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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)DescriptionActionsGraphical viewLength
Metal bindingi430IronPROSITE-ProRule annotation1
Metal bindingi432IronPROSITE-ProRule annotation1
Metal bindingi501IronPROSITE-ProRule annotation1
Binding sitei5112-oxoglutaratePROSITE-ProRule annotation1

GO - Molecular functioni

Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Ligandi

Iron, Metal-binding, Vitamin C

Enzyme and pathway databases

BioCyciZFISH:HS01076-MONOMER.
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

HGNCiHGNC:8547. P4HA2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

P4HA2 mutations may be a cause of myopia, a 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.

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi8974.
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...)Sequence analysis1
Glycosylationi264N-linked (GlcNAc...)Sequence analysis1
Modified residuei480N6-succinyllysineBy similarity1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiO15460.
MaxQBiO15460.
PaxDbiO15460.
PeptideAtlasiO15460.
PRIDEiO15460.

PTM databases

iPTMnetiO15460.
PhosphoSitePlusiO15460.

Expressioni

Gene expression databases

BgeeiENSG00000072682.
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. 84 interactors.
IntActiO15460. 19 interactors.
MINTiMINT-1035479.
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
Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation
Contains 1 TPR repeat.PROSITE-ProRule annotation

Keywords - Domaini

Signal, TPR repeat

Phylogenomic databases

eggNOGiKOG1591. Eukaryota.
ENOG410XS5J. LUCA.
GeneTreeiENSGT00390000018885.
HOGENOMiHOG000230465.
HOVERGENiHBG006834.
InParanoidiO15460.
KOiK00472.
OMAiERDIYES.
OrthoDBiEOG091G0749.
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]
PfamiPF13640. 2OG-FeII_Oxy_3. 1 hit.
PF08336. P4Ha_N. 1 hit.
[Graphical view]
SMARTiSM00702. P4Hc. 1 hit.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
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: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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074026140Q → R Probable disease-associated mutation found in patients with myopia. 1 PublicationCorresponds to variant rs764211125dbSNPEnsembl.1
Natural variantiVAR_074027150I → V Found in a patient with myopia; unknown pathological significance. 1 PublicationCorresponds to variant rs771208496dbSNPEnsembl.1
Natural variantiVAR_074028291E → K Probable disease-associated mutation found in patients with myopia; decreases protein abundance. 1 PublicationCorresponds to variant rs758872875dbSNPEnsembl.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

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

ProteinModelPortaliO15460.
SMRiO15460.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114464. 84 interactors.
IntActiO15460. 19 interactors.
MINTiMINT-1035479.
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.

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.
GeneCardsiP4HA2.
HGNCiHGNC:8547. P4HA2.
HPAiCAB062557.
HPA016997.
HPA027824.
MIMi600608. gene.
neXtProtiNX_O15460.
OpenTargetsiENSG00000072682.
PharmGKBiPA32875.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS01076-MONOMER.
BRENDAi1.14.11.2. 2681.
ReactomeiR-HSA-1650814. Collagen biosynthesis and modifying enzymes.

Miscellaneous databases

GeneWikiiP4HA2.
GenomeRNAii8974.
PROiO15460.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000072682.
CleanExiHS_P4HA2.
ExpressionAtlasiO15460. baseline and differential.
GenevisibleiO15460. HS.

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]
PfamiPF13640. 2OG-FeII_Oxy_3. 1 hit.
PF08336. P4Ha_N. 1 hit.
[Graphical view]
SMARTiSM00702. P4Hc. 1 hit.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
PROSITEiPS51471. FE2OG_OXY. 1 hit.
PS50005. TPR. 1 hit.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 167 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. 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

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 one 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.