HIF1A

HIF1A
ساختارهای موجود
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1H2K, 1H2L, 1H2M, 1L3E, 1L8C, 1LM8, 1LQB, 2ILM, 3HQR, 3HQU, 4AJY, 4H6J
معین‌کننده‌ها
نام‌های دیگر	HIF1A, HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1, PASD8, bHLHe78, hypoxia inducible factor 1 alpha subunit, hypoxia inducible factor 1 subunit alpha, HIF-1α
شناسه‌های بیرونی	OMIM: 603348 MGI: 106918 HomoloGene: 1171 GeneCards: HIF1A
Gene location (Mouse)
Chr.	Chromosome 12 (mouse)[1]
End	73,947,530 bp[1]
الگوی گسترش RNA
	More reference expression data
هستی‌شناسی ژن
عملکرد ملکولی	• protein dimerization activity; • GO:0001131، GO:0001151، GO:0001130، GO:0001204 DNA-binding transcription factor activity; • GO:0001077، GO:0001212، GO:0001213، GO:0001211، GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific; • histone deacetylase binding; • transcription factor binding; • enzyme binding; • GO:0001948 پیوند پروتئینی; • histone acetyltransferase binding; • protein kinase binding; • Hsp90 protein binding; • sequence-specific DNA binding; • DNA binding; • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; • ubiquitin protein ligase binding; • protein heterodimerization activity; • E-box binding; • p53 binding; • protein domain specific binding; • GO:0001200، GO:0001133، GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific; • RNA polymerase II transcription regulatory region sequence-specific DNA binding;
ترکیبات سلولی	• سیتوپلاسم; • سیتوزول; • هسته یاخته; • nuclear speck; • motile cilium; • transcription regulator complex; • RNA polymerase II transcription regulator complex; • axon cytoplasm; • نوکلئوپلاسم; • nuclear body; • protein-containing complex;
فرایند زیستی	• negative regulation of neuron apoptotic process; • B-1 B cell homeostasis; • regulation of transforming growth factor beta2 production; • muscle cell cellular homeostasis; • outflow tract morphogenesis; • negative regulation of ossification; • heart looping; • negative regulation of TOR signaling; • blood vessel development; • hemoglobin biosynthetic process; • رگ‌زایی; • positive regulation of chemokine-mediated signaling pathway; • positive regulation of insulin secretion involved in cellular response to glucose stimulus; • positive regulation of hormone biosynthetic process; • negative regulation of mesenchymal cell apoptotic process; • regulation of aerobic respiration; • positive regulation of neuroblast proliferation; • dopaminergic neuron differentiation; • lactate metabolic process; • regulation of transcription, DNA-templated; • blood vessel morphogenesis; • positive regulation of erythrocyte differentiation; • glucose homeostasis; • vascular endothelial growth factor production; • regulation of thymocyte apoptotic process; • positive regulation of epithelial cell migration; • negative regulation of thymocyte apoptotic process; • transcription, DNA-templated; • positive regulation of transcription, DNA-templated; • axonal transport of mitochondrion; • positive regulation of macroautophagy; • cartilage development; • positive regulation of nitric-oxide synthase activity; • regulation of transcription from RNA polymerase II promoter in response to hypoxia; • lactation; • negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; • positive regulation of pri-miRNA transcription by RNA polymerase II; • digestive tract morphogenesis; • دگرگونی یاخته‌; • neural fold elevation formation; • positive regulation of autophagy; • retina vasculature development in camera-type eye; • collagen metabolic process; • embryonic placenta development; • negative regulation of apoptotic process; • positive regulation of angiogenesis; • regulation of glycolytic process; • گذار اپیتلیال-مزانشیمی; • cerebral cortex development; • ساماندهی بیان ژن; • positive regulation of chemokine production; • intestinal epithelial cell maturation; • GO:0048552 regulation of catalytic activity; • positive regulation of autophagy of mitochondrion; • cardiac ventricle morphogenesis; • response to muscle activity; • epithelial cell differentiation involved in mammary gland alveolus development; • یادگیری بصری; • positive regulation of vascular endothelial growth factor receptor signaling pathway; • negative regulation of bone mineralization; • negative regulation of growth; • response to hypoxia; • positive regulation of endothelial cell proliferation; • regulation of transcription from RNA polymerase II promoter in response to oxidative stress; • iris morphogenesis; • mRNA transcription by RNA polymerase II; • hypoxia-inducible factor-1alpha signaling pathway; • vasculature development; • regulation of cell population proliferation; • neural crest cell migration; • embryonic hemopoiesis; • connective tissue replacement involved in inflammatory response wound healing; • positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; • negative regulation of reactive oxygen species metabolic process; • positive regulation of vascular endothelial growth factor production; • elastin metabolic process; • positive regulation of glycolytic process; • oxygen homeostasis; • ورارسانی پیام; • positive regulation of transcription by RNA polymerase II; • cellular iron ion homeostasis; • camera-type eye morphogenesis; • cellular response to hypoxia; • cellular response to interleukin-1; • transcription by RNA polymerase II; • protein deubiquitination; • پیرایش پسارونویسی; • response to iron ion; • negative regulation of gene expression; • positive regulation of blood vessel endothelial cell migration; • positive regulation of gene expression; • cytokine-mediated signaling pathway; • regulation of transcription by RNA polymerase II; • protein ubiquitination;
	Sources:آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
	3091
	15251
	ENSG00000100644
	ENSMUSG00000021109
	Q16665
	Q61221
	NM_001243084، NM_001530 NM_181054، NM_001243084، NM_001530
	XM_006515478، NM_001313919، NM_001313920، XM_017314961 NM_010431، XM_006515478، NM_001313919، NM_001313920، XM_017314961
	NP_001521، NP_851397 NP_001230013، NP_001521، NP_851397; NP_001521.1
	NP_001300849، NP_034561، XP_006515541، XP_017170450، XP_036013089 NP_001300848، NP_001300849، NP_034561، XP_006515541، XP_017170450، XP_036013089
	ویکی‌داده
مشاهده/ویرایش Human	View/Edit Mouse

فاکتور ۱-آلفا القاشونده توسط هیپوکسی (انگلیسی: Hypoxia-inducible factor 1-alpha‎) یک پروتئین است که در انسان توسط ژن «HIF1A» کُدگذاری می‌شود.[4][5][6]

عملکرد

این مولکول یک زیرواحد از فاکتور رونویسی القاشونده توسط هیپوکسی و یکی از عوامل مهم ساماندهی بیان ژن در پاسخ به هیپوکسی است. هرگونه تغییر در ژن سازندهٔ این پروتئین در بروز برخی انواع سرطان، و همچنین در تغییر در فرایندهایی نظیر رگ‌زایی، سوخت‌وساز، دوام سلول و تهاجم تومورها نقش دارد.[6][7]

اهمیت بالینی

افزایش بیان ژن HIF-1 در بسیاری از سرطان‌های انسان مشاهده شده‌است[8][9] که از آن میان می‌توان به سرطان روده بزرگ، سرطان پستان، سرطان لوزالمعده، سرطان کلیه، سرطان پروستات، سرطان تخمدان، تومور مغزی و سرطان مثانه اشاره کرد.[9][8]

افزایش سطح Hif-1a در سرطان دهانه رحم، سرطان ریه غیر سلول کوچک، سرطان پستان، اولیگودندروگلیومای مغز، سرطان دهان و گلو، سرطان تخمدان، سرطان مخاط رحم، سرطان مری، سرطان‌های سر و گردن و سرطان معده مشاهده شده و با افزایش پیشرفت سریع بیماری مرتبط است به نحوی که می‌توان از آن، جهت تعیین پیش‌آگهی بیماری و پیش‌بینی احتمال مقاومت به پرتودرمانی و شیمی‌درمانی و افزایش احتمال مرگ استفاده نمود.[7][10][11][12][13][14][10]

منابع

GRCm38: Ensembl release 89: ENSMUSG00000021109 - 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.
Semenza GL, Rue EA, Iyer NV, Pang MG, Kearns WG (June 1996). "Assignment of the hypoxia-inducible factor 1alpha gene to a region of conserved synteny on mouse chromosome 12 and human chromosome 14q". Genomics. 34 (3): 437–9. doi:10.1006/geno.1996.0311. PMID 8786149.
Hogenesch JB, Chan WK, Jackiw VH, Brown RC, Gu YZ, Pray-Grant M, Perdew GH, Bradfield CA (March 1997). "Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway". The Journal of Biological Chemistry. 272 (13): 8581–93. doi:10.1074/jbc.272.13.8581. PMID 9079689.
"Entrez Gene: HIF1A hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)".
Semenza GL (October 2003). "Targeting HIF-1 for cancer therapy". Nature Reviews. Cancer. 3 (10): 721–32. doi:10.1038/nrc1187. PMID 13130303.
Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, Simons JW (November 1999). "Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases". Cancer Research. 59 (22): 5830–5. PMID 10582706.
Talks KL, Turley H, Gatter KC, Maxwell PH, Pugh CW, Ratcliffe PJ, Harris AL (August 2000). "The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages". The American Journal of Pathology. 157 (2): 411–21. doi:10.1016/s0002-9440(10)64554-3. PMC 1850121. PMID 10934146.
Aebersold DM, Burri P, Beer KT, Laissue J, Djonov V, Greiner RH, Semenza GL (April 2001). "Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer". Cancer Research. 61 (7): 2911–6. PMID 11306467.
Höckel M, Vaupel P (February 2001). "Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects". Journal of the National Cancer Institute. 93 (4): 266–76. doi:10.1093/jnci/93.4.266. PMID 11181773.
Dvorák K (May 1990). "[Intravenous systemic thrombolysis using streptokinase in the treatment of developing cardiogenic shock in myocardial infarct]". Vnitrni Lekarstvi (به Czech). 36 (5): 426–34. PMID 2375073.
Birner P, Schindl M, Obermair A, Breitenecker G, Oberhuber G (June 2001). "Expression of hypoxia-inducible factor 1alpha in epithelial ovarian tumors: its impact on prognosis and on response to chemotherapy". Clinical Cancer Research. 7 (6): 1661–8. PMID 11410504.
Bos R, van der Groep P, Greijer AE, Shvarts A, Meijer S, Pinedo HM, Semenza GL, van Diest PJ, van der Wall E (March 2003). "Levels of hypoxia-inducible factor-1alpha independently predict prognosis in patients with lymph node negative breast carcinoma". Cancer. 97 (6): 1573–81. doi:10.1002/cncr.11246. PMID 12627523.

مشارکت‌کنندگان ویکی‌پدیا. «HIF1A». در دانشنامهٔ ویکی‌پدیای انگلیسی، بازبینی‌شده در ۱۶ مارس ۲۰۲۰.

برای مطالعهٔ بیشتر

Semenza GL (August 2000). "HIF-1 and human disease: one highly involved factor". Genes & Development. 14 (16): 1983–91. PMID 10950862.
Semenza G (September 2002). "Signal transduction to hypoxia-inducible factor 1". Biochemical Pharmacology. 64 (5–6): 993–8. doi:10.1016/S0006-2952(02)01168-1. PMID 12213597.
Arbeit JM (2002). "Quiescent hypervascularity mediated by gain of HIF-1 alpha function". Cold Spring Harbor Symposia on Quantitative Biology. 67: 133–42. doi:10.1101/sqb.2002.67.133. PMID 12858534.
Sitkovsky M, Lukashev D (September 2005). "Regulation of immune cells by local-tissue oxygen tension: HIF1 alpha and adenosine receptors". Nature Reviews. Immunology. 5 (9): 712–21. doi:10.1038/nri1685. PMID 16110315.
Mobasheri A, Richardson S, Mobasheri R, Shakibaei M, Hoyland JA (October 2005). "Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes". Histology and Histopathology. 20 (4): 1327–38. doi:10.14670/HH-20.1327. PMID 16136514.
Schipani E (2006). "Hypoxia and HIF-1 alpha in chondrogenesis". Seminars in Cell & Developmental Biology. 16 (4–5): 539–46. doi:10.1016/j.semcdb.2005.03.003. PMID 16144691.
Haase VH (August 2006). "Hypoxia-inducible factors in the kidney". American Journal of Physiology. Renal Physiology. 291 (2): F271–81. doi:10.1152/ajprenal.00071.2006. PMC 4232221. PMID 16554418.
Liang D, Kong X, Sang N (November 2006). "Effects of histone deacetylase inhibitors on HIF-1". Cell Cycle. 5 (21): 2430–5. doi:10.4161/cc.5.21.3409. PMC 4505804. PMID 17102633.

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[refGRCm38Ensembl-1] GRCm38: Ensembl release 89: ENSMUSG00000021109 - 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.

[pmid8786149-4] Semenza GL, Rue EA, Iyer NV, Pang MG, Kearns WG (June 1996). "Assignment of the hypoxia-inducible factor 1alpha gene to a region of conserved synteny on mouse chromosome 12 and human chromosome 14q". Genomics. 34 (3): 437–9. doi:10.1006/geno.1996.0311. PMID 8786149.

[pmid9079689-5] Hogenesch JB, Chan WK, Jackiw VH, Brown RC, Gu YZ, Pray-Grant M, Perdew GH, Bradfield CA (March 1997). "Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway". The Journal of Biological Chemistry. 272 (13): 8581–93. doi:10.1074/jbc.272.13.8581. PMID 9079689.

[entrez-6] "Entrez Gene: HIF1A hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)".

[Targeting_HIF-1_for_cancer_therapy-7] Semenza GL (October 2003). "Targeting HIF-1 for cancer therapy". Nature Reviews. Cancer. 3 (10): 721–32. doi:10.1038/nrc1187. PMID 13130303.

[ReferenceE-8] Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, Simons JW (November 1999). "Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases". Cancer Research. 59 (22): 5830–5. PMID 10582706.

[ReferenceF-9] Talks KL, Turley H, Gatter KC, Maxwell PH, Pugh CW, Ratcliffe PJ, Harris AL (August 2000). "The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages". The American Journal of Pathology. 157 (2): 411–21. doi:10.1016/s0002-9440(10)64554-3. PMC 1850121. PMID 10934146.

[ReferenceI-10] Aebersold DM, Burri P, Beer KT, Laissue J, Djonov V, Greiner RH, Semenza GL (April 2001). "Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer". Cancer Research. 61 (7): 2911–6. PMID 11306467.

[11] Höckel M, Vaupel P (February 2001). "Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects". Journal of the National Cancer Institute. 93 (4): 266–76. doi:10.1093/jnci/93.4.266. PMID 11181773.

[12] Dvorák K (May 1990). "[Intravenous systemic thrombolysis using streptokinase in the treatment of developing cardiogenic shock in myocardial infarct]". Vnitrni Lekarstvi (به Czech). 36 (5): 426–34. PMID 2375073.

[ReferenceJ-13] Birner P, Schindl M, Obermair A, Breitenecker G, Oberhuber G (June 2001). "Expression of hypoxia-inducible factor 1alpha in epithelial ovarian tumors: its impact on prognosis and on response to chemotherapy". Clinical Cancer Research. 7 (6): 1661–8. PMID 11410504.

[ReferenceG-14] Bos R, van der Groep P, Greijer AE, Shvarts A, Meijer S, Pinedo HM, Semenza GL, van Diest PJ, van der Wall E (March 2003). "Levels of hypoxia-inducible factor-1alpha independently predict prognosis in patients with lymph node negative breast carcinoma". Cancer. 97 (6): 1573–81. doi:10.1002/cncr.11246. PMID 12627523.