O15460 (P4HA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prolyl 4-hydroxylase subunit alpha-2
Short name=4-PH alpha-2
EC=1.14.11.2

Alternative name(s):
Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-2

Gene names

Name:	P4HA2
ORF Names:	UNQ290/PRO330

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	535 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	L-proline-[procollagen] + 2-oxoglutarate + O2 = trans-4-hydroxy-L-proline-[procollagen] + succinate + CO2.
Cofactor	Binds 1 Fe2+ ion per subunit By similarity. Ascorbate By similarity.
Subunit structure	Heterotetramer of two alpha-2 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 Fe2OG dioxygenase 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	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	peptidyl-proline hydroxylation to 4-hydroxy-L-proline Inferred from electronic annotation. Source: Compara
Cellular_component	endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	L-ascorbic acid binding Inferred from electronic annotation. Source: UniProtKB-KW electron carrier activity Traceable author statement Ref.1. Source: UniProtKB 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 Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform IIb (identifier: O15460-1)

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 IIa (identifier: O15460-2)

The sequence of this isoform differs from the canonical sequence as follows:
     436-451: NDERDTFKHLGTGNRV → RPFDSGLKTEGNRL

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 535	514	Prolyl 4-hydroxylase subunit alpha-2		PRO_0000022726
Regions
	Repeat	207 – 240	34	TPR
	Domain	412 – 520	109	Fe2OG dioxygenase
Sites
	Metal binding	430	1	Iron By similarity
	Metal binding	432	1	Iron By similarity
	Metal binding	501	1	Iron By similarity
	Binding site	511	1	2-oxoglutarate Potential
Amino acid modifications
	Glycosylation	115	1	N-linked (GlcNAc...) Potential
	Glycosylation	264	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	436 – 451	16	NDERD…TGNRV → RPFDSGLKTEGNRL in isoform IIa.		VSP_004506

Sequences

	Sequence		Length	Mass (Da)
	Isoform IIb [UniParc]. Last modified January 1, 1998. Version 1. Checksum: FD04467B098F63CF	FASTA	535	60,902
	10 20 30 40 50 60 MKLWVSALLM AWFGVLSCVQ AEFFTSIGHM TDLIYAEKEL VQSLKEYILV EEAKLSKIKS 70 80 90 100 110 120 WANKMEALTS KSAADAEGYL AHPVNAYKLV KRLNTDWPAL EDLVLQDSAA GFIANLSVQR 130 140 150 160 170 180 QFFPTDEDEI GAAKALMRLQ DTYRLDPGTI SRGELPGTKY QAMLSVDDCF GMGRSAYNEG 190 200 210 220 230 240 DYYHTVLWME QVLKQLDAGE EATTTKSQVL DYLSYAVFQL GDLHRALELT RRLLSLDPSH 250 260 270 280 290 300 ERAGGNLRYF EQLLEEEREK TLTNQTEAEL ATPEGIYERP VDYLPERDVY ESLCRGEGVK 310 320 330 340 350 360 LTPRRQKRLF CRYHHGNRAP QLLIAPFKEE DEWDSPHIVR YYDVMSDEEI ERIKEIAKPK 370 380 390 400 410 420 LARATVRDPK TGVLTVASYR VSKSSWLEED DDPVVARVNR RMQHITGLTV KTAELLQVAN 430 440 450 460 470 480 YGVGGQYEPH FDFSRNDERD TFKHLGTGNR VATFLNYMSD VEAGGATVFP DLGAAIWPKK 490 500 510 520 530 GTAVFWYNLL RSGEGDYRTR HAACPVLVGC KWVSNKWFHE RGQEFLRPCG STEVD
	Isoform IIa [UniParc]. Checksum: 8C875AD482B0DBD2	FASTA	533	60,633
	10 20 30 40 50 60 MKLWVSALLM AWFGVLSCVQ AEFFTSIGHM TDLIYAEKEL VQSLKEYILV EEAKLSKIKS 70 80 90 100 110 120 WANKMEALTS KSAADAEGYL AHPVNAYKLV KRLNTDWPAL EDLVLQDSAA GFIANLSVQR 130 140 150 160 170 180 QFFPTDEDEI GAAKALMRLQ DTYRLDPGTI SRGELPGTKY QAMLSVDDCF GMGRSAYNEG 190 200 210 220 230 240 DYYHTVLWME QVLKQLDAGE EATTTKSQVL DYLSYAVFQL GDLHRALELT RRLLSLDPSH 250 260 270 280 290 300 ERAGGNLRYF EQLLEEEREK TLTNQTEAEL ATPEGIYERP VDYLPERDVY ESLCRGEGVK 310 320 330 340 350 360 LTPRRQKRLF CRYHHGNRAP QLLIAPFKEE DEWDSPHIVR YYDVMSDEEI ERIKEIAKPK 370 380 390 400 410 420 LARATVRDPK TGVLTVASYR VSKSSWLEED DDPVVARVNR RMQHITGLTV KTAELLQVAN 430 440 450 460 470 480 YGVGGQYEPH FDFSRRPFDS GLKTEGNRLA TFLNYMSDVE AGGATVFPDL GAAIWPKKGT 490 500 510 520 530 AVFWYNLLRS GEGDYRTRHA ACPVLVGCKW VSNKWFHERG QEFLRPCGST EVD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the human prolyl 4-hydroxylase alpha subunit isoform alpha(II) and characterization of the type II enzyme tetramer. The alpha(I) and alpha(II) subunits do not form a mixed alpha(I)alpha(II)beta2 tetramer." Annunen P., Helaakoski T., Myllyharju J., Veijola J., Pihlajaniemi T., Kivirikko K.I. J. Biol. Chem. 272:17342-17348(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IIB). Tissue: Lung.
[2]	"Characterization of the human and mouse genes for the alpha subunit of type II prolyl 4-hydroxylase. Identification of a previously unknown alternatively spliced exon and its expression in various tissues." Nokelainen M., Nissi R., Kukkola L., Helaakoski T., Myllyharju J. Eur. J. Biochem. 268:5300-5309(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS IIA AND IIB).
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IIA).
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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 IIA). Tissue: Brain.
[6]	"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].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00003128. IPI00182373.
RefSeq	NP_001017973.1. NM_001017973.1. NP_001017974.1. NM_001017974.1. NP_001136070.1. NM_001142598.1. NP_001136071.1. NM_001142599.1. NP_004190.1. NM_004199.2.
UniGene	Hs.519568.
3D structure databases
ProteinModelPortal	O15460.
ModBase	Search...
Protein-protein interaction databases
IntAct	O15460. 5 interactions.
MINT	MINT-1035479.
STRING	9606.ENSP00000166534.
PTM databases
PhosphoSite	O15460.
Proteomic databases
PaxDb	O15460.
PRIDE	O15460.
Protocols and materials databases
DNASU	8974.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000166534; ENSP00000166534; ENSG00000072682. ENST00000360568; ENSP00000353772; ENSG00000072682. ENST00000379086; ENSP00000368379; ENSG00000072682. ENST00000379100; ENSP00000368394; ENSG00000072682. ENST00000379104; ENSP00000368398; ENSG00000072682. ENST00000401867; ENSP00000384999; ENSG00000072682.
GeneID	8974.
KEGG	hsa:8974.
UCSC	uc003kwg.3. human. uc003kwh.3. human.
Organism-specific databases
CTD	8974.
GeneCards	GC05M131531.
HGNC	HGNC:8547. P4HA2.
MIM	600608. gene.
neXtProt	NX_O15460.
PharmGKB	PA32875.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG78926.
HOGENOM	HOG000230465.
HOVERGEN	HBG006834.
InParanoid	O15460.
KO	K00472.
OMA	CKWVSNK.
OrthoDB	EOG4QJRN3.
PhylomeDB	O15460.
Enzyme and pathway databases
BRENDA	1.14.11.2. 2681.
Gene expression databases
ArrayExpress	O15460.
Bgee	O15460.
CleanEx	HS_P4HA2.
Genevestigator	O15460.
GermOnline	ENSG00000072682. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.10. 2 hits.
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. IPR019734. TPR_repeat. [Graphical view]
Pfam	PF03171. 2OG-FeII_Oxy. 1 hit. PF08336. P4Ha_N. 1 hit. [Graphical view]
SMART	SM00702. P4Hc. 1 hit. [Graphical view]
PROSITE	PS51471. FE2OG_OXY. 1 hit. PS50005. TPR. 1 hit. PS50293. TPR_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL5640.
DrugBank	DB00172. L-Proline. DB00139. Succinic acid.
GenomeRNAi	8974.
NextBio	33677.
SOURCE	Search...

Entry information

Entry name

P4HA2_HUMAN

Accession

Primary (citable) accession number: O15460
Secondary accession number(s): D3DQ85, D3DQ86, Q8WWN0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 2, 2002
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 131 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.