ASPH

Aspartate beta-hydroxylase

Human aspartate beta-hydroxylase isoform A. PDB 3rcq.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
3RCQ

Identifiers

Symbols

ASPH ; AAH; BAH; CASQ2BP1; FDLAB; HAAH; JCTN; junctin

External IDs

OMIM: 600582 MGI: 1914186 HomoloGene: 20910 GeneCards: ASPH Gene

EC number

1.14.11.16

Gene ontology
Molecular function	• peptide-aspartate beta-dioxygenase activity • structural molecule activity • calcium ion binding • protein binding • structural constituent of muscle • electron carrier activity • ion channel binding
Cellular component	• endoplasmic reticulum • endoplasmic reticulum membrane • plasma membrane • junctional sarcoplasmic reticulum membrane • integral component of membrane • integral component of endoplasmic reticulum membrane • cortical endoplasmic reticulum • sarcoplasmic reticulum membrane • sarcoplasmic reticulum lumen • calcium channel complex
Biological process	• detection of calcium ion • muscle contraction • pattern specification process • negative regulation of cell proliferation • positive regulation of calcium ion transport into cytosol • regulation of cell communication by electrical coupling • regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum • regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion • regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity • regulation of protein stability • activation of store-operated calcium channel activity • response to ATP • limb morphogenesis • peptidyl-aspartic acid hydroxylation • positive regulation of proteolysis • positive regulation of transcription, DNA-templated • oxidation-reduction process • palate development • regulation of ryanodine-sensitive calcium-release channel activity • positive regulation of ryanodine-sensitive calcium-release channel activity • face morphogenesis • calcium ion transmembrane transport • cellular response to calcium ion • positive regulation of intracellular protein transport • activation of cysteine-type endopeptidase activity • regulation of protein depolymerization
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

444

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 8:
61.5 – 61.71 Mb

Chr 4:
9.45 – 9.67 Mb

PubMed search

For camera lenses, see Aspheric lens#Camera lenses.

Aspartyl/asparaginyl beta-hydroxylase (HAAH) is an enzyme that in humans is encoded by the ASPH gene.^[1]^[2]^[3]

Function

This gene is thought to play an important role in calcium homeostasis. Alternative splicing of this gene results in five transcript variants which vary in protein translation, the coding of catalytic domains, and tissue expression. Variation among these transcripts impacts their functions which involve roles in the calcium storage and release process in the endoplasmic and sarcoplasmic reticulum as well as hydroxylation of aspartic acid and asparagine in epidermal growth factor-like domains of various proteins.^[3]

Clinical significance

As early as 1996, the over-expression of HAAH was recognized as an indicator of carcinoma in humans. Further research has correlated elevated HAAH levels (variously in affected tissue or blood serum) with hepatocellular (liver) carcinoma^[4]^[5] adenocarcinoma (pancreatic cancer),^[6] colorectal cancer,^[7] prostate cancer.^[5] and lung cancer.^[8] The pancreatic study^[6] showed elevated HAAH only in diseased tissue, but not in adjacent normal and inflamed tissue.

Mutations in ASPH cause Traboulsi syndrome .Patel, N; Khan, A. O.; Mansour, A; Mohamed, J. Y.; Al-Assiri, A; Haddad, R; Jia, X; Xiong, Y; Mégarbané, A; Traboulsi, E. I.; Alkuraya, F. S. (2014). "Mutations in ASPH Cause Facial Dysmorphism, Lens Dislocation, Anterior-Segment Abnormalities, and Spontaneous Filtering Blebs, or Traboulsi Syndrome". The American Journal of Human Genetics 94 (5): 755–9. doi:10.1016/j.ajhg.2014.04.002. PMID 24768550.

References

↑ Korioth F, Gieffers C, Frey J (Feb 1995). "Cloning and characterization of the human gene encoding aspartyl beta-hydroxylase". Gene 150 (2): 395–9. doi:10.1016/0378-1119(94)90460-X. PMID 7821814.
↑ Lim KY, Hong CS, Kim DH (Nov 2000). "cDNA cloning and characterization of human cardiac junctin". Gene 255 (1): 35–42. doi:10.1016/S0378-1119(00)00299-7. PMID 10974562.
1 2 "Entrez Gene: ASPH aspartate beta-hydroxylase".
↑ Ince N, de la Monte SM, Wands JR (March 2000). "Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformation". Cancer Res. 60 (5): 1261–6. PMID 10728685.
1 2 Xue T, Xue XP, Huang QS, Wei L, Sun K, Xue T (August 2009). "Monoclonal antibodies against human aspartyl (asparaginyl) beta-hydroxylase developed by DNA immunization". Hybridoma (Larchmt) 28 (4): 251–7. doi:10.1089/hyb.2009.0017. PMID 19663697.
1 2 Palumbo KS, Wands JR, Safran H, King T, Carlson RI, de la Monte SM (July 2002). "Human aspartyl (asparaginyl) beta-hydroxylase monoclonal antibodies: potential biomarkers for pancreatic carcinoma". Pancreas 25 (1): 39–44. doi:10.1097/00006676-200207000-00010. PMID 12131769.
↑ "CC Detect - Serum-Based Diagnostic Test For Colon Cancer Available".
↑ Hampton T (November 2007). "New screening techniques show potential for early detection of lung cancer". JAMA 298 (17): 1997. doi:10.1001/jama.298.17.1997. PMID 17986689.

Hirota K, Semenza GL (2005). "Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases". Biochem. Biophys. Res. Commun. 338 (1): 610–6. doi:10.1016/j.bbrc.2005.08.193. PMID 16154531.
Lavaissiere L, Jia S, Nishiyama M; et al. (1996). "Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma". J. Clin. Invest. 98 (6): 1313–23. doi:10.1172/JCI118918. PMC 507557. PMID 8823296.
Zhang L, Kelley J, Schmeisser G; et al. (1997). "Complex formation between junctin, triadin, calsequestrin, and the ryanodine receptor. Proteins of the cardiac junctional sarcoplasmic reticulum membrane". J. Biol. Chem. 272 (37): 23389–97. doi:10.1074/jbc.272.37.23389. PMID 9287354.
Wetzel GT, Ding S, Chen F (2000). "Molecular cloning of junctin from human and developing rabbit heart". Mol. Genet. Metab. 69 (3): 252–8. doi:10.1006/mgme.2000.2966. PMID 10767180.
Dinchuk JE, Henderson NL, Burn TC; et al. (2001). "Aspartyl beta -hydroxylase (Asph) and an evolutionarily conserved isoform of Asph missing the catalytic domain share exons with junctin". J. Biol. Chem. 275 (50): 39543–54. doi:10.1074/jbc.M006753200. PMID 10956665.
Treves S, Feriotto G, Moccagatta L; et al. (2001). "Molecular cloning, expression, functional characterization, chromosomal localization, and gene structure of junctate, a novel integral calcium binding protein of sarco(endo)plasmic reticulum membrane". J. Biol. Chem. 275 (50): 39555–68. doi:10.1074/jbc.M005473200. PMID 11007777.
Kirchhefer U, Neumann J, Baba HA; et al. (2001). "Cardiac hypertrophy and impaired relaxation in transgenic mice overexpressing triadin 1". J. Biol. Chem. 276 (6): 4142–9. doi:10.1074/jbc.M006443200. PMID 11069905.
Sepe PS, Lahousse SA, Gemelli B; et al. (2002). "Role of the aspartyl-asparaginyl-beta-hydroxylase gene in neuroblastoma cell motility". Lab. Invest. 82 (7): 881–91. doi:10.1097/01.lab.0000020406.91689.7f. PMID 12118090.
Ho SP, Scully MS, Krauthauser CM; et al. (2002). "Antisense oligonucleotides selectively regulate aspartyl beta-hydroxylase and its truncated protein isoform in vitro but distribute poorly into A549 tumors in vivo". J. Pharmacol. Exp. Ther. 302 (2): 795–803. doi:10.1124/jpet.302.2.795. PMID 12130746.
Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Maeda T, Sepe P, Lahousse S; et al. (2004). "Antisense oligodeoxynucleotides directed against aspartyl (asparaginyl) beta-hydroxylase suppress migration of cholangiocarcinoma cells". J. Hepatol. 38 (5): 615–22. doi:10.1016/S0168-8278(03)00052-7. PMID 12713872.
Treves S, Franzini-Armstrong C, Moccagatta L; et al. (2004). "Junctate is a key element in calcium entry induced by activation of InsP3 receptors and/or calcium store depletion". J. Cell Biol. 166 (4): 537–48. doi:10.1083/jcb.200404079. PMC 1868564. PMID 15302852.
Beausoleil SA, Jedrychowski M, Schwartz D; et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
Xian ZH, Zhang SH, Cong WM; et al. (2006). "Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma". Mod. Pathol. 19 (2): 280–6. doi:10.1038/modpathol.3800530. PMID 16341145.
de la Monte SM, Tamaki S, Cantarini MC; et al. (2006). "Aspartyl-(asparaginyl)-beta-hydroxylase regulates hepatocellular carcinoma invasiveness". J. Hepatol. 44 (5): 971–83. doi:10.1016/j.jhep.2006.01.038. PMID 16564107.
Feldmann G, Nattermann J, Nischalke HD; et al. (2006). "Detection of human aspartyl (asparaginyl) beta-hydroxylase and homeobox B7 mRNA in brush cytology specimens from patients with bile duct cancer". Endoscopy 38 (6): 604–9. doi:10.1055/s-2006-925065. PMID 16673309.
Gundogan F, Elwood G, Greco D; et al. (2007). "Role of aspartyl-(asparaginyl) beta-hydroxylase in placental implantation: Relevance to early pregnancy loss". Hum. Pathol. 38 (1): 50–9. doi:10.1016/j.humpath.2006.06.005. PMID 16949909.

Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14)

1.14.11: 2-oxoglutarate	Prolyl hydroxylase Lysyl hydroxylase

1.14.13: NADH or NADPH	Flavin-containing monooxygenase FMO1 FMO2 FMO3 FMO4 FMO5 Nitric oxide synthase NOS1 NOS2 NOS3 Cholesterol 7 alpha-hydroxylase Methane monooxygenase 3A4 Lanosterol 14 alpha-demethylase

1.14.14: reduced flavin or flavoprotein	19A1 2D6 2E1

1.14.15: reduced iron-sulfur protein	11B1 11B2 11A1

1.14.16: reduced pteridine (BH4 dependent)	Phenylalanine hydroxylase Tyrosine hydroxylase Tryptophan hydroxylase

1.14.17: reduced ascorbate	Dopamine beta-hydroxylase

1.14.18-19: other	Tyrosinase Stearoyl-CoA desaturase-1

1.14.99 - miscellaneous	Cyclooxygenase Heme oxygenase (HMOX1) Squalene monooxygenase 17A1 21A2

Proteins: enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

This article is issued from Wikipedia - version of the Thursday, December 31, 2015. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.

ASPH

Function

Clinical significance

References

Further reading