Reviewed, UniProtKB/Swiss-Prot Q32P28 (P3H1_HUMAN)

Names and origin

Protein names

Recommended name:
    Prolyl 3-hydroxylase 1
    EC=1.14.11.7
Alternative name(s):
    Leucine- and proline-enriched proteoglycan 1
      Short name=Leprecan-1
    Growth suppressor 1

Gene names

Name:	LEPRE1
Synonyms:	GROS1, P3H1
ORF Names:	PSEC0109

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	Basement membrane-associated chondroitin sulfate proteoglycan (CSPG). 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. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts. Ref.1
Catalytic activity	Procollagen L-proline + 2-oxoglutarate + O2 = procollagen trans-3-hydroxy-L-proline + succinate + CO2.
Cofactor	Iron By similarity. Ascorbate By similarity.
Subcellular location	Endoplasmic reticulum By similarity. Secreted › extracellular space › extracellular matrix By similarity. Note: Secreted into the extracellular matrix as a chondroitin sulfate proteoglycan (CSPG).
Post-translational modification	O-glycosylated; chondroitin sulfate By similarity.
Involvement in disease	Defects in LEPRE1 are the cause of osteogenesis imperfecta type 8 (OI8) [MIM:610915]. Osteogenesis imperfecta is a connective tissue disorder characterized by bone fragility and low bone mass. OI8 is a form of autosomal recessive OI characterized by white sclerae, severe growth deficiency, extreme skeletal undermineralization, and bulbous metaphyses. Ref.6
Sequence similarities	Belongs to the leprecan family. Contains 1 PKHD (prolyl/lysyl hydroxylase) domain. Contains 4 TPR repeats.
Sequence caution	The sequence AAI08312.1 differs from that shown. Reason: Miscellaneous discrepancy. Intron retention.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Extracellular matrix Secreted
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
Gene Ontology (GO)
Biological process	negative regulation of cell proliferation Ref.1 Non-traceable author statement. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell proteinaceous extracellular matrix 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: UniProtKB-KW 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 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q32P28-1)

Also known as: GROS1-L;

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: Q32P28-2)

Also known as: GROS1-S;

The sequence of this isoform differs from the canonical sequence as follows:
     361-363: SAK → QGT
     364-736: Missing.

Isoform 3 (identifier: Q32P28-3)

The sequence of this isoform differs from the canonical sequence as follows:
     686-736: DRVQADDLVK...GSESKPKDEL → VRAARAGESS...NLPCPLGSSS

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 736	714	Prolyl 3-hydroxylase 1		PRO_0000240352
Regions
	Repeat	35 – 68	34	TPR 1
	Repeat	143 – 176	34	TPR 2
	Repeat	205 – 238	34	TPR 3
	Repeat	301 – 334	34	TPR 4
	Domain	469 – 677	209	PKHD
	Coiled coil	401 – 439	39	Potential
	Motif	733 – 736	4	Prevents secretion from ER Potential
Sites
	Active site	669	1	By similarity
	Metal binding	587	1	Iron
	Metal binding	589	1	Iron
	Metal binding	659	1	Iron
Amino acid modifications
	Glycosylation	316	1	N-linked (GlcNAc...) Potential
	Glycosylation	467	1	N-linked (GlcNAc...) Potential
	Glycosylation	540	1	N-linked (GlcNAc...) Ref.8
Natural variations
	Alternative sequence	361 – 363	3	SAK → QGT in isoform 2.		VSP_019346
	Alternative sequence	364 – 736	373	Missing in isoform 2.		VSP_019347
	Alternative sequence	686 – 736	51	DRVQA…PKDEL → VRAARAGESSWCCGDPFPER PWFAFLFPKSHCQWLRHERS TWDTSSNALSLWSHCLVLPG PAVNGIQVGKEVKTGSDAEF LVPSLGPTSAVLFQRVGPAG KEMSLGPLRNLPCPLGSSS in isoform 3.		VSP_019348
	Natural variant	349	1	G → R: dbSNP rs6700677.		VAR_033252
	Natural variant	506	1	P → R: dbSNP rs3738501.		VAR_033253
	Natural variant	549	1	M → I: dbSNP rs11581921.		VAR_033254
	Natural variant	644	1	Q → K: dbSNP rs3738497.		VAR_050442
Experimental info
	Sequence conflict	102	1	A → G in AAG31018. Ref.1
	Sequence conflict	102	1	A → G in AAG31019. Ref.1
	Sequence conflict	321	1	V → G in AAG31018. Ref.1
	Sequence conflict	321	1	V → G in AAG31019. Ref.1
	Sequence conflict	396	1	E → G in BAB55264. Ref.2
	Sequence conflict	469	1	S → Y in AAG31019. Ref.1
	Sequence conflict	605	1	P → L in BAB15256. Ref.2
	Sequence conflict	711	1	L → M in BAB55291. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (GROS1-L) [UniParc]. Last modified June 27, 2006. Version 2. Checksum: EA1909828FAE685E	FASTA	736	83,394
	10 20 30 40 50 60 MAVRALKLLT TLLAVVAAAS QAEVESEAGW GMVTPDLLFA EGTAAYARGD WPGVVLSMER 70 80 90 100 110 120 ALRSRAALRA LRLRCRTQCA ADFPWELDPD WSPSPAQASG AAALRDLSFF GGLLRRAACL 130 140 150 160 170 180 RRCLGPPAAH SLSEEMELEF RKRSPYNYLQ VAYFKINKLE KAVAAAHTFF VGNPEHMEMQ 190 200 210 220 230 240 QNLDYYQTMS GVKEADFKDL ETQPHMQEFR LGVRLYSEEQ PQEAVPHLEA ALQEYFVAYE 250 260 270 280 290 300 ECRALCEGPY DYDGYNYLEY NADLFQAITD HYIQVLNCKQ NCVTELASHP SREKPFEDFL 310 320 330 340 350 360 PSHYNYLQFA YYNIGNYTQA VECAKTYLLF FPNDEVMNQN LAYYAAMLGE EHTRSIGPRE 370 380 390 400 410 420 SAKEYRQRSL LEKELLFFAY DVFGIPFVDP DSWTPEEVIP KRLQEKQKSE RETAVRISQE 430 440 450 460 470 480 IGNLMKEIET LVEEKTKESL DVSRLTREGG PLLYEGISLT MNSKLLNGSQ RVVMDGVISD 490 500 510 520 530 540 HECQELQRLT NVAATSGDGY RGQTSPHTPN EKFYGVTVFK ALKLGQEGKV PLQSAHLYYN 550 560 570 580 590 600 VTEKVRRIME SYFRLDTPLY FSYSHLVCRT AIEEVQAERK DDSHPVHVDN CILNAETLVC 610 620 630 640 650 660 VKEPPAYTFR DYSAILYLNG DFDGGNFYFT ELDAKTVTAE VQPQCGRAVG FSSGTENPHG 670 680 690 700 710 720 VKAVTRGQRC AIALWFTLDP RHSERDRVQA DDLVKMLFSP EEMDLSQEQP LDAQQGPPEP 730 AQESLSGSES KPKDEL
	Isoform 2 (GROS1-S). Checksum: 5B1837D6923D9C4A	FASTA	363	41,215
	10 20 30 40 50 60 MAVRALKLLT TLLAVVAAAS QAEVESEAGW GMVTPDLLFA EGTAAYARGD WPGVVLSMER 70 80 90 100 110 120 ALRSRAALRA LRLRCRTQCA ADFPWELDPD WSPSPAQASG AAALRDLSFF GGLLRRAACL 130 140 150 160 170 180 RRCLGPPAAH SLSEEMELEF RKRSPYNYLQ VAYFKINKLE KAVAAAHTFF VGNPEHMEMQ 190 200 210 220 230 240 QNLDYYQTMS GVKEADFKDL ETQPHMQEFR LGVRLYSEEQ PQEAVPHLEA ALQEYFVAYE 250 260 270 280 290 300 ECRALCEGPY DYDGYNYLEY NADLFQAITD HYIQVLNCKQ NCVTELASHP SREKPFEDFL 310 320 330 340 350 360 PSHYNYLQFA YYNIGNYTQA VECAKTYLLF FPNDEVMNQN LAYYAAMLGE EHTRSIGPRE QGT
	Isoform 3. Checksum: DF635702F430A113	FASTA	804	90,616
	10 20 30 40 50 60 MAVRALKLLT TLLAVVAAAS QAEVESEAGW GMVTPDLLFA EGTAAYARGD WPGVVLSMER 70 80 90 100 110 120 ALRSRAALRA LRLRCRTQCA ADFPWELDPD WSPSPAQASG AAALRDLSFF GGLLRRAACL 130 140 150 160 170 180 RRCLGPPAAH SLSEEMELEF RKRSPYNYLQ VAYFKINKLE KAVAAAHTFF VGNPEHMEMQ 190 200 210 220 230 240 QNLDYYQTMS GVKEADFKDL ETQPHMQEFR LGVRLYSEEQ PQEAVPHLEA ALQEYFVAYE 250 260 270 280 290 300 ECRALCEGPY DYDGYNYLEY NADLFQAITD HYIQVLNCKQ NCVTELASHP SREKPFEDFL 310 320 330 340 350 360 PSHYNYLQFA YYNIGNYTQA VECAKTYLLF FPNDEVMNQN LAYYAAMLGE EHTRSIGPRE 370 380 390 400 410 420 SAKEYRQRSL LEKELLFFAY DVFGIPFVDP DSWTPEEVIP KRLQEKQKSE RETAVRISQE 430 440 450 460 470 480 IGNLMKEIET LVEEKTKESL DVSRLTREGG PLLYEGISLT MNSKLLNGSQ RVVMDGVISD 490 500 510 520 530 540 HECQELQRLT NVAATSGDGY RGQTSPHTPN EKFYGVTVFK ALKLGQEGKV PLQSAHLYYN 550 560 570 580 590 600 VTEKVRRIME SYFRLDTPLY FSYSHLVCRT AIEEVQAERK DDSHPVHVDN CILNAETLVC 610 620 630 640 650 660 VKEPPAYTFR DYSAILYLNG DFDGGNFYFT ELDAKTVTAE VQPQCGRAVG FSSGTENPHG 670 680 690 700 710 720 VKAVTRGQRC AIALWFTLDP RHSERVRAAR AGESSWCCGD PFPERPWFAF LFPKSHCQWL 730 740 750 760 770 780 RHERSTWDTS SNALSLWSHC LVLPGPAVNG IQVGKEVKTG SDAEFLVPSL GPTSAVLFQR 790 800 VGPAGKEMSL GPLRNLPCPL GSSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Gros1, a potential growth suppressor on chromosome 1: its identity to basement membrane-associated proteoglycan, leprecan." Kaul S.C., Sugihara T., Yoshida A., Nomura H., Wadhwa R. Oncogene 19:3576-3583(2000) [PubMed: 10951563] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION. Tissue: Testis.
[2]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Tissue: Epithelium and Teratocarcinoma.
[3]	"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries." Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T. DNA Res. 12:117-126(2005) [PubMed: 16303743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Teratocarcinoma.
[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: Duodenum and Testis.
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 347-736 (ISOFORM 1).
[6]	"Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta." Cabral W.A., Chang W., Barnes A.M., Weis M., Scott M.A., Leikin S., Makareeva E., Kuznetsova N.V., Rosenbaum K.N., Tifft C.J., Bulas D.I., Kozma C., Smith P.A., Eyre D.R., Marini J.C. Nat. Genet. 39:359-365(2007) [PubMed: 17277775] [Abstract] Cited for: INVOLVEMENT IN OI8.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-540, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF097431 mRNA. Translation: AAG31018.1. AF097432 mRNA. Translation: AAG31019.1. AK025841 mRNA. Translation: BAB15256.1. Different initiation. AK027648 mRNA. Translation: BAB55264.1. AK027680 mRNA. Translation: BAB55291.1. AK027697 mRNA. Translation: BAB55305.1. AK075418 mRNA. Translation: BAC11608.1. BC015309 mRNA. Translation: AAH15309.2. Different initiation. BC108311 mRNA. Translation: AAI08312.1. Sequence problems. BT007039 mRNA. Translation: AAP35688.1.
IPI	IPI00045839. IPI00163381. IPI00761114.
RefSeq	NP_001139761.1. NP_071751.3.
UniGene	Hs.714743
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q32P28.
Proteomic databases
PRIDE	Q32P28.
Genome annotation databases
Ensembl	ENST00000236040; ENSP00000236040; ENSG00000117385; Homo sapiens. [Genome view] ENST00000296388; ENSP00000296388; ENSG00000117385; Homo sapiens. [Genome view] ENST00000372526; ENSP00000361604; ENSG00000117385; Homo sapiens. [Genome view] ENST00000397054; ENSP00000380245; ENSG00000117385; Homo sapiens. [Genome view] ENST00000431412; ENSP00000408056; ENSG00000117385; Homo sapiens. [Genome view] ENST00000447502; ENSP00000394294; ENSG00000117385; Homo sapiens. [Genome view]
GeneID	64175.
KEGG	hsa:64175.
UCSC	uc001chv.2. human. uc001chw.2. human. uc001chx.2. human.
Organism-specific databases
CTD	64175.
GeneCards	GC01M042984.
HGNC	HGNC:19316. LEPRE1.
MIM	610339. gene. 610915. phenotype.
Orphanet	666. Osteogenesis imperfecta.
PharmGKB	PA134930599.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q32P28.
OMA	LELEFRK.
Enzyme and pathway databases
BRENDA	1.14.11.7. 247.
Gene expression databases
ArrayExpress	Q32P28.
Bgee	Q32P28.
Genevestigator	Q32P28.
GermOnline	ENSG00000117385. Homo sapiens.
Family and domain databases
InterPro	IPR000886. ER_target_seq_motif. IPR005123. Oxoglutarate/Fe-dep_oxygenase. IPR006620. Pro_4_hyd_alph. [Graphical view]
Pfam	PF03171. 2OG-FeII_Oxy. 1 hit. [Graphical view]
SMART	SM00702. P4Hc. 1 hit. [Graphical view]
PROSITE	PS00014. ER_TARGET. 1 hit. PS50005. TPR. False negative. PS50293. TPR_REGION. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00172. L-Proline. DB00139. Succinic acid. DB00126. Vitamin C.
NextBio	66095.
SOURCE	Search...

Entry information

Entry name

P3H1_HUMAN

Accession

Primary (citable) accession number: Q32P28
Secondary accession number(s): Q7KZR4 , Q96BR8, Q96SK8, Q96SL5, Q96SN3, Q9H6K3, Q9HC86, Q9HC87

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 27, 2006
Last sequence update:	June 27, 2006
Last modified:	November 3, 2009
This is version 48 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.