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O15460

- P4HA2_HUMAN

UniProt

O15460 - P4HA2_HUMAN

Protein

Prolyl 4-hydroxylase subunit alpha-2

Gene

P4HA2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 144 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.

    Catalytic activityi

    L-proline-[procollagen] + 2-oxoglutarate + O2 = trans-4-hydroxy-L-proline-[procollagen] + succinate + CO2.

    Cofactori

    Binds 1 Fe2+ ion per subunit.PROSITE-ProRule annotation
    Ascorbate.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi430 – 4301IronPROSITE-ProRule annotation
    Metal bindingi432 – 4321IronPROSITE-ProRule annotation
    Metal bindingi501 – 5011IronPROSITE-ProRule annotation
    Binding sitei511 – 51112-oxoglutaratePROSITE-ProRule annotation

    GO - Molecular functioni

    1. electron carrier activity Source: UniProtKB
    2. iron ion binding Source: InterPro
    3. L-ascorbic acid binding Source: UniProtKB-KW
    4. oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Source: InterPro
    5. procollagen-proline 4-dioxygenase activity Source: ProtInc

    GO - Biological processi

    1. peptidyl-proline hydroxylation to 4-hydroxy-L-proline Source: Ensembl

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Ligandi

    Iron, Metal-binding, Vitamin C

    Enzyme and pathway databases

    BRENDAi1.14.11.2. 2681.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Prolyl 4-hydroxylase subunit alpha-2 (EC:1.14.11.2)
    Short name:
    4-PH alpha-2
    Alternative name(s):
    Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-2
    Gene namesi
    Name:P4HA2
    ORF Names:UNQ290/PRO330
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:8547. P4HA2.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: HPA
    2. endoplasmic reticulum Source: HPA
    3. endoplasmic reticulum lumen Source: UniProtKB-SubCell
    4. intracellular membrane-bounded organelle Source: HPA
    5. nucleus Source: HPA

    Keywords - Cellular componenti

    Endoplasmic reticulum

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA32875.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2121Sequence AnalysisAdd
    BLAST
    Chaini22 – 535514Prolyl 4-hydroxylase subunit alpha-2PRO_0000022726Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi115 – 1151N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi264 – 2641N-linked (GlcNAc...)Sequence Analysis
    Modified residuei480 – 4801N6-succinyllysineBy similarity

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    MaxQBiO15460.
    PaxDbiO15460.
    PRIDEiO15460.

    PTM databases

    PhosphoSiteiO15460.

    Expressioni

    Gene expression databases

    ArrayExpressiO15460.
    BgeeiO15460.
    CleanExiHS_P4HA2.
    GenevestigatoriO15460.

    Organism-specific databases

    HPAiCAB062557.
    HPA016997.
    HPA027824.

    Interactioni

    Subunit structurei

    Heterotetramer of two alpha-2 chains and two beta chains (the beta chain is the multi-functional PDI).

    Protein-protein interaction databases

    BioGridi114464. 6 interactions.
    IntActiO15460. 8 interactions.
    MINTiMINT-1035479.
    STRINGi9606.ENSP00000166534.

    Structurei

    3D structure databases

    ProteinModelPortaliO15460.
    SMRiO15460. Positions 23-257, 335-519.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati207 – 24034TPRAdd
    BLAST
    Domaini412 – 520109Fe2OG dioxygenasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the P4HA family.Curated
    Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation
    Contains 1 TPR repeat.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal, TPR repeat

    Phylogenomic databases

    eggNOGiNOG78926.
    HOGENOMiHOG000230465.
    HOVERGENiHBG006834.
    InParanoidiO15460.
    KOiK00472.
    OMAiCKWVSNK.
    OrthoDBiEOG7W6WKC.
    PhylomeDBiO15460.
    TreeFamiTF313393.

    Family and domain databases

    Gene3Di1.25.40.10. 2 hits.
    InterProiIPR005123. Oxoglu/Fe-dep_dioxygenase.
    IPR006620. Pro_4_hyd_alph.
    IPR013547. Pro_4_hyd_alph_N.
    IPR013026. TPR-contain_dom.
    IPR011990. TPR-like_helical.
    IPR019734. TPR_repeat.
    [Graphical view]
    PfamiPF03171. 2OG-FeII_Oxy. 1 hit.
    PF08336. P4Ha_N. 1 hit.
    [Graphical view]
    SMARTiSM00702. P4Hc. 1 hit.
    [Graphical view]
    PROSITEiPS51471. FE2OG_OXY. 1 hit.
    PS50005. TPR. 1 hit.
    PS50293. TPR_REGION. 1 hit.
    [Graphical view]

    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. Align

    Isoform IIb (identifier: O15460-1) [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

    MKLWVSALLM AWFGVLSCVQ AEFFTSIGHM TDLIYAEKEL VQSLKEYILV    50
    EEAKLSKIKS WANKMEALTS KSAADAEGYL AHPVNAYKLV KRLNTDWPAL 100
    EDLVLQDSAA GFIANLSVQR QFFPTDEDEI GAAKALMRLQ DTYRLDPGTI 150
    SRGELPGTKY QAMLSVDDCF GMGRSAYNEG DYYHTVLWME QVLKQLDAGE 200
    EATTTKSQVL DYLSYAVFQL GDLHRALELT RRLLSLDPSH ERAGGNLRYF 250
    EQLLEEEREK TLTNQTEAEL ATPEGIYERP VDYLPERDVY ESLCRGEGVK 300
    LTPRRQKRLF CRYHHGNRAP QLLIAPFKEE DEWDSPHIVR YYDVMSDEEI 350
    ERIKEIAKPK LARATVRDPK TGVLTVASYR VSKSSWLEED DDPVVARVNR 400
    RMQHITGLTV KTAELLQVAN YGVGGQYEPH FDFSRNDERD TFKHLGTGNR 450
    VATFLNYMSD VEAGGATVFP DLGAAIWPKK GTAVFWYNLL RSGEGDYRTR 500
    HAACPVLVGC KWVSNKWFHE RGQEFLRPCG STEVD 535
    Length:535
    Mass (Da):60,902
    Last modified:January 1, 1998 - v1
    Checksum:iFD04467B098F63CF
    GO
    Isoform IIa (identifier: O15460-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         436-451: NDERDTFKHLGTGNRV → RPFDSGLKTEGNRL

    Show »
    Length:533
    Mass (Da):60,633
    Checksum:i8C875AD482B0DBD2
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei436 – 45116NDERD…TGNRV → RPFDSGLKTEGNRL in isoform IIa. 2 PublicationsVSP_004506Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U90441 mRNA. Translation: AAB71339.1.
    AJ314859 Genomic DNA. Translation: CAC85688.1.
    AJ314859 Genomic DNA. Translation: CAC85689.1.
    AY358970 mRNA. Translation: AAQ89329.1.
    CH471062 Genomic DNA. Translation: EAW62341.1.
    CH471062 Genomic DNA. Translation: EAW62342.1.
    CH471062 Genomic DNA. Translation: EAW62343.1.
    CH471062 Genomic DNA. Translation: EAW62346.1.
    BC035813 mRNA. Translation: AAH35813.1.
    CCDSiCCDS34230.1. [O15460-2]
    CCDS4151.1. [O15460-1]
    RefSeqiNP_001017973.1. NM_001017973.1. [O15460-2]
    NP_001017974.1. NM_001017974.1. [O15460-2]
    NP_001136070.1. NM_001142598.1. [O15460-2]
    NP_001136071.1. NM_001142599.1. [O15460-1]
    NP_004190.1. NM_004199.2. [O15460-1]
    XP_005272173.1. XM_005272116.2. [O15460-1]
    XP_005272174.1. XM_005272117.2. [O15460-1]
    XP_005272175.1. XM_005272118.2. [O15460-1]
    XP_005272176.1. XM_005272119.2. [O15460-1]
    XP_005272177.1. XM_005272120.2. [O15460-1]
    XP_006714791.1. XM_006714728.1. [O15460-1]
    XP_006714792.1. XM_006714729.1. [O15460-2]
    XP_006714793.1. XM_006714730.1. [O15460-2]
    UniGeneiHs.519568.

    Genome annotation databases

    EnsembliENST00000166534; ENSP00000166534; ENSG00000072682. [O15460-1]
    ENST00000360568; ENSP00000353772; ENSG00000072682. [O15460-2]
    ENST00000379086; ENSP00000368379; ENSG00000072682. [O15460-2]
    ENST00000379100; ENSP00000368394; ENSG00000072682. [O15460-2]
    ENST00000379104; ENSP00000368398; ENSG00000072682. [O15460-1]
    ENST00000401867; ENSP00000384999; ENSG00000072682. [O15460-1]
    GeneIDi8974.
    KEGGihsa:8974.
    UCSCiuc003kwg.3. human. [O15460-2]
    uc003kwh.3. human. [O15460-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U90441 mRNA. Translation: AAB71339.1 .
    AJ314859 Genomic DNA. Translation: CAC85688.1 .
    AJ314859 Genomic DNA. Translation: CAC85689.1 .
    AY358970 mRNA. Translation: AAQ89329.1 .
    CH471062 Genomic DNA. Translation: EAW62341.1 .
    CH471062 Genomic DNA. Translation: EAW62342.1 .
    CH471062 Genomic DNA. Translation: EAW62343.1 .
    CH471062 Genomic DNA. Translation: EAW62346.1 .
    BC035813 mRNA. Translation: AAH35813.1 .
    CCDSi CCDS34230.1. [O15460-2 ]
    CCDS4151.1. [O15460-1 ]
    RefSeqi NP_001017973.1. NM_001017973.1. [O15460-2 ]
    NP_001017974.1. NM_001017974.1. [O15460-2 ]
    NP_001136070.1. NM_001142598.1. [O15460-2 ]
    NP_001136071.1. NM_001142599.1. [O15460-1 ]
    NP_004190.1. NM_004199.2. [O15460-1 ]
    XP_005272173.1. XM_005272116.2. [O15460-1 ]
    XP_005272174.1. XM_005272117.2. [O15460-1 ]
    XP_005272175.1. XM_005272118.2. [O15460-1 ]
    XP_005272176.1. XM_005272119.2. [O15460-1 ]
    XP_005272177.1. XM_005272120.2. [O15460-1 ]
    XP_006714791.1. XM_006714728.1. [O15460-1 ]
    XP_006714792.1. XM_006714729.1. [O15460-2 ]
    XP_006714793.1. XM_006714730.1. [O15460-2 ]
    UniGenei Hs.519568.

    3D structure databases

    ProteinModelPortali O15460.
    SMRi O15460. Positions 23-257, 335-519.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114464. 6 interactions.
    IntActi O15460. 8 interactions.
    MINTi MINT-1035479.
    STRINGi 9606.ENSP00000166534.

    Chemistry

    ChEMBLi CHEMBL5640.
    DrugBanki DB00172. L-Proline.
    DB00139. Succinic acid.

    PTM databases

    PhosphoSitei O15460.

    Proteomic databases

    MaxQBi O15460.
    PaxDbi O15460.
    PRIDEi O15460.

    Protocols and materials databases

    DNASUi 8974.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000166534 ; ENSP00000166534 ; ENSG00000072682 . [O15460-1 ]
    ENST00000360568 ; ENSP00000353772 ; ENSG00000072682 . [O15460-2 ]
    ENST00000379086 ; ENSP00000368379 ; ENSG00000072682 . [O15460-2 ]
    ENST00000379100 ; ENSP00000368394 ; ENSG00000072682 . [O15460-2 ]
    ENST00000379104 ; ENSP00000368398 ; ENSG00000072682 . [O15460-1 ]
    ENST00000401867 ; ENSP00000384999 ; ENSG00000072682 . [O15460-1 ]
    GeneIDi 8974.
    KEGGi hsa:8974.
    UCSCi uc003kwg.3. human. [O15460-2 ]
    uc003kwh.3. human. [O15460-1 ]

    Organism-specific databases

    CTDi 8974.
    GeneCardsi GC05M131531.
    HGNCi HGNC:8547. P4HA2.
    HPAi CAB062557.
    HPA016997.
    HPA027824.
    MIMi 600608. gene.
    neXtProti NX_O15460.
    PharmGKBi PA32875.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG78926.
    HOGENOMi HOG000230465.
    HOVERGENi HBG006834.
    InParanoidi O15460.
    KOi K00472.
    OMAi CKWVSNK.
    OrthoDBi EOG7W6WKC.
    PhylomeDBi O15460.
    TreeFami TF313393.

    Enzyme and pathway databases

    BRENDAi 1.14.11.2. 2681.

    Miscellaneous databases

    GeneWikii P4HA2.
    GenomeRNAii 8974.
    NextBioi 33677.
    PROi O15460.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O15460.
    Bgeei O15460.
    CleanExi HS_P4HA2.
    Genevestigatori O15460.

    Family and domain databases

    Gene3Di 1.25.40.10. 2 hits.
    InterProi IPR005123. Oxoglu/Fe-dep_dioxygenase.
    IPR006620. Pro_4_hyd_alph.
    IPR013547. Pro_4_hyd_alph_N.
    IPR013026. TPR-contain_dom.
    IPR011990. TPR-like_helical.
    IPR019734. TPR_repeat.
    [Graphical view ]
    Pfami PF03171. 2OG-FeII_Oxy. 1 hit.
    PF08336. P4Ha_N. 1 hit.
    [Graphical view ]
    SMARTi SM00702. P4Hc. 1 hit.
    [Graphical view ]
    PROSITEi PS51471. FE2OG_OXY. 1 hit.
    PS50005. TPR. 1 hit.
    PS50293. TPR_REGION. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning of the human prolyl 4-hydroxylase alpha subunit isoform alpha(II) and characterization of the type II enzyme tetramer. The alpha(I) and alpha(II) subunits do not form a mixed alpha(I)alpha(II)beta2 tetramer."
      Annunen P., Helaakoski T., Myllyharju J., Veijola J., Pihlajaniemi T., Kivirikko K.I.
      J. Biol. Chem. 272:17342-17348(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IIB).
      Tissue: Lung.
    2. "Characterization of the human and mouse genes for the alpha subunit of type II prolyl 4-hydroxylase. Identification of a previously unknown alternatively spliced exon and its expression in various tissues."
      Nokelainen M., Nissi R., Kukkola L., Helaakoski T., Myllyharju J.
      Eur. J. Biochem. 268:5300-5309(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS IIA AND IIB).
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IIA).
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IIA).
      Tissue: Brain.
    6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiP4HA2_HUMAN
    AccessioniPrimary (citable) accession number: O15460
    Secondary accession number(s): D3DQ85, D3DQ86, Q8WWN0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 2, 2002
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 144 of the entry and version 1 of the sequence. [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 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3