Reviewed,
UniProtKB/Swiss-Prot Q32P28 (P3H1_HUMAN)
Last modified
November 3, 2009.
Version 48.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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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 |
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| 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
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
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References
| « Hide '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. 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. 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. |
Cross-references
Sequence databases | |
|---|---|
| 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 Q9HC87 | ||||||||
| Entry history |
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| 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. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


