HK2

HK2
ساختارهای موجود
PDB	جستجوی هم‌ساخت‌شناسی: PDBe RCSB
فهرست شناسه‌های PDB
	2NZT, 5HFU, 5HG1, 5HEX
معین‌کننده‌ها
نام‌های دیگر	HK2, HKII, HXK2, hexokinase 2
شناسه‌های بیرونی	OMIM: 601125 MGI: 1315197 HomoloGene: 37273 GeneCards: HK2
موقعیت ژن (موش)
کروموزوم	کروموزوم ۶ (موش)
پایان	82,751,435 bp
هستی‌شناسی ژن
عملکرد ملکولی	• transferase activity; • nucleotide binding; • mannokinase activity; • hexokinase activity; • phosphotransferase activity, alcohol group as acceptor; • kinase activity; • glucose binding; • catalytic activity; • GO:0001948، GO:0016582 پیوند پروتئینی; • fructokinase activity; • ATP binding; • glucokinase activity;
ترکیبات سلولی	• سیتوزول; • membrane; • mitochondrial outer membrane; • میتوکندری; • پوسته یاخته; • شبکه سارکوپلاسمی;
فرایند زیستی	• فسفرگیری; • regulation of glucose import; • canonical glycolysis; • cellular glucose homeostasis; • negative regulation of mitochondrial membrane permeability; • carbohydrate phosphorylation; • پاسخ به ایسکمی; • maintenance of protein location in mitochondrion; • establishment of protein localization to mitochondrion; • apoptotic mitochondrial changes; • negative regulation of reactive oxygen species metabolic process; • hexose metabolic process; • دگرگشت; • lactation; • قندکافت; • positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization; • glucose metabolic process; • glucose 6-phosphate metabolic process; • cellular response to leukemia inhibitory factor; • سوخت‌وساز کربوهیدرات; • response to hypoxia; • positive regulation of angiogenesis;
	منابع: آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
	3099
	15277
	ENSG00000159399
	ENSMUSG00000000628
	P52789
	O08528
	NM_000189، XM_005264280، XM_017003945، NM_001371525، XM_047444084، XM_047444085 XM_011532807، NM_000189، XM_005264280، XM_017003945، NM_001371525، XM_047444084، XM_047444085
	XM_017321401، XM_036165880 NM_013820، XM_017321401، XM_036165880
	XP_005264337، XP_011531109، XP_016859434، NP_001358454 NP_000180، XP_005264337، XP_011531109، XP_016859434، NP_001358454
	XP_017176890، XP_036021773 NP_038848، XP_017176890، XP_036021773
	ویکی‌داده
مشاهده/ویرایش انسان	مشاهده/ویرایش موش

هگزوکیناز ۲ (انگلیسی: Hexokinase 2) یک آنزیم است که در انسان توسط ژن «HK2» بر روی کروموزوم ۲ کدگذاری می‌شود.^[۴]^[۵]هگزوکیناز، گلوکز را فسفریله می‌کند تا مادهٔ گلوکز ۶-فسفات پدید آید که نخستین گام در بیشتر راه‌های متابولیسم گلوکز محسوب می‌شود.

این آنزیم بیشتر در ماهیچه اسکلتی بدن و در غشاء خارجی میتوکندریها قرار دارد و بیان آن به ترشح انسولین پاسخ می‌دهد. پژوهش‌های انجام شده بر روی موش‌های صحرایی نشان می‌دهد که افزایش این آنزیم با تشدید نرخ گلیکولیز که در سلول‌های سرطانی در حال رشد مشاهده می‌شود، مرتبط است.^[۵]

اهمیت بالینی ویرایش

ژن HK2 در تعدادی از سرطان‌ها به شدت بیان می‌شود که از آن جمله می‌توان به سرطان پستان و سرطان روده بزرگ اشاره کرد.^[۶]^[۷]^[۸] نقص در این ژن همچنین در مبتلایان به دیابت نوع ۲ یافت شده‌است.^[۷]^[۸]

جستارهای وابسته ویرایش

HK1

منابع ویرایش

↑ ^۱٫۰ ^۱٫۱ ^۱٫۲ GRCm38: Ensembl release 89: ENSMUSG00000000628 - Ensembl, May 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.
↑ Lehto M, Xiang K, Stoffel M, Espinosa R, Groop LC, Le Beau MM, Bell GI (Dec 1993). "Human hexokinase II: localization of the polymorphic gene to chromosome 2". Diabetologia. 36 (12): 1299–302. doi:10.1007/BF00400809. PMID 8307259.
↑ ^۵٫۰ ^۵٫۱ "Entrez Gene: HK2 hexokinase 2".
↑ Schindler A, Foley E (Dec 2013). "Hexokinase 1 blocks apoptotic signals at the mitochondria". Cellular Signalling. 25 (12): 2685–92. doi:10.1016/j.cellsig.2013.08.035. PMID 24018046.
↑ ^۷٫۰ ^۷٫۱ Palmieri D, Fitzgerald D, Shreeve SM, Hua E, Bronder JL, Weil RJ, Davis S, Stark AM, Merino MJ, Kurek R, Mehdorn HM, Davis G, Steinberg SM, Meltzer PS, Aldape K, Steeg PS (Sep 2009). "Analyses of resected human brain metastases of breast cancer reveal the association between up-regulation of hexokinase 2 and poor prognosis". Molecular Cancer Research. 7 (9): 1438–45. doi:10.1158/1541-7786.MCR-09-0234. PMC 2746883. PMID 19723875.
↑ ^۸٫۰ ^۸٫۱ Peng Q, Zhou J, Zhou Q, Pan F, Zhong D, Liang H (2009). "Silencing hexokinase II gene sensitizes human colon cancer cells to 5-fluorouracil". Hepato-Gastroenterology. 56 (90): 355–60. PMID 19579598.

مشارکت‌کنندگان ویکی‌پدیا. «HK2». در دانشنامهٔ ویکی‌پدیای انگلیسی، بازبینی‌شده در ۲۰ اکتبر ۲۰۱۸.

بیشتر بخوانید ویرایش

Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
Mamede M, Higashi T, Kitaichi M, Ishizu K, Ishimori T, Nakamoto Y, Yanagihara K, Li M, Tanaka F, Wada H, Manabe T, Saga T (Apr 2005). "[18F]FDG uptake and PCNA, Glut-1, and Hexokinase-II expressions in cancers and inflammatory lesions of the lung". Neoplasia. 7 (4): 369–79. doi:10.1593/neo.04577. PMC 1501150. PMID 15967114.
Machida K, Ohta Y, Osada H (May 2006). "Suppression of apoptosis by cyclophilin D via stabilization of hexokinase II mitochondrial binding in cancer cells". The Journal of Biological Chemistry. 281 (20): 14314–20. doi:10.1074/jbc.M513297200. PMID 16551620.
Ahn KJ, Kim J, Yun M, Park JH, Lee JD (Jun 2009). "Enzymatic properties of the N- and C-terminal halves of human hexokinase II". BMB Reports. 42 (6): 350–5. doi:10.5483/BMBRep.2009.42.6.350. PMID 19558793.
Printz RL, Osawa H, Ardehali H, Koch S, Granner DK (Feb 1997). "Hexokinase II gene: structure, regulation and promoter organization". Biochemical Society Transactions. 25 (1): 107–12. doi:10.1042/bst0250107. PMID 9056853.
Peng Q, Zhou J, Zhou Q, Pan F, Zhong D, Liang H (2009). "Silencing hexokinase II gene sensitizes human colon cancer cells to 5-fluorouracil". Hepato-Gastroenterology. 56 (90): 355–60. PMID 19579598.
Shulga N, Wilson-Smith R, Pastorino JG (Oct 2009). "Hexokinase II detachment from the mitochondria potentiates cisplatin induced cytotoxicity through a caspase-2 dependent mechanism". Cell Cycle. 8 (20): 3355–64. doi:10.4161/cc.8.20.9853. PMC 2829766. PMID 19770592.
He HC, Bi XC, Zheng ZW, Dai QS, Han ZD, Liang YX, Ye YK, Zeng GH, Zhu G, Zhong WD (2009). "Real-time quantitative RT-PCR assessment of PIM-1 and hK2 mRNA expression in benign prostate hyperplasia and prostate cancer". Medical Oncology. 26 (3): 303–8. doi:10.1007/s12032-008-9120-9. PMID 19003546.
Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
Sakai N, Terami H, Suzuki S, Haga M, Nomoto K, Tsuchida N, Morohashi K, Saito N, Asada M, Hashimoto M, Harada D, Asahara H, Ishikawa T, Shimada F, Sakurada K (Sep 2008). "Identification of NR5A1 (SF-1/AD4BP) gene expression modulators by large-scale gain and loss of function studies". The Journal of Endocrinology. 198 (3): 489–97. doi:10.1677/JOE-08-0027. PMID 18579725.
Foster LJ, Rudich A, Talior I, Patel N, Huang X, Furtado LM, Bilan PJ, Mann M, Klip A (Jan 2006). "Insulin-dependent interactions of proteins with GLUT4 revealed through stable isotope labeling by amino acids in cell culture (SILAC)". Journal of Proteome Research. 5 (1): 64–75. doi:10.1021/pr0502626. PMID 16396496.
Arzoine L, Zilberberg N, Ben-Romano R, Shoshan-Barmatz V (Feb 2009). "Voltage-dependent anion channel 1-based peptides interact with hexokinase to prevent its anti-apoptotic activity". The Journal of Biological Chemistry. 284 (6): 3946–55. doi:10.1074/jbc.M803614200. PMID 19049977.
Gimenez-Cassina A, Lim F, Cerrato T, Palomo GM, Diaz-Nido J (Jan 2009). "Mitochondrial hexokinase II promotes neuronal survival and acts downstream of glycogen synthase kinase-3". The Journal of Biological Chemistry. 284 (5): 3001–11. doi:10.1074/jbc.M808698200. PMID 19033437.
Peng Q, Zhou Q, Zhou J, Zhong D, Pan F, Liang H (Jul 2008). "Stable RNA interference of hexokinase II gene inhibits human colon cancer LoVo cell growth in vitro and in vivo". Cancer Biology & Therapy. 7 (7): 1128–35. doi:10.4161/cbt.7.7.6199. PMID 18535403.
Rodríguez-Enríquez S, Marín-Hernández A, Gallardo-Pérez JC, Moreno-Sánchez R (Dec 2009). "Kinetics of transport and phosphorylation of glucose in cancer cells". Journal of Cellular Physiology. 221 (3): 552–9. doi:10.1002/jcp.21885. PMID 19681047.
Kim JW, Gao P, Liu YC, Semenza GL, Dang CV (Nov 2007). "Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1". Molecular and Cellular Biology. 27 (21): 7381–93. doi:10.1128/MCB.00440-07. PMC 2169056. PMID 17785433.
Fonteyne P, Casneuf V, Pauwels P, Van Damme N, Peeters M, Dierckx R, Van de Wiele C (Aug 2009). "Expression of hexokinases and glucose transporters in treated and untreated oesophageal adenocarcinoma". Histology and Histopathology. 24 (8): 971–7. PMID 19554504.
Palmieri D, Fitzgerald D, Shreeve SM, Hua E, Bronder JL, Weil RJ, Davis S, Stark AM, Merino MJ, Kurek R, Mehdorn HM, Davis G, Steinberg SM, Meltzer PS, Aldape K, Steeg PS (Sep 2009). "Analyses of resected human brain metastases of breast cancer reveal the association between up-regulation of hexokinase 2 and poor prognosis". Molecular Cancer Research. 7 (9): 1438–45. doi:10.1158/1541-7786.MCR-09-0234. PMC 2746883. PMID 19723875.
Peng QP, Zhou JM, Zhou Q, Pan F, Zhong DP, Liang HJ (2008). "Downregulation of the hexokinase II gene sensitizes human colon cancer cells to 5-fluorouracil". Chemotherapy. 54 (5): 357–63. doi:10.1159/000153655. PMID 18772588.
Paudyal B, Oriuchi N, Paudyal P, Higuchi T, Nakajima T, Endo K (Feb 2008). "Expression of glucose transporters and hexokinase II in cholangiocellular carcinoma compared using [18F]-2-fluro-2-deoxy-D-glucose positron emission tomography". Cancer Science. 99 (2): 260–6. doi:10.1111/j.1349-7006.2007.00683.x. PMID 18271924.

[refGRCm38Ensembl-1] ۱٫۰ ^۱٫۱ ^۱٫۲ GRCm38: Ensembl release 89: ENSMUSG00000000628 - Ensembl, May 2017

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

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

[pmid8307259-4] Lehto M, Xiang K, Stoffel M, Espinosa R, Groop LC, Le Beau MM, Bell GI (Dec 1993). "Human hexokinase II: localization of the polymorphic gene to chromosome 2". Diabetologia. 36 (12): 1299–302. doi:10.1007/BF00400809. PMID 8307259.

[entrez-5] ۵٫۰ ^۵٫۱ "Entrez Gene: HK2 hexokinase 2".

[pmid24018046-6] Schindler A, Foley E (Dec 2013). "Hexokinase 1 blocks apoptotic signals at the mitochondria". Cellular Signalling. 25 (12): 2685–92. doi:10.1016/j.cellsig.2013.08.035. PMID 24018046.

[pmid19723875-7] ۷٫۰ ^۷٫۱ Palmieri D, Fitzgerald D, Shreeve SM, Hua E, Bronder JL, Weil RJ, Davis S, Stark AM, Merino MJ, Kurek R, Mehdorn HM, Davis G, Steinberg SM, Meltzer PS, Aldape K, Steeg PS (Sep 2009). "Analyses of resected human brain metastases of breast cancer reveal the association between up-regulation of hexokinase 2 and poor prognosis". Molecular Cancer Research. 7 (9): 1438–45. doi:10.1158/1541-7786.MCR-09-0234. PMC 2746883. PMID 19723875.

[pmid19579598-8] ۸٫۰ ^۸٫۱ Peng Q, Zhou J, Zhou Q, Pan F, Zhong D, Liang H (2009). "Silencing hexokinase II gene sensitizes human colon cancer cells to 5-fluorouracil". Hepato-Gastroenterology. 56 (90): 355–60. PMID 19579598.

[۴]

[۵]

[۱]

[۲]

[۳]

[۶]

[۷]

[۸]