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Protein

Prolyl 4-hydroxylase subunit alpha-2

Gene

P4HA2

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

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

Protein has several cofactor binding sites:
  • Fe2+PROSITE-ProRule annotationNote: Binds 1 Fe2+ ion per subunit.PROSITE-ProRule annotation
  • L-ascorbateBy 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
Complete GO annotation...

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 Componenti: 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
  6. procollagen-proline 4-dioxygenase complex Source: Ensembl
Complete GO annotation...

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

BgeeiO15460.
CleanExiHS_P4HA2.
ExpressionAtlasiO15460. baseline and differential.
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. 11 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.
GeneTreeiENSGT00390000018885.
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_dom.
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. AlignAdd to basket

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

        10         20         30         40         50
MKLWVSALLM AWFGVLSCVQ AEFFTSIGHM TDLIYAEKEL VQSLKEYILV
60 70 80 90 100
EEAKLSKIKS WANKMEALTS KSAADAEGYL AHPVNAYKLV KRLNTDWPAL
110 120 130 140 150
EDLVLQDSAA GFIANLSVQR QFFPTDEDEI GAAKALMRLQ DTYRLDPGTI
160 170 180 190 200
SRGELPGTKY QAMLSVDDCF GMGRSAYNEG DYYHTVLWME QVLKQLDAGE
210 220 230 240 250
EATTTKSQVL DYLSYAVFQL GDLHRALELT RRLLSLDPSH ERAGGNLRYF
260 270 280 290 300
EQLLEEEREK TLTNQTEAEL ATPEGIYERP VDYLPERDVY ESLCRGEGVK
310 320 330 340 350
LTPRRQKRLF CRYHHGNRAP QLLIAPFKEE DEWDSPHIVR YYDVMSDEEI
360 370 380 390 400
ERIKEIAKPK LARATVRDPK TGVLTVASYR VSKSSWLEED DDPVVARVNR
410 420 430 440 450
RMQHITGLTV KTAELLQVAN YGVGGQYEPH FDFSRNDERD TFKHLGTGNR
460 470 480 490 500
VATFLNYMSD VEAGGATVFP DLGAAIWPKK GTAVFWYNLL RSGEGDYRTR
510 520 530
HAACPVLVGC KWVSNKWFHE RGQEFLRPCG STEVD
Length:535
Mass (Da):60,902
Last modified:December 31, 1997 - 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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi114464. 11 interactions.
IntActiO15460. 8 interactions.
MINTiMINT-1035479.
STRINGi9606.ENSP00000166534.

Chemistry

ChEMBLiCHEMBL5640.
DrugBankiDB00172. L-Proline.
DB00139. Succinic acid.

PTM databases

PhosphoSiteiO15460.

Proteomic databases

MaxQBiO15460.
PaxDbiO15460.
PRIDEiO15460.

Protocols and materials databases

DNASUi8974.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi8974.
GeneCardsiGC05M131531.
HGNCiHGNC:8547. P4HA2.
HPAiCAB062557.
HPA016997.
HPA027824.
MIMi600608. gene.
neXtProtiNX_O15460.
PharmGKBiPA32875.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG78926.
GeneTreeiENSGT00390000018885.
HOGENOMiHOG000230465.
HOVERGENiHBG006834.
InParanoidiO15460.
KOiK00472.
OMAiCKWVSNK.
OrthoDBiEOG7W6WKC.
PhylomeDBiO15460.
TreeFamiTF313393.

Enzyme and pathway databases

BRENDAi1.14.11.2. 2681.

Miscellaneous databases

GeneWikiiP4HA2.
GenomeRNAii8974.
NextBioi33677.
PROiO15460.
SOURCEiSearch...

Gene expression databases

BgeeiO15460.
CleanExiHS_P4HA2.
ExpressionAtlasiO15460. baseline and differential.
GenevestigatoriO15460.

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_dom.
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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1996) [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(2000) [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(2003) [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 1, 2002
Last sequence update: December 31, 1997
Last modified: March 3, 2015
This is version 149 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.