Q8IVL5 (P3H2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prolyl 3-hydroxylase 2
EC=1.14.11.7

Alternative name(s):
Leprecan-like protein 1
Myxoid liposarcoma-associated protein 4

Gene names

Name:	LEPREL1
Synonyms:	MLAT4, P3H2

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	708 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	Shows prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly-sequences in collagens, especially types II, IV and V By similarity. Ref.2
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. Golgi apparatus Ref.2.
Tissue specificity	Expressed in heart, placenta, lung, liver, skeletal muscle and kidney. Expression localized to the epithelia of bile ducts and to the sacroplasm of heart muscle and skeletal muscle. In the pancreas, localized to a subpopulation of Langerhans islet cells and in the salivary gland, expressed in acinar cells. Ref.2
Involvement in disease	Myopia, high, with cataract and vitreoretinal degeneration (MCVD) [MIM:614292]: A disorder characterized by severe myopia with variable expressivity of cataract and vitreoretinal degeneration. Some patients manifest lens subluxation, lens instability and retinal detachment. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the leprecan family. Contains 1 Fe2OG dioxygenase domain. Contains 4 TPR repeats.
Sequence caution	The sequence BAA91769.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Golgi apparatus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	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	collagen metabolic process Inferred from direct assay PubMed 18487197. Source: UniProtKB extracellular matrix organization Traceable author statement. Source: Reactome negative regulation of cell proliferation Inferred from direct assay PubMed 19436308. Source: UniProtKB peptidyl-proline hydroxylation Inferred from direct assay PubMed 18487197. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from direct assay Ref.2. Source: UniProtKB basement membrane Inferred from sequence or structural similarity. Source: UniProtKB 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 direct assay PubMed 18487197. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 708	684	Prolyl 3-hydroxylase 2		PRO_0000240356
Regions
	Repeat	44 – 77	34	TPR 1
	Repeat	148 – 181	34	TPR 2
	Repeat	210 – 243	34	TPR 3
	Repeat	306 – 339	34	TPR 4
	Domain	557 – 671	115	Fe2OG dioxygenase
	Motif	705 – 708	4	Prevents secretion from ER Potential
	Compositional bias	93 – 99	7	Poly-Pro
Sites
	Active site	662	1	By similarity
	Metal binding	580	1	Iron
	Metal binding	582	1	Iron
	Metal binding	652	1	Iron
Amino acid modifications
	Glycosylation	449	1	N-linked (GlcNAc...) Potential
	Glycosylation	549	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	508	1	G → V in MCVD; loss of function. Ref.7		VAR_066637
	Natural variant	613	1	D → N in a breast cancer sample; somatic mutation. Ref.6		VAR_036123
Experimental info
	Sequence conflict	477	1	R → Q Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8IVL5 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: B9E680C90D607291	FASTA	708	80,984
	10 20 30 40 50 60 MRERIWAPPL LLLLPLLLPP PLWGGPPDSP RRELELEPGP LQPFDLLYAS GAAAYYSGDY 70 80 90 100 110 120 ERAVRDLEAA LRSHRRLREI RTRCARHCAA RHPLPPPPPG EGPGAELPLF RSLLGRARCY 130 140 150 160 170 180 RSCETQRLGG PASRHRVSED VRSDFQRRVP YNYLQRAYIK LNQLEKAVEA AHTFFVANPE 190 200 210 220 230 240 HMEMQQNIEN YRATAGVEAL QLVDREAKPH MESYNAGVKH YEADDFEMAI RHFEQALREY 250 260 270 280 290 300 FVEDTECRTL CEGPQRFEEY EYLGYKAGLY EAIADHYMQV LVCQHECVRE LATRPGRLSP 310 320 330 340 350 360 IENFLPLHYD YLQFAYYRVG EYVKALECAK AYLLCHPDDE DVLDNVDYYE SLLDDSIDPA 370 380 390 400 410 420 SIEAREDLTM FVKRHKLESE LIKSAAEGLG FSYTEPNYWI RYGGRQDENR VPSGVNVEGA 430 440 450 460 470 480 EVHGFSMGKK LSPKIDRDLR EGGPLLYENI TFVYNSEQLN GTQRVLLDNV LSEEQCRELH 490 500 510 520 530 540 SVASGIMLVG DGYRGKTSPH TPNEKFEGAT VLKALKSGYE GRVPLKSARL FYDISEKARR 550 560 570 580 590 600 IVESYFMLNS TLYFSYTHMV CRTALSGQQD RRNDLSHPIH ADNCLLDPEA NECWKEPPAY 610 620 630 640 650 660 TFRDYSALLY MNDDFEGGEF IFTEMDAKTV TASIKPKCGR MISFSSGGEN PHGVKAVTKG 670 680 690 700 KRCAVALWFT LDPLYRELER IQADEVIAIL DQEQQGKHEL NINPKDEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of genes differentially expressed in TLS-CHOP carrying myxoid liposarcomas." Thelin-Jaernum S., Lassen C., Panagopoulos I., Mandahl N., Aaman P. Int. J. Cancer 83:30-33(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liposarcoma.
[2]	"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], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, POSSIBLE FUNCTION. Tissue: Liposarcoma.
[3]	"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]. Tissue: Teratocarcinoma and Tongue.
[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] OF 161-708. Tissue: Lung.
[6]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-613.
[7]	"High myopia caused by a mutation in LEPREL1, encoding prolyl 3-hydroxylase 2." Mordechai S., Gradstein L., Pasanen A., Ofir R., El Amour K., Levy J., Belfair N., Lifshitz T., Joshua S., Narkis G., Elbedour K., Myllyharju J., Birk O.S. Am. J. Hum. Genet. 89:438-445(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MCVD VAL-508, CHARACTERIZATION OF VARIANT MCVD VAL-508.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ430351 mRNA. Translation: CAD23039.2. AK001580 mRNA. Translation: BAA91769.1. Different initiation. AK056447 mRNA. No translation available. AK125134 mRNA. Translation: BAG54151.1. CH471052 Genomic DNA. Translation: EAW78109.1. BC005029 mRNA. Translation: AAH05029.1.
IPI	IPI00217055.
RefSeq	NP_001127890.1. NM_001134418.1. NP_060662.2. NM_018192.3.
UniGene	Hs.374191.
3D structure databases
ProteinModelPortal	Q8IVL5.
SMR	Q8IVL5. Positions 40-74, 155-185.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8IVL5. 3 interactions.
STRING	9606.ENSP00000316881.
PTM databases
PhosphoSite	Q8IVL5.
Polymorphism databases
DMDM	74714365.
Proteomic databases
PaxDb	Q8IVL5.
PRIDE	Q8IVL5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000319332; ENSP00000316881; ENSG00000090530.
GeneID	55214.
KEGG	hsa:55214.
UCSC	uc003fsg.3. human.
Organism-specific databases
CTD	55214.
GeneCards	GC03M189674.
HGNC	HGNC:19317. LEPREL1.
HPA	HPA007890. HPA013355.
MIM	610341. gene. 614292. phenotype.
neXtProt	NX_Q8IVL5.
Orphanet	98619. Rare isolated myopia.
PharmGKB	PA134922807.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG269251.
HOGENOM	HOG000231087.
HOVERGEN	HBG053224.
InParanoid	Q8IVL5.
OMA	QGKHELN.
OrthoDB	EOG4WSW97.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization.
Gene expression databases
ArrayExpress	Q8IVL5.
Bgee	Q8IVL5.
CleanEx	HS_LEPREL1.
Genevestigator	Q8IVL5.
GermOnline	ENSG00000090530. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.10. 4 hits.
InterPro	IPR005123. Oxoglu/Fe-dep_dioxygenase. IPR006620. Pro_4_hyd_alph. IPR011990. TPR-like_helical. IPR013105. TPR_2. [Graphical view]
Pfam	PF13640. 2OG-FeII_Oxy_3. 1 hit. PF07719. TPR_2. 2 hits. [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	55214.
NextBio	59168.
SOURCE	Search...

Entry information

Entry name

P3H2_HUMAN

Accession

Primary (citable) accession number: Q8IVL5
Secondary accession number(s): B3KWI9, Q9NVI2

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 27, 2006
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 88 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.