ASPH

ASPH
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	5APA
Identifikatori
Aliasi	ASPH
Vanjski ID-jevi	OMIM: 600582 MGI: 1914186 HomoloGene: 20910 GeneCards: ASPH
EC broj	1.14.11.16
Lokacija gena (čovjek)
Hrom.	Hromosom 8 (čovjek)
Kraj	61,714,640 bp
Lokacija gena (miš)
Hrom.	Hromosom 4 (miš)
Kraj	9,669,344 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• transmembrane transporter binding; • dioxygenase activity; • structural molecule activity; • vezivanje iona metala; • GO:0001948, GO:0016582 vezivanje za proteine; • electron transfer activity; • oxidoreductase activity; • structural constituent of muscle; • calcium ion binding; • peptidyl-aspartic acid 3-dioxygenase activity;
Ćelijska komponenta	• integral component of membrane; • Kalcijski kanal; • membrana; • ćelijska membrana; • cortical endoplasmic reticulum; • junctional sarcoplasmic reticulum membrane; • Sarkoplazmatski retikulum; • integral component of endoplasmic reticulum membrane; • sarcoplasmic reticulum membrane; • sarcoplasmic reticulum lumen; • endoplasmic reticulum membrane; • Endoplazmatski retikulum; • citoplazma;
Biološki proces	• cellular response to calcium ion; • positive regulation of intracellular protein transport; • regulation of ryanodine-sensitive calcium-release channel activity; • regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity; • response to ATP; • regulation of cardiac conduction; • Mišićna kontrakcija; • positive regulation of calcium ion transport into cytosol; • regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; • peptidyl-amino acid modification; • detection of calcium ion; • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • positive regulation of ryanodine-sensitive calcium-release channel activity; • ion transmembrane transport; • activation of cysteine-type endopeptidase activity; • calcium ion transmembrane transport; • positive regulation of proteolysis; • regulation of cell communication by electrical coupling; • regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; • activation of store-operated calcium channel activity; • pattern specification process; • negative regulation of cell population proliferation; • regulation of protein stability; • limb morphogenesis; • peptidyl-aspartic acid hydroxylation; • roof of mouth development; • face morphogenesis; • regulation of protein depolymerization; • Lanac transporta elektrona;
	Izvori:Amigo / QuickGO
Ortolozi
	444
	65973
	ENSG00000198363
	ENSMUSG00000028207
	Q12797
	Q8BSY0
NM_001164750; NM_001164751; NM_001164752; NM_001164753; NM_001164754;
	NM_001164755; NM_001164756; NM_004318; NM_020164; NM_032466; NM_032467; NM_032468
NM_001177849; NM_001177850; NM_001177851; NM_001177852; NM_001177853;
	NM_001177854; NM_001177855; NM_001177856; NM_001290367; NM_023066; NM_133723
NP_001158222; NP_001158223; NP_001158224; NP_001158225; NP_001158226;
	NP_001158227; NP_001158228; NP_004309; NP_064549; NP_115855; NP_115856; NP_115857
NP_001171320; NP_001171321; NP_001171322; NP_001171323; NP_001171324;
	NP_001171325; NP_001171326; NP_001171327; NP_001277296; NP_075553; NP_598484
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Aspartil/asparaginil beta-hidroksilaza (HAAH) je enzim koji je kod ljudi kodiran genom ASPH.^[5]^[6]^[7] ASPH alfa-ketoglutarat-ovisna hidroksilaza, član superporodice nehem proteina koji sadrže gvožđe.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 758 aminokiselina, а molekulska težina 85.863 Da.^[8]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MAQRKNAKSS	GNSSSSGSGS	GSTSAGSSSP	GARRETKHGG	HKNGRKGGLS
GTSFFTWFMV	IALLGVWTSV	AVVWFDLVDY	EEVLGKLGIY	DADGDGDFDV
DDAKVLLGLK	ERSTSEPAVP	PEEAEPHTEP	EEQVPVEAEP	QNIEDEAKEQ
IQSLLHEMVH	AEHVEGEDLQ	QEDGPTGEPQ	QEDDEFLMAT	DVDDRFETLE
PEVSHEETEH	SYHVEETVSQ	DCNQDMEEMM	SEQENPDSSE	PVVEDERLHH
DTDDVTYQVY	EEQAVYEPLE	NEGIEITEVT	APPEDNPVED	SQVIVEEVSI
FPVEEQQEVP	PETNRKTDDP	EQKAKVKKKK	PKLLNKFDKT	IKAELDAAEK
LRKRGKIEEA	VNAFKELVRK	YPQSPRARYG	KAQCEDDLAE	KRRSNEVLRG
AIETYQEVAS	LPDVPADLLK	LSLKRRSDRQ	QFLGHMRGSL	LTLQRLVQLF
PNDTSLKNDL	GVGYLLIGDN	DNAKKVYEEV	LSVTPNDGFA	KVHYGFILKA
QNKIAESIPY	LKEGIESGDP	GTDDGRFYFH	LGDAMQRVGN	KEAYKWYELG
HKRGHFASVW	QRSLYNVNGL	KAQPWWTPKE	TGYTELVKSL	ERNWKLIRDE
GLAVMDKAKG	LFLPEDENLR	EKGDWSQFTL	WQQGRRNENA	CKGAPKTCTL
LEKFPETTGC	RRGQIKYSIM	HPGTHVWPHT	GPTNCRLRMH	LGLVIPKEGC
KIRCANETKT	WEEGKVLIFD	DSFEHEVWQD	ASSFRLIFIV	DVWHPELTPQ
QRRSLPAI

Funkcija

Smatra se da ovaj gen igra važnu ulogu u homeostazi kalcija. Alternativna prerada ovog gena rezultira u pet varijanti transkripta koje se razlikuju u translaciji proteina, kodiranju katalitskih domena i tkivnoj ekspresiji. Varijacije među ovim transkriptima utiču na njihove funkcije, koje uključuju uloge u procesu skladištenja i oslobađanja kalcija u endoplazmatskom i sarkoplazmatskom retikulumu, kao i hidroksilaciji asparaginske kiseline i asparagina u domenama različitih proteina sličnih epidermnim faktorima rasta.^[7]

Klinički značaj

Još 1996. prekomjerna ekspresija HAAH prepoznata je kao pokazatelj karcinoma kod ljudi. Dalja istraživanja su povezala povišene nivoe HAAH (različito u zahvaćenom tkivu ili serumu) sa hepatoćelijskim (jetrenim) karcinomom^[9]^[10] adenokarcinomom (rak gušterače),^[11] kolorektumskim kancerom,^[12] rakom prostate.^[10] i kancerom pluća.^[13] Studija gušterače ^[11] pokazala je povišeni HAAH samo u oboljelom tkivu, ali ne i u susjednom normalnom i upaljenom tkivu.

Mutacije u ASPH-u uzrokuju Traboulsijev sindrom.^[14]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000198363 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000028207 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Korioth F, Gieffers C, Frey J (decembar 1994). "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 (septembar 2000). "cDNA cloning and characterization of human cardiac junctin". Gene. 255 (1): 35–42. doi:10.1016/S0378-1119(00)00299-7. PMID 10974562.
^ ^a ^b "Entrez Gene: ASPH aspartate beta-hydroxylase".
^ "UniProt, Q12797". Pristupljeno 13. 9. 2021.
^ Ince N, de la Monte SM, Wands JR (mart 2000). "Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformation". Cancer Research. 60 (5): 1261–6. PMID 10728685.
^ ^a ^b 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. 28 (4): 251–7. doi:10.1089/hyb.2009.0017. PMID 19663697.
^ ^a ^b Palumbo KS, Wands JR, Safran H, King T, Carlson RI, de la Monte SM (juli 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. S2CID 2098747.
^ "CC Detect - Serum-Based Diagnostic Test For Colon Cancer Available". Arhivirano s originala, 8. 2. 2021. Pristupljeno 13. 9. 2021.
^ Hampton T (novembar 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.
^ Patel N, Khan AO, Mansour A, Mohamed JY, Al-Assiri A, Haddad R, et al. (maj 2014). "Mutations in ASPH cause facial dysmorphism, lens dislocation, anterior-segment abnormalities, and spontaneous filtering blebs, or Traboulsi syndrome". American Journal of Human Genetics. 94 (5): 755–9. doi:10.1016/j.ajhg.2014.04.002. PMC 4067561. PMID 24768550.

Dopunska literatura

Hirota K, Semenza GL (decembar 2005). "Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases". Biochemical and Biophysical Research Communications. 338 (1): 610–6. doi:10.1016/j.bbrc.2005.08.193. PMID 16154531.
Lavaissiere L, Jia S, Nishiyama M, de la Monte S, Stern AM, Wands JR, Friedman PA (septembar 1996). "Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma". The Journal of Clinical Investigation. 98 (6): 1313–23. doi:10.1172/JCI118918. PMC 507557. PMID 8823296.
Zhang L, Kelley J, Schmeisser G, Kobayashi YM, Jones LR (septembar 1997). "Complex formation between junctin, triadin, calsequestrin, and the ryanodine receptor. Proteins of the cardiac junctional sarcoplasmic reticulum membrane". The Journal of Biological Chemistry. 272 (37): 23389–97. doi:10.1074/jbc.272.37.23389. PMID 9287354.
Wetzel GT, Ding S, Chen F (mart 2000). "Molecular cloning of junctin from human and developing rabbit heart". Molecular Genetics and Metabolism. 69 (3): 252–8. doi:10.1006/mgme.2000.2966. PMID 10767180.
Dinchuk JE, Henderson NL, Burn TC, Huber R, Ho SP, Link J, et al. (decembar 2000). "Aspartyl beta -hydroxylase (Asph) and an evolutionarily conserved isoform of Asph missing the catalytic domain share exons with junctin". The Journal of Biological Chemistry. 275 (50): 39543–54. doi:10.1074/jbc.M006753200. PMID 10956665.
Treves S, Feriotto G, Moccagatta L, Gambari R, Zorzato F (decembar 2000). "Molecular cloning, expression, functional characterization, chromosomal localization, and gene structure of junctate, a novel integral calcium binding protein of sarco(endo)plasmic reticulum membrane". The Journal of Biological Chemistry. 275 (50): 39555–68. doi:10.1074/jbc.M005473200. PMID 11007777.
Kirchhefer U, Neumann J, Baba HA, Begrow F, Kobayashi YM, Reinke U, et al. (februar 2001). "Cardiac hypertrophy and impaired relaxation in transgenic mice overexpressing triadin 1". The Journal of Biological Chemistry. 276 (6): 4142–9. doi:10.1074/jbc.M006443200. PMID 11069905.
Sepe PS, Lahousse SA, Gemelli B, Chang H, Maeda T, Wands JR, de la Monte SM (juli 2002). "Role of the aspartyl-asparaginyl-beta-hydroxylase gene in neuroblastoma cell motility". Laboratory Investigation; A Journal of Technical Methods and Pathology. 82 (7): 881–91. doi:10.1097/01.lab.0000020406.91689.7f. PMID 12118090.
Ho SP, Scully MS, Krauthauser CM, Wexler EJ, Stow MD, Dinchuk JE, et al. (august 2002). "Antisense oligonucleotides selectively regulate aspartyl beta-hydroxylase and its truncated protein isoform in vitro but distribute poorly into A549 tumors in vivo". The Journal of Pharmacology and Experimental Therapeutics. 302 (2): 795–803. doi:10.1124/jpet.302.2.795. PMID 12130746.
Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (decembar 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Maeda T, Sepe P, Lahousse S, Tamaki S, Enjoji M, Wands JR, de la Monte SM (maj 2003). "Antisense oligodeoxynucleotides directed against aspartyl (asparaginyl) beta-hydroxylase suppress migration of cholangiocarcinoma cells". Journal of Hepatology. 38 (5): 615–22. doi:10.1016/S0168-8278(03)00052-7. PMID 12713872.
Treves S, Franzini-Armstrong C, Moccagatta L, Arnoult C, Grasso C, Schrum A, et al. (august 2004). "Junctate is a key element in calcium entry induced by activation of InsP3 receptors and/or calcium store depletion". The Journal of Cell Biology. 166 (4): 537–48. doi:10.1083/jcb.200404079. PMC 1868564. PMID 15302852.
Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, et al. (august 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
Xian ZH, Zhang SH, Cong WM, Yan HX, Wang K, Wu MC (februar 2006). "Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma". Modern Pathology. 19 (2): 280–6. doi:10.1038/modpathol.3800530. PMID 16341145.
de la Monte SM, Tamaki S, Cantarini MC, Ince N, Wiedmann M, Carter JJ, et al. (maj 2006). "Aspartyl-(asparaginyl)-beta-hydroxylase regulates hepatocellular carcinoma invasiveness". Journal of Hepatology. 44 (5): 971–83. doi:10.1016/j.jhep.2006.01.038. PMID 16564107.
Feldmann G, Nattermann J, Nischalke HD, Gorschlüter M, Kuntzen T, Ahlenstiel G, et al. (juni 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, Rubin LP, Pinar H, Carlson RI, et al. (januar 2007). "Role of aspartyl-(asparaginyl) beta-hydroxylase in placental implantation: Relevance to early pregnancy loss". Human Pathology. 38 (1): 50–9. doi:10.1016/j.humpath.2006.06.005. PMID 16949909.

Vanjski linkovi

Lokacija ljudskog genoma ASPH i stranica sa detaljima o genu ASPH u UCSC Genome Browseru.
Q12797

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000198363 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000028207 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid7821814-5] Korioth F, Gieffers C, Frey J (decembar 1994). "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.

[pmid10974562-6] Lim KY, Hong CS, Kim DH (septembar 2000). "cDNA cloning and characterization of human cardiac junctin". Gene. 255 (1): 35–42. doi:10.1016/S0378-1119(00)00299-7. PMID 10974562.

[entrez-7] "Entrez Gene: ASPH aspartate beta-hydroxylase".

[UniProt-8] "UniProt, Q12797". Pristupljeno 13. 9. 2021.

[Ince_2000-9] Ince N, de la Monte SM, Wands JR (mart 2000). "Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformation". Cancer Research. 60 (5): 1261–6. PMID 10728685.

[Xue_2009-10] 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. 28 (4): 251–7. doi:10.1089/hyb.2009.0017. PMID 19663697.

[Palumbo_2002-11] Palumbo KS, Wands JR, Safran H, King T, Carlson RI, de la Monte SM (juli 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. S2CID 2098747.

[urlCC_Detect_-_Serum-Based_Diagnostic_Test_For_Colon_Cancer_Available-12] "CC Detect - Serum-Based Diagnostic Test For Colon Cancer Available". Arhivirano s originala, 8. 2. 2021. Pristupljeno 13. 9. 2021.

[pmid17986689-13] Hampton T (novembar 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.

[14] Patel N, Khan AO, Mansour A, Mohamed JY, Al-Assiri A, Haddad R, et al. (maj 2014). "Mutations in ASPH cause facial dysmorphism, lens dislocation, anterior-segment abnormalities, and spontaneous filtering blebs, or Traboulsi syndrome". American Journal of Human Genetics. 94 (5): 755–9. doi:10.1016/j.ajhg.2014.04.002. PMC 4067561. PMID 24768550.

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