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Protein

Prolyl 4-hydroxylase subunit alpha-2

Gene

P4HA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Metal bindingi430IronPROSITE-ProRule annotation1
Metal bindingi432IronPROSITE-ProRule annotation1
Metal bindingi501IronPROSITE-ProRule annotation1
Binding sitei5112-oxoglutaratePROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • peptidyl-proline hydroxylation to 4-hydroxy-L-proline Source: GO_Central

Keywordsi

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

Enzyme and pathway databases

BRENDAi1.14.11.2 2681
ReactomeiR-HSA-1650814 Collagen biosynthesis and modifying enzymes

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
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000072682.18
HGNCiHGNC:8547 P4HA2
MIMi600608 gene
neXtProtiNX_O15460

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

Pathology & Biotechi

Involvement in diseasei

Myopia 25, autosomal dominant (MYP25)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far.
See also OMIM:617238
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074026140Q → R in MYP25. 1 PublicationCorresponds to variant dbSNP:rs764211125EnsemblClinVar.1
Natural variantiVAR_074027150I → V in MYP25; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs771208496Ensembl.1
Natural variantiVAR_074028291E → K in MYP25; decreases protein abundance. 1 PublicationCorresponds to variant dbSNP:rs758872875EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi8974
MalaCardsiP4HA2
MIMi617238 phenotype
OpenTargetsiENSG00000072682
PharmGKBiPA32875

Chemistry databases

ChEMBLiCHEMBL5640
DrugBankiDB00172 L-Proline
DB00139 Succinic acid

Polymorphism and mutation databases

BioMutaiP4HA2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000002272622 – 535Prolyl 4-hydroxylase subunit alpha-2Add BLAST514

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi115N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi264N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei480N6-succinyllysineBy similarity1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiO15460
MaxQBiO15460
PaxDbiO15460
PeptideAtlasiO15460
PRIDEiO15460
ProteomicsDBi48680
48681 [O15460-2]

PTM databases

iPTMnetiO15460
PhosphoSitePlusiO15460

Expressioni

Gene expression databases

BgeeiENSG00000072682 Expressed in 211 organ(s), highest expression level in tibia
CleanExiHS_P4HA2
ExpressionAtlasiO15460 baseline and differential
GenevisibleiO15460 HS

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).

Binary interactionsi

WithEntry#Exp.IntActNotes
FHL3Q136433EBI-10182841,EBI-741101

Protein-protein interaction databases

BioGridi114464, 96 interactors
IntActiO15460, 21 interactors
MINTiO15460
STRINGi9606.ENSP00000166534

Structurei

3D structure databases

ProteinModelPortaliO15460
SMRiO15460
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati207 – 240TPRAdd BLAST34
Domaini412 – 520Fe2OG dioxygenasePROSITE-ProRule annotationAdd BLAST109

Sequence similaritiesi

Belongs to the P4HA family.Curated

Keywords - Domaini

Signal, TPR repeat

Phylogenomic databases

eggNOGiKOG1591 Eukaryota
ENOG410XS5J LUCA
GeneTreeiENSGT00390000018885
HOGENOMiHOG000230465
HOVERGENiHBG006834
InParanoidiO15460
KOiK00472
OMAiHHGNRTP
OrthoDBiEOG091G0749
PhylomeDBiO15460
TreeFamiTF313393

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR005123 Oxoglu/Fe-dep_dioxygenase
IPR006620 Pro_4_hyd_alph
IPR013547 Pro_4_hyd_alph_N
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR019734 TPR_repeat
PfamiView protein in Pfam
PF13640 2OG-FeII_Oxy_3, 1 hit
PF08336 P4Ha_N, 1 hit
SMARTiView protein in SMART
SM00702 P4Hc, 1 hit
SUPFAMiSSF48452 SSF48452, 1 hit
PROSITEiView protein in PROSITE
PS51471 FE2OG_OXY, 1 hit
PS50005 TPR, 1 hit
PS50293 TPR_REGION, 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

This entry has 2 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All

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: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

Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A8MXE0A8MXE0_HUMAN
Prolyl 4-hydroxylase subunit alpha-...
P4HA2
167Annotation score:
C9JX45C9JX45_HUMAN
Prolyl 4-hydroxylase subunit alpha-...
P4HA2
153Annotation score:
E7ENX0E7ENX0_HUMAN
Prolyl 4-hydroxylase subunit alpha-...
P4HA2
204Annotation score:
E7ERI1E7ERI1_HUMAN
Prolyl 4-hydroxylase subunit alpha-...
P4HA2
184Annotation score:
C9JCP0C9JCP0_HUMAN
Prolyl 4-hydroxylase subunit alpha-...
P4HA2
146Annotation score:
E7EPI9E7EPI9_HUMAN
Prolyl 4-hydroxylase subunit alpha-...
P4HA2
236Annotation score:
C9JN43C9JN43_HUMAN
Prolyl 4-hydroxylase subunit alpha-...
P4HA2
101Annotation score:
C9JIG4C9JIG4_HUMAN
Prolyl 4-hydroxylase subunit alpha-...
P4HA2
114Annotation score:
C9JFJ1C9JFJ1_HUMAN
Prolyl 4-hydroxylase subunit alpha-...
P4HA2
50Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074026140Q → R in MYP25. 1 PublicationCorresponds to variant dbSNP:rs764211125EnsemblClinVar.1
Natural variantiVAR_074027150I → V in MYP25; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs771208496Ensembl.1
Natural variantiVAR_074028291E → K in MYP25; decreases protein abundance. 1 PublicationCorresponds to variant dbSNP:rs758872875EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004506436 – 451NDERD…TGNRV → RPFDSGLKTEGNRL in isoform IIa. 2 PublicationsAdd BLAST16

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_005272116.4 [O15460-1]
XP_005272174.1, XM_005272117.4 [O15460-1]
XP_005272175.1, XM_005272118.4 [O15460-1]
XP_005272176.1, XM_005272119.4 [O15460-1]
XP_005272177.1, XM_005272120.4 [O15460-1]
XP_006714791.1, XM_006714728.3 [O15460-1]
XP_006714792.1, XM_006714729.3 [O15460-2]
XP_006714793.1, XM_006714730.3 [O15460-2]
XP_016865500.1, XM_017010011.1 [O15460-2]
UniGeneiHs.519568
Hs.659712

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.4 human [O15460-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

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_005272116.4 [O15460-1]
XP_005272174.1, XM_005272117.4 [O15460-1]
XP_005272175.1, XM_005272118.4 [O15460-1]
XP_005272176.1, XM_005272119.4 [O15460-1]
XP_005272177.1, XM_005272120.4 [O15460-1]
XP_006714791.1, XM_006714728.3 [O15460-1]
XP_006714792.1, XM_006714729.3 [O15460-2]
XP_006714793.1, XM_006714730.3 [O15460-2]
XP_016865500.1, XM_017010011.1 [O15460-2]
UniGeneiHs.519568
Hs.659712

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6EVLX-ray1.87A163-257[»]
6EVMX-ray2.00A163-257[»]
6EVNX-ray1.48A163-257[»]
6EVOX-ray1.55A163-257[»]
6EVPX-ray1.68A163-257[»]
ProteinModelPortaliO15460
SMRiO15460
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114464, 96 interactors
IntActiO15460, 21 interactors
MINTiO15460
STRINGi9606.ENSP00000166534

Chemistry databases

ChEMBLiCHEMBL5640
DrugBankiDB00172 L-Proline
DB00139 Succinic acid

PTM databases

iPTMnetiO15460
PhosphoSitePlusiO15460

Polymorphism and mutation databases

BioMutaiP4HA2

Proteomic databases

EPDiO15460
MaxQBiO15460
PaxDbiO15460
PeptideAtlasiO15460
PRIDEiO15460
ProteomicsDBi48680
48681 [O15460-2]

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.4 human [O15460-1]

Organism-specific databases

CTDi8974
DisGeNETi8974
EuPathDBiHostDB:ENSG00000072682.18
GeneCardsiP4HA2
HGNCiHGNC:8547 P4HA2
HPAiCAB062557
HPA016997
HPA027824
MalaCardsiP4HA2
MIMi600608 gene
617238 phenotype
neXtProtiNX_O15460
OpenTargetsiENSG00000072682
PharmGKBiPA32875
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1591 Eukaryota
ENOG410XS5J LUCA
GeneTreeiENSGT00390000018885
HOGENOMiHOG000230465
HOVERGENiHBG006834
InParanoidiO15460
KOiK00472
OMAiHHGNRTP
OrthoDBiEOG091G0749
PhylomeDBiO15460
TreeFamiTF313393

Enzyme and pathway databases

BRENDAi1.14.11.2 2681
ReactomeiR-HSA-1650814 Collagen biosynthesis and modifying enzymes

Miscellaneous databases

ChiTaRSiP4HA2 human
GeneWikiiP4HA2
GenomeRNAii8974
PROiPR:O15460
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000072682 Expressed in 211 organ(s), highest expression level in tibia
CleanExiHS_P4HA2
ExpressionAtlasiO15460 baseline and differential
GenevisibleiO15460 HS

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR005123 Oxoglu/Fe-dep_dioxygenase
IPR006620 Pro_4_hyd_alph
IPR013547 Pro_4_hyd_alph_N
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR019734 TPR_repeat
PfamiView protein in Pfam
PF13640 2OG-FeII_Oxy_3, 1 hit
PF08336 P4Ha_N, 1 hit
SMARTiView protein in SMART
SM00702 P4Hc, 1 hit
SUPFAMiSSF48452 SSF48452, 1 hit
PROSITEiView protein in PROSITE
PS51471 FE2OG_OXY, 1 hit
PS50005 TPR, 1 hit
PS50293 TPR_REGION, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiP4HA2_HUMAN
AccessioniPrimary (citable) accession number: O15460
Secondary accession number(s): D3DQ85, D3DQ86, Q8WWN0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 184 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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