGDVARTVGGGQKVRWLKKEMEKYADREDMIIMFVDSYDVILAGSPTELLKKFVQSGSRLLFSAESFCWPEWGLAEQYPEVGTGKRFLNSGGFIGFATTIHQIVRQWKYKDDDDDQLFYTRLYLDPGLREKLSLNLDHKSRIFQNLNGALDEVVLKFDRNRVRIRNVAYDTLPIVVHGNGPTKLQLNYLGNYVPNGWTPEGGCGFCNQDRRTLPGGQPPPRVFLAVFVEQPTPFLPRFLQRLLLLDYPPDRVTLFLHNNEVFHEPHIADSWPQLQDHFSAVKLVGPEEALSPGEARDMAMDLCRQDPECEFYFSLDADAVLTNLQTLRILIEENRKVIAPMLSRHGKLWSNFWGALSPDEYYARSEDYVELVQRKRVGVWNVPYISQAYVIRGDTLRMELPQRDVFSGSDTDPDMAFCKSFRDKGIFLHLSNQHEFGRLLATSRYDTEHLHPDLWQIFDNPVDWKEQYIHENYSRALEGEGIVEQPCPDVYWFPLLSEQMCDELVAEMEHYGQWSGGRHEDSRLAGGYENVPTVDIHMKQVGYEDQWLQLLRTYVGPMTESLFPGYHTKARAVMNFVVRYRPDEQPSLRPHHDSSTFTLNVALNHKGLDYEGGGCRFLRYDCVISSPRKGWALLHPGRLTHYHEGLPTTWGTRYIMVSFVDP | |||||||
Glycosylation | 63 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 279↔282 | UniProt | |||||
Sequence: CGFC | |||||||
Disulfide bond | 379↔385 | UniProt | |||||
Sequence: CRQDPEC | |||||||
Glycosylation | 548 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 563↔698 | UniProt | |||||
Sequence: CPDVYWFPLLSEQMCDELVAEMEHYGQWSGGRHEDSRLAGGYENVPTVDIHMKQVGYEDQWLQLLRTYVGPMTESLFPGYHTKARAVMNFVVRYRPDEQPSLRPHHDSSTFTLNVALNHKGLDYEGGGCRFLRYDC | |||||||
Modified residue (large scale data) | 701 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Homodimer.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O60568 | COIL P38432 | 3 | EBI-741582, EBI-945751 | |
BINARY | O60568 | COL17A1 Q9UMD9 | 3 | EBI-741582, EBI-2528742 | |
BINARY | O60568 | CRIP3 Q6Q6R5-3 | 3 | EBI-741582, EBI-12925520 | |
BINARY | O60568 | EFHC2 Q5JST6 | 12 | EBI-741582, EBI-2349927 | |
BINARY | O60568 | EHMT2 A2ABF9 | 3 | EBI-741582, EBI-10174566 | |
BINARY | O60568 | EHMT2 Q96KQ7 | 8 | EBI-741582, EBI-744366 | |
BINARY | O60568 | IP6K2 Q9UHH9 | 3 | EBI-741582, EBI-747509 | |
BINARY | O60568 | KCTD9 Q7L273 | 3 | EBI-741582, EBI-4397613 | |
BINARY | O60568 | KHNYN O15037 | 3 | EBI-741582, EBI-6148525 | |
BINARY | O60568 | L3MBTL3 Q96JM7-2 | 3 | EBI-741582, EBI-11985629 | |
BINARY | O60568 | NAB2 Q15742 | 3 | EBI-741582, EBI-8641936 | |
BINARY | O60568 | RAB3IP Q96QF0 | 4 | EBI-741582, EBI-747844 | |
BINARY | O60568 | RAB3IP Q96QF0-2 | 3 | EBI-741582, EBI-747865 | |
BINARY | O60568 | RALY Q53GL6 | 3 | EBI-741582, EBI-9512693 | |
BINARY | O60568 | RHOXF2 Q9BQY4 | 2 | EBI-741582, EBI-372094 | |
BINARY | O60568 | SORBS3 O60504 | 3 | EBI-741582, EBI-741237 | |
BINARY | O60568 | ZNF620 Q6ZNG0 | 3 | EBI-741582, EBI-4395669 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 25-290 | Required for glycosyltransferase activity | ||||
Sequence: SDRPRGRDPVNPEKLLVITVATAETEGYLRFLRSAEFFNYTVRTLGLGEEWRGGDVARTVGGGQKVRWLKKEMEKYADREDMIIMFVDSYDVILAGSPTELLKKFVQSGSRLLFSAESFCWPEWGLAEQYPEVGTGKRFLNSGGFIGFATTIHQIVRQWKYKDDDDDQLFYTRLYLDPGLREKLSLNLDHKSRIFQNLNGALDEVVLKFDRNRVRIRNVAYDTLPIVVHGNGPTKLQLNYLGNYVPNGWTPEGGCGFCNQDRRTLP | ||||||
Region | 295-520 | Accessory region | ||||
Sequence: PPRVFLAVFVEQPTPFLPRFLQRLLLLDYPPDRVTLFLHNNEVFHEPHIADSWPQLQDHFSAVKLVGPEEALSPGEARDMAMDLCRQDPECEFYFSLDADAVLTNLQTLRILIEENRKVIAPMLSRHGKLWSNFWGALSPDEYYARSEDYVELVQRKRVGVWNVPYISQAYVIRGDTLRMELPQRDVFSGSDTDPDMAFCKSFRDKGIFLHLSNQHEFGRLLATSR | ||||||
Domain | 647-738 | Fe2OG dioxygenase | ||||
Sequence: RAVMNFVVRYRPDEQPSLRPHHDSSTFTLNVALNHKGLDYEGGGCRFLRYDCVISSPRKGWALLHPGRLTHYHEGLPTTWGTRYIMVSFVDP | ||||||
Region | 672-715 | Important for dimerization | ||||
Sequence: TFTLNVALNHKGLDYEGGGCRFLRYDCVISSPRKGWALLHPGRL |
Domain
The N-terminal domain mediates glycosyltransferase activity.
The C-terminal domain that mediates lysyl hydroxylase activity is also important for homodimerization.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length738
- Mass (Da)84,785
- Last updated1998-08-01 v1
- Checksum08424B46985941F9
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF046889 EMBL· GenBank· DDBJ | AAC39753.1 EMBL· GenBank· DDBJ | mRNA | ||
AF068229 EMBL· GenBank· DDBJ | AAC34808.1 EMBL· GenBank· DDBJ | mRNA | ||
AF207069 EMBL· GenBank· DDBJ | AAF63701.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AY220458 EMBL· GenBank· DDBJ | AAO61775.1 EMBL· GenBank· DDBJ | mRNA | ||
AK312743 EMBL· GenBank· DDBJ | BAG35613.1 EMBL· GenBank· DDBJ | mRNA | ||
AC004876 EMBL· GenBank· DDBJ | AAD45831.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471197 EMBL· GenBank· DDBJ | EAW50205.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC011674 EMBL· GenBank· DDBJ | AAH11674.1 EMBL· GenBank· DDBJ | mRNA |