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Protein

Prolyl 3-hydroxylase 2

Gene

P3H2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Prolyl 3-hydroxylase that catalyzes the post-translational formation of 3-hydroxyproline on collagens (PubMed:18487197). Contributes to proline 3-hydroxylation of collagen COL4A1 and COL1A1 in tendons, the eye sclera and in the eye lens capsule (By similarity). Has high activity with the type IV collagen COL4A1, and lower activity with COL1A1 (PubMed:18487197). Catalyzes hydroxylation of the first Pro in Gly-Pro-Hyp sequences where Hyp is 4-hydroxyproline (PubMed:18487197). Has no activity on substrates that lack 4-hydroxyproline in the third position (PubMed:18487197).By similarity1 Publication

Catalytic activityi

L-proline-[procollagen] + 2-oxoglutarate + O2 = trans-3-hydroxy-L-proline-[procollagen] + succinate + CO2.1 Publication

Cofactori

Protein has several cofactor binding sites:
  • Fe cation1 Publication
  • L-ascorbate1 Publication

Enzyme regulationi

Inhibited by pyridine 2,4-dicarboxylate, an analog of 2-oxoglutarate.1 Publication

Kineticsi

  1. KM=80 µM for 2-oxoglutarate1 Publication
  2. KM=110 µM for ascorbate1 Publication
  3. KM=0.5 µM for Fe2+1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi580Iron1
    Metal bindingi582Iron1
    Metal bindingi652Iron1
    Active sitei662By similarity1

    GO - Molecular functioni

    GO - Biological processi

    • collagen metabolic process Source: UniProtKB
    • negative regulation of cell proliferation Source: UniProtKB
    • peptidyl-proline hydroxylation Source: UniProtKB

    Keywordsi

    Molecular functionDioxygenase, Oxidoreductase
    LigandIron, Metal-binding, Vitamin C

    Enzyme and pathway databases

    BRENDAi1.14.11.7. 2681.
    ReactomeiR-HSA-1650814. Collagen biosynthesis and modifying enzymes.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Prolyl 3-hydroxylase 2Imported (EC:1.14.11.71 Publication)
    Alternative name(s):
    Leprecan-like protein 11 Publication
    Myxoid liposarcoma-associated protein 41 Publication
    Gene namesi
    Name:P3H2Imported
    Synonyms:LEPREL11 Publication, MLAT41 Publication
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 3

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000090530.9.
    HGNCiHGNC:19317. P3H2.

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Endoplasmic reticulum, Golgi apparatus, Sarcoplasmic reticulum

    Pathology & Biotechi

    Involvement in diseasei

    Myopia, high, with cataract and vitreoretinal degeneration (MCVD)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA disorder characterized by severe myopia with variable expressivity of cataract and vitreoretinal degeneration. Some patients manifest lens subluxation, lens instability and retinal detachment.
    See also OMIM:614292
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_066637508G → V in MCVD; loss of function. 1 PublicationCorresponds to variant dbSNP:rs724159988Ensembl.1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi55214.
    MalaCardsiP3H2.
    MIMi614292. phenotype.
    OpenTargetsiENSG00000090530.
    Orphaneti98619. Rare isolated myopia.
    PharmGKBiPA134922807.

    Chemistry databases

    DrugBankiDB00172. L-Proline.
    DB00139. Succinic acid.
    DB00126. Vitamin C.

    Polymorphism and mutation databases

    BioMutaiLEPREL1.
    DMDMi74714365.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 24Sequence analysisAdd BLAST24
    ChainiPRO_000024035625 – 708Prolyl 3-hydroxylase 2Add BLAST684

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi449N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi549N-linked (GlcNAc...) asparagineSequence analysis1

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    EPDiQ8IVL5.
    MaxQBiQ8IVL5.
    PaxDbiQ8IVL5.
    PeptideAtlasiQ8IVL5.
    PRIDEiQ8IVL5.

    PTM databases

    iPTMnetiQ8IVL5.
    PhosphoSitePlusiQ8IVL5.

    Expressioni

    Tissue specificityi

    Expression localized to the epithelia of bile ducts and to the sacroplasm of heart muscle and skeletal muscle. In the pancreas, localized to a subpopulation of Langerhans islet cells and in the salivary gland, expressed in acinar cells (at protein level) (PubMed:15063763). Expressed in adult heart, placenta, lung, liver, skeletal muscle and kidney (PubMed:15063763, PubMed:18487197). Detected in fetal heart, spleen, lung, liver skeletal muscle and kidney (PubMed:18487197).2 Publications

    Gene expression databases

    BgeeiENSG00000090530.
    CleanExiHS_LEPREL1.
    ExpressionAtlasiQ8IVL5. baseline and differential.
    GenevisibleiQ8IVL5. HS.

    Organism-specific databases

    HPAiHPA007890.
    HPA013355.

    Interactioni

    Protein-protein interaction databases

    BioGridi120510. 16 interactors.
    IntActiQ8IVL5. 9 interactors.
    STRINGi9606.ENSP00000316881.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8IVL5.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Repeati44 – 77TPR 1Add BLAST34
    Repeati148 – 181TPR 2Add BLAST34
    Repeati210 – 243TPR 3Add BLAST34
    Repeati306 – 339TPR 4Add BLAST34
    Domaini557 – 671Fe2OG dioxygenaseAdd BLAST115

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi705 – 708Prevents secretion from ER4

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi93 – 99Poly-Pro7

    Sequence similaritiesi

    Belongs to the leprecan family.Curated

    Keywords - Domaini

    Repeat, Signal, TPR repeat

    Phylogenomic databases

    eggNOGiKOG4459. Eukaryota.
    ENOG410XPXF. LUCA.
    GeneTreeiENSGT00550000074573.
    HOGENOMiHOG000231087.
    HOVERGENiHBG053224.
    InParanoidiQ8IVL5.
    OMAiNINPKDE.
    OrthoDBiEOG091G06WO.
    PhylomeDBiQ8IVL5.
    TreeFamiTF320837.

    Family and domain databases

    Gene3Di1.25.40.10. 2 hits.
    InterProiView protein in InterPro
    IPR005123. Oxoglu/Fe-dep_dioxygenase.
    IPR006620. Pro_4_hyd_alph.
    IPR011990. TPR-like_helical_dom_sf.
    PfamiView protein in Pfam
    PF13640. 2OG-FeII_Oxy_3. 1 hit.
    SMARTiView protein in SMART
    SM00702. P4Hc. 1 hit.
    SUPFAMiSSF48452. SSF48452. 4 hits.
    PROSITEiView protein in PROSITE
    PS00014. ER_TARGET. 1 hit.
    PS51471. FE2OG_OXY. 1 hit.

    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. AlignAdd to basket

    Isoform 1 (identifier: Q8IVL5-1) [UniParc]FASTAAdd to basket

    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

            10         20         30         40         50
    MRERIWAPPL LLLLPLLLPP PLWGGPPDSP RRELELEPGP LQPFDLLYAS
    60 70 80 90 100
    GAAAYYSGDY ERAVRDLEAA LRSHRRLREI RTRCARHCAA RHPLPPPPPG
    110 120 130 140 150
    EGPGAELPLF RSLLGRARCY RSCETQRLGG PASRHRVSED VRSDFQRRVP
    160 170 180 190 200
    YNYLQRAYIK LNQLEKAVEA AHTFFVANPE HMEMQQNIEN YRATAGVEAL
    210 220 230 240 250
    QLVDREAKPH MESYNAGVKH YEADDFEMAI RHFEQALREY FVEDTECRTL
    260 270 280 290 300
    CEGPQRFEEY EYLGYKAGLY EAIADHYMQV LVCQHECVRE LATRPGRLSP
    310 320 330 340 350
    IENFLPLHYD YLQFAYYRVG EYVKALECAK AYLLCHPDDE DVLDNVDYYE
    360 370 380 390 400
    SLLDDSIDPA SIEAREDLTM FVKRHKLESE LIKSAAEGLG FSYTEPNYWI
    410 420 430 440 450
    RYGGRQDENR VPSGVNVEGA EVHGFSMGKK LSPKIDRDLR EGGPLLYENI
    460 470 480 490 500
    TFVYNSEQLN GTQRVLLDNV LSEEQCRELH SVASGIMLVG DGYRGKTSPH
    510 520 530 540 550
    TPNEKFEGAT VLKALKSGYE GRVPLKSARL FYDISEKARR IVESYFMLNS
    560 570 580 590 600
    TLYFSYTHMV CRTALSGQQD RRNDLSHPIH ADNCLLDPEA NECWKEPPAY
    610 620 630 640 650
    TFRDYSALLY MNDDFEGGEF IFTEMDAKTV TASIKPKCGR MISFSSGGEN
    660 670 680 690 700
    PHGVKAVTKG KRCAVALWFT LDPLYRELER IQADEVIAIL DQEQQGKHEL

    NINPKDEL
    Length:708
    Mass (Da):80,984
    Last modified:March 1, 2003 - v1
    Checksum:iB9E680C90D607291
    GO
    Isoform 2 (identifier: Q8IVL5-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-181: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:527
    Mass (Da):60,387
    Checksum:iD3B80AE780F6D8DD
    GO

    Sequence cautioni

    The sequence BAA91769 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti477R → Q in BAG51712 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_066637508G → V in MCVD; loss of function. 1 PublicationCorresponds to variant dbSNP:rs724159988Ensembl.1
    Natural variantiVAR_036123613D → N in a breast cancer sample; somatic mutation. 1 Publication1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0538141 – 181Missing in isoform 2. CuratedAdd BLAST181

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AJ430351 mRNA. Translation: CAD23039.2.
    AK001580 mRNA. Translation: BAA91769.1. Different initiation.
    AK056447 mRNA. Translation: BAG51712.1.
    AK125134 mRNA. Translation: BAG54151.1.
    AC016966 Genomic DNA. No translation available.
    AC063939 Genomic DNA. No translation available.
    AC099660 Genomic DNA. No translation available.
    CH471052 Genomic DNA. Translation: EAW78109.1.
    CH471052 Genomic DNA. Translation: EAW78110.1.
    CH471052 Genomic DNA. Translation: EAW78111.1.
    BC005029 mRNA. Translation: AAH05029.1.
    CCDSiCCDS3294.1. [Q8IVL5-1]
    CCDS46981.1. [Q8IVL5-2]
    RefSeqiNP_001127890.1. NM_001134418.1. [Q8IVL5-2]
    NP_060662.2. NM_018192.3. [Q8IVL5-1]
    XP_011511257.1. XM_011512955.1. [Q8IVL5-2]
    UniGeneiHs.374191.

    Genome annotation databases

    EnsembliENST00000319332; ENSP00000316881; ENSG00000090530. [Q8IVL5-1]
    ENST00000427335; ENSP00000408947; ENSG00000090530. [Q8IVL5-2]
    GeneIDi55214.
    KEGGihsa:55214.
    UCSCiuc003fsg.4. human. [Q8IVL5-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiP3H2_HUMAN
    AccessioniPrimary (citable) accession number: Q8IVL5
    Secondary accession number(s): B3KPK0
    , B3KWI9, D3DNV8, Q9NVI2
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 27, 2006
    Last sequence update: March 1, 2003
    Last modified: November 22, 2017
    This is version 132 of the entry and version 1 of the sequence. See 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