View source for ASPH

{{Short description|Protein and coding gene in humans}}
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{{For|camera lenses|Aspheric lens#Camera lenses}}
{{Infobox_gene}}
'''Aspartyl/asparaginyl beta-hydroxylase''' (''HAAH'') is an [[enzyme]] that in humans is encoded by the ''ASPH'' [[gene]].<ref name="pmid7821814">{{cite journal | vauthors = Korioth F, Gieffers C, Frey J | title = Cloning and characterization of the human gene encoding aspartyl beta-hydroxylase | journal = Gene | volume = 150 | issue = 2 | pages = 395–9 | date = December 1994 | pmid = 7821814 | doi = 10.1016/0378-1119(94)90460-X }}</ref><ref name="pmid10974562">{{cite journal | vauthors = Lim KY, Hong CS, Kim DH | title = cDNA cloning and characterization of human cardiac junctin | journal = Gene | volume = 255 | issue = 1 | pages = 35–42 | date = September 2000 | pmid = 10974562 | doi = 10.1016/S0378-1119(00)00299-7 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ASPH aspartate beta-hydroxylase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=444}}</ref> ASPH is an [[alpha-ketoglutarate-dependent hydroxylase]], a superfamily non-haem iron-containing proteins.

== 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.<ref name="entrez" />

== 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]]<ref name="Ince_2000">{{cite journal | vauthors = Ince N, de la Monte SM, Wands JR | title = Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformation | journal = Cancer Research | volume = 60 | issue = 5 | pages = 1261–6 | date = March 2000 | pmid = 10728685 }}</ref><ref name="Xue_2009">{{cite journal | vauthors = Xue T, Xue XP, Huang QS, Wei L, Sun K, Xue T | title = Monoclonal antibodies against human aspartyl (asparaginyl) beta-hydroxylase developed by DNA immunization | journal = Hybridoma | volume = 28 | issue = 4 | pages = 251–7 | date = August 2009 | pmid = 19663697 | doi = 10.1089/hyb.2009.0017 }}</ref> [[adenocarcinoma]] ([[pancreatic cancer]]),<ref name="Palumbo_2002">{{cite journal | vauthors = Palumbo KS, Wands JR, Safran H, King T, Carlson RI, de la Monte SM | title = Human aspartyl (asparaginyl) beta-hydroxylase monoclonal antibodies: potential biomarkers for pancreatic carcinoma | journal = Pancreas | volume = 25 | issue = 1 | pages = 39–44 | date = July 2002 | pmid = 12131769 | doi = 10.1097/00006676-200207000-00010 | s2cid = 2098747 }}</ref> [[colorectal cancer]],<ref name="urlCC Detect - Serum-Based Diagnostic Test For Colon Cancer Available">{{cite web | url = http://www.emaxhealth.com/100/18177.html | title = CC Detect - Serum-Based Diagnostic Test For Colon Cancer Available | access-date = 2011-11-29 | archive-date = 2021-02-08 | archive-url = https://web.archive.org/web/20210208135602/https://www.emaxhealth.com/100/18177.html | url-status = dead }}</ref> [[prostate cancer]].<ref name="Xue_2009" /> and [[lung cancer]].<ref name="pmid17986689">{{cite journal | vauthors = Hampton T | title = New screening techniques show potential for early detection of lung cancer | journal = JAMA | volume = 298 | issue = 17 | pages = 1997 | date = November 2007 | pmid = 17986689 | doi = 10.1001/jama.298.17.1997 }}</ref> The pancreatic study<ref name="Palumbo_2002" /> showed elevated ''HAAH'' only in diseased tissue, but not in adjacent normal and inflamed tissue.

Mutations in ''ASPH'' cause ''[[Traboulsi syndrome]]''.<ref>{{cite journal | vauthors = Patel N, Khan AO, Mansour A, Mohamed JY, Al-Assiri A, Haddad R, Jia X, Xiong Y, Mégarbané A, Traboulsi EI, Alkuraya FS | display-authors = 6 | title = Mutations in ASPH cause facial dysmorphism, lens dislocation, anterior-segment abnormalities, and spontaneous filtering blebs, or Traboulsi syndrome | journal = American Journal of Human Genetics | volume = 94 | issue = 5 | pages = 755–9 | date = May 2014 | pmid = 24768550 | pmc = 4067561 | doi = 10.1016/j.ajhg.2014.04.002 }}</ref>

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Hirota K, Semenza GL | title = Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases | journal = Biochemical and Biophysical Research Communications | volume = 338 | issue = 1 | pages = 610–6 | date = December 2005 | pmid = 16154531 | doi = 10.1016/j.bbrc.2005.08.193 | doi-access = free }}
* {{cite journal | vauthors = Lavaissiere L, Jia S, Nishiyama M, de la Monte S, Stern AM, Wands JR, Friedman PA | title = Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma | journal = The Journal of Clinical Investigation | volume = 98 | issue = 6 | pages = 1313–23 | date = September 1996 | pmid = 8823296 | pmc = 507557 | doi = 10.1172/JCI118918 }}
* {{cite journal | vauthors = Zhang L, Kelley J, Schmeisser G, Kobayashi YM, Jones LR | title = Complex formation between junctin, triadin, calsequestrin, and the ryanodine receptor. Proteins of the cardiac junctional sarcoplasmic reticulum membrane | journal = The Journal of Biological Chemistry | volume = 272 | issue = 37 | pages = 23389–97 | date = September 1997 | pmid = 9287354 | doi = 10.1074/jbc.272.37.23389 | doi-access = free }}
* {{cite journal | vauthors = Wetzel GT, Ding S, Chen F | title = Molecular cloning of junctin from human and developing rabbit heart | journal = Molecular Genetics and Metabolism | volume = 69 | issue = 3 | pages = 252–8 | date = March 2000 | pmid = 10767180 | doi = 10.1006/mgme.2000.2966 }}
* {{cite journal | vauthors = Dinchuk JE, Henderson NL, Burn TC, Huber R, Ho SP, Link J, O'Neil KT, Focht RJ, Scully MS, Hollis JM, Hollis GF, Friedman PA | display-authors = 6 | title = Aspartyl beta -hydroxylase (Asph) and an evolutionarily conserved isoform of Asph missing the catalytic domain share exons with junctin | journal = The Journal of Biological Chemistry | volume = 275 | issue = 50 | pages = 39543–54 | date = December 2000 | pmid = 10956665 | doi = 10.1074/jbc.M006753200 | doi-access = free }}
* {{cite journal | vauthors = Treves S, Feriotto G, Moccagatta L, Gambari R, Zorzato F | title = Molecular cloning, expression, functional characterization, chromosomal localization, and gene structure of junctate, a novel integral calcium binding protein of sarco(endo)plasmic reticulum membrane | journal = The Journal of Biological Chemistry | volume = 275 | issue = 50 | pages = 39555–68 | date = December 2000 | pmid = 11007777 | doi = 10.1074/jbc.M005473200 | doi-access = free }}
* {{cite journal | vauthors = Kirchhefer U, Neumann J, Baba HA, Begrow F, Kobayashi YM, Reinke U, Schmitz W, Jones LR | display-authors = 6 | title = Cardiac hypertrophy and impaired relaxation in transgenic mice overexpressing triadin 1 | journal = The Journal of Biological Chemistry | volume = 276 | issue = 6 | pages = 4142–9 | date = February 2001 | pmid = 11069905 | doi = 10.1074/jbc.M006443200 | doi-access = free }}
* {{cite journal | vauthors = Sepe PS, Lahousse SA, Gemelli B, Chang H, Maeda T, Wands JR, de la Monte SM | title = Role of the aspartyl-asparaginyl-beta-hydroxylase gene in neuroblastoma cell motility | journal = Laboratory Investigation; A Journal of Technical Methods and Pathology | volume = 82 | issue = 7 | pages = 881–91 | date = July 2002 | pmid = 12118090 | doi = 10.1097/01.lab.0000020406.91689.7f | doi-access = free }}
* {{cite journal | vauthors = Ho SP, Scully MS, Krauthauser CM, Wexler EJ, Stow MD, Dinchuk JE, Kerr JS, Friedman PA | display-authors = 6 | title = Antisense oligonucleotides selectively regulate aspartyl beta-hydroxylase and its truncated protein isoform in vitro but distribute poorly into A549 tumors in vivo | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 302 | issue = 2 | pages = 795–803 | date = August 2002 | pmid = 12130746 | doi = 10.1124/jpet.302.2.795 | s2cid = 7167890 }}
* {{cite journal | vauthors = Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA | display-authors = 6 | title = Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 26 | pages = 16899–903 | date = December 2002 | pmid = 12477932 | pmc = 139241 | doi = 10.1073/pnas.242603899 | bibcode = 2002PNAS...9916899M | doi-access = free }}
* {{cite journal | vauthors = Maeda T, Sepe P, Lahousse S, Tamaki S, Enjoji M, Wands JR, de la Monte SM | title = Antisense oligodeoxynucleotides directed against aspartyl (asparaginyl) beta-hydroxylase suppress migration of cholangiocarcinoma cells | journal = Journal of Hepatology | volume = 38 | issue = 5 | pages = 615–22 | date = May 2003 | pmid = 12713872 | doi = 10.1016/S0168-8278(03)00052-7 }}
* {{cite journal | vauthors = Treves S, Franzini-Armstrong C, Moccagatta L, Arnoult C, Grasso C, Schrum A, Ducreux S, Zhu MX, Mikoshiba K, Girard T, Smida-Rezgui S, Ronjat M, Zorzato F | display-authors = 6 | title = Junctate is a key element in calcium entry induced by activation of InsP3 receptors and/or calcium store depletion | journal = The Journal of Cell Biology | volume = 166 | issue = 4 | pages = 537–48 | date = August 2004 | pmid = 15302852 | pmc = 1868564 | doi = 10.1083/jcb.200404079 }}
* {{cite journal | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | display-authors = 6 | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–5 | date = August 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 | bibcode = 2004PNAS..10112130B | doi-access = free }}
* {{cite journal | vauthors = Xian ZH, Zhang SH, Cong WM, Yan HX, Wang K, Wu MC | title = Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma | journal = Modern Pathology | volume = 19 | issue = 2 | pages = 280–6 | date = February 2006 | pmid = 16341145 | doi = 10.1038/modpathol.3800530 | doi-access = free }}
* {{cite journal | vauthors = de la Monte SM, Tamaki S, Cantarini MC, Ince N, Wiedmann M, Carter JJ, Lahousse SA, Califano S, Maeda T, Ueno T, D'Errico A, Trevisani F, Wands JR | display-authors = 6 | title = Aspartyl-(asparaginyl)-beta-hydroxylase regulates hepatocellular carcinoma invasiveness | journal = Journal of Hepatology | volume = 44 | issue = 5 | pages = 971–83 | date = May 2006 | pmid = 16564107 | doi = 10.1016/j.jhep.2006.01.038 }}
* {{cite journal | vauthors = Feldmann G, Nattermann J, Nischalke HD, Gorschlüter M, Kuntzen T, Ahlenstiel G, Gerhardt T, Wolff M, Sauerbruch T, Spengler U, Dumoulin FL | display-authors = 6 | title = Detection of human aspartyl (asparaginyl) beta-hydroxylase and homeobox B7 mRNA in brush cytology specimens from patients with bile duct cancer | journal = Endoscopy | volume = 38 | issue = 6 | pages = 604–9 | date = June 2006 | pmid = 16673309 | doi = 10.1055/s-2006-925065 | s2cid = 33900440 }}
* {{cite journal | vauthors = Gundogan F, Elwood G, Greco D, Rubin LP, Pinar H, Carlson RI, Wands JR, de la Monte SM | display-authors = 6 | title = Role of aspartyl-(asparaginyl) beta-hydroxylase in placental implantation: Relevance to early pregnancy loss | journal = Human Pathology | volume = 38 | issue = 1 | pages = 50–9 | date = January 2007 | pmid = 16949909 | doi = 10.1016/j.humpath.2006.06.005 }}
{{refend}}

== External links ==
* {{UCSC gene info|ASPH}}
* {{PDBe-KB2|Q12797|Aspartyl/asparaginyl beta-hydroxylase}}

{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Biology|border=no}}

[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]