433:
410:
332:
307:
3716:
684:
3701:
439:
338:
3731:
64:
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1301:
1411:. It is then capable to stabilize and thus elongate microtubules. This function plays a key role in the stabilisation of the spindle during mitosis. Deletion of VHL causes a drastic increase of misorientated and rotating spindles during mitosis. Through a not-yet-known mechanism, VHL also increases the concentration of
1392:(adrenal gland tumors). Type 2 VHL has been linked to missense mutations and is linked to a high risk of pheochromocytoma. Type 2 has also been further subdivided based on risks of renal cell carcinoma. In types 1, 2A and 2B the mutant pVHL is defective in HIF regulation, while type 2C mutant are defective in
1360:(GWAS) of HIF binding in kidney cancer showed that HIF1A binds upstream of majorly good prognosis genes, while HIF2A binds upstream to majorly poor prognosis genes. This indicates that the HIF transcription factor distribution in kidney cancer is of major importance in determining the outcome of the patients.
1297:(HIFs), which are transcription factors that play a central role regulating gene expression in response to changing oxygen levels. RNA polymerase II subunit POLR2G/RPB7 is also reported to be a target of this protein. Alternatively spliced transcript variants encoding distinct isoforms have been observed.
1524:
Since iron, 2-oxoglutarate and oxygen are necessary for the inactivation of HIF, it has been theorized that a lack of these cofactors could reduce the ability of hydroxylases in inactivating HIF. A recent study has shown that in cells with a high activation of HIF even in oxygenated environments was
1382:
HIF can help explain the organ-specific nature of VHL syndrome. It has been theorized that constitutively activating HIF in any cell could lead to cancer, but that there are redundant regulators of HIF in organs not affected by VHL syndrome. This theory has been disproved multiple times since in all
1347:
It is clear that VHL and HIFs interact closely. Firstly, all renal cell carcinoma mutations in VHL that have been tested affect the protein's ability to modify HIF. Additionally, HIF activation can be detected in the earliest events in tumorigenesis in patients with VHL syndrome. In normal cells in
1304:
The regulation of HIF1α by pVHL. Under normal oxygen levels, HIF1α binds pVHL through 2 hydroxylated proline residues and is polyubiquitinated by pVHL. This leads to its degradation via the proteasome. During hypoxia, the proline residues are not hydroxylated and pVHL cannot bind. HIF1α causes the
1438:
of this gene is the basis of familial inheritance of VHL syndrome. Individuals with VHL syndrome inherit one mutation in the VHL protein that causes the protein's normal function to be lost or altered. Over time, sporadic mutation in the second copy of the VHL protein can lead to carcinomas, in
1403:
The involvement in VHL in renal cell cancer can be rationalized via multiple characteristics of renal cells. First, they are more sensitive to the effects of growth factors created downstream of HIF activation than other cells. Secondly, the link to Cyclin D1 (as mentioned above) is only seen in
1387:
cells this leads to no advantage in proliferation or survival. Additionally, the nature of the mutation in the VHL protein leads to phenotypic manifestations in the pattern of cancer that develops. Nonsense or deletion mutations of VHL protein have been linked to type 1 VHL with a low risk of
1367:
and oxygen are present, HIF is inactivated by HIF hydroxylases. Hydroxylation of HIF creates a binding site for pVHL (the protein product of the VHL gene). pVHL directs the polyubiquitylation of HIF1A, ensuring that this protein will be degraded by the proteasome. In hypoxic conditions, HIF1A
90:
3057:
Park YK, Ahn DR, Oh M, Lee T, Yang EG, Son M, Park H (July 2008). "Nitric oxide donor, (+/-)-S-nitroso-N-acetylpenicillamine, stabilizes transactive hypoxia-inducible factor-1alpha by inhibiting von Hippel–Lindau recruitment and asparagine hydroxylation".
1372:) and erythropoietin, proteins that are both involved in angiogenesis. Cells with abnormal pVHL are unable to disrupt the formation of these dimers, and therefore behave like they are hypoxic even in oxygenated environments.
1348:
hypoxic conditions, HIF1A is activated with little activation of HIF2A. However, in tumors the balance of HIF1A and HIF2A is tipped towards HIF2A. While HIF1A serves as a pro-apoptotic factor, HIF2A interacts with
446:
345:
1462:. Additionally, VHL has been implicated in maintaining the differentiated phenotype in renal cells. Furthermore, cell culture experiments with VHL -/- cells have shown that the addition of pVHL can induce a
1335:
HIFs are necessary for tumor growth because most cancers demand high metabolic activity and are only supplied by structurally or functionally inadequate vasculature. Activation of HIFs allow for enhanced
2119:
Formenti F, Beer PA, Croft QP, Dorrington KL, Gale DP, Lappin TR, Lucas GS, Maher ER, Maxwell PH, McMullin MF, O'Connor DF, Percy MJ, Pugh CW, Ratcliffe PJ, Smith TG, Talbot NP, Robbins PA (June 2011).
1383:
cell types loss of VHL function leads to constitutive activation of HIF and its downstream effects. Another theory holds that although in all cells loss of VHL leads to activation of HIF, in
2033:
Lolkema MP, Mehra N, Jorna AS, van Beest M, Giles RH, Voest EE (December 2004). "The von Hippel–Lindau tumor suppressor protein influences microtubule dynamics at the cell periphery".
1404:
renal cells. Finally, many cells in the kidney normally operate under hypoxic conditions. This may give them a proliferative advantage over other cells while in hypoxic environments.
3715:
1368:
subunits accumulate and bind to HIFB. This heterodimer of HIF is a transcription factor that activates genes that encode for proteins such as vascular endothelial growth factor (
2076:
Thoma CA, Toso A, Gutbrodt KL, Reggi SP, Frew IJ, Schraml P, Hergovich A, Loch H, Meraldi P, Trek W (2009). "VHL loss causes spindle disorientation and chromosome instability".
3771:
2757:, El-Deiry WS (November 2003). "Tat-binding protein-1, a component of the 26S proteasome, contributes to the E3 ubiquitin ligase function of the von Hippel–Lindau protein".
1305:
transcription of genes that contain the hypoxia response element. In VHL disease, genetic mutations cause alterations to the pVHL protein, usually to the HIF1α binding site.
4614:
2122:"Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel–Lindau disease and HIF-2alpha gain-of-function mutation"
5418:
1317:. The main action of the VHL protein is thought to be its E3 ubiquitin ligase activity that results in specific target proteins being 'marked' for degradation.
1357:
4867:
2555:
Tsuchiya H, Iseda T, Hino O (July 1996). "Identification of a novel protein (VBP-1) binding to the von Hippel–Lindau (VHL) tumor suppressor gene product".
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of VHL-deficient cells. In classical VHL disease a single wild-type allele in VHL appears to be sufficient to maintain normal cardiopulmonary function.
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Hoebeeck J, Vandesompele J, Nilsson H, De Preter K, Van Roy N, De Smet E, Yigit N, De Paepe A, Laureys G, Påhlman S, Speleman F (August 2006).
2212:
Knowles HJ, Raval RR, Harris AL, Ratcliffe PJ (April 2003). "Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cells".
1269:, which is characterized by hemangioblastomas of the brain, spinal cord and retina. It is also associated with kidney and pancreatic lesions.
3585:"A novel mutation in the von Hippel–Lindau tumor suppressor gene identified in a Japanese family with pheochromocytoma and hepatic hemangioma"
1415:, an important protein of the spindle checkpoint. Thus VHL loss leads to a weakened checkpoint and subsequently chromosome missegregation and
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1709:
87:
1691:
5648:
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2469:"Muf1, a novel Elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase"
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1194:
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4102:
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formation. This protein may also be important in inhibition of matrix metalloproteinases. These ideas are extremely important in the
1187:
5724:
5166:
5161:
5136:
5126:
5121:
5111:
3700:
3482:
Neumann HP, Wiestler OD (May 1991). "Clustering of features of von Hippel–Lindau syndrome: evidence for a complex genetic locus".
5182:
5116:
4600:
3416:
Kralovics R, Skoda RC (January 2005). "Molecular pathogenesis of
Philadelphia chromosome negative myeloproliferative disorders".
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1434:
predisposing to a variety of malignant and benign tumors of the eye, brain, spinal cord, kidney, pancreas, and adrenal glands. A
5413:
3648:
3680:
3398:
3644:
GeneReviews/NCBI/NIH/UW entry on Von Hippel–Lindau
Syndrome or Angiomatosis Retinae, VHL Syndrome, von Hippel–Lindau Disease
2467:
Kamura T, Burian D, Yan Q, Schmidt SL, Lane WS, Querido E, Branton PE, Shilatifard A, Conaway RC, Conaway JW (August 2001).
1674:
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5638:
1363:
In the normal cell with active VHL protein, HIF alpha is regulated by hydroxylation in the presence of oxygen. When iron,
3106:"Ubiquitination of a novel deubiquitinating enzyme requires direct binding to von Hippel–Lindau tumor suppressor protein"
1653:
1489:
Suggested targets for VHL-related cancers include targets of the HIF pathway, such as VEGF. Inhibitors of VEGF receptor
5460:
5430:
3445:
Lonser RR, Glenn GM, Walther M, Chew EY, Libutti SK, Linehan WM, Oldfield EH (June 2003). "von Hippel–Lindau disease".
3166:
2587:"FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity"
1447:
1369:
2957:
Jung JE, Kim HS, Lee CS, Shin YJ, Kim YN, Kang GH, Kim TY, Juhnn YS, Kim SJ, Park JW, Ye SK, Chung MH (October 2008).
1470:
transition. This evidence suggests that VHL has a central role in maintaining a differentiated phenotype in the cell.
1340:, which in turn allow for increased glucose uptake. While HIFs are mostly active in hypoxic conditions, VHL-defective
5784:
2246:"Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes and its regulation by the COP9 signalosome"
1938:
Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW, Kaelin WG (December 2004).
432:
5739:
3954:
3583:
Takahashi K, Iida K, Okimura Y, Takahashi Y, Naito J, Nishikawa S, Kadowaki S, Iguchi G, Kaji H, Chihara K (2006).
3235:"Formation of primary cilia in the renal epithelium is regulated by the von Hippel–Lindau tumor suppressor protein"
2851:"Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel–Lindau tumor suppressor protein"
6090:
5744:
4623:
3730:
1678:
1657:
409:
3381:
Kamura T, Conaway JW, Conaway RC (2002). "Roles of SCF and VHL Ubiquitin
Ligases in Regulation of Cell Growth".
1379:, a central controller of growth decisions. It has recently been shown that HIF activation can inactivate mTOR.
5734:
5628:
4823:
3816:
1427:
1012:
2354:
Ohh M, Takagi Y, Aso T, Stebbins CE, Pavletich NP, Zbar B, Conaway RC, Conaway JW, Kaelin WG (December 1999).
1439:
particular hemangioblastomas affecting the liver and kidneys, renal (and vaginal) clear cell adenocarcinomas.
1277:
The protein encoded by the VHL gene is the substrate recognition component of a protein complex that includes
5940:
5751:
5577:
5453:
2356:"Synthetic peptides define critical contacts between elongin C, elongin B, and the von Hippel–Lindau protein"
1266:
3204:
Czyzyk-Krzeska MF, Meller J (April 2004). "von Hippel–Lindau tumor suppressor: not only HIF's executioner".
1782:
Czyzyk-Krzeska MF, Meller J (April 2004). "von Hippel–Lindau tumor suppressor: not only HIF's executioner".
993:
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248:
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1321:
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1940:"Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex"
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5719:
5714:
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5517:
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3724:: Crystal structure of a hydroxylated HIF-1 alpha peptide bound to the pVHL/elongin-C/elongin-B complex
2802:"The VHL protein recruits a novel KRAB-A domain protein to repress HIF-1alpha transcriptional activity"
1442:
The loss of VHL protein activity results in an increased amount of HIF1a, and thus increased levels of
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regulation. These genotype–phenotype correlations suggest that missense mutations of pVHL lead to a '
1294:
235:
3270:"The von Hippel–Lindau tumor suppressor gene expression level has prognostic value in neuroblastoma"
3196:
438:
337:
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4921:
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3821:
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3008:"Identification of an alternative mechanism of degradation of the hypoxia-inducible factor-1alpha"
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The von Hippel–Lindau tumor suppressor complex and regulation of hypoxia-inducible transcription
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Salama R, Masson N, Simpson P, Sciesielski LK, Sun M, Tian YM, Ratcliffe PJ, Mole DR (2015).
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negative regulation of transcription from RNA polymerase II promoter in response to hypoxia
320:
2513:"The von Hippel–Lindau tumor suppressor stabilizes novel plant homeodomain protein Jade-1"
8:
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2015:
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activity. This complex is involved in the ubiquitination and subsequent degradation of
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3521:"The role of VHL in the regulation of E-cadherin: a new connection in an old pathway"
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2007:
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Kaelin WG (September 2002). "Molecular basis of the VHL hereditary cancer syndrome".
1969:
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228:
80:
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2900:"HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation"
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2019:
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2695:"Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling"
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regulation of transcription from RNA polymerase II promoter in response to hypoxia
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2302:"Large-scale mapping of human protein-protein interactions by mass spectrometry"
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1714:
National Center for
Biotechnology Information, U.S. National Library of Medicine
1696:
National Center for
Biotechnology Information, U.S. National Library of Medicine
1407:
In addition to its interaction with HIF the VHL protein can also associate with
6069:
5958:
5899:
5704:
4960:
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4379:
3429:
3348:"The von Hippel–Lindau tumor suppressor protein and clear cell renal carcinoma"
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Proceedings of the
National Academy of Sciences of the United States of America
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1899:"The von Hippel–Lindau tumor suppressor protein and clear cell renal carcinoma"
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3385:. Progress in Molecular and Subcellular Biology. Vol. 29. pp. 1–15.
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2959:"STAT3 inhibits the degradation of HIF-1alpha by pVHL-mediated ubiquitination"
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1831:"Heterogeneous Effects of Direct Hypoxia Pathway Activation in Kidney Cancer"
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2011:
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cells show constitutive activation of HIF even in oxygenated environments.
1337:
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Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007).
2138:
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1038:
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and increased proliferation due to the activation of cyclin D1. Recent
417:
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63:
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Graff JW (2005). "The VHL Handbook: What You Need to Know about VHL".
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2641:"Nur77 upregulates HIF-alpha by inhibiting pVHL-mediated degradation"
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Zhou MI, Wang H, Ross JJ, Kuzmin I, Xu C, Cohen HT (October 2002).
2003:
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Li Z, Na X, Wang D, Schoen SR, Messing EM, Wu G (February 2002).
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3313:"The von Hippel–Lindau tumor suppressor gene and kidney cancer"
2848:
2173:"The von Hippel–Lindau tumor suppressor gene and kidney cancer"
1594:
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1202:
934:
692:
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2800:
Li Z, Wang D, Na X, Schoen SR, Messing EM, Wu G (April 2003).
1828:
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negative regulation of receptor signaling pathway via JAK-STAT
32:"VHL" redirects here. For the Vysshaya Khokkeynaya Liga (VHL,
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Tanimoto K, Makino Y, Pereira T, Poellinger L (August 2000).
1612:
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1570:
1459:
2410:"VHL type 2B mutations retain VBC complex form and function"
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The resultant protein is produced in two forms, an 18
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2032:
1937:
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1352:. This leads to increased survival due to lower rates of
1310:
828:
negative regulation of transcription by RNA polymerase II
3779:
3233:
Esteban MA, Harten SK, Tran MG, Maxwell PH (July 2006).
3232:
1720:
508:
239:, HRCA1, RCA1, VHL1, pvon Hippel-Lindau tumor suppressor
1631:
Pages displaying short descriptions of redirect targets
3709:: Structure of a HIF-1a-pVHL-ElonginB-ElonginC Complex
3444:
2466:
2408:
Hacker KE, Lee CM, Rathmell WK (2008). Zhang B (ed.).
2075:
1525:
reversed by supplying the cells with ascorbate. Thus,
6053:
3638:
2243:
1769:"Entrez Gene: VHL von Hippel–Lindau tumor suppressor"
1726:
1537:
Von Hippel–Lindau tumor suppressor has been shown to
1529:
may be a potential treatment for HIF induced tumors.
673:
3380:
3203:
2353:
1781:
863:
negative regulation of cell population proliferation
2244:Menon S, Tsuge T, Dohmae N, Takio K, Wei N (2008).
838:
positive regulation of transcription, DNA-templated
616:
dentate gyrus of hippocampal formation granule cell
4622:
4537:
2692:
2584:
2510:
1670:
1668:
1666:
1649:
1647:
1645:
1505:have been approved by the FDA. The mTOR inhibitor
2554:
2407:
1265:. Mutations of the VHL gene are associated with
455:
354:
6077:
2639:Kim BY, Kim H, Cho EJ, Youn HD (February 2008).
2299:
3481:
3099:
3097:
2748:
2746:
2688:
2686:
2684:
2634:
2632:
2630:
2585:Mahon PC, Hirota K, Semenza GL (October 2001).
2580:
2578:
2506:
2504:
2403:
2401:
2399:
2349:
2347:
2345:
2295:
2293:
2291:
2239:
2237:
2235:
1815:
1813:
1663:
1642:
3415:
3148:
3103:
2956:
2898:Yu F, White SB, Zhao Q, Lee FS (August 2001).
2897:
2799:
2550:
2548:
1985:
1983:
1892:
1890:
1888:
1886:
1884:
1675:GRCm38: Ensembl release 89: ENSMUSG00000033933
1313:and a 30 kDa protein that functions as a
5778:
5461:
4608:
3800:
3765:
3674:
3239:Journal of the American Society of Nephrology
2638:
3556:Seminars in Cell & Developmental Biology
3094:
3056:
3050:
3005:
2999:
2950:
2891:
2842:
2793:
2743:
2681:
2627:
2575:
2501:
2460:
2396:
2342:
2288:
2232:
2112:
2026:
1810:
2545:
1980:
1881:
1822:
1654:GRCh38: Ensembl release 89: ENSG00000134086
1430:(VHL) is a dominantly inherited hereditary
1328:that induces the expression of a number of
843:positive regulation of cell differentiation
5785:
5771:
5468:
5454:
4615:
4601:
3772:
3758:
3681:
3667:
3649:Von+Hippel–Lindau+Tumor+Suppressor+Protein
3518:
813:regulation of transcription, DNA-templated
3651:at the U.S. National Library of Medicine
3600:
3536:
3383:Protein Degradation in Health and Disease
3363:
3328:
3285:
3250:
3121:
3033:
3023:
2982:
2933:
2923:
2874:
2825:
2718:
2664:
2610:
2528:
2484:
2443:
2433:
2379:
2325:
2271:
2261:
2188:
2147:
2137:
1963:
1914:
1864:
1854:
1744:
3553:
1320:The most researched of these targets is
1299:
823:negative regulation of apoptotic process
878:post-translational protein modification
14:
6078:
3345:
3310:
2170:
1989:
1896:
1458:growth, one of the prerequisites of a
868:negative regulation of gene expression
736:ubiquitin-protein transferase activity
5766:
5533:D-alanine—poly(phosphoribitol) ligase
5449:
4596:
3753:
3739:: THE VHL-ELONGINC-ELONGINB STRUCTURE
3662:
3617:
2963:Experimental & Molecular Medicine
2645:Experimental & Molecular Medicine
2360:The Journal of Clinical Investigation
1454:. In turn, this leads to unregulated
460:
421:
416:
359:
318:
313:
3006:André H, Pereira TS (October 2008).
1727:Ben-Skowronek I, Kozaczuk S (2015).
1473:Additionally, pVHL is important for
3998:
3943:
3809:
3110:The Journal of Biological Chemistry
3012:The Journal of Biological Chemistry
2517:The Journal of Biological Chemistry
2473:The Journal of Biological Chemistry
1627:Von Hippel–Lindau binding protein 1
1258:that, in humans, is encoded by the
24:
5673:Von Hippel–Lindau tumor suppressor
5431:Prokaryotic ubiquitin-like protein
4387:
4169:
4090:
3914:
3885:
3856:
3519:Russell RC, Ohh M (January 2007).
3141:
1248:Von Hippel–Lindau tumor suppressor
25:
6107:
3632:
726:ubiquitin protein ligase activity
29:Mammalian protein found in humans
6063:
5639:Long-chain-fatty-acid—CoA ligase
3729:
3714:
3699:
3602:10.2169/internalmedicine.45.1547
3330:10.1158/1078-0432.CCR-sup-040025
2190:10.1158/1078-0432.CCR-sup-040025
682:
444:
437:
431:
408:
343:
336:
330:
305:
62:
3688:
3274:International Journal of Cancer
3153:. Vol. 85. pp. 1–12.
3149:Conaway RC, Conaway JW (2003).
2205:
2164:
2069:
1931:
1733:Hormone Research in Paediatrics
1532:
5735:Carbamoyl phosphate synthetase
5629:Succinyl coenzyme A synthetase
4961:Mitochondrial targeting signal
4624:Posttranslational modification
1775:
1761:
1702:
1684:
693:More reference expression data
662:More reference expression data
13:
1:
3459:10.1016/S0140-6736(03)13643-4
3365:10.1158/1078-0432.CCR-06-1865
3159:10.1016/S0065-230X(02)85001-1
1916:10.1158/1078-0432.CCR-06-1865
1636:
429:
328:
5037:Ubiquitin-conjugating enzyme
4029:Intracellular signaling P+Ps
3568:10.1016/j.semcdb.2005.03.003
3496:10.1016/0140-6736(91)91705-Y
3311:Kaelin WG (September 2004).
3218:10.1016/j.molmed.2004.02.004
3206:Trends in Molecular Medicine
2435:10.1371/journal.pone.0003801
2171:Kaelin WG (September 2004).
1856:10.1371/journal.pone.0134645
1796:10.1016/j.molmed.2004.02.004
1784:Trends in Molecular Medicine
1729:"Von Hippel–Lindau Syndrome"
1517:or VEGF monoclonal antibody
1484:
1422:
1375:HIF has also been linked to
731:transcription factor binding
7:
6086:Genes on human chromosome 3
5792:
5325:E2 SUMO-conjugating enzyme
4982:Ubiquitin-activating enzyme
3391:10.1007/978-3-642-56373-7_1
2047:10.1016/j.yexcr.2004.07.016
1620:
1322:hypoxia inducible factor 1a
1272:
558:stromal cell of endometrium
38:Высшая хоккейная лига (ВХЛ)
10:
6112:
5720:Holocarboxylase synthetase
5715:Argininosuccinate synthase
5688:Anaphase-promoting complex
5308:E1 SUMO-activating enzyme
4083:TGF beta signaling pathway
3991:JAK-STAT signaling pathway
3907:TGF beta signaling pathway
3878:Hedgehog signaling pathway
3430:10.1016/j.blre.2004.02.002
3346:Kaelin WG (January 2007).
2035:Experimental Cell Research
1897:Kaelin WG (January 2007).
1428:Von Hippel–Lindau syndrome
620:medial ganglionic eminence
31:
5949:
5941:Michaelis–Menten kinetics
5913:
5882:
5851:
5800:
5752:Glutamate–cysteine ligase
5710:Adenylosuccinate synthase
5647:
5618:
5503:Aminoacyl tRNA synthetase
5492:
5366:
5297:
5286:
4969:
4946:
4904:
4644:
4630:
4564:
4528:
4504:
4471:
4462:
4442:
4421:
4412:
4374:
4335:
4309:
4300:
4291:
4267:
4251:
4244:
4224:
4198:
4189:
4160:
4140:
4124:
4117:Akt/PKB signaling pathway
4115:
4081:
4061:
4045:
4036:
4027:
3989:
3934:
3905:
3876:
3847:
3838:
3791:
3694:
2975:10.3858/emm.2008.40.5.479
2306:Molecular Systems Biology
1710:"Mouse PubMed Reference:"
1692:"Human PubMed Reference:"
1629: – Chaperone protein
1295:hypoxia-inducible factors
1267:Von Hippel–Lindau disease
1233:
1228:
1224:
1217:
1201:
1182:
1167:
1163:
1134:
1130:
1123:
1108:
1104:
1079:
1075:
1068:
1055:
1051:
1036:
1032:
1023:
1010:
1006:
991:
987:
978:
965:
961:
946:
942:
933:
918:
911:
907:
891:
711:
707:
690:
681:
672:
659:
608:
599:
546:
537:
507:
499:
495:
478:
465:
428:
407:
398:
394:
377:
364:
327:
304:
295:
291:
246:
243:
233:
226:
221:
106:
101:
84:
79:
74:
70:
61:
56:
37:
5833:Diffusion-limited enzyme
4922:Survival of motor neuron
3936:Receptor tyrosine kinase
3653:Medical Subject Headings
3352:Clinical Cancer Research
3317:Clinical Cancer Research
2867:10.1093/emboj/19.16.4298
2657:10.3858/emm.2008.40.1.71
2177:Clinical Cancer Research
1903:Clinical Cancer Research
1195:Chr 6: 113.6 – 113.61 Mb
5288:Ubiquitin-like proteins
5247:Deubiquitinating enzyme
4162:Hippo signaling pathway
2720:10.1126/science.1073440
2591:Genes & Development
1944:Genes & Development
1521:may also be an option.
1188:Chr 3: 10.14 – 10.15 Mb
6091:Tumor suppressor genes
5700:Glutathione synthetase
4177:Neurofibromin 2/Merlin
3781:Tumor suppressor genes
3252:10.1681/ASN.2006020181
3123:10.1074/jbc.M108269200
3072:10.1124/mol.108.045278
3060:Molecular Pharmacology
3025:10.1074/jbc.M805919200
2925:10.1073/pnas.181341498
2753:Corn PG, McDonald ER,
2530:10.1074/jbc.M205040200
2486:10.1074/jbc.M103093200
1992:Nature Reviews. Cancer
1577:Nerve Growth factor IB
1306:
873:protein ubiquitination
644:neural layer of retina
5926:Eadie–Hofstee diagram
5859:Allosteric regulation
5730:Asparagine synthetase
5634:Acetyl—CoA synthetase
4038:Wnt signaling pathway
3849:Wnt signaling pathway
3358:(2 Pt 2): 680s–684s.
3323:(18 Pt 2): 6290S–5S.
2263:10.1186/1471-2091-9-1
2183:(18 Pt 2): 6290S–5S.
1909:(2 Pt 2): 680s–684s.
1303:
818:protein stabilization
787:endoplasmic reticulum
49:Supreme Hockey League
5936:Lineweaver–Burk plot
5658:Glutamine synthetase
4464:Transcription factor
2818:10.1093/emboj/cdg173
2139:10.1096/fj.10-177378
1475:extracellular matrix
1358:genome-wide analysis
1326:transcription factor
462:6 E3|6 52.81 cM
423:Chromosome 6 (mouse)
321:Chromosome 3 (human)
102:List of PDB id codes
75:Available structures
4646:Heat shock proteins
4539:Apoptosis inhibitor
3922:TGF beta receptor 2
3620:VHL Family Alliance
3538:10.4161/cc.6.1.3668
2916:2001PNAS...98.9630Y
2711:2002Sci...296.1886M
2426:2008PLoSO...3.3801H
2078:Nature Cell Biology
1956:10.1101/gad.1256804
1847:2015PLoSO..1034645S
1446:factors, including
1289:, and possesses E3
582:epithelium of colon
574:islet of Langerhans
554:ganglionic eminence
5895:Enzyme superfamily
5828:Enzyme promiscuity
2603:10.1101/gad.924501
2318:10.1038/msb4100134
1307:
1013:ENSMUSG00000033933
848:cell morphogenesis
806:Biological process
755:Cellular component
719:Molecular function
566:buccal mucosa cell
6051:
6050:
5760:
5759:
5651:: Carbon-Nitrogen
5443:
5442:
5439:
5438:
4948:Protein targeting
4942:
4941:
4590:
4589:
4560:
4559:
4524:
4523:
4520:
4519:
4458:
4457:
4408:
4407:
4370:
4369:
4287:
4286:
4283:
4282:
4240:
4239:
4185:
4184:
4156:
4155:
4111:
4110:
4077:
4076:
4023:
4022:
4019:
4018:
3985:
3984:
3930:
3929:
3901:
3900:
3872:
3871:
3834:
3833:
3830:
3829:
3747:
3746:
3589:Internal Medicine
3453:(9374): 2059–67.
3400:978-3-642-62714-9
3287:10.1002/ijc.21888
1746:10.1159/000431323
1436:germline mutation
1332:related factors.
1244:
1243:
1240:
1239:
1213:
1212:
1178:
1177:
1157:
1156:
1119:
1118:
1098:
1097:
1064:
1063:
1045:
1044:
1019:
1018:
1000:
999:
974:
973:
955:
954:
903:
902:
703:
702:
699:
698:
668:
667:
655:
654:
593:
592:
491:
490:
390:
389:
217:
216:
213:
212:
85:Ortholog search:
16:(Redirected from
6103:
6068:
6067:
6059:
5931:Hanes–Woolf plot
5874:Enzyme activator
5869:Enzyme inhibitor
5843:Enzyme catalysis
5787:
5780:
5773:
5764:
5763:
5663:Ubiquitin ligase
5470:
5463:
5456:
5447:
5446:
5295:
5294:
5208:Ubiquitin ligase
4974:(ubiquitylation)
4912:Alpha crystallin
4642:
4641:
4617:
4610:
4603:
4594:
4593:
4535:
4534:
4469:
4468:
4419:
4418:
4414:Ubiquitin ligase
4385:
4384:
4307:
4306:
4298:
4297:
4249:
4248:
4196:
4195:
4191:MAPK/ERK pathway
4167:
4166:
4122:
4121:
4088:
4087:
4043:
4042:
4034:
4033:
3996:
3995:
3941:
3940:
3912:
3911:
3883:
3882:
3854:
3853:
3845:
3844:
3807:
3806:
3798:
3797:
3774:
3767:
3760:
3751:
3750:
3733:
3718:
3703:
3683:
3676:
3669:
3660:
3659:
3627:
3614:
3604:
3579:
3550:
3540:
3515:
3490:(8749): 1052–4.
3478:
3441:
3412:
3377:
3367:
3342:
3332:
3307:
3289:
3264:
3254:
3229:
3200:
3194:
3190:
3188:
3180:
3136:
3135:
3125:
3101:
3092:
3091:
3054:
3048:
3047:
3037:
3027:
3018:(43): 29375–84.
3003:
2997:
2996:
2986:
2954:
2948:
2947:
2937:
2927:
2895:
2889:
2888:
2878:
2861:(16): 4298–309.
2855:The EMBO Journal
2846:
2840:
2839:
2829:
2806:The EMBO Journal
2797:
2791:
2790:
2750:
2741:
2740:
2722:
2705:(5574): 1886–9.
2690:
2679:
2678:
2668:
2636:
2625:
2624:
2614:
2582:
2573:
2572:
2552:
2543:
2542:
2532:
2523:(42): 39887–98.
2508:
2499:
2498:
2488:
2479:(32): 29748–53.
2464:
2458:
2457:
2447:
2437:
2405:
2394:
2393:
2383:
2351:
2340:
2339:
2329:
2297:
2286:
2285:
2275:
2265:
2250:BMC Biochemistry
2241:
2230:
2229:
2209:
2203:
2202:
2192:
2168:
2162:
2161:
2151:
2141:
2116:
2110:
2109:
2073:
2067:
2066:
2030:
2024:
2023:
1987:
1978:
1977:
1967:
1950:(23): 2893–904.
1935:
1929:
1928:
1918:
1894:
1879:
1878:
1868:
1858:
1826:
1820:
1817:
1808:
1807:
1779:
1773:
1772:
1765:
1759:
1758:
1748:
1724:
1718:
1717:
1706:
1700:
1699:
1688:
1682:
1672:
1661:
1651:
1632:
1398:gain of function
1394:protein kinase C
1390:pheochromocytoma
1315:tumor suppressor
1291:ubiquitin ligase
1226:
1225:
1197:
1190:
1173:
1161:
1160:
1152:
1128:
1127:
1124:RefSeq (protein)
1114:
1102:
1101:
1093:
1073:
1072:
1049:
1048:
1030:
1029:
1004:
1003:
985:
984:
959:
958:
940:
939:
909:
908:
709:
708:
695:
686:
679:
678:
664:
648:genital tubercle
640:ventricular zone
604:
602:Top expressed in
597:
596:
562:ventricular zone
542:
540:Top expressed in
535:
534:
514:
513:
497:
496:
487:
474:
463:
448:
441:
435:
424:
412:
396:
395:
386:
373:
362:
347:
340:
334:
323:
309:
293:
292:
287:
238:
231:
208:
99:
98:
93:
72:
71:
66:
54:
53:
39:
21:
6111:
6110:
6106:
6105:
6104:
6102:
6101:
6100:
6076:
6075:
6074:
6062:
6054:
6052:
6047:
5959:Oxidoreductases
5945:
5921:Enzyme kinetics
5909:
5905:List of enzymes
5878:
5847:
5818:Catalytic triad
5796:
5791:
5761:
5756:
5643:
5622:: Carbon-Sulfur
5614:
5496:: Carbon-Oxygen
5488:
5479:: CO CS and CN
5474:
5444:
5435:
5362:
5337:E3 SUMO ligase
5301:
5290:
5282:
4973:
4965:
4938:
4900:
4879:
4871:
4649:
4637:protein folding
4635:
4626:
4621:
4591:
4586:
4565:Other/ungrouped
4556:
4516:
4500:
4454:
4438:
4404:
4366:
4331:
4279:
4263:
4236:
4232:Neurofibromin 1
4220:
4181:
4152:
4136:
4107:
4073:
4057:
4015:
3981:
3926:
3897:
3868:
3826:
3787:
3778:
3748:
3743:
3740:
3734:
3725:
3719:
3710:
3704:
3690:
3687:
3635:
3630:
3562:(4–5): 539–46.
3401:
3192:
3191:
3182:
3181:
3169:
3144:
3142:Further reading
3139:
3102:
3095:
3055:
3051:
3004:
3000:
2955:
2951:
2896:
2892:
2847:
2843:
2798:
2794:
2759:Nature Genetics
2751:
2744:
2691:
2682:
2637:
2628:
2597:(20): 2675–86.
2583:
2576:
2557:Cancer Research
2553:
2546:
2509:
2502:
2465:
2461:
2406:
2397:
2372:10.1172/JCI8161
2366:(11): 1583–91.
2352:
2343:
2298:
2289:
2242:
2233:
2214:Cancer Research
2210:
2206:
2169:
2165:
2117:
2113:
2090:10.1038/ncb1912
2084:(8): 994–1001.
2074:
2070:
2031:
2027:
1988:
1981:
1936:
1932:
1895:
1882:
1841:(8): e0134645.
1827:
1823:
1818:
1811:
1780:
1776:
1767:
1766:
1762:
1725:
1721:
1708:
1707:
1703:
1690:
1689:
1685:
1673:
1664:
1652:
1643:
1639:
1630:
1623:
1618:
1535:
1501:, and recently
1487:
1432:cancer syndrome
1425:
1342:renal carcinoma
1275:
1235:View/Edit Mouse
1230:View/Edit Human
1193:
1186:
1183:Location (UCSC)
1169:
1148:
1144:
1140:
1136:
1110:
1089:
1085:
1081:
994:ENSG00000134086
887:
801:
750:
741:protein binding
691:
660:
651:
646:
642:
638:
634:
630:
626:
622:
618:
614:
600:
589:
584:
580:
576:
572:
568:
564:
560:
556:
552:
538:
482:
469:
461:
451:
450:
449:
442:
422:
399:Gene location (
381:
368:
360:
350:
349:
348:
341:
319:
296:Gene location (
285:VHL - orthologs
247:
234:
227:
108:
86:
52:
30:
23:
22:
15:
12:
11:
5:
6109:
6099:
6098:
6093:
6088:
6073:
6072:
6049:
6048:
6046:
6045:
6032:
6019:
6006:
5993:
5980:
5967:
5953:
5951:
5947:
5946:
5944:
5943:
5938:
5933:
5928:
5923:
5917:
5915:
5911:
5910:
5908:
5907:
5902:
5897:
5892:
5886:
5884:
5883:Classification
5880:
5879:
5877:
5876:
5871:
5866:
5861:
5855:
5853:
5849:
5848:
5846:
5845:
5840:
5835:
5830:
5825:
5820:
5815:
5810:
5804:
5802:
5798:
5797:
5790:
5789:
5782:
5775:
5767:
5758:
5757:
5755:
5754:
5749:
5748:
5747:
5742:
5732:
5727:
5722:
5717:
5712:
5707:
5705:CTP synthetase
5702:
5697:
5696:
5695:
5690:
5685:
5680:
5675:
5670:
5660:
5654:
5652:
5645:
5644:
5642:
5641:
5636:
5631:
5625:
5623:
5616:
5615:
5613:
5612:
5611:
5610:
5605:
5600:
5595:
5590:
5585:
5580:
5575:
5570:
5565:
5560:
5555:
5550:
5545:
5540:
5535:
5530:
5525:
5520:
5515:
5510:
5499:
5497:
5490:
5489:
5473:
5472:
5465:
5458:
5450:
5441:
5440:
5437:
5436:
5434:
5433:
5427:
5426:
5421:
5416:
5411:
5406:
5401:
5396:
5386:
5381:
5376:
5370:
5368:
5364:
5363:
5361:
5360:
5359:
5358:
5353:
5348:
5343:
5334:
5333:
5332:
5331:
5322:
5321:
5320:
5319:
5314:
5305:
5303:
5292:
5284:
5283:
5281:
5280:
5275:
5270:
5264:
5263:
5258:
5253:
5243:
5242:
5241:
5240:
5235:
5230:
5225:
5220:
5215:
5203:
5202:
5201:
5200:
5195:
5190:
5185:
5180:
5175:
5169:
5164:
5159:
5154:
5149:
5144:
5139:
5134:
5129:
5124:
5119:
5114:
5109:
5104:
5099:
5094:
5089:
5084:
5079:
5074:
5069:
5064:
5059:
5054:
5049:
5044:
5032:
5031:
5030:
5029:
5024:
5019:
5014:
5009:
5004:
4999:
4994:
4989:
4977:
4975:
4967:
4966:
4964:
4963:
4958:
4956:Signal peptide
4952:
4950:
4944:
4943:
4940:
4939:
4937:
4936:
4935:
4934:
4929:
4919:
4914:
4908:
4906:
4902:
4901:
4899:
4898:
4897:
4896:
4891:
4886:
4881:
4877:
4873:
4869:
4859:
4858:
4857:
4856:
4851:
4846:
4841:
4836:
4831:
4826:
4821:
4816:
4811:
4806:
4801:
4796:
4785:
4784:
4783:
4782:
4777:
4772:
4767:
4762:
4757:
4752:
4747:
4742:
4737:
4732:
4727:
4722:
4717:
4712:
4707:
4702:
4697:
4692:
4681:
4680:
4671:
4666:
4661:
4655:
4653:
4639:
4628:
4627:
4620:
4619:
4612:
4605:
4597:
4588:
4587:
4585:
4584:
4579:
4574:
4568:
4566:
4562:
4561:
4558:
4557:
4555:
4554:
4549:
4543:
4541:
4532:
4526:
4525:
4522:
4521:
4518:
4517:
4515:
4514:
4508:
4506:
4502:
4501:
4499:
4498:
4493:
4492:
4491:
4486:
4475:
4473:
4466:
4460:
4459:
4456:
4455:
4453:
4452:
4446:
4444:
4440:
4439:
4437:
4436:
4431:
4425:
4423:
4416:
4410:
4409:
4406:
4405:
4403:
4402:
4397:
4391:
4389:
4382:
4372:
4371:
4368:
4367:
4365:
4364:
4355:
4350:
4345:
4339:
4337:
4333:
4332:
4330:
4329:
4324:
4319:
4313:
4311:
4304:
4295:
4289:
4288:
4285:
4284:
4281:
4280:
4278:
4277:
4271:
4269:
4265:
4264:
4262:
4261:
4255:
4253:
4246:
4242:
4241:
4238:
4237:
4235:
4234:
4228:
4226:
4222:
4221:
4219:
4218:
4213:
4208:
4202:
4200:
4193:
4187:
4186:
4183:
4182:
4180:
4179:
4173:
4171:
4164:
4158:
4157:
4154:
4153:
4151:
4150:
4144:
4142:
4138:
4137:
4135:
4134:
4128:
4126:
4119:
4113:
4112:
4109:
4108:
4106:
4105:
4100:
4094:
4092:
4085:
4079:
4078:
4075:
4074:
4072:
4071:
4065:
4063:
4059:
4058:
4056:
4055:
4049:
4047:
4040:
4031:
4025:
4024:
4021:
4020:
4017:
4016:
4014:
4013:
4008:
4002:
4000:
3993:
3987:
3986:
3983:
3982:
3980:
3979:
3974:
3969:
3968:
3967:
3962:
3947:
3945:
3938:
3932:
3931:
3928:
3927:
3925:
3924:
3918:
3916:
3909:
3903:
3902:
3899:
3898:
3896:
3895:
3889:
3887:
3880:
3874:
3873:
3870:
3869:
3867:
3866:
3860:
3858:
3851:
3842:
3836:
3835:
3832:
3831:
3828:
3827:
3825:
3824:
3819:
3813:
3811:
3804:
3802:Growth factors
3795:
3789:
3788:
3777:
3776:
3769:
3762:
3754:
3745:
3744:
3742:
3741:
3735:
3728:
3726:
3720:
3713:
3711:
3705:
3698:
3695:
3692:
3691:
3686:
3685:
3678:
3671:
3663:
3657:
3656:
3646:
3641:
3634:
3633:External links
3631:
3629:
3628:
3615:
3580:
3551:
3516:
3479:
3442:
3413:
3399:
3378:
3343:
3308:
3265:
3230:
3201:
3193:|journal=
3168:978-0120066858
3167:
3145:
3143:
3140:
3138:
3137:
3116:(7): 4656–62.
3093:
3049:
2998:
2949:
2910:(17): 9630–5.
2890:
2841:
2812:(8): 1857–67.
2792:
2771:10.1038/ng1254
2742:
2680:
2626:
2574:
2563:(13): 2881–5.
2544:
2500:
2459:
2395:
2341:
2287:
2231:
2204:
2163:
2132:(6): 2001–11.
2111:
2068:
2025:
2004:10.1038/nrc885
1979:
1930:
1880:
1821:
1809:
1774:
1760:
1719:
1701:
1683:
1662:
1640:
1638:
1635:
1634:
1633:
1622:
1619:
1617:
1616:
1610:
1604:
1598:
1592:
1586:
1580:
1574:
1568:
1562:
1556:
1550:
1543:
1534:
1531:
1486:
1483:
1424:
1421:
1365:2-oxoglutarate
1274:
1271:
1250:also known as
1242:
1241:
1238:
1237:
1232:
1222:
1221:
1215:
1214:
1211:
1210:
1208:
1206:
1199:
1198:
1191:
1184:
1180:
1179:
1176:
1175:
1165:
1164:
1158:
1155:
1154:
1132:
1131:
1125:
1121:
1120:
1117:
1116:
1106:
1105:
1099:
1096:
1095:
1077:
1076:
1070:
1066:
1065:
1062:
1061:
1053:
1052:
1046:
1043:
1042:
1034:
1033:
1027:
1021:
1020:
1017:
1016:
1008:
1007:
1001:
998:
997:
989:
988:
982:
976:
975:
972:
971:
963:
962:
956:
953:
952:
944:
943:
937:
931:
930:
925:
920:
916:
915:
905:
904:
901:
900:
889:
888:
886:
885:
880:
875:
870:
865:
860:
855:
850:
845:
840:
835:
830:
825:
820:
815:
809:
807:
803:
802:
800:
799:
794:
789:
784:
779:
774:
769:
764:
758:
756:
752:
751:
749:
748:
746:enzyme binding
743:
738:
733:
728:
722:
720:
716:
715:
705:
704:
701:
700:
697:
696:
688:
687:
676:
670:
669:
666:
665:
657:
656:
653:
652:
650:
649:
645:
641:
637:
633:
629:
625:
621:
617:
613:
609:
606:
605:
594:
591:
590:
588:
587:
583:
579:
575:
571:
567:
563:
559:
555:
551:
547:
544:
543:
531:
530:
522:
511:
505:
504:
501:RNA expression
493:
492:
489:
488:
480:
476:
475:
467:
464:
459:
453:
452:
443:
436:
430:
426:
425:
420:
414:
413:
405:
404:
392:
391:
388:
387:
379:
375:
374:
366:
363:
358:
352:
351:
342:
335:
329:
325:
324:
317:
311:
310:
302:
301:
289:
288:
245:
241:
240:
232:
224:
223:
219:
218:
215:
214:
211:
210:
104:
103:
95:
94:
83:
77:
76:
68:
67:
59:
58:
28:
9:
6:
4:
3:
2:
6108:
6097:
6094:
6092:
6089:
6087:
6084:
6083:
6081:
6071:
6066:
6061:
6060:
6057:
6043:
6039:
6038:
6033:
6030:
6026:
6025:
6020:
6017:
6013:
6012:
6007:
6004:
6000:
5999:
5994:
5991:
5987:
5986:
5981:
5978:
5974:
5973:
5968:
5965:
5961:
5960:
5955:
5954:
5952:
5948:
5942:
5939:
5937:
5934:
5932:
5929:
5927:
5924:
5922:
5919:
5918:
5916:
5912:
5906:
5903:
5901:
5900:Enzyme family
5898:
5896:
5893:
5891:
5888:
5887:
5885:
5881:
5875:
5872:
5870:
5867:
5865:
5864:Cooperativity
5862:
5860:
5857:
5856:
5854:
5850:
5844:
5841:
5839:
5836:
5834:
5831:
5829:
5826:
5824:
5823:Oxyanion hole
5821:
5819:
5816:
5814:
5811:
5809:
5806:
5805:
5803:
5799:
5795:
5788:
5783:
5781:
5776:
5774:
5769:
5768:
5765:
5753:
5750:
5746:
5743:
5741:
5738:
5737:
5736:
5733:
5731:
5728:
5726:
5723:
5721:
5718:
5716:
5713:
5711:
5708:
5706:
5703:
5701:
5698:
5694:
5691:
5689:
5686:
5684:
5681:
5679:
5676:
5674:
5671:
5669:
5666:
5665:
5664:
5661:
5659:
5656:
5655:
5653:
5650:
5646:
5640:
5637:
5635:
5632:
5630:
5627:
5626:
5624:
5621:
5617:
5609:
5606:
5604:
5601:
5599:
5596:
5594:
5591:
5589:
5586:
5584:
5581:
5579:
5578:Phenylalanine
5576:
5574:
5571:
5569:
5566:
5564:
5561:
5559:
5556:
5554:
5551:
5549:
5546:
5544:
5541:
5539:
5536:
5534:
5531:
5529:
5526:
5524:
5521:
5519:
5516:
5514:
5511:
5509:
5506:
5505:
5504:
5501:
5500:
5498:
5495:
5491:
5486:
5482:
5478:
5471:
5466:
5464:
5459:
5457:
5452:
5451:
5448:
5432:
5429:
5428:
5425:
5422:
5420:
5417:
5415:
5412:
5410:
5407:
5405:
5402:
5400:
5397:
5394:
5390:
5387:
5385:
5382:
5380:
5377:
5375:
5372:
5371:
5369:
5365:
5357:
5354:
5352:
5349:
5347:
5344:
5342:
5339:
5338:
5336:
5335:
5330:
5327:
5326:
5324:
5323:
5318:
5315:
5313:
5310:
5309:
5307:
5306:
5304:
5302:(SUMOylation)
5300:
5296:
5293:
5289:
5285:
5279:
5276:
5274:
5271:
5269:
5266:
5265:
5262:
5259:
5257:
5254:
5252:
5248:
5245:
5244:
5239:
5236:
5234:
5231:
5229:
5226:
5224:
5221:
5219:
5216:
5214:
5211:
5210:
5209:
5205:
5204:
5199:
5196:
5194:
5191:
5189:
5186:
5184:
5181:
5179:
5176:
5173:
5170:
5168:
5165:
5163:
5160:
5158:
5155:
5153:
5150:
5148:
5145:
5143:
5140:
5138:
5135:
5133:
5130:
5128:
5125:
5123:
5120:
5118:
5115:
5113:
5110:
5108:
5105:
5103:
5100:
5098:
5095:
5093:
5090:
5088:
5085:
5083:
5080:
5078:
5075:
5073:
5070:
5068:
5065:
5063:
5060:
5058:
5055:
5053:
5050:
5048:
5045:
5043:
5040:
5039:
5038:
5034:
5033:
5028:
5025:
5023:
5020:
5018:
5015:
5013:
5010:
5008:
5005:
5003:
5000:
4998:
4995:
4993:
4990:
4988:
4985:
4984:
4983:
4979:
4978:
4976:
4972:
4968:
4962:
4959:
4957:
4954:
4953:
4951:
4949:
4945:
4933:
4930:
4928:
4925:
4924:
4923:
4920:
4918:
4915:
4913:
4910:
4909:
4907:
4903:
4895:
4892:
4890:
4887:
4885:
4882:
4880:
4874:
4872:
4866:
4865:
4864:
4861:
4860:
4855:
4852:
4850:
4847:
4845:
4842:
4840:
4837:
4835:
4832:
4830:
4827:
4825:
4822:
4820:
4817:
4815:
4812:
4810:
4807:
4805:
4802:
4800:
4797:
4795:
4792:
4791:
4790:
4787:
4786:
4781:
4778:
4776:
4773:
4771:
4768:
4766:
4763:
4761:
4758:
4756:
4753:
4751:
4748:
4746:
4743:
4741:
4738:
4736:
4733:
4731:
4728:
4726:
4723:
4721:
4718:
4716:
4713:
4711:
4708:
4706:
4703:
4701:
4698:
4696:
4693:
4691:
4688:
4687:
4686:
4683:
4682:
4679:
4675:
4672:
4670:
4667:
4665:
4662:
4660:
4657:
4656:
4654:
4652:
4647:
4643:
4640:
4638:
4633:
4629:
4625:
4618:
4613:
4611:
4606:
4604:
4599:
4598:
4595:
4583:
4580:
4578:
4575:
4573:
4570:
4569:
4567:
4563:
4553:
4550:
4548:
4545:
4544:
4542:
4540:
4536:
4533:
4531:
4530:Mitochondrion
4527:
4513:
4510:
4509:
4507:
4503:
4497:
4494:
4490:
4487:
4485:
4482:
4481:
4480:
4477:
4476:
4474:
4470:
4467:
4465:
4461:
4451:
4448:
4447:
4445:
4441:
4435:
4432:
4430:
4427:
4426:
4424:
4420:
4417:
4415:
4411:
4401:
4398:
4396:
4393:
4392:
4390:
4386:
4383:
4381:
4377:
4373:
4363:
4359:
4356:
4354:
4351:
4349:
4346:
4344:
4341:
4340:
4338:
4334:
4328:
4325:
4323:
4320:
4318:
4315:
4314:
4312:
4308:
4305:
4303:
4299:
4296:
4294:
4290:
4276:
4273:
4272:
4270:
4266:
4260:
4257:
4256:
4254:
4250:
4247:
4245:Other/unknown
4243:
4233:
4230:
4229:
4227:
4223:
4217:
4214:
4212:
4209:
4207:
4204:
4203:
4201:
4197:
4194:
4192:
4188:
4178:
4175:
4174:
4172:
4168:
4165:
4163:
4159:
4149:
4146:
4145:
4143:
4139:
4133:
4130:
4129:
4127:
4123:
4120:
4118:
4114:
4104:
4101:
4099:
4096:
4095:
4093:
4089:
4086:
4084:
4080:
4070:
4067:
4066:
4064:
4060:
4054:
4051:
4050:
4048:
4044:
4041:
4039:
4035:
4032:
4030:
4026:
4012:
4009:
4007:
4004:
4003:
4001:
3997:
3994:
3992:
3988:
3978:
3975:
3973:
3970:
3966:
3963:
3961:
3958:
3957:
3956:
3952:
3949:
3948:
3946:
3942:
3939:
3937:
3933:
3923:
3920:
3919:
3917:
3913:
3910:
3908:
3904:
3894:
3891:
3890:
3888:
3884:
3881:
3879:
3875:
3865:
3862:
3861:
3859:
3855:
3852:
3850:
3846:
3843:
3841:
3837:
3823:
3820:
3818:
3815:
3814:
3812:
3808:
3805:
3803:
3799:
3796:
3794:
3790:
3786:
3782:
3775:
3770:
3768:
3763:
3761:
3756:
3755:
3752:
3738:
3732:
3727:
3723:
3717:
3712:
3708:
3702:
3697:
3696:
3693:
3684:
3679:
3677:
3672:
3670:
3665:
3664:
3661:
3654:
3650:
3647:
3645:
3642:
3640:
3637:
3636:
3625:
3621:
3616:
3612:
3608:
3603:
3598:
3594:
3590:
3586:
3581:
3577:
3573:
3569:
3565:
3561:
3557:
3552:
3548:
3544:
3539:
3534:
3530:
3526:
3522:
3517:
3513:
3509:
3505:
3501:
3497:
3493:
3489:
3485:
3480:
3476:
3472:
3468:
3464:
3460:
3456:
3452:
3448:
3443:
3439:
3435:
3431:
3427:
3423:
3419:
3418:Blood Reviews
3414:
3410:
3406:
3402:
3396:
3392:
3388:
3384:
3379:
3375:
3371:
3366:
3361:
3357:
3353:
3349:
3344:
3340:
3336:
3331:
3326:
3322:
3318:
3314:
3309:
3305:
3301:
3297:
3293:
3288:
3283:
3279:
3275:
3271:
3266:
3262:
3258:
3253:
3248:
3245:(7): 1801–6.
3244:
3240:
3236:
3231:
3227:
3223:
3219:
3215:
3211:
3207:
3202:
3198:
3186:
3178:
3174:
3170:
3164:
3160:
3156:
3152:
3147:
3146:
3133:
3129:
3124:
3119:
3115:
3111:
3107:
3100:
3098:
3089:
3085:
3081:
3077:
3073:
3069:
3066:(1): 236–45.
3065:
3061:
3053:
3045:
3041:
3036:
3031:
3026:
3021:
3017:
3013:
3009:
3002:
2994:
2990:
2985:
2980:
2976:
2972:
2969:(5): 479–85.
2968:
2964:
2960:
2953:
2945:
2941:
2936:
2931:
2926:
2921:
2917:
2913:
2909:
2905:
2901:
2894:
2886:
2882:
2877:
2872:
2868:
2864:
2860:
2856:
2852:
2845:
2837:
2833:
2828:
2823:
2819:
2815:
2811:
2807:
2803:
2796:
2788:
2784:
2780:
2776:
2772:
2768:
2765:(3): 229–37.
2764:
2760:
2756:
2749:
2747:
2738:
2734:
2730:
2726:
2721:
2716:
2712:
2708:
2704:
2700:
2696:
2689:
2687:
2685:
2676:
2672:
2667:
2662:
2658:
2654:
2650:
2646:
2642:
2635:
2633:
2631:
2622:
2618:
2613:
2608:
2604:
2600:
2596:
2592:
2588:
2581:
2579:
2570:
2566:
2562:
2558:
2551:
2549:
2540:
2536:
2531:
2526:
2522:
2518:
2514:
2507:
2505:
2496:
2492:
2487:
2482:
2478:
2474:
2470:
2463:
2455:
2451:
2446:
2441:
2436:
2431:
2427:
2423:
2420:(11): e3801.
2419:
2415:
2411:
2404:
2402:
2400:
2391:
2387:
2382:
2377:
2373:
2369:
2365:
2361:
2357:
2350:
2348:
2346:
2337:
2333:
2328:
2323:
2319:
2315:
2311:
2307:
2303:
2296:
2294:
2292:
2283:
2279:
2274:
2269:
2264:
2259:
2255:
2251:
2247:
2240:
2238:
2236:
2227:
2223:
2220:(8): 1764–8.
2219:
2215:
2208:
2200:
2196:
2191:
2186:
2182:
2178:
2174:
2167:
2159:
2155:
2150:
2145:
2140:
2135:
2131:
2127:
2126:FASEB Journal
2123:
2115:
2107:
2103:
2099:
2095:
2091:
2087:
2083:
2079:
2072:
2064:
2060:
2056:
2052:
2048:
2044:
2041:(2): 139–46.
2040:
2036:
2029:
2021:
2017:
2013:
2009:
2005:
2001:
1998:(9): 673–82.
1997:
1993:
1986:
1984:
1975:
1971:
1966:
1961:
1957:
1953:
1949:
1945:
1941:
1934:
1926:
1922:
1917:
1912:
1908:
1904:
1900:
1893:
1891:
1889:
1887:
1885:
1876:
1872:
1867:
1862:
1857:
1852:
1848:
1844:
1840:
1836:
1832:
1825:
1819:Maxwell, 2005
1816:
1814:
1805:
1801:
1797:
1793:
1789:
1785:
1778:
1770:
1764:
1756:
1752:
1747:
1742:
1739:(3): 145–52.
1738:
1734:
1730:
1723:
1715:
1711:
1705:
1697:
1693:
1687:
1680:
1676:
1671:
1669:
1667:
1659:
1655:
1650:
1648:
1646:
1641:
1628:
1625:
1624:
1614:
1611:
1608:
1605:
1602:
1599:
1596:
1593:
1590:
1587:
1584:
1581:
1578:
1575:
1572:
1569:
1566:
1563:
1560:
1557:
1554:
1551:
1548:
1545:
1544:
1542:
1540:
1530:
1528:
1522:
1520:
1516:
1512:
1508:
1504:
1500:
1496:
1492:
1482:
1480:
1476:
1471:
1469:
1465:
1461:
1457:
1453:
1449:
1445:
1440:
1437:
1433:
1429:
1420:
1418:
1414:
1410:
1405:
1401:
1399:
1395:
1391:
1386:
1380:
1378:
1373:
1371:
1366:
1361:
1359:
1355:
1351:
1345:
1343:
1339:
1333:
1331:
1327:
1323:
1318:
1316:
1312:
1302:
1298:
1296:
1292:
1288:
1284:
1280:
1270:
1268:
1264:
1261:
1257:
1253:
1249:
1236:
1231:
1227:
1223:
1220:
1216:
1209:
1207:
1204:
1200:
1196:
1192:
1189:
1185:
1181:
1174:
1172:
1166:
1162:
1159:
1153:
1151:
1147:
1143:
1139:
1133:
1129:
1126:
1122:
1115:
1113:
1107:
1103:
1100:
1094:
1092:
1088:
1084:
1078:
1074:
1071:
1069:RefSeq (mRNA)
1067:
1060:
1059:
1054:
1050:
1047:
1041:
1040:
1035:
1031:
1028:
1026:
1022:
1015:
1014:
1009:
1005:
1002:
996:
995:
990:
986:
983:
981:
977:
970:
969:
964:
960:
957:
951:
950:
945:
941:
938:
936:
932:
929:
926:
924:
921:
917:
914:
910:
906:
899:
895:
890:
884:
881:
879:
876:
874:
871:
869:
866:
864:
861:
859:
856:
854:
851:
849:
846:
844:
841:
839:
836:
834:
831:
829:
826:
824:
821:
819:
816:
814:
811:
810:
808:
805:
804:
798:
795:
793:
792:mitochondrion
790:
788:
785:
783:
780:
778:
775:
773:
770:
768:
765:
763:
760:
759:
757:
754:
753:
747:
744:
742:
739:
737:
734:
732:
729:
727:
724:
723:
721:
718:
717:
714:
713:Gene ontology
710:
706:
694:
689:
685:
680:
677:
675:
671:
663:
658:
647:
643:
639:
635:
631:
627:
623:
619:
615:
611:
610:
607:
603:
598:
595:
585:
581:
577:
573:
569:
565:
561:
557:
553:
549:
548:
545:
541:
536:
533:
532:
529:
527:
523:
521:
520:
516:
515:
512:
510:
506:
502:
498:
494:
486:
481:
477:
473:
468:
458:
454:
447:
440:
434:
427:
419:
415:
411:
406:
402:
397:
393:
385:
380:
376:
372:
367:
357:
353:
346:
339:
333:
326:
322:
316:
312:
308:
303:
299:
294:
290:
286:
282:
278:
274:
270:
266:
262:
258:
254:
250:
242:
237:
230:
225:
220:
209:
207:
203:
199:
195:
191:
187:
183:
179:
175:
171:
167:
163:
159:
155:
151:
147:
143:
139:
135:
131:
127:
123:
119:
115:
111:
105:
100:
97:
96:
92:
89:
82:
78:
73:
69:
65:
60:
55:
50:
46:
43:
35:
27:
19:
6037:Translocases
6034:
6021:
6008:
5995:
5982:
5972:Transferases
5969:
5956:
5813:Binding site
5725:GMP synthase
5672:
5299:SUMO protein
5212:
4449:
4053:Beta-catenin
3736:
3721:
3706:
3639:VHL Alliance
3623:
3619:
3595:(5): 265–9.
3592:
3588:
3559:
3555:
3528:
3524:
3487:
3483:
3450:
3446:
3421:
3417:
3382:
3355:
3351:
3320:
3316:
3280:(3): 624–9.
3277:
3273:
3242:
3238:
3212:(4): 146–9.
3209:
3205:
3150:
3113:
3109:
3063:
3059:
3052:
3015:
3011:
3001:
2966:
2962:
2952:
2907:
2903:
2893:
2858:
2854:
2844:
2809:
2805:
2795:
2762:
2758:
2702:
2698:
2651:(1): 71–83.
2648:
2644:
2594:
2590:
2560:
2556:
2520:
2516:
2476:
2472:
2462:
2417:
2413:
2363:
2359:
2309:
2305:
2253:
2249:
2217:
2213:
2207:
2180:
2176:
2166:
2129:
2125:
2114:
2081:
2077:
2071:
2038:
2034:
2028:
1995:
1991:
1947:
1943:
1933:
1906:
1902:
1838:
1834:
1824:
1790:(4): 146–9.
1787:
1783:
1777:
1763:
1736:
1732:
1722:
1713:
1704:
1695:
1686:
1536:
1533:Interactions
1523:
1515:temsirolimus
1488:
1472:
1456:blood vessel
1441:
1426:
1406:
1402:
1384:
1381:
1374:
1362:
1346:
1338:angiogenesis
1334:
1330:angiogenesis
1319:
1308:
1276:
1259:
1251:
1247:
1245:
1168:
1146:NP_001341652
1135:
1109:
1091:NM_001354723
1080:
1056:
1037:
1011:
992:
966:
947:
927:
922:
628:cumulus cell
624:spermatocyte
524:
517:
483:113,608,594
470:113,600,920
244:External IDs
107:
26:
5808:Active site
5393:neddylation
4659:Hsp10/GroES
4651:Chaperonins
3689:PDB gallery
3531:(1): 56–9.
3424:(1): 1–13.
1519:bevacizumab
1464:mesenchymal
1400:' protein.
1324:(HIF1a), a
1150:NP_000542.1
833:proteolysis
782:nucleoplasm
772:VCB complex
636:granulocyte
570:granulocyte
382:10,153,667
369:10,141,778
222:Identifiers
6080:Categories
6011:Isomerases
5985:Hydrolases
5852:Regulation
5598:Tryptophan
5573:Methionine
5558:Isoleucine
5518:Asparagine
4685:Hsp40/DnaJ
4632:Chaperones
4376:DNA repair
4302:Cell cycle
3817:c-Sis/PDGF
3626:(1): 1–56.
3525:Cell Cycle
1681:, May 2017
1660:, May 2017
1637:References
1511:everolimus
1479:metastasis
1468:epithelial
1444:angiogenic
1417:aneuploidy
578:lymph node
528:(ortholog)
265:HomoloGene
5890:EC number
5593:Threonine
5553:Histidine
5543:Glutamine
5538:Glutamate
5523:Aspartate
4971:Ubiquitin
4917:Clusterin
3785:Oncogenes
3195:ignored (
3185:cite book
2755:Herman JG
1527:Vitamin C
1507:rapamycin
1499:pazopanib
1495:sunitinib
1491:sorafenib
1485:Treatment
1423:Pathology
1354:apoptosis
1350:cyclin D1
1283:elongin C
1279:elongin B
1171:NP_033533
1142:NP_937799
1138:NP_000542
1112:NM_009507
1087:NM_198156
1083:NM_000551
913:Orthologs
762:cytoplasm
612:spermatid
273:GeneCards
5914:Kinetics
5838:Cofactor
5801:Activity
5603:Tyrosine
5528:Cysteine
5513:Arginine
5487:6.1-6.3)
5251:Ataxin 3
4582:Stathmin
4327:Cyclin E
4322:Cyclin D
3960:HER2/neu
3840:Receptor
3611:16595991
3576:16144691
3547:17245122
3512:24022884
3475:13783714
3467:12814730
3438:15572213
3409:11908068
3374:17255293
3339:15448019
3296:16506218
3261:16775032
3226:15162797
3177:12374282
3132:11739384
3088:31675735
3080:18426857
3044:18694926
2993:18985005
2944:11504942
2885:10944113
2836:12682018
2787:22798700
2779:14556007
2737:19641938
2729:12004076
2675:18305400
2621:11641274
2539:12169691
2495:11384984
2454:19030229
2414:PLOS ONE
2390:10587522
2336:17353931
2282:18173839
2226:12702559
2199:15448019
2158:21389259
2098:19620968
2063:37709417
2055:15530850
2020:20186415
2012:12209156
1974:15545625
1925:17255293
1875:26262842
1835:PLOS ONE
1804:15162797
1755:26279462
1677:–
1656:–
1621:See also
1539:interact
1509:analogs
1503:axitinib
1287:cullin-2
1273:Function
1219:Wikidata
892:Sources:
777:membrane
550:monocyte
6070:Biology
6024:Ligases
5794:Enzymes
5583:Proline
5563:Leucine
5548:Glycine
5508:Alanine
5481:ligases
5477:Enzymes
5174:(CDC34)
4572:c-Bcl-2
4380:Fanconi
4293:Nucleus
3504:1673491
3035:2662024
2984:2679355
2912:Bibcode
2707:Bibcode
2699:Science
2666:2679322
2569:8674032
2445:2583047
2422:Bibcode
2327:1847948
2273:2265268
2149:3159892
2106:5287739
1866:4532367
1843:Bibcode
1679:Ensembl
1658:Ensembl
1559:Filamin
1409:tubulin
1256:protein
1025:UniProt
980:Ensembl
919:Species
898:QuickGO
797:nucleus
767:cytosol
503:pattern
229:Aliases
34:Russian
6096:EC 6.3
6056:Portal
5998:Lyases
5668:Cullin
5608:Valine
5588:Serine
5568:Lysine
5218:Cullin
4362:p14arf
4275:Maspin
3955:c-ErbB
3793:Ligand
3655:(MeSH)
3609:
3574:
3545:
3510:
3502:
3484:Lancet
3473:
3465:
3447:Lancet
3436:
3407:
3397:
3372:
3337:
3304:632377
3302:
3294:
3259:
3224:
3175:
3165:
3130:
3086:
3078:
3042:
3032:
2991:
2981:
2942:
2932:
2883:
2876:302039
2873:
2834:
2827:154465
2824:
2785:
2777:
2735:
2727:
2673:
2663:
2619:
2612:312814
2609:
2567:
2537:
2493:
2452:
2442:
2388:
2381:481054
2378:
2334:
2324:
2312:: 89.
2280:
2270:
2224:
2197:
2156:
2146:
2104:
2096:
2061:
2053:
2018:
2010:
1972:
1965:534650
1962:
1923:
1873:
1863:
1802:
1753:
1595:SAP130
1565:HIF1AN
1547:CCDC82
1541:with:
1285:, and
1205:search
1203:PubMed
1058:P40338
1039:P40337
935:Entrez
674:BioGPS
632:morula
586:rectum
361:3p25.3
261:103223
253:608537
47:, see
45:league
42:hockey
5950:Types
5678:UBE3A
5409:ATG12
5399:FAT10
5389:NEDD8
5374:ISG15
5367:Other
5356:PIAS4
5351:PIAS3
5346:PIAS2
5341:PIAS1
5291:(UBL)
5273:BIRC6
5233:FANCL
4905:Other
4894:TRAP1
4863:Hsp90
4789:Hsp70
4678:GroEL
4674:HSP60
4669:Hsp47
4664:Hsp27
4577:Notch
4496:c-Myc
4489:c-Jun
4484:c-Fos
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