Q7Z4N8 (P4HA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prolyl 4-hydroxylase subunit alpha-3
Short name=4-PH alpha-3
EC=1.14.11.2

Alternative name(s):
Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-3

Gene names

Name:	P4HA3
ORF Names:	UNQ711/PRO1374

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	544 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. Ref.1 Ref.2
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-3 chains and two beta chains (the beta chain is the multi-functional PDI). Ref.1 Ref.2
Subcellular location	Endoplasmic reticulum lumen Probable.
Tissue specificity	Highly expressed in placenta, liver and fetal skin. Weakly expressed in fetal epiphyseal cartilage, fetal liver, fibroblast, lung and skeletal muscle. Expressed also in fibrous cap of carotid atherosclerotic lesions. Ref.1 Ref.2
Post-translational modification	N-glycosylation plays no role in the catalytic activity.
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 Polymorphism
Domain	Coiled coil Signal TPR repeat
Ligand	Iron Metal-binding Vitamin C
Molecular function	Dioxygenase Oxidoreductase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
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 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: InterPro procollagen-proline 4-dioxygenase activity Inferred from electronic annotation. Source: UniProtKB-EC
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7Z4N8-1)

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: Q7Z4N8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     257-257: S → R
     258-544: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q7Z4N8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     490-544: NAALFWWNLH...RRPCSSSPED → HCFGGTCTGV...CYQGTLRMYI

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 544	525	Prolyl 4-hydroxylase subunit alpha-3		PRO_0000317766
Regions
	Repeat	227 – 260	34	TPR
	Domain	422 – 529	108	Fe2OG dioxygenase
	Coiled coil	107 – 131	25	Potential
Sites
	Metal binding	440	1	Iron By similarity
	Metal binding	442	1	Iron By similarity
	Metal binding	510	1	Iron By similarity
	Binding site	520	1	2-oxoglutarate Potential
Amino acid modifications
	Glycosylation	242	1	N-linked (GlcNAc...) Potential
	Glycosylation	482	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	257	1	S → R in isoform 2.		VSP_031146
	Alternative sequence	258 – 544	287	Missing in isoform 2.		VSP_031147
	Alternative sequence	490 – 544	55	NAALF…SSPED → HCFGGTCTGVVKGTVTHFML AVLSWWEISGWPTSGYMSMD RNSADPAAPALKTELLAERS WWSPVAFQRSQEPKAGVGEE KAEQPPGRRPCQLCLCLANQ RQGRGCYQGTLRMYI in isoform 3.		VSP_054131
	Natural variant	400	1	D → N. Ref.8 Corresponds to variant rs2282488 [ dbSNP | Ensembl ].		VAR_038675
Experimental info
	Sequence conflict	222	1	D → Y in AAH89446. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2003. Version 1. Checksum: 1C88C168A268572F	FASTA	544	61,126
	10 20 30 40 50 60 MGPGARLAAL LAVLALGTGD PERAAARGDT FSALTSVARA LAPERRLLGL LRRYLRGEEA 70 80 90 100 110 120 RLRDLTRFYD KVLSLHEDST TPVANPLLAF TLIKRLQSDW RNVVHSLEAS ENIRALKDGY 130 140 150 160 170 180 EKVEQDLPAF EDLEGAARAL MRLQDVYMLN VKGLARGVFQ RVTGSAITDL YSPKRLFSLT 190 200 210 220 230 240 GDDCFQVGKV AYDMGDYYHA IPWLEEAVSL FRGSYGEWKT EDEASLEDAL DHLAFAYFRA 250 260 270 280 290 300 GNVSCALSLS REFLLYSPDN KRMARNVLKY ERLLAESPNH VVAEAVIQRP NIPHLQTRDT 310 320 330 340 350 360 YEGLCQTLGS QPTLYQIPSL YCSYETNSNA YLLLQPIRKE VIHLEPYIAL YHDFVSDSEA 370 380 390 400 410 420 QKIRELAEPW LQRSVVASGE KQLQVEYRIS KSAWLKDTVD PKLVTLNHRI AALTGLDVRP 430 440 450 460 470 480 PYAEYLQVVN YGIGGHYEPH FDHATSPSSP LYRMKSGNRV ATFMIYLSSV EAGGATAFIY 490 500 510 520 530 540 ANLSVPVVRN AALFWWNLHR SGEGDSDTLH AGCPVLVGDK WVANKWIHEY GQEFRRPCSS SPED
	Isoform 2 [UniParc]. Checksum: A610B9B8CF4E4238	FASTA	257	28,701
	10 20 30 40 50 60 MGPGARLAAL LAVLALGTGD PERAAARGDT FSALTSVARA LAPERRLLGL LRRYLRGEEA 70 80 90 100 110 120 RLRDLTRFYD KVLSLHEDST TPVANPLLAF TLIKRLQSDW RNVVHSLEAS ENIRALKDGY 130 140 150 160 170 180 EKVEQDLPAF EDLEGAARAL MRLQDVYMLN VKGLARGVFQ RVTGSAITDL YSPKRLFSLT 190 200 210 220 230 240 GDDCFQVGKV AYDMGDYYHA IPWLEEAVSL FRGSYGEWKT EDEASLEDAL DHLAFAYFRA 250 GNVSCALSLS REFLLYR
	Isoform 3 [UniParc]. Checksum: E2A37A126C60A2A0	FASTA	604	67,591
	10 20 30 40 50 60 MGPGARLAAL LAVLALGTGD PERAAARGDT FSALTSVARA LAPERRLLGL LRRYLRGEEA 70 80 90 100 110 120 RLRDLTRFYD KVLSLHEDST TPVANPLLAF TLIKRLQSDW RNVVHSLEAS ENIRALKDGY 130 140 150 160 170 180 EKVEQDLPAF EDLEGAARAL MRLQDVYMLN VKGLARGVFQ RVTGSAITDL YSPKRLFSLT 190 200 210 220 230 240 GDDCFQVGKV AYDMGDYYHA IPWLEEAVSL FRGSYGEWKT EDEASLEDAL DHLAFAYFRA 250 260 270 280 290 300 GNVSCALSLS REFLLYSPDN KRMARNVLKY ERLLAESPNH VVAEAVIQRP NIPHLQTRDT 310 320 330 340 350 360 YEGLCQTLGS QPTLYQIPSL YCSYETNSNA YLLLQPIRKE VIHLEPYIAL YHDFVSDSEA 370 380 390 400 410 420 QKIRELAEPW LQRSVVASGE KQLQVEYRIS KSAWLKDTVD PKLVTLNHRI AALTGLDVRP 430 440 450 460 470 480 PYAEYLQVVN YGIGGHYEPH FDHATSPSSP LYRMKSGNRV ATFMIYLSSV EAGGATAFIY 490 500 510 520 530 540 ANLSVPVVRH CFGGTCTGVV KGTVTHFMLA VLSWWEISGW PTSGYMSMDR NSADPAAPAL 550 560 570 580 590 600 KTELLAERSW WSPVAFQRSQ EPKAGVGEEK AEQPPGRRPC QLCLCLANQR QGRGCYQGTL RMYI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of a third human, rat, and mouse collagen prolyl 4-hydroxylase isoenzyme." Kukkola L., Hieta R., Kivirikko K.I., Myllyharju J. J. Biol. Chem. 278:47685-47693(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBUNIT, TISSUE SPECIFICITY. Tissue: Umbilical vein endothelial cell.
[2]	"Cloning of a novel prolyl 4-hydroxylase subunit expressed in the fibrous cap of human atherosclerotic plaque." Van Den Diepstraten C., Papay K., Bolender Z., Brown A., Pickering J.G. Circulation 108:508-511(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBUNIT, TISSUE SPECIFICITY. Tissue: Vascular smooth muscle.
[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 1).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[6]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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), VARIANT ASN-400. Tissue: Colon.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY313448 mRNA. Translation: AAQ87603.1. AY327887 mRNA. Translation: AAP97874.1. AY358521 mRNA. Translation: AAQ88885.1. AK300598 mRNA. Translation: BAG62295.1. AP000577 Genomic DNA. No translation available. AP001085 Genomic DNA. No translation available. AL833965 mRNA. Translation: CAI46215.1. CH471076 Genomic DNA. Translation: EAW74935.1. BC089446 mRNA. Translation: AAH89446.1. BC117333 mRNA. Translation: AAI17334.1. BC126170 mRNA. Translation: AAI26171.1.
RefSeq	NP_878907.1. NM_182904.4.
UniGene	Hs.660541.
3D structure databases
ProteinModelPortal	Q7Z4N8.
SMR	Q7Z4N8. Positions 44-276, 338-528.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	129495. 1 interaction.
STRING	9606.ENSP00000332170.
PTM databases
PhosphoSite	Q7Z4N8.
Polymorphism databases
DMDM	74738714.
Proteomic databases
PaxDb	Q7Z4N8.
PRIDE	Q7Z4N8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000331597; ENSP00000332170; ENSG00000149380. [Q7Z4N8-1] ENST00000427714; ENSP00000401749; ENSG00000149380. ENST00000524388; ENSP00000433860; ENSG00000149380. [Q7Z4N8-2]
GeneID	283208.
KEGG	hsa:283208.
UCSC	uc001ouz.3. human. [Q7Z4N8-1]
Organism-specific databases
CTD	283208.
GeneCards	GC11M073947.
HGNC	HGNC:30135. P4HA3.
HPA	HPA007897.
MIM	608987. gene.
neXtProt	NX_Q7Z4N8.
PharmGKB	PA134870931.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG289769.
HOGENOM	HOG000230465.
HOVERGEN	HBG006834.
InParanoid	Q7Z4N8.
KO	K00472.
OrthoDB	EOG7W6WKC.
PhylomeDB	Q7Z4N8.
TreeFam	TF313393.
Enzyme and pathway databases
BRENDA	1.14.11.2. 2681.
Gene expression databases
ArrayExpress	Q7Z4N8.
Bgee	Q7Z4N8.
CleanEx	HS_P4HA3.
Genevestigator	Q7Z4N8.
Family and domain databases
Gene3D	1.25.40.10. 1 hit.
InterPro	IPR005123. Oxoglu/Fe-dep_dioxygenase. IPR006620. Pro_4_hyd_alph. IPR013547. Pro_4_hyd_alph_N. IPR011990. TPR-like_helical. [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. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	P4HA3. human.
GenomeRNAi	283208.
NextBio	93714.
PRO	Q7Z4N8.
SOURCE	Search...

Entry information

Entry name

P4HA3_HUMAN

Accession

Primary (citable) accession number: Q7Z4N8
Secondary accession number(s): A0AV13 , B4DUD3, Q5EBL3, Q5JPA9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 5, 2008
Last sequence update:	October 1, 2003
Last modified:	April 16, 2014
This is version 101 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.