Q8IVL6 (P3H3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prolyl 3-hydroxylase 3
EC=1.14.11.7

Alternative name(s):
Leprecan-like protein 2
Protein B

Gene names

Name:	LEPREL2
Synonyms:	P3H3

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	736 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	Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly-sequences in collagens, especially types IV and V By similarity.
Catalytic activity	L-proline-[procollagen] + 2-oxoglutarate + O2 = trans-3-hydroxy-L-proline-[procollagen] + succinate + CO2.
Cofactor	Iron By similarity. Ascorbate By similarity.
Subcellular location	Endoplasmic reticulum By similarity.
Tissue specificity	Weak expression in heart, lung, ovary and skeletal muscle. Ref.1
Sequence similarities	Belongs to the leprecan family. Contains 1 Fe2OG dioxygenase domain. Contains 4 TPR repeats.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Repeat 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	extracellular matrix organization Traceable author statement. Source: Reactome negative regulation of cell proliferation Inferred from direct assay PubMed 19436308. Source: UniProtKB
Cellular_component	endoplasmic reticulum lumen Traceable author statement. Source: Reactome
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 3-dioxygenase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q8IVL6-1)

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: Q8IVL6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-185: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 736	716	Prolyl 3-hydroxylase 3		PRO_0000240360
Regions
	Repeat	37 – 70	34	TPR 1
	Repeat	154 – 187	34	TPR 2
	Repeat	216 – 249	34	TPR 3
	Repeat	316 – 349	34	TPR 4
	Domain	561 – 675	115	Fe2OG dioxygenase
	Coiled coil	681 – 709	29	Potential
	Motif	733 – 736	4	Prevents secretion from ER Potential
	Compositional bias	173 – 177	5	Poly-Ala
	Compositional bias	267 – 270	4	Poly-Glu
	Compositional bias	696 – 704	9	Poly-Glu
Sites
	Active site	666	1	By similarity
	Metal binding	584	1	Iron
	Metal binding	586	1	Iron
	Metal binding	656	1	Iron
Amino acid modifications
	Glycosylation	331	1	N-linked (GlcNAc...) Potential
	Glycosylation	462	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 185	185	Missing in isoform 2.		VSP_019352
	Natural variant	301	1	T → A. Ref.1 Corresponds to variant rs10744716 [ dbSNP | Ensembl ].		VAR_050443
	Natural variant	304	1	R → C. Corresponds to variant rs35359746 [ dbSNP | Ensembl ].		VAR_050444
	Natural variant	385	1	G → E. Corresponds to variant rs1047771 [ dbSNP | Ensembl ].		VAR_050445
	Natural variant	685	1	I → T. Ref.4 Corresponds to variant rs1129649 [ dbSNP | Ensembl ].		VAR_050446
	Natural variant	705	1	M → T. Corresponds to variant rs3213431 [ dbSNP | Ensembl ].		VAR_050447
Experimental info
	Sequence conflict	79 – 82	4	ASCA → RTRG in AAH67251. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 82526D30C9788369	FASTA	736	81,837
	10 20 30 40 50 60 MLRLLRPLLL LLLLPPPGSP EPPGLTQLSP GAPPQAPDLL YADGLRAYAA GAWAPAVALL 70 80 90 100 110 120 REALRSQAAL GRVRLDCGAS CAADPGAALP AVLLGAPEPD SGPGPTQGSW ERQLLRAALR 130 140 150 160 170 180 RADCLTQCAA RRLGPGGAAR LRVGSALRDA FRRREPYNYL QRAYYQLKKL DLAAAAAHTF 190 200 210 220 230 240 FVANPMHLQM REDMAKYRRM SGVRPQSFRD LETPPHWAAY DTGLELLGRQ EAGLALPRLE 250 260 270 280 290 300 EALQGSLAQM ESCRADCEGP EEQQGAEEEE DGAASQGGLY EAIAGHWIQV LQCRQRCVGE 310 320 330 340 350 360 TATRPGRSFP VPDFLPNQLR RLHEAHAQVG NLSQAIENVL SVLLFYPEDE AAKRALNQYQ 370 380 390 400 410 420 AQLGEPRPGL GPREDIQRFI LRSLGEKRQL YYAMEHLGTS FKDPDPWTPA ALIPEALREK 430 440 450 460 470 480 LREDQEKRPW DHEPVKPKPL TYWKDVLLLE GVTLTQDSRQ LNGSERAVLD GLLTPAECGV 490 500 510 520 530 540 LLQLAKDAAG AGARSGYRGR RSPHTPHERF EGLTVLKAAQ LARAGTVGSQ GAKLLLEVSE 550 560 570 580 590 600 RVRTLTQAYF SPERPLHLSF THLVCRSAIE GEQEQRMDLS HPVHADNCVL DPDTGECWRE 610 620 630 640 650 660 PPAYTYRDYS GLLYLNDDFQ GGDLFFTEPN ALTVTARVRP RCGRLVAFSS GVENPHGVWA 670 680 690 700 710 720 VTRGRRCALA LWHTWAPEHR EQEWIEAKEL LQESQEEEEE EEEEMPSKDP SPEPPSRRHQ 730 RVQDKTGRAP RVREEL
	Isoform 2 [UniParc]. Checksum: 1CAA483E15659886	FASTA	551	62,295
	10 20 30 40 50 60 MHLQMREDMA KYRRMSGVRP QSFRDLETPP HWAAYDTGLE LLGRQEAGLA LPRLEEALQG 70 80 90 100 110 120 SLAQMESCRA DCEGPEEQQG AEEEEDGAAS QGGLYEAIAG HWIQVLQCRQ RCVGETATRP 130 140 150 160 170 180 GRSFPVPDFL PNQLRRLHEA HAQVGNLSQA IENVLSVLLF YPEDEAAKRA LNQYQAQLGE 190 200 210 220 230 240 PRPGLGPRED IQRFILRSLG EKRQLYYAME HLGTSFKDPD PWTPAALIPE ALREKLREDQ 250 260 270 280 290 300 EKRPWDHEPV KPKPLTYWKD VLLLEGVTLT QDSRQLNGSE RAVLDGLLTP AECGVLLQLA 310 320 330 340 350 360 KDAAGAGARS GYRGRRSPHT PHERFEGLTV LKAAQLARAG TVGSQGAKLL LEVSERVRTL 370 380 390 400 410 420 TQAYFSPERP LHLSFTHLVC RSAIEGEQEQ RMDLSHPVHA DNCVLDPDTG ECWREPPAYT 430 440 450 460 470 480 YRDYSGLLYL NDDFQGGDLF FTEPNALTVT ARVRPRCGRL VAFSSGVENP HGVWAVTRGR 490 500 510 520 530 540 RCALALWHTW APEHREQEWI EAKELLQESQ EEEEEEEEEM PSKDPSPEPP SRRHQRVQDK 550 TGRAPRVREE L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13." Ansari-Lari M.A., Muzny D.M., Lu J., Lu F., Lilley C.E., Spanos S., Malley T., Gibbs R.A. Genome Res. 6:314-326(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2), TISSUE SPECIFICITY, VARIANT ALA-301. Tissue: Fibrosarcoma.
[2]	"Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination." Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A. Genome Res. 7:268-280(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"LEPREL1, a novel ER and Golgi resident member of the Leprecan family." Jaernum S., Kjellman C., Darabi A., Nilsson I., Edvardsen K., Aaman P. Biochem. Biophys. Res. Commun. 317:342-351(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 54-736 (ISOFORM 1), VARIANT THR-685. Tissue: Eye and Uterus.
[5]	"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	U47924 Genomic DNA. Translation: AAB51312.1. U47926 mRNA. Translation: AAC50464.1. AJ430349 mRNA. Translation: CAD23037.1. BC017217 mRNA. Translation: AAH17217.2. BC067251 mRNA. Translation: AAH67251.1. BC080630 mRNA. Translation: AAH80630.1.
IPI	IPI00217056. IPI00760934.
RefSeq	NP_055077.2. NM_014262.3.
UniGene	Hs.631655.
3D structure databases
ProteinModelPortal	Q8IVL6.
SMR	Q8IVL6. Positions 38-66, 320-358.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000311528.
PTM databases
PhosphoSite	Q8IVL6.
Polymorphism databases
DMDM	74714366.
Proteomic databases
PRIDE	Q8IVL6.
Protocols and materials databases
DNASU	10536.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000290510; ENSP00000290510; ENSG00000110811. ENST00000595716; ENSP00000471901; ENSG00000268828.
GeneID	10536.
KEGG	hsa:10536.
UCSC	uc001qra.1. human.
Organism-specific databases
CTD	10536.
GeneCards	GC12P007020.
HGNC	HGNC:19318. LEPREL2.
HPA	HPA043695.
MIM	610342. gene.
neXtProt	NX_Q8IVL6.
PharmGKB	PA134890414.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HOG000231087.
HOVERGEN	HBG053224.
InParanoid	Q8IVL6.
OrthoDB	EOG4VX24V.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization.
Gene expression databases
ArrayExpress	Q8IVL6.
Bgee	Q8IVL6.
CleanEx	HS_LEPREL2.
Genevestigator	Q8IVL6.
GermOnline	ENSG00000110811. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.10. 3 hits.
InterPro	IPR005123. Oxoglu/Fe-dep_dioxygenase. IPR006620. Pro_4_hyd_alph. IPR011990. TPR-like_helical. [Graphical view]
Pfam	PF13640. 2OG-FeII_Oxy_3. 1 hit. [Graphical view]
SMART	SM00702. P4Hc. 1 hit. [Graphical view]
PROSITE	PS00014. ER_TARGET. 1 hit. PS51471. FE2OG_OXY. 1 hit. PS50005. TPR. False negative. PS50293. TPR_REGION. False negative. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00172. L-Proline. DB00139. Succinic acid. DB00126. Vitamin C.
GenomeRNAi	10536.
NextBio	39973.
SOURCE	Search...

Entry information

Entry name

P3H3_HUMAN

Accession

Primary (citable) accession number: Q8IVL6
Secondary accession number(s): Q13512 , Q15740, Q66K32, Q6NX61, Q7L2T1

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 27, 2006
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 87 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.