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P13674 (P4HA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 162. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Prolyl 4-hydroxylase subunit alpha-1

Short name=4-PH alpha-1
EC=1.14.11.2
Alternative name(s):
Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-1
Gene names
Name:P4HA1
Synonyms:P4HA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length534 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

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

Cofactor

Binds 1 Fe2+ ion per subunit.

Ascorbate.

Subunit structure

Heterotetramer of two alpha-1 chains and two beta chains (the beta chain is the multi-functional PDI). Ref.8

Subcellular location

Endoplasmic reticulum lumen.

Sequence similarities

Belongs to the P4HA family.

Contains 1 Fe2OG dioxygenase domain.

Contains 1 TPR repeat.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

HTTP428585EBI-1237386,EBI-466029

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P13674-1)

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.
Isoform 2 (identifier: P13674-2)

The sequence of this isoform differs from the canonical sequence as follows:
     361-380: RRATISNPITGDLETVHYRI → SRATVHDPETGKLTTAQYRV
Isoform 3 (identifier: P13674-3)

The sequence of this isoform differs from the canonical sequence as follows:
     361-380: RRATISNPITGDLETVHYRI → SRATVHDPETGKLTTAQYRV
     417-434: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717
Chain18 – 534517Prolyl 4-hydroxylase subunit alpha-1
PRO_0000022723

Regions

Repeat205 – 23834TPR
Domain411 – 519109Fe2OG dioxygenase

Sites

Metal binding4291Iron By similarity
Metal binding4311Iron By similarity
Metal binding5001Iron By similarity
Binding site51012-oxoglutarate Potential

Amino acid modifications

Glycosylation1131N-linked (GlcNAc...) Ref.6
Glycosylation2591N-linked (GlcNAc...)

Natural variations

Alternative sequence361 – 38020RRATI…VHYRI → SRATVHDPETGKLTTAQYRV in isoform 2 and isoform 3.
VSP_004504
Alternative sequence417 – 43418Missing in isoform 3.
VSP_044578

Experimental info

Mutagenesis2101Y → A: Strongly reduced affinity for peptide substrate. Ref.8
Mutagenesis2131Y → A: Strongly reduced affinity for peptide substrate. Ref.8
Mutagenesis2471Y → A: Strongly reduced affinity for peptide substrate. Ref.8
Sequence conflict119 – 1224QYFP → PVLS in AAA36534. Ref.1
Sequence conflict119 – 1224QYFP → PVLS in AAA36535. Ref.1

Secondary structure

........................... 534
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: EBAFA8CCF09A1DDB

FASTA53461,049
        10         20         30         40         50         60 
MIWYILIIGI LLPQSLAHPG FFTSIGQMTD LIHTEKDLVT SLKDYIKAEE DKLEQIKKWA 

        70         80         90        100        110        120 
EKLDRLTSTA TKDPEGFVGH PVNAFKLMKR LNTEWSELEN LVLKDMSDGF ISNLTIQRQY 

       130        140        150        160        170        180 
FPNDEDQVGA AKALLRLQDT YNLDTDTISK GNLPGVKHKS FLTAEDCFEL GKVAYTEADY 

       190        200        210        220        230        240 
YHTELWMEQA LRQLDEGEIS TIDKVSVLDY LSYAVYQQGD LDKALLLTKK LLELDPEHQR 

       250        260        270        280        290        300 
ANGNLKYFEY IMAKEKDVNK SASDDQSDQK TTPKKKGVAV DYLPERQKYE MLCRGEGIKM 

       310        320        330        340        350        360 
TPRRQKKLFC RYHDGNRNPK FILAPAKQED EWDKPRIIRF HDIISDAEIE IVKDLAKPRL 

       370        380        390        400        410        420 
RRATISNPIT GDLETVHYRI SKSAWLSGYE NPVVSRINMR IQDLTGLDVS TAEELQVANY 

       430        440        450        460        470        480 
GVGGQYEPHF DFARKDEPDA FKELGTGNRI ATWLFYMSDV SAGGATVFPE VGASVWPKKG 

       490        500        510        520        530 
TAVFWYNLFA SGEGDYSTRH AACPVLVGNK WVSNKWLHER GQEFRRPCTL SELE 

« Hide

Isoform 2 [UniParc].

Checksum: 5FE1B10A8AC5E792
Show »

FASTA53460,967
Isoform 3 [UniParc].

Checksum: ED30BECCFB48CD7E
Show »

FASTA51658,958

References

« Hide 'large scale' references
[1]"Molecular cloning of the alpha-subunit of human prolyl 4-hydroxylase: the complete cDNA-derived amino acid sequence and evidence for alternative splicing of RNA transcripts."
Helaakoski T., Vuori K., Myllylae R., Kivirikko K.I., Pihlajaniemi T.
Proc. Natl. Acad. Sci. U.S.A. 86:4392-4396(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[2]"Structure and expression of the human gene for the alpha subunit of prolyl 4-hydroxylase. The two alternatively spliced types of mRNA correspond to two homologous exons the sequences of which are expressed in a variety of tissues."
Helaakoski T., Veijola J., Vuori K., Rehn M., Chow L.T., Taillon-Miller P., Kivirikko K.I., Pihlajaniemi T.
J. Biol. Chem. 269:27847-27854(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
[3]"PCR isolation and cloning of novel splice variant mRNAs from known drug target genes."
Jin P., Fu G.K., Wilson A.D., Yang J., Chien D., Hawkins P.R., Au-Young J., Stuve L.L.
Genomics 83:566-571(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[4]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
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 1).
Tissue: Brain.
[6]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-113.
Tissue: Liver.
[7]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"The peptide-substrate-binding domain of collagen prolyl 4-hydroxylases is a tetratricopeptide repeat domain with functional aromatic residues."
Pekkala M., Hieta R., Bergmann U., Kivirikko K.I., Wierenga R.K., Myllyharju J.
J. Biol. Chem. 279:52255-52261(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 161-261, SUBUNIT, MUTAGENESIS OF TYR-210; TYR-213 AND TYR-247.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M24486 mRNA. Translation: AAA36534.1.
M24487 mRNA. Translation: AAA36535.1.
U14620 expand/collapse EMBL AC list , U14607, U14605, U14608, U14609, U14611, U14610, U14612, U14614, U14615, U14616, U14617, U14618, U14619 Genomic DNA. Translation: AAA59068.1.
U14620 expand/collapse EMBL AC list , 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.
PIRDAHUA1. A33919.
DAHUA2. I37173.
RefSeqNP_000908.2. NM_000917.3.
NP_001017962.1. NM_001017962.2.
NP_001136067.1. NM_001142595.1.
NP_001136068.1. NM_001142596.1.
UniGeneHs.500047.
Hs.593005.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP13674.
SMRP13674. Positions 18-254, 335-518.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111072. 13 interactions.
DIPDIP-38180N.
IntActP13674. 6 interactions.
MINTMINT-4657265.
STRING9606.ENSP00000263556.

Chemistry

ChEMBLCHEMBL1250350.
DrugBankDB01275. Hydralazine.
DB00172. L-Proline.
DB00139. Succinic acid.
DB00126. Vitamin C.

PTM databases

PhosphoSiteP13674.

Polymorphism databases

DMDM2507090.

Proteomic databases

PaxDbP13674.
PRIDEP13674.

Protocols and materials databases

DNASU5033.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263556; ENSP00000263556; ENSG00000122884. [P13674-2]
ENST00000307116; ENSP00000307318; ENSG00000122884. [P13674-1]
ENST00000373008; ENSP00000362099; ENSG00000122884. [P13674-2]
ENST00000394890; ENSP00000378353; ENSG00000122884. [P13674-1]
ENST00000412021; ENSP00000411688; ENSG00000122884. [P13674-1]
ENST00000440381; ENSP00000414464; ENSG00000122884. [P13674-3]
GeneID5033.
KEGGhsa:5033.
UCSCuc001jtg.3. human. [P13674-1]

Organism-specific databases

CTD5033.
GeneCardsGC10M074767.
HGNCHGNC:8546. P4HA1.
HPAHPA007599.
HPA026593.
MIM176710. gene.
neXtProtNX_P13674.
PharmGKBPA32874.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG78926.
HOGENOMHOG000230465.
HOVERGENHBG006834.
InParanoidP13674.
KOK00472.
OMAAKEKDDN.
OrthoDBEOG7W6WKC.
PhylomeDBP13674.
TreeFamTF313393.

Enzyme and pathway databases

BRENDA1.14.11.2. 2681.

Gene expression databases

ArrayExpressP13674.
BgeeP13674.
CleanExHS_P4HA1.
GenevestigatorP13674.

Family and domain databases

Gene3D1.25.40.10. 2 hits.
InterProIPR005123. 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]
PfamPF03171. 2OG-FeII_Oxy. 1 hit.
PF08336. P4Ha_N. 1 hit.
[Graphical view]
SMARTSM00702. P4Hc. 1 hit.
[Graphical view]
PROSITEPS51471. FE2OG_OXY. 1 hit.
PS50005. TPR. 1 hit.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP13674.
GeneWikiP4HA1.
GenomeRNAi5033.
NextBio19392.
PROP13674.
SOURCESearch...

Entry information

Entry nameP4HA1_HUMAN
AccessionPrimary (citable) accession number: P13674
Secondary accession number(s): C9JL12 expand/collapse secondary AC list , Q15082, Q15083, Q5VSQ5
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: November 1, 1997
Last modified: April 16, 2014
This is version 162 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM