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Protein

Prolyl 4-hydroxylase subunit alpha-1

Gene

P4HA1

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:

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi429IronPROSITE-ProRule annotation1
Metal bindingi431IronPROSITE-ProRule annotation1
Metal bindingi500IronPROSITE-ProRule annotation1
Binding sitei5102-oxoglutaratePROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Ligandi

Iron, Metal-binding, Vitamin C

Enzyme and pathway databases

BioCyciZFISH:HS04613-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-1 (EC:1.14.11.2)
Short name:
4-PH alpha-1
Alternative name(s):
Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-1
Gene namesi
Name:P4HA1
Synonyms:P4HA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:8546. P4HA1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi210Y → A: Strongly reduced affinity for peptide substrate. 1 Publication1
Mutagenesisi213Y → A: Strongly reduced affinity for peptide substrate. 1 Publication1
Mutagenesisi247Y → A: Strongly reduced affinity for peptide substrate. 1 Publication1

Organism-specific databases

DisGeNETi5033.
OpenTargetsiENSG00000122884.
PharmGKBiPA32874.

Chemistry databases

ChEMBLiCHEMBL1250350.
DrugBankiDB01275. Hydralazine.
DB00172. L-Proline.
DB00139. Succinic acid.
DB00126. Vitamin C.

Polymorphism and mutation databases

BioMutaiP4HA1.
DMDMi2507090.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Combined sourcesAdd BLAST17
ChainiPRO_000002272318 – 534Prolyl 4-hydroxylase subunit alpha-1Add BLAST517

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi113N-linked (GlcNAc...)1 Publication1
Glycosylationi259N-linked (GlcNAc...)1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiP13674.
MaxQBiP13674.
PaxDbiP13674.
PeptideAtlasiP13674.
PRIDEiP13674.

PTM databases

iPTMnetiP13674.
PhosphoSitePlusiP13674.
SwissPalmiP13674.

Expressioni

Gene expression databases

BgeeiENSG00000122884.
CleanExiHS_P4HA1.
ExpressionAtlasiP13674. baseline and differential.
GenevisibleiP13674. HS.

Organism-specific databases

HPAiHPA007599.
HPA026593.

Interactioni

Subunit structurei

Heterotetramer of two alpha-1 chains and two beta chains (the beta chain is the multi-functional PDI).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
HTTP428585EBI-1237386,EBI-466029

Protein-protein interaction databases

BioGridi111072. 40 interactors.
DIPiDIP-38180N.
IntActiP13674. 34 interactors.
MINTiMINT-4657265.
STRINGi9606.ENSP00000263556.

Structurei

Secondary structure

1534
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi21 – 71Combined sources51
Helixi74 – 79Combined sources6
Helixi81 – 92Combined sources12
Helixi94 – 103Combined sources10
Helixi108 – 118Combined sources11
Helixi124 – 141Combined sources18
Helixi145 – 149Combined sources5
Beta strandi153 – 156Combined sources4
Helixi164 – 176Combined sources13
Helixi180 – 195Combined sources16
Helixi204 – 217Combined sources14
Helixi221 – 234Combined sources14
Helixi239 – 252Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TJCX-ray2.30A/B161-261[»]
2V5FX-ray2.03A161-263[»]
2YQ8X-ray2.99A/B18-255[»]
4BT8X-ray2.20A/B18-255[»]
4BT9X-ray1.90A/B18-255[»]
4BTAX-ray2.95A/B18-261[»]
4BTBX-ray1.90A18-255[»]
ProteinModelPortaliP13674.
SMRiP13674.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13674.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati205 – 238TPRAdd BLAST34
Domaini411 – 519Fe2OG 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.
InParanoidiP13674.
KOiK00472.
OMAiFLTVEDC.
PhylomeDBiP13674.
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 (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P13674-1) [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
MIWYILIIGI LLPQSLAHPG FFTSIGQMTD LIHTEKDLVT SLKDYIKAEE
60 70 80 90 100
DKLEQIKKWA EKLDRLTSTA TKDPEGFVGH PVNAFKLMKR LNTEWSELEN
110 120 130 140 150
LVLKDMSDGF ISNLTIQRQY FPNDEDQVGA AKALLRLQDT YNLDTDTISK
160 170 180 190 200
GNLPGVKHKS FLTAEDCFEL GKVAYTEADY YHTELWMEQA LRQLDEGEIS
210 220 230 240 250
TIDKVSVLDY LSYAVYQQGD LDKALLLTKK LLELDPEHQR ANGNLKYFEY
260 270 280 290 300
IMAKEKDVNK SASDDQSDQK TTPKKKGVAV DYLPERQKYE MLCRGEGIKM
310 320 330 340 350
TPRRQKKLFC RYHDGNRNPK FILAPAKQED EWDKPRIIRF HDIISDAEIE
360 370 380 390 400
IVKDLAKPRL RRATISNPIT GDLETVHYRI SKSAWLSGYE NPVVSRINMR
410 420 430 440 450
IQDLTGLDVS TAEELQVANY GVGGQYEPHF DFARKDEPDA FKELGTGNRI
460 470 480 490 500
ATWLFYMSDV SAGGATVFPE VGASVWPKKG TAVFWYNLFA SGEGDYSTRH
510 520 530
AACPVLVGNK WVSNKWLHER GQEFRRPCTL SELE
Length:534
Mass (Da):61,049
Last modified:November 1, 1997 - v2
Checksum:iEBAFA8CCF09A1DDB
GO
Isoform 2 (identifier: P13674-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     361-380: RRATISNPITGDLETVHYRI → SRATVHDPETGKLTTAQYRV

Show »
Length:534
Mass (Da):60,967
Checksum:i5FE1B10A8AC5E792
GO
Isoform 3 (identifier: P13674-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     361-380: RRATISNPITGDLETVHYRI → SRATVHDPETGKLTTAQYRV
     417-434: Missing.

Note: No experimental confirmation available.
Show »
Length:516
Mass (Da):58,958
Checksum:iED30BECCFB48CD7E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti119 – 122QYFP → PVLS in AAA36534 (PubMed:2543975).Curated4
Sequence conflicti119 – 122QYFP → PVLS in AAA36535 (PubMed:2543975).Curated4

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004504361 – 380RRATI…VHYRI → SRATVHDPETGKLTTAQYRV in isoform 2 and isoform 3. 2 PublicationsAdd BLAST20
Alternative sequenceiVSP_044578417 – 434Missing in isoform 3. 1 PublicationAdd BLAST18

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M24486 mRNA. Translation: AAA36534.1.
M24487 mRNA. Translation: AAA36535.1.
U14620
, U14607, U14605, U14608, U14609, U14611, U14610, U14612, U14614, U14615, U14616, U14617, U14618, U14619 Genomic DNA. Translation: AAA59068.1.
U14620
, U14607, U14605, U14608, U14609, U14611, U14610, U14612, U14613, U14615, U14616, U14617, U14618, U14619 Genomic DNA. Translation: AAA59069.1.
CD013929 Genomic DNA. No translation available.
AL731563 Genomic DNA. Translation: CAH72754.1.
BC034998 mRNA. Translation: AAH34998.1.
CCDSiCCDS41537.1. [P13674-1]
CCDS44432.1. [P13674-3]
CCDS7320.1. [P13674-2]
PIRiA33919. DAHUA1.
I37173. DAHUA2.
RefSeqiNP_000908.2. NM_000917.3. [P13674-2]
NP_001017962.1. NM_001017962.2. [P13674-1]
NP_001136067.1. NM_001142595.1. [P13674-1]
NP_001136068.1. NM_001142596.1. [P13674-3]
UniGeneiHs.500047.
Hs.593005.

Genome annotation databases

EnsembliENST00000263556; ENSP00000263556; ENSG00000122884. [P13674-2]
ENST00000307116; ENSP00000307318; ENSG00000122884. [P13674-1]
ENST00000373008; ENSP00000362099; ENSG00000122884. [P13674-2]
ENST00000394890; ENSP00000378353; ENSG00000122884. [P13674-1]
ENST00000440381; ENSP00000414464; ENSG00000122884. [P13674-3]
GeneIDi5033.
KEGGihsa:5033.
UCSCiuc001jtg.4. human. [P13674-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M24486 mRNA. Translation: AAA36534.1.
M24487 mRNA. Translation: AAA36535.1.
U14620
, U14607, U14605, U14608, U14609, U14611, U14610, U14612, U14614, U14615, U14616, U14617, U14618, U14619 Genomic DNA. Translation: AAA59068.1.
U14620
, U14607, U14605, U14608, U14609, U14611, U14610, U14612, U14613, U14615, U14616, U14617, U14618, U14619 Genomic DNA. Translation: AAA59069.1.
CD013929 Genomic DNA. No translation available.
AL731563 Genomic DNA. Translation: CAH72754.1.
BC034998 mRNA. Translation: AAH34998.1.
CCDSiCCDS41537.1. [P13674-1]
CCDS44432.1. [P13674-3]
CCDS7320.1. [P13674-2]
PIRiA33919. DAHUA1.
I37173. DAHUA2.
RefSeqiNP_000908.2. NM_000917.3. [P13674-2]
NP_001017962.1. NM_001017962.2. [P13674-1]
NP_001136067.1. NM_001142595.1. [P13674-1]
NP_001136068.1. NM_001142596.1. [P13674-3]
UniGeneiHs.500047.
Hs.593005.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TJCX-ray2.30A/B161-261[»]
2V5FX-ray2.03A161-263[»]
2YQ8X-ray2.99A/B18-255[»]
4BT8X-ray2.20A/B18-255[»]
4BT9X-ray1.90A/B18-255[»]
4BTAX-ray2.95A/B18-261[»]
4BTBX-ray1.90A18-255[»]
ProteinModelPortaliP13674.
SMRiP13674.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111072. 40 interactors.
DIPiDIP-38180N.
IntActiP13674. 34 interactors.
MINTiMINT-4657265.
STRINGi9606.ENSP00000263556.

Chemistry databases

ChEMBLiCHEMBL1250350.
DrugBankiDB01275. Hydralazine.
DB00172. L-Proline.
DB00139. Succinic acid.
DB00126. Vitamin C.

PTM databases

iPTMnetiP13674.
PhosphoSitePlusiP13674.
SwissPalmiP13674.

Polymorphism and mutation databases

BioMutaiP4HA1.
DMDMi2507090.

Proteomic databases

EPDiP13674.
MaxQBiP13674.
PaxDbiP13674.
PeptideAtlasiP13674.
PRIDEiP13674.

Protocols and materials databases

DNASUi5033.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263556; ENSP00000263556; ENSG00000122884. [P13674-2]
ENST00000307116; ENSP00000307318; ENSG00000122884. [P13674-1]
ENST00000373008; ENSP00000362099; ENSG00000122884. [P13674-2]
ENST00000394890; ENSP00000378353; ENSG00000122884. [P13674-1]
ENST00000440381; ENSP00000414464; ENSG00000122884. [P13674-3]
GeneIDi5033.
KEGGihsa:5033.
UCSCiuc001jtg.4. human. [P13674-1]

Organism-specific databases

CTDi5033.
DisGeNETi5033.
GeneCardsiP4HA1.
HGNCiHGNC:8546. P4HA1.
HPAiHPA007599.
HPA026593.
MIMi176710. gene.
neXtProtiNX_P13674.
OpenTargetsiENSG00000122884.
PharmGKBiPA32874.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1591. Eukaryota.
ENOG410XS5J. LUCA.
GeneTreeiENSGT00390000018885.
HOGENOMiHOG000230465.
HOVERGENiHBG006834.
InParanoidiP13674.
KOiK00472.
OMAiFLTVEDC.
PhylomeDBiP13674.
TreeFamiTF313393.

Enzyme and pathway databases

BioCyciZFISH:HS04613-MONOMER.
BRENDAi1.14.11.2. 2681.
ReactomeiR-HSA-1650814. Collagen biosynthesis and modifying enzymes.

Miscellaneous databases

EvolutionaryTraceiP13674.
GeneWikiiP4HA1.
GenomeRNAii5033.
PROiP13674.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000122884.
CleanExiHS_P4HA1.
ExpressionAtlasiP13674. baseline and differential.
GenevisibleiP13674. 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 nameiP4HA1_HUMAN
AccessioniPrimary (citable) accession number: P13674
Secondary accession number(s): C9JL12
, Q15082, Q15083, Q5VSQ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: November 1, 1997
Last modified: November 30, 2016
This is version 190 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.