Reviewed, UniProtKB/Swiss-Prot P13674 (P4HA1_HUMAN)

Names and origin

Protein names

Recommended name:
    Prolyl 4-hydroxylase subunit alpha-1
    EC=1.14.11.2
Alternative name(s):
    4-PH alpha-1
    Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-1

Gene names

Name:	P4HA1
Synonyms:	P4HA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	534 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Procollagen L-proline + 2-oxoglutarate + O(2) = procollagen trans-4-hydroxy-L-proline + succinate + CO(2).
Cofactor	Binds 1 Fe(2+) ion per subunit. Ascorbate.
Subunit structure	Heterotetramer of two alpha-1 chains and two beta chains (the beta chain is the multi-functional PDI).
Subcellular location	Endoplasmic reticulum lumen.
Sequence similarities	Belongs to the P4HA family. Contains 1 PKHD (prolyl/lysyl hydroxylase) domain. Contains 1 TPR repeat.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Alternative splicing
Domain	Signal TPR repeat
Ligand	Iron Metal-binding Vitamin C
Molecular function	Dioxygenase Oxidoreductase
PTM	Glycoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW protein metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	endoplasmic reticulum Ref.1 Traceable author statement. Source: ProtInc endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay. Source: HPA
Molecular function	L-ascorbic acid binding Inferred from electronic annotation. Source: UniProtKB-KW iron ion binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW procollagen-proline 4-dioxygenase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Chain

18 – 534

517

Prolyl 4-hydroxylase subunit alpha-1

PRO_0000022723

Regions

Repeat

205 – 238

34

TPR

Domain

335 – 518

184

PKHD

Sites

Metal binding

429

1

Iron By similarity

Metal binding

431

1

Iron By similarity

Metal binding

500

1

Iron By similarity

Binding site

510

1

2-oxoglutarate Potential

Amino acid modifications

Glycosylation

113

1

N-linked (GlcNAc...)

Glycosylation

259

1

N-linked (GlcNAc...)

Natural variations

Alternative sequence

361 – 380

20

RRATI…VHYRI → SRATVHDPETGKLTTAQYRV in isoform 2.

VSP_004504

Experimental info

Mutagenesis

210

1

Y → A: Strongly reduced affinity for peptide substrate

Mutagenesis

213

1

Y → A: Strongly reduced affinity for peptide substrate

Mutagenesis

247

1

Y → A: Strongly reduced affinity for peptide substrate

Sequence conflict

119 – 122

4

QYFP → PVLS in AAA36534 and AAA36535. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

534

Helix Strand Turn

Details...

Helix

164 – 176

13

Helix

180 – 195

16

Helix

204 – 217

14

Helix

221 – 234

14

Helix

239 – 253

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: EBAFA8CCF09A1DDB	FASTA	534	61,049
	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
	Isoform 2 [UniParc]. Checksum: 5FE1B10A8AC5E792		534	60,967
	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 SRATVHDPET GKLTTAQYRV 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

References

	« Hide 'large scale' referencesShow '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: 2543975] [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: 7961714] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
[3]	"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. , 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: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[5]	"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: 15456751] [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

EMBLGenBankDDBJ

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.
AL731563 Genomic DNA. Translation: CAH72754.1.
BC034998 mRNA. Translation: AAH34998.1.

PIR

DAHUA1. A33919.
DAHUA2. I37173.

RefSeq

NP_000908.2.
NP_001017962.1.

UniGene

Hs.500047

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TJC	X-ray	2.30	A/B	161-261	[»]

ModBase

Search...

PTM databases

PhosphoSite

P13674.

Genome annotation databases

Ensembl

ENSG00000122884. Homo sapiens. [Contig view]

GeneID

5033.

KEGG

hsa:5033.

Organism-specific databases

H-InvDB

HIX0025926.

HGNC

HGNC:8546. P4HA1.

HPA

HPA007599.

MIM

176710. gene.

PharmGKB

PA32874.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P13674.

Gene expression databases

ArrayExpress

P13674.

CleanEx

HS_P4HA1.

GermOnline

ENSG00000122884. Homo sapiens.

Family and domain databases

InterPro

IPR005123. 2OG-FeII_Oase.
IPR006620. Pro_4_hyd_alph.
IPR013547. Pro_4_hyd_alph_N.
IPR011990. TPR-like_helical.
IPR013105. TPR_2.
IPR013026. TPR_region.
[Graphical view]

Gene3D

G3DSA:1.25.40.10. TPR-like_helical. 1 hit.

Pfam

PF03171. 2OG-FeII_Oxy. 1 hit.
PF08336. P4Ha_N. 1 hit.
PF07719. TPR_2. 1 hit.
[Graphical view]

SMART

SM00702. P4Hc. 1 hit.
[Graphical view]

PROSITE

PS50005. TPR. 1 hit.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB01275. Hydralazine.
DB00172. L-Proline.
DB00139. Succinic acid.
DB00126. Vitamin C.

LinkHub

P13674.

NextBio

19392.

SOURCE

Search...

Entry information

Entry name

P4HA1_HUMAN

Accession

Primary (citable) accession number: P13674
Secondary accession number(s): Q15082, Q15083, Q5VSQ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	November 1, 1997
Last modified:	November 25, 2008
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)