VHL_HUMAN
ID VHL_HUMAN Reviewed; 213 AA.
AC P40337; B2RE45; Q13599; Q6PDA9;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 03-AUG-2022, entry version 240.
DE RecName: Full=von Hippel-Lindau disease tumor suppressor;
DE AltName: Full=Protein G7;
DE AltName: Full=pVHL;
GN Name=VHL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANTS VHLD ILE-75
RP DEL AND ARG-82--84-VAL DEL, AND ALTERNATIVE SPLICING (ISOFORM 2).
RX PubMed=8493574; DOI=10.1126/science.8493574;
RA Latif F., Tory K., Gnarra J., Yao M., Duh F.-M., Orcutt M.L.,
RA Stackhouse T., Kuzmin I., Modi W., Geil L., Schmidt L., Zhou F., Li H.,
RA Wei M.H., Chen F., Glenn G., Choyke P., Walther M.M., Weng Y.,
RA Duan D.-S.R., Dean M., Glavac D., Richards F.M., Crossey P.A.,
RA Ferguson-Smith M.A., le Paslier D., Chumakov I., Cohen D., Chinault A.C.,
RA Maher E.R., Linehan W.M., Zbar B., Lerman M.I.;
RT "Identification of the von Hippel-Lindau disease tumor suppressor gene.";
RL Science 260:1317-1320(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT TYR-110.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 33-67 AND 156-213, AND VARIANT
RP PRO-163.
RC TISSUE=Renal cell carcinoma;
RA Wenzel M.;
RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP DEVELOPMENTAL STAGE, AND ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
RX PubMed=8733131; DOI=10.1093/hmg/5.5.639;
RA Richards F.M., Schofield P.N., Fleming S., Maher E.R.;
RT "Expression of the von Hippel-Lindau disease tumour suppressor gene during
RT human embryogenesis.";
RL Hum. Mol. Genet. 5:639-644(1996).
RN [8]
RP INTERACTION WITH CUL2.
RX PubMed=9122164; DOI=10.1073/pnas.94.6.2156;
RA Pause A., Lee S., Worrel R., Chen D.Y.T., Burgess W.H., Linehan W.M.,
RA Klausner R.D.;
RT "The von Hippel-Lindau tumor-suppressor gene product forms a stable complex
RT with human CUL-2, a member of the Cdc53 family of proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:2156-2161(1997).
RN [9]
RP ALTERNATIVE SPLICING (ISOFORM 3).
RX PubMed=9671762; DOI=10.1073/pnas.95.15.8817;
RA Schoenfeld A., Davidowitz E.J., Burk R.D.;
RT "A second major native von Hippel-Lindau gene product, initiated from an
RT internal translation start site, functions as a tumor suppressor.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8817-8822(1998).
RN [10]
RP INTERACTION WITH ELONGIN BC COMPLEX.
RX PubMed=7660130; DOI=10.1126/science.7660130;
RA Kibel A., Iliopoulos O., DeCaprio J.A., Kaelin W.G. Jr.;
RT "Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and
RT C.";
RL Science 269:1444-1446(1995).
RN [11]
RP FUNCTION (ISOFORM 3), AND SUBCELLULAR LOCATION.
RX PubMed=9751722; DOI=10.1073/pnas.95.20.11661;
RA Iliopoulos O., Ohh M., Kaelin W.G. Jr.;
RT "pVHL19 is a biologically active product of the von Hippel-Lindau gene
RT arising from internal translation initiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:11661-11666(1998).
RN [12]
RP INTERACTION WITH CHAPERONES, AND VARIANT VHLD PRO-158.
RX PubMed=10635329; DOI=10.1016/s1097-2765(00)80233-6;
RA Feldman D.E., Thulasiraman V., Ferreyra R.G., Frydman J.;
RT "Formation of the VHL-elongin BC tumor suppressor complex is mediated by
RT the chaperonin TRiC.";
RL Mol. Cell 4:1051-1061(1999).
RN [13]
RP INTERACTION WITH HIF1A, FUNCTION, CHARACTERIZATION OF VARIANT PHE-162, AND
RP MUTAGENESIS OF TYR-98.
RX PubMed=10944113; DOI=10.1093/emboj/19.16.4298;
RA Tanimoto K., Makino Y., Pereira T., Poellinger L.;
RT "Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von
RT Hippel-Lindau tumor suppressor protein.";
RL EMBO J. 19:4298-4309(2000).
RN [14]
RP IDENTIFICATION IN E3 UBIQUITIN-PROTEIN LIGASE COMPLEXES.
RX PubMed=11384984; DOI=10.1074/jbc.m103093200;
RA Kamura T., Burian D., Yan Q., Schmidt S.L., Lane W.S., Querido E.,
RA Branton P.E., Shilatifard A., Conaway R.C., Conaway J.W.;
RT "Muf1, a novel elongin BC-interacting leucine-rich repeat protein that can
RT assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase.";
RL J. Biol. Chem. 276:29748-29753(2001).
RN [15]
RP INTERACTION WITH HIF1AN; HIF1A AND HISTONE DEACETYLASES.
RC TISSUE=Brain;
RX PubMed=11641274; DOI=10.1101/gad.924501;
RA Mahon P.C., Hirota K., Semenza G.L.;
RT "FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate
RT repression of HIF-1 transcriptional activity.";
RL Genes Dev. 15:2675-2686(2001).
RN [16]
RP INTERACTION WITH USP33.
RX PubMed=11739384; DOI=10.1074/jbc.m108269200;
RA Li Z., Na X., Wang D., Schoen S.R., Messing E.M., Wu G.;
RT "Ubiquitination of a novel deubiquitinating enzyme requires direct binding
RT to von Hippel-Lindau tumor suppressor protein.";
RL J. Biol. Chem. 277:4656-4662(2002).
RN [17]
RP INTERACTION WITH JADE1.
RX PubMed=12169691; DOI=10.1074/jbc.m205040200;
RA Zhou M.I., Wang H., Ross J.J., Kuzmin I., Xu C., Cohen H.T.;
RT "The von Hippel-Lindau tumor suppressor stabilizes novel plant homeodomain
RT protein Jade-1.";
RL J. Biol. Chem. 277:39887-39898(2002).
RN [18]
RP INTERACTION WITH RNF139.
RX PubMed=12032852; DOI=10.1038/sj.onc.1205437;
RA Gemmill R.M., Bemis L.T., Lee J.P., Sozen M.A., Baron A., Zeng C.,
RA Erickson P.F., Hooper J.E., Drabkin H.A.;
RT "The TRC8 hereditary kidney cancer gene suppresses growth and functions
RT with VHL in a common pathway.";
RL Oncogene 21:3507-3516(2002).
RN [19]
RP FUNCTION, AND INTERACTION WITH HIF1A.
RX PubMed=17981124; DOI=10.1016/j.cell.2007.08.045;
RA Cheng J., Kang X., Zhang S., Yeh E.T.H.;
RT "SUMO-specific protease 1 is essential for stabilization of HIF1alpha
RT during hypoxia.";
RL Cell 131:584-595(2007).
RN [20]
RP INTERACTION WITH EPAS1.
RX PubMed=19208626; DOI=10.1074/jbc.m808737200;
RA Furlow P.W., Percy M.J., Sutherland S., Bierl C., McMullin M.F.,
RA Master S.R., Lappin T.R., Lee F.S.;
RT "Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role
RT for residues C-terminal to the hydroxylacceptor proline.";
RL J. Biol. Chem. 284:9050-9058(2009).
RN [21]
RP INTERACTION WITH ADRB2, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=19584355; DOI=10.1126/scisignal.2000444;
RA Xie L., Xiao K., Whalen E.J., Forrester M.T., Freeman R.S., Fong G.,
RA Gygi S.P., Lefkowitz R.J., Stamler J.S.;
RT "Oxygen-regulated beta(2)-adrenergic receptor hydroxylation by EGLN3 and
RT ubiquitylation by pVHL.";
RL Sci. Signal. 2:RA33-RA33(2009).
RN [22]
RP INTERACTION WITH LIMD1; AJUBA AND WTIP, AND IDENTIFICATION IN A COMPLEX
RP WITH LIMD1; EGLN1/PHD2; ELOB AND CUL2.
RX PubMed=22286099; DOI=10.1038/ncb2424;
RA Foxler D.E., Bridge K.S., James V., Webb T.M., Mee M., Wong S.C., Feng Y.,
RA Constantin-Teodosiu D., Petursdottir T.E., Bjornsson J., Ingvarsson S.,
RA Ratcliffe P.J., Longmore G.D., Sharp T.V.;
RT "The LIMD1 protein bridges an association between the prolyl hydroxylases
RT and VHL to repress HIF-1 activity.";
RL Nat. Cell Biol. 14:201-208(2012).
RN [23]
RP INTERACTION WITH DCUN1D1.
RX PubMed=23401859; DOI=10.1128/mcb.01342-12;
RA Heir P., Sufan R.I., Greer S.N., Poon B.P., Lee J.E., Ohh M.;
RT "DCNL1 functions as a substrate sensor and activator of cullin 2-RING
RT ligase.";
RL Mol. Cell. Biol. 33:1621-1631(2013).
RN [24]
RP INTERACTION WITH ALAS1.
RX PubMed=16234850; DOI=10.1139/o05-045;
RA Abu-Farha M., Niles J., Willmore W.G.;
RT "Erythroid-specific 5-aminolevulinate synthase protein is stabilized by low
RT oxygen and proteasomal inhibition.";
RL Biochem. Cell Biol. 83:620-630(2005).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 54-213 IN COMPLEX WITH 556-575 OF
RP HIF1A; ELOB AND ELOC.
RX PubMed=12004076; DOI=10.1126/science.1073440;
RA Min J.-H., Yang H., Ivan M., Gertler F., Kaelin W.G. Jr., Pavletich N.P.;
RT "Structure of an HIF-1alpha-pVHL complex: hydroxyproline recognition in
RT signaling.";
RL Science 296:1886-1889(2002).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 52-213 IN COMPLEX WITH 549-582 OF
RP HIF1A; 17-112 OF ELOB AND ELOC.
RX PubMed=12050673; DOI=10.1038/nature00767;
RA Hon W.-C., Wilson M.I., Harlos K., Claridge T.D.W., Schofield C.J.,
RA Pugh C.W., Maxwell P.H., Ratcliffe P.J., Stuart D.I., Jones E.Y.;
RT "Structural basis for the recognition of hydroxyproline in HIF-1 alpha by
RT pVHL.";
RL Nature 417:975-978(2002).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 54-213 IN COMPLEX WITH 17-112 OF
RP ELOB AND ELOC.
RX PubMed=10205047; DOI=10.1126/science.284.5413.455;
RA Stebbins C.E., Kaelin W.G. Jr., Pavletich N.P.;
RT "Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor
RT suppressor function.";
RL Science 284:455-461(1999).
RN [28]
RP VARIANT HEMANGIOBLASTOMA PHE-135.
RX PubMed=8069849;
RA Kanno H., Kondo K., Ito S., Yamamoto I., Fujii S., Torigoe S., Sakai N.,
RA Hosaka M., Shuin T., Yao M.;
RT "Somatic mutations of the von Hippel-Lindau tumor suppressor gene in
RT sporadic central nervous system hemangioblastomas.";
RL Cancer Res. 54:4845-4847(1994).
RN [29]
RP VARIANTS IN LUNG CANCER.
RX PubMed=8183553;
RA Sekido Y., Bader S., Latif F., Gnarra J.R., Gazdar A.F., Linehan W.M.,
RA Zbar B., Lerman M.I., Minna J.D.;
RT "Molecular analysis of the von Hippel-Lindau disease tumor suppressor gene
RT in human lung cancer cell lines.";
RL Oncogene 9:1599-1604(1994).
RN [30]
RP VARIANTS VHLD.
RX PubMed=7987306; DOI=10.1093/hmg/3.8.1303;
RA Crossey P.A., Richards F.M., Foster K., Green J.S., Prowse A., Latif F.,
RA Lerman M.I., Zbar B., Affara N.A., Ferguson-Smith M.A., Maher E.R.;
RT "Identification of intragenic mutations in the von Hippel-Lindau disease
RT tumour suppressor gene and correlation with disease phenotype.";
RL Hum. Mol. Genet. 3:1303-1308(1994).
RN [31]
RP VARIANTS VHLD.
RX PubMed=7728151; DOI=10.1002/humu.1380050109;
RA Chen F., Kishida T., Yao M., Hustad T., Glavac D., Dean M., Gnarra J.R.,
RA Orcutt M.L., Duh F.-M., Glenn G., Green J.S., Hsia Y.E., Lamiell J., Li H.,
RA Wei M.H., Schmidt L., Tory K., Kuzmin I., Stackhouse T., Latif F.,
RA Linehan W.M., Lerman M.I., Zbar B.;
RT "Germline mutations in the von Hippel-Lindau disease tumor suppressor gene:
RT correlations with phenotype.";
RL Hum. Mutat. 5:66-75(1995).
RN [32]
RP VARIANTS VHLD.
RX PubMed=8634692; DOI=10.1093/hmg/4.12.2233;
RA Kondo K., Sakai N., Kaneko S., Kobayashi K., Hosaka M., Ito S., Fujii S.,
RA Yamamoto I., Kim I., Miyagami M., Shidara N., Shinohara N., Koyanagi T.,
RA Kato N., Yamanaka H., Kuratu J., Fujioka M., Nakatsu H., Shimazaki J.,
RA Yoshida J., Sugita K., Hirao Y., Okajima E., Tanigawa T., Sato S.,
RA Fujino H., Nagata M., Kanayama H., Kagawa S., Yamashima T., Furuta T.,
RA Saito Y., Kanno H., Yao M., Shuin T.;
RT "Germline mutations in the von Hippel-Lindau disease (VHL) gene in Japanese
RT VHL. Clinical Research Group for VHL in Japan.";
RL Hum. Mol. Genet. 4:2233-2237(1995).
RN [33]
RP VARIANTS VHLD LEU-84 AND TRP-167.
RX PubMed=8592333; DOI=10.1136/jmg.32.11.885;
RA Crossey P.A., Eng C., Ginalska-Malinowska M., Lennard T.W.J., Wheeler D.C.,
RA Ponder B.A.J., Maher E.R.;
RT "Molecular genetic diagnosis of von Hippel-Lindau disease in familial
RT phaeochromocytoma.";
RL J. Med. Genet. 32:885-886(1995).
RN [34]
RP VARIANTS VHLD SER-114; SER-119; GLU-143 AND ARG-164.
RX PubMed=8825918; DOI=10.1136/jmg.32.12.934;
RA Eng C., Crossey P.A., Mulligan L.M., Healey C.S., Houghton C., Prowse A.,
RA Chew S.L., Dahia P.L.M., O'Riordan J.L.H., Toledo S.P.A., Smith D.P.,
RA Maher E.R., Ponder B.A.J.;
RT "Mutations in the RET proto-oncogene and the von Hippel-Lindau disease
RT tumour suppressor gene in sporadic and syndromic phaeochromocytomas.";
RL J. Med. Genet. 32:934-937(1995).
RN [35]
RP VARIANTS VHLD PRO-96; VAL-116; ARG-118; PHE-166; ASP-170 AND GLU-186 DEL.
RX PubMed=8730290; DOI=10.1136/jmg.33.4.328;
RA Maher E.R., Webster A.R., Richards F.M., Green J.S., Crossey P.A.,
RA Payne S.J., Moore A.T.;
RT "Phenotypic expression in von Hippel-Lindau disease: correlations with
RT germline VHL gene mutations.";
RL J. Med. Genet. 33:328-332(1996).
RN [36]
RP VARIANTS VHLD LEU-65; TRP-65; GLY-74; PHE-76 DEL; ILE-76; HIS-78; SER-78;
RP THR-78; ARG-80; ASN-80; ILE-80; SER-81; ALA-86; LEU-86; ARG-88; SER-88;
RP PRO-89; ARG-101; ARG-111; ASN-111; CYS-114; TYR-115; CYS-117; PRO-118;
RP GLY-121; LEU-130; PRO-158; VAL-158; PRO-161; ARG-162; PHE-162; TYR-162;
RP TRP-162; ARG-164; GLN-167; TRP-167; GLY-170; PRO-178; VAL-180; ARG-184;
RP PRO-184; LYS-186; GLN-188 AND TRP-200.
RX PubMed=8956040;
RX DOI=10.1002/(sici)1098-1004(1996)8:4<348::aid-humu8>3.0.co;2-3;
RA Zbar B., Kishida T., Chen F., Schmidt L., Maher E.R., Richards F.M.,
RA Crossey P.A., Webster A.R., Affara N.A., Ferguson-Smith M.A., Brauch H.,
RA Glavac D., Neumann H.P.H., Tisherman S., Mulvihill J.J., Gross D.J.,
RA Shuin T., Whaley J., Seizinger B., Kley N., Olschwang S., Boisson C.,
RA Richard S., Lips C.H.M., Linehan W.M., Lerman M.I.;
RT "Germline mutations in the von Hippel-Lindau disease (VHL) gene in families
RT from North America, Europe, and Japan.";
RL Hum. Mutat. 8:348-357(1996).
RN [37]
RP VARIANTS VHLD PRO-38; LEU-76 AND PHE-162.
RX PubMed=9452032; DOI=10.1002/humu.1380110111;
RA Li C., Weber G., Ekman P., Lagercrantz J., Norlen B.J., Aakerstroem G.,
RA Nordenskjoeld M., Bergerheim U.S.R.;
RT "Germline mutations detected in the von Hippel-Lindau disease tumor
RT suppressor gene by Southern blot and direct genomic DNA sequencing.";
RL Hum. Mutat. Suppl. 1:S31-S33(1998).
RN [38]
RP VARIANT VHLD THR-149.
RX PubMed=9452106; DOI=10.1002/humu.1380110185;
RA Mandich P., Montera M., Bellone E., Trojani A., Daniele S., Ajmar F.;
RT "Three novel mutations in the von Hippel-Lindau tumour suppressor gene in
RT Italian patients.";
RL Hum. Mutat. Suppl. 1:S268-S270(1998).
RN [39]
RP VARIANT VHLD TRP-68.
RX PubMed=10627136;
RX DOI=10.1002/(sici)1098-1004(1998)12:1<71::aid-humu16>3.0.co;2-4;
RA Martin R., Hockey A., Walpole I., Goldblatt J.;
RT "Variable penetrance of familial pheochromocytoma associated with the von
RT Hippel-Lindau gene mutation, S68W.";
RL Hum. Mutat. 12:71-71(1998).
RN [40]
RP VARIANTS VHLD TRP-65; SER-76; SER-81; ARG-86; ARG-88; GLY-101; PRO-107;
RP ASN-111; CYS-117; THR-131; PHE-162; GLY-167; ASP-175; PRO-184 AND LYS-186.
RX PubMed=9829911;
RX DOI=10.1002/(sici)1098-1004(1998)12:6<417::aid-humu8>3.0.co;2-k;
RA Stolle C., Glenn G., Zbar B., Humphrey J.S., Choyke P., Walther M.,
RA Pack S., Hurley K., Andrey C., Klausner R., Linehan W.M.;
RT "Improved detection of germline mutations in the von Hippel-Lindau disease
RT tumor suppressor gene.";
RL Hum. Mutat. 12:417-423(1998).
RN [41]
RP VARIANTS VHLD LYS-52; LEU-65; LYS-70; ASN-80; ARG-80; SER-86; SER-88;
RP LEU-91; ALA-104; PRO-105; GLN-115; CYS-117; PRO-118; LEU-130; LYS-131;
RP SER-136; ASP-156; CYS-156; ILE-157; PRO-158; GLN-161; TRP-162; PHE-166;
RP GLN-167; TRP-167; GLY-170; PRO-188 AND TRP-200.
RX PubMed=9829912;
RX DOI=10.1002/(sici)1098-1004(1998)12:6<424::aid-humu9>3.0.co;2-h;
RA Olschwang S., Richard S., Boisson C., Giraud S., Laurent-Puig P.,
RA Resche F., Thomas G.;
RT "Germline mutation profile of the VHL gene in von Hippel-Lindau disease and
RT in sporadic hemangioblastoma.";
RL Hum. Mutat. 12:424-430(1998).
RN [42]
RP VARIANTS PHEOCHROMOCYTOMA LEU-25; PRO-63; PRO-64 AND THR-147.
RX PubMed=9663592;
RX DOI=10.1002/(sici)1097-0215(19980729)77:3<337::aid-ijc5>3.0.co;2-p;
RA van der Harst E., de Krijger R.R., Dinjens W.N.M., Weeks L.E., Bonjer H.J.,
RA Bruining H.A., Lamberts S.W.J., Koper J.W.;
RT "Germline mutations in the vhl gene in patients presenting with
RT phaeochromocytomas.";
RL Int. J. Cancer 77:337-340(1998).
RN [43]
RP VARIANTS VHLD CYS-93; GLY-155 AND ILE-157.
RA Murigia M.;
RL Unpublished observations (MAY-1999).
RN [44]
RP VARIANT VHLD ASN-112.
RX PubMed=10533030;
RX DOI=10.1002/(sici)1096-8628(19991119)87:2<163::aid-ajmg7>3.0.co;2-a;
RA Bradley J.F., Collins D.L., Schimke R.N., Parrott H.N., Rothberg P.G.;
RT "Two distinct phenotypes caused by two different missense mutations in the
RT same codon of the VHL gene.";
RL Am. J. Med. Genet. 87:163-167(1999).
RN [45]
RP VARIANTS VHLD.
RX PubMed=10408776;
RX DOI=10.1002/(sici)1098-1004(1999)13:6<464::aid-humu6>3.0.co;2-a;
RA Gallou C., Joly D., Mejean A., Staroz F., Martin N., Tarlet G.,
RA Orfanelli M.T., Bouvier R., Droz D., Chretien Y., Marechal J.M.,
RA Richard S., Junien C., Beroud C.;
RT "Mutations of the VHL gene in sporadic renal cell carcinoma: definition of
RT a risk factor for VHL patients to develop an RCC.";
RL Hum. Mutat. 13:464-475(1999).
RN [46]
RP VARIANT RCC PRO-163, AND CHARACTERIZATION OF VARIANT RCC PRO-163.
RX PubMed=11986208; DOI=10.1182/blood.v99.10.3562;
RA Wiesener M.S., Seyfarth M., Warnecke C., Juergensen J.S., Rosenberger C.,
RA Morgan N.V., Maher E.R., Frei U., Eckardt K.-U.;
RT "Paraneoplastic erythrocytosis associated with an inactivating point
RT mutation of the von Hippel-Lindau gene in a renal cell carcinoma.";
RL Blood 99:3562-3565(2002).
RN [47]
RP VARIANTS PHEOCHROMOCYTOMA ALA-65; TRP-68; ASN-80; SER-93; CYS-93; HIS-98;
RP GLY-107; LEU-119; ILE-122; CYS-136; ASN-156; CYS-156; GLN-161; PRO-161;
RP TRP-167; GLN-167; VAL-188 AND GLN-198.
RX PubMed=12000816; DOI=10.1056/nejmoa020152;
RG The Freiburg-Warsaw-Columbus pheochromocytoma study group;
RA Neumann H.P.H., Bausch B., McWhinney S.R., Bender B.U., Gimm O., Franke G.,
RA Schipper J., Klisch J., Altehoefer C., Zerres K., Januszewicz A.,
RA Smith W.M., Munk R., Manz T., Glaesker S., Apel T.W., Treier M.,
RA Reineke M., Walz M.K., Hoang-Vu C., Brauckhoff M., Klein-Franke A.,
RA Klose P., Schmidt H., Maier-Woelfle M., Peczkowska M., Szmigielski C.,
RA Eng C.;
RT "Germ-line mutations in nonsyndromic pheochromocytoma.";
RL N. Engl. J. Med. 346:1459-1466(2002).
RN [48]
RP VARIANTS ECYT2 VAL-188; ASP-191; SER-192 AND TRP-200.
RX PubMed=12844285; DOI=10.1086/377108;
RA Pastore Y.D., Jedlickova K., Guan Y., Liu E., Fahner J., Hasle H.,
RA Prchal J.F., Prchal J.T.;
RT "Mutations of von Hippel-Lindau tumor-suppressor gene and congenital
RT polycythemia.";
RL Am. J. Hum. Genet. 73:412-419(2003).
RN [49]
RP VARIANTS PHEOCHROMOCYTOMA LEU-25 AND CYS-156.
RX PubMed=14500403;
RA Gimenez-Roqueplo A.-P., Favier J., Rustin P., Rieubland C., Crespin M.,
RA Nau V., Khau Van Kien P., Corvol P., Plouin P.-F., Jeunemaitre X.;
RT "Mutations in the SDHB gene are associated with extra-adrenal and/or
RT malignant phaeochromocytomas.";
RL Cancer Res. 63:5615-5621(2003).
RN [50]
RP ERRATUM OF PUBMED:14500403.
RA Pastore Y.D., Jedlickova K., Guan Y., Liu E., Fahner J., Hasle H.,
RA Prchal J.F., Prchal J.T.;
RL Am. J. Hum. Genet. 74:598-598(2004).
RN [51]
RP VARIANTS ECYT2 TYR-126; LEU-130 AND TRP-200.
RX PubMed=12393546; DOI=10.1182/blood-2002-06-1843;
RA Pastore Y.D., Jelinek J., Ang S., Guan Y., Liu E., Jedlickova K.,
RA Krishnamurti L., Prchal J.T.;
RT "Mutations in the VHL gene in sporadic apparently congenital
RT polycythemia.";
RL Blood 101:1591-1595(2003).
RN [52]
RP VARIANT VHLD LEU-84.
RX PubMed=16502427; DOI=10.1002/ajmg.a.31116;
RA Abbott M.-A., Nathanson K.L., Nightingale S., Maher E.R., Greenstein R.M.;
RT "The von Hippel-Lindau (VHL) germline mutation V84L manifests as early-
RT onset bilateral pheochromocytoma.";
RL Am. J. Med. Genet. A 140:685-690(2006).
RN [53]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-25 AND SER-86.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Involved in the ubiquitination and subsequent proteasomal
CC degradation via the von Hippel-Lindau ubiquitination complex. Seems to
CC act as a target recruitment subunit in the E3 ubiquitin ligase complex
CC and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic
CC conditions. Involved in transcriptional repression through interaction
CC with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an
CC oxygen-responsive manner, ADRB2. {ECO:0000269|PubMed:10944113,
CC ECO:0000269|PubMed:17981124, ECO:0000269|PubMed:19584355}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the VCB (VHL-Elongin BC-CUL2) complex; this
CC complex acts as a ubiquitin-ligase E3 and directs proteasome-dependent
CC degradation of targeted proteins. Interacts with CUL2; this interaction
CC is dependent on the integrity of the trimeric VCB complex. Interacts
CC (via the beta domain) with HIF1A (via the NTAD domain); this
CC interaction mediates degradation of HIF1A in normoxia and, in hypoxia,
CC prevents ubiquitination and degradation of HIF1A by mediating hypoxia-
CC induced translocation to the nucleus, a process which requires a
CC hypoxia-dependent regulatory signal. Interacts with ADRB2; the
CC interaction, in normoxia, is dependent on hydroxylation of ADRB2 and
CC the subsequent VCB-mediated ubiquitination and degradation of ADRB2.
CC Under hypoxia, hydroxylation, interaction with VHL, ubiquitination and
CC subsequent degradation of ADRB2 are dramatically decreased. Interacts
CC with RNF139, USP33 and JADE1. Found in a complex composed of LIMD1,
CC VHL, EGLN1/PHD2, ELOB and CUL2. Isoform 1 and isoform 3 interact with
CC LIMD1 (via LIM zinc-binding 2), AJUBA (via LIM domains) and WTIP (via
CC LIM domains). Interacts with EPAS1. Interacts with CARD9. Interacts
CC with DCUN1D1 independently of CUL2; this interaction engages DCUN1D1 in
CC the VCB complex and triggers CUL2 neddylation and consequently cullin
CC ring ligase (CRL) substrates polyubiquitylation (PubMed:23401859).
CC Interacts with ALAS1 (hydroxylated form) (PubMed:16234850).
CC {ECO:0000269|PubMed:10205047, ECO:0000269|PubMed:10635329,
CC ECO:0000269|PubMed:10944113, ECO:0000269|PubMed:11384984,
CC ECO:0000269|PubMed:11641274, ECO:0000269|PubMed:11739384,
CC ECO:0000269|PubMed:12004076, ECO:0000269|PubMed:12032852,
CC ECO:0000269|PubMed:12050673, ECO:0000269|PubMed:12169691,
CC ECO:0000269|PubMed:16234850, ECO:0000269|PubMed:17981124,
CC ECO:0000269|PubMed:19208626, ECO:0000269|PubMed:19584355,
CC ECO:0000269|PubMed:22286099, ECO:0000269|PubMed:23401859,
CC ECO:0000269|PubMed:7660130, ECO:0000269|PubMed:9122164}.
CC -!- INTERACTION:
CC P40337; Q13617: CUL2; NbExp=16; IntAct=EBI-301246, EBI-456179;
CC P40337; P02751: FN1; NbExp=2; IntAct=EBI-301246, EBI-1220319;
CC P40337; Q9UM11: FZR1; NbExp=2; IntAct=EBI-301246, EBI-724997;
CC P40337; Q16665: HIF1A; NbExp=18; IntAct=EBI-301246, EBI-447269;
CC P40337; P14866: HNRNPL; NbExp=2; IntAct=EBI-301246, EBI-719024;
CC P40337; Q99750: MDFI; NbExp=4; IntAct=EBI-301246, EBI-724076;
CC P40337; Q05513: PRKCZ; NbExp=3; IntAct=EBI-301246, EBI-295351;
CC P40337; Q99873: PRMT1; NbExp=2; IntAct=EBI-301246, EBI-78738;
CC P40337; P63244: RACK1; NbExp=9; IntAct=EBI-301246, EBI-296739;
CC P40337; Q8WU17: RNF139; NbExp=2; IntAct=EBI-301246, EBI-1551681;
CC P40337; P21980: TGM2; NbExp=10; IntAct=EBI-301246, EBI-727668;
CC P40337; Q61221: Hif1a; Xeno; NbExp=2; IntAct=EBI-301246, EBI-298954;
CC P40337; PRO_0000037322 [P0C6X7]: rep; Xeno; NbExp=7; IntAct=EBI-301246, EBI-25487235;
CC P40337-1; Q9UM11: FZR1; NbExp=2; IntAct=EBI-3504450, EBI-724997;
CC P40337-1; P08151: GLI1; NbExp=2; IntAct=EBI-3504450, EBI-308084;
CC P40337-2; Q8WXK3: ASB13; NbExp=3; IntAct=EBI-12157263, EBI-707573;
CC P40337-2; Q9Y575-3: ASB3; NbExp=3; IntAct=EBI-12157263, EBI-14199987;
CC P40337-2; Q9H765: ASB8; NbExp=3; IntAct=EBI-12157263, EBI-3942509;
CC P40337-2; Q99700-5: ATXN2; NbExp=3; IntAct=EBI-12157263, EBI-25891409;
CC P40337-2; O14867: BACH1; NbExp=3; IntAct=EBI-12157263, EBI-1263541;
CC P40337-2; Q8TAB7: CCDC26; NbExp=3; IntAct=EBI-12157263, EBI-10271580;
CC P40337-2; Q13939: CCIN; NbExp=3; IntAct=EBI-12157263, EBI-25879469;
CC P40337-2; P24863: CCNC; NbExp=3; IntAct=EBI-12157263, EBI-395261;
CC P40337-2; Q8TBB7: DCAF5; NbExp=3; IntAct=EBI-12157263, EBI-25895525;
CC P40337-2; Q5TAQ9-2: DCAF8; NbExp=3; IntAct=EBI-12157263, EBI-25842815;
CC P40337-2; Q92466: DDB2; NbExp=3; IntAct=EBI-12157263, EBI-1176171;
CC P40337-2; Q9NX09: DDIT4; NbExp=3; IntAct=EBI-12157263, EBI-715104;
CC P40337-2; G5E9A7: DMWD; NbExp=3; IntAct=EBI-12157263, EBI-10976677;
CC P40337-2; Q01658: DR1; NbExp=3; IntAct=EBI-12157263, EBI-750300;
CC P40337-2; Q9NZJ0: DTL; NbExp=3; IntAct=EBI-12157263, EBI-1176075;
CC P40337-2; O75530-2: EED; NbExp=3; IntAct=EBI-12157263, EBI-11132357;
CC P40337-2; Q9UI10: EIF2B4; NbExp=3; IntAct=EBI-12157263, EBI-2340132;
CC P40337-2; Q8IYF1: ELOA2; NbExp=3; IntAct=EBI-12157263, EBI-741705;
CC P40337-2; Q9H2C0: GAN; NbExp=3; IntAct=EBI-12157263, EBI-764342;
CC P40337-2; P62879: GNB2; NbExp=3; IntAct=EBI-12157263, EBI-356942;
CC P40337-2; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-12157263, EBI-1054873;
CC P40337-2; O75031: HSF2BP; NbExp=6; IntAct=EBI-12157263, EBI-7116203;
CC P40337-2; P42858: HTT; NbExp=12; IntAct=EBI-12157263, EBI-466029;
CC P40337-2; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-12157263, EBI-1055254;
CC P40337-2; Q9BVA0: KATNB1; NbExp=3; IntAct=EBI-12157263, EBI-11147603;
CC P40337-2; O60333-2: KIF1B; NbExp=3; IntAct=EBI-12157263, EBI-10975473;
CC P40337-2; Q9NR64: KLHL1; NbExp=3; IntAct=EBI-12157263, EBI-6426228;
CC P40337-2; Q53G59: KLHL12; NbExp=3; IntAct=EBI-12157263, EBI-740929;
CC P40337-2; Q6TDP4: KLHL17; NbExp=3; IntAct=EBI-12157263, EBI-21328926;
CC P40337-2; Q8NBE8: KLHL23; NbExp=3; IntAct=EBI-12157263, EBI-2512246;
CC P40337-2; O60662: KLHL41; NbExp=3; IntAct=EBI-12157263, EBI-5353084;
CC P40337-2; Q8IXQ5-4: KLHL7; NbExp=3; IntAct=EBI-12157263, EBI-25895859;
CC P40337-2; Q08380: LGALS3BP; NbExp=3; IntAct=EBI-12157263, EBI-354956;
CC P40337-2; Q99750: MDFI; NbExp=4; IntAct=EBI-12157263, EBI-724076;
CC P40337-2; Q96BF6: NACC2; NbExp=3; IntAct=EBI-12157263, EBI-3942475;
CC P40337-2; P35240-4: NF2; NbExp=3; IntAct=EBI-12157263, EBI-1014514;
CC P40337-2; O00746: NME4; NbExp=3; IntAct=EBI-12157263, EBI-744871;
CC P40337-2; C9J082: NPHP1; NbExp=3; IntAct=EBI-12157263, EBI-25830675;
CC P40337-2; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-12157263, EBI-1058491;
CC P40337-2; Q9NV79: PCMTD2; NbExp=3; IntAct=EBI-12157263, EBI-6309018;
CC P40337-2; Q8WWQ0: PHIP; NbExp=3; IntAct=EBI-12157263, EBI-722984;
CC P40337-2; Q8TCD6: PHOSPHO2; NbExp=3; IntAct=EBI-12157263, EBI-2861380;
CC P40337-2; O60260-5: PRKN; NbExp=3; IntAct=EBI-12157263, EBI-21251460;
CC P40337-2; O14744: PRMT5; NbExp=3; IntAct=EBI-12157263, EBI-351098;
CC P40337-2; Q8TAS3: PRRG2; NbExp=3; IntAct=EBI-12157263, EBI-10272071;
CC P40337-2; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-12157263, EBI-396669;
CC P40337-2; Q15393: SF3B3; NbExp=3; IntAct=EBI-12157263, EBI-346977;
CC P40337-2; Q8IYM2: SLFN12; NbExp=3; IntAct=EBI-12157263, EBI-2822550;
CC P40337-2; P37840: SNCA; NbExp=3; IntAct=EBI-12157263, EBI-985879;
CC P40337-2; O14508: SOCS2; NbExp=3; IntAct=EBI-12157263, EBI-617737;
CC P40337-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-12157263, EBI-5235340;
CC P40337-2; Q96A44: SPSB4; NbExp=3; IntAct=EBI-12157263, EBI-2323233;
CC P40337-2; Q13148: TARDBP; NbExp=3; IntAct=EBI-12157263, EBI-372899;
CC P40337-2; O43493-5: TGOLN2; NbExp=3; IntAct=EBI-12157263, EBI-25830716;
CC P40337-2; Q8NFB2: TMEM185A; NbExp=3; IntAct=EBI-12157263, EBI-21757569;
CC P40337-2; P61086: UBE2K; NbExp=3; IntAct=EBI-12157263, EBI-473850;
CC P40337-2; Q9C0C9: UBE2O; NbExp=3; IntAct=EBI-12157263, EBI-2339946;
CC P40337-2; Q16763: UBE2S; NbExp=3; IntAct=EBI-12157263, EBI-2339823;
CC P40337-2; Q5VVX9-2: UBE2U; NbExp=3; IntAct=EBI-12157263, EBI-21897992;
CC P40337-2; Q8N0U8: VKORC1L1; NbExp=3; IntAct=EBI-12157263, EBI-11337915;
CC P40337-2; Q9GZL7: WDR12; NbExp=3; IntAct=EBI-12157263, EBI-2490660;
CC P40337-2; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-12157263, EBI-358545;
CC P40337-2; Q8N5D0-4: WDTC1; NbExp=3; IntAct=EBI-12157263, EBI-15821254;
CC P40337-2; Q9Y6I7: WSB1; NbExp=3; IntAct=EBI-12157263, EBI-1171494;
CC P40337-2; Q8NCP5-3: ZBTB44; NbExp=3; IntAct=EBI-12157263, EBI-25895743;
CC P40337-2; Q6ZSB9: ZBTB49; NbExp=3; IntAct=EBI-12157263, EBI-2859943;
CC P40337-2; Q15916: ZBTB6; NbExp=3; IntAct=EBI-12157263, EBI-7227791;
CC P40337-2; P52739-2: ZNF131; NbExp=3; IntAct=EBI-12157263, EBI-10213055;
CC P40337-2; Q96BH6; NbExp=3; IntAct=EBI-12157263, EBI-25872486;
CC P40337-3; O75912: DGKI; NbExp=3; IntAct=EBI-301270, EBI-1765520;
CC P40337-3; Q9UM11: FZR1; NbExp=2; IntAct=EBI-301270, EBI-724997;
CC P40337-3; P08151: GLI1; NbExp=2; IntAct=EBI-301270, EBI-308084;
CC P40337-3; Q15311: RALBP1; NbExp=3; IntAct=EBI-301270, EBI-749285;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. Membrane; Peripheral
CC membrane protein. Nucleus. Note=Found predominantly in the cytoplasm
CC and with less amounts nuclear or membrane-associated. Colocalizes with
CC ADRB2 at the cell membrane.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm. Nucleus. Note=Equally
CC distributed between the nucleus and the cytoplasm but not membrane-
CC associated.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC Name=1; Synonyms=VHL30, VHLp24(MPR);
CC IsoId=P40337-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P40337-2; Sequence=VSP_004488;
CC Name=3; Synonyms=VHL19, VHLp18(MEA);
CC IsoId=P40337-3; Sequence=VSP_007740;
CC -!- TISSUE SPECIFICITY: Expressed in the adult and fetal brain and kidney.
CC -!- DEVELOPMENTAL STAGE: At 4-10 weeks pc, strong expression in the
CC developing central nervous system, kidneys, testis and lung.
CC Differentially expressed within renal tubules.
CC {ECO:0000269|PubMed:8733131}.
CC -!- DOMAIN: The Elongin BC complex binding domain is also known as BC-box
CC with the consensus [APST]-L-x(3)-C-x(3)-[AILV].
CC -!- DISEASE: Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-producing
CC tumor of chromaffin tissue of the adrenal medulla or sympathetic
CC paraganglia. The cardinal symptom, reflecting the increased secretion
CC of epinephrine and norepinephrine, is hypertension, which may be
CC persistent or intermittent. {ECO:0000269|PubMed:12000816,
CC ECO:0000269|PubMed:14500403, ECO:0000269|PubMed:9663592}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- DISEASE: von Hippel-Lindau disease (VHLD) [MIM:193300]: VHLD is a
CC dominantly inherited familial cancer syndrome predisposing to a variety
CC of malignant and benign neoplasms, most frequently retinal, cerebellar
CC and spinal hemangioblastoma, renal cell carcinoma (RCC),
CC pheochromocytoma, and pancreatic tumors. VHL type 1 is without
CC pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is
CC further subdivided into types 2A (pheochromocytoma, retinal angioma,
CC and hemangioblastomas without renal cell carcinoma and pancreatic cyst)
CC and 2B (pheochromocytoma, retinal angioma, and hemangioblastomas with
CC renal cell carcinoma and pancreatic cyst).
CC {ECO:0000269|PubMed:10408776, ECO:0000269|PubMed:10533030,
CC ECO:0000269|PubMed:10627136, ECO:0000269|PubMed:10635329,
CC ECO:0000269|PubMed:16502427, ECO:0000269|PubMed:7728151,
CC ECO:0000269|PubMed:7987306, ECO:0000269|PubMed:8493574,
CC ECO:0000269|PubMed:8592333, ECO:0000269|PubMed:8634692,
CC ECO:0000269|PubMed:8730290, ECO:0000269|PubMed:8825918,
CC ECO:0000269|PubMed:8956040, ECO:0000269|PubMed:9452032,
CC ECO:0000269|PubMed:9452106, ECO:0000269|PubMed:9829911,
CC ECO:0000269|PubMed:9829912, ECO:0000269|Ref.43}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Erythrocytosis, familial, 2 (ECYT2) [MIM:263400]: An autosomal
CC recessive disorder characterized by an increase in serum red blood cell
CC mass, hypersensitivity of erythroid progenitors to erythropoietin,
CC increased erythropoietin serum levels, and normal oxygen affinity.
CC Patients with ECYT2 carry a high risk for peripheral thrombosis and
CC cerebrovascular events. {ECO:0000269|PubMed:12393546,
CC ECO:0000269|PubMed:12844285}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma
CC is a heterogeneous group of sporadic or hereditary carcinoma derived
CC from cells of the proximal renal tubular epithelium. It is
CC subclassified into clear cell renal carcinoma (non-papillary
CC carcinoma), papillary renal cell carcinoma, chromophobe renal cell
CC carcinoma, collecting duct carcinoma with medullary carcinoma of the
CC kidney, and unclassified renal cell carcinoma. Clear cell renal cell
CC carcinoma is the most common subtype. {ECO:0000269|PubMed:11986208}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: [Isoform 1]: Major isoform.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative initiation at Met-
CC 54 of isoform 1. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the VHL family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/132/vhl-(von-hippel-lindau-tumor-suppressor)";
CC ---------------------------------------------------------------------------
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DR EMBL; AF010238; AAB64200.1; -; Genomic_DNA.
DR EMBL; L15409; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK315799; BAG38142.1; -; mRNA.
DR EMBL; AC034193; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW64064.1; -; Genomic_DNA.
DR EMBL; BC058831; AAH58831.1; -; mRNA.
DR EMBL; U54612; AAA98614.1; -; Genomic_DNA.
DR EMBL; X96489; CAA65343.1; -; Genomic_DNA.
DR CCDS; CCDS2597.1; -. [P40337-1]
DR CCDS; CCDS2598.1; -. [P40337-2]
DR PIR; I38926; I38926.
DR RefSeq; NP_000542.1; NM_000551.3. [P40337-1]
DR RefSeq; NP_937799.1; NM_198156.2. [P40337-2]
DR PDB; 1LM8; X-ray; 1.85 A; V=54-213.
DR PDB; 1LQB; X-ray; 2.00 A; C=54-213.
DR PDB; 1VCB; X-ray; 2.70 A; C/F/I/L=54-213.
DR PDB; 3ZRC; X-ray; 2.90 A; C/F/I/L=54-213.
DR PDB; 3ZRF; X-ray; 2.80 A; C/F/I/L=54-213.
DR PDB; 3ZTC; X-ray; 2.65 A; C/F/I/L=54-213.
DR PDB; 3ZTD; X-ray; 2.79 A; C/F/I/L=54-213.
DR PDB; 3ZUN; X-ray; 2.50 A; C/F/I/L=54-213.
DR PDB; 4AJY; X-ray; 1.73 A; V=54-213.
DR PDB; 4AWJ; X-ray; 2.50 A; C/F/I/L=54-213.
DR PDB; 4B95; X-ray; 2.80 A; C/F/I/L=54-213.
DR PDB; 4B9K; X-ray; 2.00 A; C/F/I/L=54-213.
DR PDB; 4BKS; X-ray; 2.20 A; C/F/I/L=54-213.
DR PDB; 4BKT; X-ray; 2.35 A; C/F/I/L=54-213.
DR PDB; 4W9C; X-ray; 2.20 A; C/F/I/L=54-213.
DR PDB; 4W9D; X-ray; 2.20 A; C/F/I/L=54-213.
DR PDB; 4W9E; X-ray; 2.60 A; C/F/I/L=54-213.
DR PDB; 4W9F; X-ray; 2.10 A; C/F/I/L=54-213.
DR PDB; 4W9G; X-ray; 2.70 A; C/F/I/L=54-213.
DR PDB; 4W9H; X-ray; 2.10 A; C/F/I/L=54-213.
DR PDB; 4W9I; X-ray; 2.40 A; C/F/I/L=54-213.
DR PDB; 4W9J; X-ray; 2.20 A; C/F/I/L=54-213.
DR PDB; 4W9K; X-ray; 2.10 A; C/F/I/L=54-213.
DR PDB; 4W9L; X-ray; 2.20 A; C/F/I/L=54-213.
DR PDB; 4WQO; X-ray; 3.20 A; A=1-213.
DR PDB; 5LLI; X-ray; 2.40 A; C/F/I/L=54-213.
DR PDB; 5N4W; X-ray; 3.90 A; V=54-213.
DR PDB; 5NVV; X-ray; 2.10 A; C/F/I/L=54-213.
DR PDB; 5NVW; X-ray; 2.20 A; C/F/I/L=54-213.
DR PDB; 5NVX; X-ray; 2.20 A; C/F/I/L=54-213.
DR PDB; 5NVY; X-ray; 2.90 A; C/F/I/L=54-213.
DR PDB; 5NVZ; X-ray; 2.70 A; C/F/I/L=54-213.
DR PDB; 5NW0; X-ray; 2.30 A; C/F/I/L=54-213.
DR PDB; 5NW1; X-ray; 2.10 A; C/F/I/L=54-213.
DR PDB; 5NW2; X-ray; 2.20 A; C/F/I/L=54-213.
DR PDB; 5T35; X-ray; 2.70 A; D/H=54-213.
DR PDB; 6BVB; X-ray; 2.00 A; V=54-213.
DR PDB; 6FMI; X-ray; 2.80 A; C/F=54-204.
DR PDB; 6FMJ; X-ray; 2.45 A; C/F/I/L=54-204.
DR PDB; 6FMK; X-ray; 2.75 A; C/F/I/L=54-204.
DR PDB; 6GFX; X-ray; 1.83 A; C=54-213.
DR PDB; 6GFY; X-ray; 2.70 A; C/F/I/L=54-213.
DR PDB; 6GFZ; X-ray; 2.30 A; C/F/I/L=54-213.
DR PDB; 6GMN; X-ray; 1.94 A; C/F/I/L=54-213.
DR PDB; 6GMQ; X-ray; 2.75 A; C/F/I/L=54-213.
DR PDB; 6GMR; X-ray; 1.75 A; V=54-213.
DR PDB; 6GMX; X-ray; 2.53 A; C/F/I/L=54-213.
DR PDB; 6HAX; X-ray; 2.35 A; B/F=54-213.
DR PDB; 6HAY; X-ray; 2.24 A; B/F=54-213.
DR PDB; 6HR2; X-ray; 1.76 A; B/F=61-209.
DR PDB; 6I7Q; X-ray; 1.80 A; V=54-213.
DR PDB; 6I7R; X-ray; 1.95 A; V=54-213.
DR PDB; 6R6H; EM; 8.40 A; V=60-207.
DR PDB; 6R7F; EM; 8.20 A; V=54-213.
DR PDB; 6SIS; X-ray; 3.50 A; D/H=54-213.
DR PDB; 6ZHC; X-ray; 1.92 A; AAA=59-213.
DR PDB; 7CJB; X-ray; 2.80 A; A/E/I/M=55-213.
DR PDB; 7JTO; X-ray; 1.70 A; L=54-213.
DR PDB; 7JTP; X-ray; 2.12 A; L=54-213.
DR PDB; 7KHH; X-ray; 2.28 A; C=55-213.
DR PDB; 7PI4; X-ray; 2.24 A; AAA=59-213.
DR PDB; 7Q2J; X-ray; 2.50 A; C=54-213.
DR PDBsum; 1LM8; -.
DR PDBsum; 1LQB; -.
DR PDBsum; 1VCB; -.
DR PDBsum; 3ZRC; -.
DR PDBsum; 3ZRF; -.
DR PDBsum; 3ZTC; -.
DR PDBsum; 3ZTD; -.
DR PDBsum; 3ZUN; -.
DR PDBsum; 4AJY; -.
DR PDBsum; 4AWJ; -.
DR PDBsum; 4B95; -.
DR PDBsum; 4B9K; -.
DR PDBsum; 4BKS; -.
DR PDBsum; 4BKT; -.
DR PDBsum; 4W9C; -.
DR PDBsum; 4W9D; -.
DR PDBsum; 4W9E; -.
DR PDBsum; 4W9F; -.
DR PDBsum; 4W9G; -.
DR PDBsum; 4W9H; -.
DR PDBsum; 4W9I; -.
DR PDBsum; 4W9J; -.
DR PDBsum; 4W9K; -.
DR PDBsum; 4W9L; -.
DR PDBsum; 4WQO; -.
DR PDBsum; 5LLI; -.
DR PDBsum; 5N4W; -.
DR PDBsum; 5NVV; -.
DR PDBsum; 5NVW; -.
DR PDBsum; 5NVX; -.
DR PDBsum; 5NVY; -.
DR PDBsum; 5NVZ; -.
DR PDBsum; 5NW0; -.
DR PDBsum; 5NW1; -.
DR PDBsum; 5NW2; -.
DR PDBsum; 5T35; -.
DR PDBsum; 6BVB; -.
DR PDBsum; 6FMI; -.
DR PDBsum; 6FMJ; -.
DR PDBsum; 6FMK; -.
DR PDBsum; 6GFX; -.
DR PDBsum; 6GFY; -.
DR PDBsum; 6GFZ; -.
DR PDBsum; 6GMN; -.
DR PDBsum; 6GMQ; -.
DR PDBsum; 6GMR; -.
DR PDBsum; 6GMX; -.
DR PDBsum; 6HAX; -.
DR PDBsum; 6HAY; -.
DR PDBsum; 6HR2; -.
DR PDBsum; 6I7Q; -.
DR PDBsum; 6I7R; -.
DR PDBsum; 6R6H; -.
DR PDBsum; 6R7F; -.
DR PDBsum; 6SIS; -.
DR PDBsum; 6ZHC; -.
DR PDBsum; 7CJB; -.
DR PDBsum; 7JTO; -.
DR PDBsum; 7JTP; -.
DR PDBsum; 7KHH; -.
DR PDBsum; 7PI4; -.
DR PDBsum; 7Q2J; -.
DR AlphaFoldDB; P40337; -.
DR SMR; P40337; -.
DR BioGRID; 113269; 444.
DR CORUM; P40337; -.
DR DIP; DIP-32585N; -.
DR IntAct; P40337; 136.
DR MINT; P40337; -.
DR STRING; 9606.ENSP00000256474; -.
DR BindingDB; P40337; -.
DR ChEMBL; CHEMBL3108660; -.
DR iPTMnet; P40337; -.
DR PhosphoSitePlus; P40337; -.
DR BioMuta; VHL; -.
DR DMDM; 4033778; -.
DR EPD; P40337; -.
DR jPOST; P40337; -.
DR MassIVE; P40337; -.
DR MaxQB; P40337; -.
DR PaxDb; P40337; -.
DR PeptideAtlas; P40337; -.
DR PRIDE; P40337; -.
DR ProteomicsDB; 55362; -. [P40337-1]
DR ProteomicsDB; 55363; -. [P40337-2]
DR ProteomicsDB; 55364; -. [P40337-3]
DR Antibodypedia; 10562; 755 antibodies from 41 providers.
DR DNASU; 7428; -.
DR Ensembl; ENST00000256474.3; ENSP00000256474.3; ENSG00000134086.8. [P40337-1]
DR Ensembl; ENST00000345392.2; ENSP00000344757.2; ENSG00000134086.8. [P40337-2]
DR GeneID; 7428; -.
DR KEGG; hsa:7428; -.
DR MANE-Select; ENST00000256474.3; ENSP00000256474.3; NM_000551.4; NP_000542.1.
DR UCSC; uc003bvc.4; human. [P40337-1]
DR CTD; 7428; -.
DR DisGeNET; 7428; -.
DR GeneCards; VHL; -.
DR GeneReviews; VHL; -.
DR HGNC; HGNC:12687; VHL.
DR HPA; ENSG00000134086; Low tissue specificity.
DR MalaCards; VHL; -.
DR MIM; 144700; phenotype.
DR MIM; 171300; phenotype.
DR MIM; 193300; phenotype.
DR MIM; 263400; phenotype.
DR MIM; 608537; gene.
DR neXtProt; NX_P40337; -.
DR OpenTargets; ENSG00000134086; -.
DR Orphanet; 238557; Chuvash erythrocytosis.
DR Orphanet; 29072; Hereditary pheochromocytoma-paraganglioma.
DR Orphanet; 276621; Sporadic pheochromocytoma/secreting paraganglioma.
DR Orphanet; 892; Von Hippel-Lindau disease.
DR PharmGKB; PA37307; -.
DR VEuPathDB; HostDB:ENSG00000134086; -.
DR eggNOG; KOG4710; Eukaryota.
DR GeneTree; ENSGT00390000014353; -.
DR HOGENOM; CLU_116090_0_0_1; -.
DR InParanoid; P40337; -.
DR OMA; VGHPWLF; -.
DR PhylomeDB; P40337; -.
DR TreeFam; TF318985; -.
DR BRENDA; 2.3.2.B13; 2681.
DR PathwayCommons; P40337; -.
DR Reactome; R-HSA-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-HSA-3232142; SUMOylation of ubiquitinylation proteins.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-9682706; Replication of the SARS-CoV-1 genome.
DR Reactome; R-HSA-9694686; Replication of the SARS-CoV-2 genome.
DR Reactome; R-HSA-9706019; RHOBTB3 ATPase cycle.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; P40337; -.
DR SIGNOR; P40337; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 7428; 609 hits in 1132 CRISPR screens.
DR ChiTaRS; VHL; human.
DR EvolutionaryTrace; P40337; -.
DR GeneWiki; Von_Hippel%E2%80%93Lindau_tumor_suppressor; -.
DR GenomeRNAi; 7428; -.
DR Pharos; P40337; Tchem.
DR PRO; PR:P40337; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P40337; protein.
DR Bgee; ENSG00000134086; Expressed in cortical plate and 110 other tissues.
DR ExpressionAtlas; P40337; baseline and differential.
DR Genevisible; P40337; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; NAS:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; NAS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0003711; F:transcription elongation regulator activity; IDA:UniProtKB.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:Reactome.
DR GO; GO:0000902; P:cell morphogenesis; NAS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; NAS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:CAFA.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:CAFA.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; IMP:CAFA.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0061428; P:negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; IDA:UniProtKB.
DR GO; GO:0045597; P:positive regulation of cell differentiation; NAS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; NAS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:BHF-UCL.
DR CDD; cd05468; pVHL; 1.
DR DisProt; DP00287; -.
DR Gene3D; 1.10.750.10; -; 1.
DR Gene3D; 2.60.40.780; -; 1.
DR IDEAL; IID00371; -.
DR InterPro; IPR002714; VHL.
DR InterPro; IPR024048; VHL_alpha_dom.
DR InterPro; IPR037139; VHL_alpha_dom_sf.
DR InterPro; IPR024053; VHL_beta_dom.
DR InterPro; IPR037140; VHL_beta_dom_sf.
DR InterPro; IPR036208; VHL_sf.
DR InterPro; IPR022772; VHL_tumour_suppress_b/a_dom.
DR PANTHER; PTHR15160:SF10; PTHR15160:SF10; 1.
DR Pfam; PF01847; VHL; 1.
DR Pfam; PF17211; VHL_C; 1.
DR SUPFAM; SSF49468; SSF49468; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Alternative splicing;
KW Congenital erythrocytosis; Cytoplasm; Disease variant; Membrane; Nucleus;
KW Reference proteome; Repeat; Tumor suppressor; Ubl conjugation pathway.
FT CHAIN 1..213
FT /note="von Hippel-Lindau disease tumor suppressor"
FT /id="PRO_0000065809"
FT REPEAT 14..18
FT /note="1"
FT REPEAT 19..23
FT /note="2"
FT REPEAT 24..28
FT /note="3"
FT REPEAT 29..33
FT /note="4"
FT REPEAT 34..38
FT /note="5"
FT REPEAT 39..43
FT /note="6"
FT REPEAT 44..48
FT /note="7"
FT REPEAT 49..53
FT /note="8"
FT REGION 1..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 14..53
FT /note="8 X 5 AA tandem repeats of G-[PAVG]-E-E-[DAYSLE]"
FT REGION 100..155
FT /note="Involved in binding to CCT complex"
FT REGION 157..166
FT /note="Interaction with Elongin BC complex"
FT COMPBIAS 12..50
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..53
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_007740"
FT VAR_SEQ 114..154
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004488"
FT VARIANT 25
FT /note="P -> L (in pheochromocytoma; likely benign variant;
FT dbSNP:rs35460768)"
FT /evidence="ECO:0000269|PubMed:14500403,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:9663592"
FT /id="VAR_034562"
FT VARIANT 38
FT /note="S -> P (in VHLD; type II)"
FT /evidence="ECO:0000269|PubMed:9452032"
FT /id="VAR_005670"
FT VARIANT 52
FT /note="E -> K (in VHLD; type I; dbSNP:rs373068386)"
FT /evidence="ECO:0000269|PubMed:9829912"
FT /id="VAR_005671"
FT VARIANT 63
FT /note="L -> P (in pheochromocytoma; dbSNP:rs104893827)"
FT /evidence="ECO:0000269|PubMed:9663592"
FT /id="VAR_034987"
FT VARIANT 64
FT /note="R -> P (in pheochromocytoma; dbSNP:rs104893826)"
FT /evidence="ECO:0000269|PubMed:9663592"
FT /id="VAR_034988"
FT VARIANT 65
FT /note="S -> A (in pheochromocytoma; dbSNP:rs869025616)"
FT /evidence="ECO:0000269|PubMed:12000816"
FT /id="VAR_034989"
FT VARIANT 65
FT /note="S -> L (in VHLD; type I; dbSNP:rs5030826)"
FT /evidence="ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829912"
FT /id="VAR_005672"
FT VARIANT 65
FT /note="S -> W (in VHLD; type I; dbSNP:rs5030826)"
FT /evidence="ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829911"
FT /id="VAR_005673"
FT VARIANT 66..73
FT /note="Missing (in VHLD; type I)"
FT /id="VAR_005674"
FT VARIANT 68
FT /note="S -> W (in pheochromocytoma and VHLD; type II)"
FT /evidence="ECO:0000269|PubMed:10627136,
FT ECO:0000269|PubMed:12000816"
FT /id="VAR_005675"
FT VARIANT 70
FT /note="E -> K (in VHLD; type I; dbSNP:rs5030802)"
FT /evidence="ECO:0000269|PubMed:9829912"
FT /id="VAR_005676"
FT VARIANT 74
FT /note="V -> G (in VHLD; type I-II; dbSNP:rs5030803)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005677"
FT VARIANT 75
FT /note="Missing (in VHLD; dbSNP:rs794729660)"
FT /evidence="ECO:0000269|PubMed:8493574"
FT /id="VAR_034990"
FT VARIANT 76
FT /note="F -> I (in VHLD; type I; dbSNP:rs1559425911)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005679"
FT VARIANT 76
FT /note="F -> L (in VHLD; type I)"
FT /evidence="ECO:0000269|PubMed:9452032"
FT /id="VAR_005680"
FT VARIANT 76
FT /note="F -> S (in VHLD; type I; dbSNP:rs730882033)"
FT /evidence="ECO:0000269|PubMed:9829911"
FT /id="VAR_005681"
FT VARIANT 76
FT /note="Missing (in VHLD; type I; common mutation)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005678"
FT VARIANT 78
FT /note="N -> H (in VHLD; type I; dbSNP:rs869025621)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005682"
FT VARIANT 78
FT /note="N -> S (in VHLD; type I; common mutation;
FT dbSNP:rs5030804)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005683"
FT VARIANT 78
FT /note="N -> T (in VHLD; type I; dbSNP:rs5030804)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005684"
FT VARIANT 79
FT /note="R -> P (in VHLD)"
FT /id="VAR_005685"
FT VARIANT 80
FT /note="S -> I (in VHLD; type I; dbSNP:rs5030805)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005686"
FT VARIANT 80
FT /note="S -> N (in pheochromocytoma and VHLD; type I;
FT dbSNP:rs5030805)"
FT /evidence="ECO:0000269|PubMed:12000816,
FT ECO:0000269|PubMed:8956040, ECO:0000269|PubMed:9829912"
FT /id="VAR_005688"
FT VARIANT 80
FT /note="S -> R (in VHLD; type I; dbSNP:rs786202787)"
FT /evidence="ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829912"
FT /id="VAR_005687"
FT VARIANT 81
FT /note="P -> S (in VHLD; type I; dbSNP:rs104893829)"
FT /evidence="ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829911"
FT /id="VAR_005689"
FT VARIANT 82..84
FT /note="Missing (in VHLD)"
FT /id="VAR_005691"
FT VARIANT 82
FT /note="R -> P (in VHLD; type I; dbSNP:rs794726890)"
FT /id="VAR_005690"
FT VARIANT 84
FT /note="V -> L (in VHLD; type II and type 2C;
FT dbSNP:rs5030827)"
FT /evidence="ECO:0000269|PubMed:16502427,
FT ECO:0000269|PubMed:8592333"
FT /id="VAR_005692"
FT VARIANT 86
FT /note="P -> A (in VHLD; type I; dbSNP:rs398123481)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005693"
FT VARIANT 86
FT /note="P -> H (in VHLD)"
FT /id="VAR_008097"
FT VARIANT 86
FT /note="P -> L (in VHLD; type I; dbSNP:rs730882034)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005694"
FT VARIANT 86
FT /note="P -> R (in VHLD; type I; dbSNP:rs730882034)"
FT /evidence="ECO:0000269|PubMed:9829911"
FT /id="VAR_005695"
FT VARIANT 86
FT /note="P -> S (in VHLD; dbSNP:rs398123481)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:9829912"
FT /id="VAR_005696"
FT VARIANT 88
FT /note="W -> R (in VHLD; type I; dbSNP:rs1553619431)"
FT /evidence="ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829911"
FT /id="VAR_005697"
FT VARIANT 88
FT /note="W -> S (in VHLD; type I; dbSNP:rs119103277)"
FT /evidence="ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829912"
FT /id="VAR_005698"
FT VARIANT 89
FT /note="L -> H (in lung cancer; dbSNP:rs5030807)"
FT /id="VAR_005699"
FT VARIANT 89
FT /note="L -> P (in VHLD; type I; dbSNP:rs5030807)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005700"
FT VARIANT 91
FT /note="F -> L (in cerebellar hemangioblastoma;
FT dbSNP:rs1060503563)"
FT /evidence="ECO:0000269|PubMed:9829912"
FT /id="VAR_005701"
FT VARIANT 92..97
FT /note="Missing (in VHLD; type I)"
FT /id="VAR_005702"
FT VARIANT 93
FT /note="G -> C (in pheochromocytoma and VHLD; type II;
FT dbSNP:rs5030808)"
FT /evidence="ECO:0000269|PubMed:12000816, ECO:0000269|Ref.43"
FT /id="VAR_005703"
FT VARIANT 93
FT /note="G -> D (in VHLD; dbSNP:rs1553619440)"
FT /id="VAR_005704"
FT VARIANT 93
FT /note="G -> S (in pheochromocytoma and VHLD; type II;
FT dbSNP:rs5030808)"
FT /evidence="ECO:0000269|PubMed:12000816"
FT /id="VAR_005705"
FT VARIANT 96
FT /note="Q -> P (in VHLD; type I; dbSNP:rs1559426089)"
FT /evidence="ECO:0000269|PubMed:8730290"
FT /id="VAR_005706"
FT VARIANT 98
FT /note="Y -> H (in pheochromocytoma and VHLD; type II;
FT dbSNP:rs5030809)"
FT /evidence="ECO:0000269|PubMed:12000816"
FT /id="VAR_005707"
FT VARIANT 101
FT /note="L -> G (in VHLD; type I; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:9829911"
FT /id="VAR_005708"
FT VARIANT 101
FT /note="L -> R (in VHLD; type I)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005709"
FT VARIANT 104
FT /note="G -> A (in cerebellar hemangioblastoma;
FT dbSNP:rs869025630)"
FT /evidence="ECO:0000269|PubMed:9829912"
FT /id="VAR_005710"
FT VARIANT 105
FT /note="T -> P (in VHLD; type I; dbSNP:rs1553619461)"
FT /evidence="ECO:0000269|PubMed:9829912"
FT /id="VAR_005711"
FT VARIANT 106
FT /note="G -> D (in lung cancer; dbSNP:rs1446876735)"
FT /id="VAR_005712"
FT VARIANT 107
FT /note="R -> G (in pheochromocytoma; dbSNP:rs397516440)"
FT /evidence="ECO:0000269|PubMed:12000816"
FT /id="VAR_034991"
FT VARIANT 107
FT /note="R -> P (in VHLD; type I; dbSNP:rs193922609)"
FT /evidence="ECO:0000269|PubMed:9829911"
FT /id="VAR_005713"
FT VARIANT 110
FT /note="H -> Y (in dbSNP:rs17855706)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_055087"
FT VARIANT 111
FT /note="S -> C (in VHLD; type II; dbSNP:rs1559426203)"
FT /id="VAR_005714"
FT VARIANT 111
FT /note="S -> N (in VHLD; type I; dbSNP:rs869025631)"
FT /evidence="ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829911"
FT /id="VAR_005715"
FT VARIANT 111
FT /note="S -> R (in VHLD; type I; dbSNP:rs765978945)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005716"
FT VARIANT 112
FT /note="Y -> H (in VHLD; type IIA; dbSNP:rs104893824)"
FT /id="VAR_005717"
FT VARIANT 112
FT /note="Y -> N (in VHLD; dbSNP:rs104893824)"
FT /evidence="ECO:0000269|PubMed:10533030"
FT /id="VAR_034992"
FT VARIANT 114
FT /note="G -> C (in VHLD; type II)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005718"
FT VARIANT 114
FT /note="G -> R (in VHLD; type I-II; dbSNP:rs869025636)"
FT /id="VAR_005719"
FT VARIANT 114
FT /note="G -> S (in VHLD; type II; dbSNP:rs869025636)"
FT /evidence="ECO:0000269|PubMed:8825918"
FT /id="VAR_005720"
FT VARIANT 115
FT /note="H -> Q (in VHLD; type II; dbSNP:rs864622646)"
FT /evidence="ECO:0000269|PubMed:9829912"
FT /id="VAR_005723"
FT VARIANT 115
FT /note="H -> R (in VHLD; type II; dbSNP:rs5030812)"
FT /id="VAR_008098"
FT VARIANT 115
FT /note="H -> Y (in VHLD; type I; dbSNP:rs5030811)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005722"
FT VARIANT 116
FT /note="L -> V (in VHLD)"
FT /evidence="ECO:0000269|PubMed:8730290"
FT /id="VAR_005724"
FT VARIANT 117
FT /note="W -> C (in VHLD; type I; dbSNP:rs727504215)"
FT /evidence="ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829911, ECO:0000269|PubMed:9829912"
FT /id="VAR_005725"
FT VARIANT 118
FT /note="L -> P (in VHLD; type I; dbSNP:rs5030830)"
FT /evidence="ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829912"
FT /id="VAR_005726"
FT VARIANT 118
FT /note="L -> R (in VHLD; dbSNP:rs5030830)"
FT /evidence="ECO:0000269|PubMed:8730290"
FT /id="VAR_005727"
FT VARIANT 119
FT /note="F -> L (in pheochromocytoma and VHLD; type II;
FT dbSNP:rs1553619948)"
FT /evidence="ECO:0000269|PubMed:12000816"
FT /id="VAR_005728"
FT VARIANT 119
FT /note="F -> S (in VHLD; type II)"
FT /evidence="ECO:0000269|PubMed:8825918"
FT /id="VAR_005729"
FT VARIANT 121
FT /note="D -> G (in VHLD; type I; dbSNP:rs5030832)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005730"
FT VARIANT 122
FT /note="A -> I (in pheochromocytoma; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:12000816"
FT /id="VAR_034993"
FT VARIANT 126
FT /note="D -> Y (in ECYT2; dbSNP:rs104893831)"
FT /evidence="ECO:0000269|PubMed:12393546"
FT /id="VAR_034994"
FT VARIANT 128
FT /note="L -> F (in VHLD; type II; dbSNP:rs1553619956)"
FT /id="VAR_005731"
FT VARIANT 129
FT /note="L -> LE (in VHLD)"
FT /id="VAR_005732"
FT VARIANT 130
FT /note="V -> L (in ECYT2 and VHLD; type I;
FT dbSNP:rs104893830)"
FT /evidence="ECO:0000269|PubMed:12393546,
FT ECO:0000269|PubMed:8956040, ECO:0000269|PubMed:9829912"
FT /id="VAR_005733"
FT VARIANT 131
FT /note="N -> K (in VHLD; type I; dbSNP:rs1064794272)"
FT /evidence="ECO:0000269|PubMed:9829912"
FT /id="VAR_005734"
FT VARIANT 131
FT /note="N -> T (in VHLD; type I)"
FT /evidence="ECO:0000269|PubMed:9829911"
FT /id="VAR_005735"
FT VARIANT 135
FT /note="L -> F (in hemangioblastoma; dbSNP:rs119103278)"
FT /evidence="ECO:0000269|PubMed:8069849"
FT /id="VAR_034995"
FT VARIANT 136
FT /note="F -> C (in pheochromocytoma and VHLD; type II;
FT dbSNP:rs5030833)"
FT /evidence="ECO:0000269|PubMed:12000816"
FT /id="VAR_005737"
FT VARIANT 136
FT /note="F -> S (in VHLD; dbSNP:rs5030833)"
FT /evidence="ECO:0000269|PubMed:9829912"
FT /id="VAR_005736"
FT VARIANT 136
FT /note="F -> Y (in VHLD)"
FT /id="VAR_008099"
FT VARIANT 143
FT /note="D -> E (in VHLD; type II; dbSNP:rs773556807)"
FT /evidence="ECO:0000269|PubMed:8825918"
FT /id="VAR_005738"
FT VARIANT 145
FT /note="Q -> H (in VHLD; dbSNP:rs771727849)"
FT /id="VAR_008100"
FT VARIANT 147
FT /note="I -> T (in pheochromocytoma; dbSNP:rs1060503555)"
FT /evidence="ECO:0000269|PubMed:9663592"
FT /id="VAR_034996"
FT VARIANT 148
FT /note="Missing (in VHLD; type I)"
FT /id="VAR_005739"
FT VARIANT 149
FT /note="A -> T (in VHLD; type II; dbSNP:rs587780077)"
FT /evidence="ECO:0000269|PubMed:9452106"
FT /id="VAR_005740"
FT VARIANT 154
FT /note="P -> L (in VHLD; type II; dbSNP:rs1399097617)"
FT /id="VAR_005741"
FT VARIANT 155
FT /note="V -> G (in VHLD; type II)"
FT /evidence="ECO:0000269|Ref.43"
FT /id="VAR_005742"
FT VARIANT 155
FT /note="V -> M (in VHLD; with RCC; dbSNP:rs869025659)"
FT /id="VAR_008101"
FT VARIANT 156
FT /note="Y -> C (in pheochromocytoma and VHLD; type I;
FT dbSNP:rs397516441)"
FT /evidence="ECO:0000269|PubMed:12000816,
FT ECO:0000269|PubMed:14500403, ECO:0000269|PubMed:9829912"
FT /id="VAR_005743"
FT VARIANT 156
FT /note="Y -> D (in VHLD; type I)"
FT /evidence="ECO:0000269|PubMed:9829912"
FT /id="VAR_005744"
FT VARIANT 156
FT /note="Y -> N (in pheochromocytoma)"
FT /evidence="ECO:0000269|PubMed:12000816"
FT /id="VAR_034997"
FT VARIANT 157
FT /note="T -> I (in VHLD; type II; dbSNP:rs869025660)"
FT /evidence="ECO:0000269|PubMed:9829912, ECO:0000269|Ref.43"
FT /id="VAR_005746"
FT VARIANT 157
FT /note="T -> TF (in VHLD; type I)"
FT /id="VAR_005747"
FT VARIANT 158
FT /note="L -> P (in VHLD; type I-II; abolishes release from
FT chaperonin complex and the interaction with Elongin BC
FT complex; dbSNP:rs121913346)"
FT /evidence="ECO:0000269|PubMed:10635329,
FT ECO:0000269|PubMed:8956040, ECO:0000269|PubMed:9829912"
FT /id="VAR_005748"
FT VARIANT 158
FT /note="L -> V (in VHLD; type I; dbSNP:rs1559429613)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005749"
FT VARIANT 159
FT /note="K -> E (in VHLD; type II; dbSNP:rs1575932011)"
FT /id="VAR_005750"
FT VARIANT 161
FT /note="R -> G (in VHLD; type II; dbSNP:rs5030818)"
FT /id="VAR_005753"
FT VARIANT 161
FT /note="R -> P (in pheochromocytoma and VHLD; type I)"
FT /evidence="ECO:0000269|PubMed:12000816,
FT ECO:0000269|PubMed:8956040"
FT /id="VAR_005752"
FT VARIANT 161
FT /note="R -> Q (in pheochromocytoma and VHLD; type II;
FT dbSNP:rs730882035)"
FT /evidence="ECO:0000269|PubMed:12000816,
FT ECO:0000269|PubMed:9829912"
FT /id="VAR_005751"
FT VARIANT 162
FT /note="C -> F (in VHLD; type I; No effect on interaction
FT with HIF1A nor on HIF1A degradation; dbSNP:rs397516444)"
FT /evidence="ECO:0000269|PubMed:10944113,
FT ECO:0000269|PubMed:8956040, ECO:0000269|PubMed:9452032,
FT ECO:0000269|PubMed:9829911"
FT /id="VAR_005754"
FT VARIANT 162
FT /note="C -> R (in VHLD; type I; dbSNP:rs1553620313)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005755"
FT VARIANT 162
FT /note="C -> W (in VHLD; type I-II; dbSNP:rs5030622)"
FT /evidence="ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829912"
FT /id="VAR_005756"
FT VARIANT 162
FT /note="C -> Y (in VHLD; type I; dbSNP:rs397516444)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005757"
FT VARIANT 163
FT /note="L -> P (in RCC; with paraneoplastic erythrocytosis;
FT inhibits binding to HIF1AN; dbSNP:rs28940297)"
FT /evidence="ECO:0000269|PubMed:11986208, ECO:0000269|Ref.6"
FT /id="VAR_034998"
FT VARIANT 164
FT /note="Q -> H (in VHLD; dbSNP:rs1352275281)"
FT /id="VAR_008102"
FT VARIANT 164
FT /note="Q -> R (in VHLD; type II; dbSNP:rs267607170)"
FT /evidence="ECO:0000269|PubMed:8825918,
FT ECO:0000269|PubMed:8956040"
FT /id="VAR_005758"
FT VARIANT 166
FT /note="V -> D (in VHLD; with RCC; dbSNP:rs397516445)"
FT /id="VAR_008103"
FT VARIANT 166
FT /note="V -> F (in VHLD; type IIA; dbSNP:rs104893825)"
FT /evidence="ECO:0000269|PubMed:8730290,
FT ECO:0000269|PubMed:9829912"
FT /id="VAR_005759"
FT VARIANT 167
FT /note="R -> G (in VHLD; type I-II; dbSNP:rs5030820)"
FT /evidence="ECO:0000269|PubMed:9829911"
FT /id="VAR_005760"
FT VARIANT 167
FT /note="R -> Q (in pheochromocytoma and VHLD; type II;
FT common mutation; dbSNP:rs5030821)"
FT /evidence="ECO:0000269|PubMed:12000816,
FT ECO:0000269|PubMed:8956040, ECO:0000269|PubMed:9829912"
FT /id="VAR_005761"
FT VARIANT 167
FT /note="R -> W (in pheochromocytoma and VHLD; type II;
FT common mutation; dbSNP:rs5030820)"
FT /evidence="ECO:0000269|PubMed:12000816,
FT ECO:0000269|PubMed:8592333, ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829912"
FT /id="VAR_005762"
FT VARIANT 170
FT /note="V -> D (in VHLD; type II; dbSNP:rs864321642)"
FT /evidence="ECO:0000269|PubMed:8730290"
FT /id="VAR_005763"
FT VARIANT 170
FT /note="V -> F (in VHLD; type II)"
FT /id="VAR_005764"
FT VARIANT 170
FT /note="V -> G (in VHLD; type I)"
FT /evidence="ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829912"
FT /id="VAR_005765"
FT VARIANT 175
FT /note="Y -> D (in VHLD; type I)"
FT /evidence="ECO:0000269|PubMed:9829911"
FT /id="VAR_005766"
FT VARIANT 176
FT /note="R -> W (in VHLD)"
FT /id="VAR_008104"
FT VARIANT 177
FT /note="R -> RLRVKPE (in VHLD; type I)"
FT /id="VAR_005767"
FT VARIANT 178
FT /note="L -> P (in VHLD; type I-II; common mutation;
FT dbSNP:rs5030822)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005768"
FT VARIANT 178
FT /note="L -> Q (in VHLD; type II; dbSNP:rs5030822)"
FT /id="VAR_005769"
FT VARIANT 180
FT /note="I -> V (in VHLD; type I; dbSNP:rs377715747)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005770"
FT VARIANT 184
FT /note="L -> P (in VHLD; type I; dbSNP:rs1064793878)"
FT /evidence="ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829911"
FT /id="VAR_005772"
FT VARIANT 184
FT /note="L -> R (in VHLD; type I)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005771"
FT VARIANT 186
FT /note="E -> K (in VHLD; type I; dbSNP:rs367545984)"
FT /evidence="ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829911"
FT /id="VAR_005773"
FT VARIANT 186
FT /note="Missing (in VHLD; dbSNP:rs1559429813)"
FT /evidence="ECO:0000269|PubMed:8730290"
FT /id="VAR_005774"
FT VARIANT 188
FT /note="L -> P (in VHLD; type I-II; dbSNP:rs1559429824)"
FT /evidence="ECO:0000269|PubMed:9829912"
FT /id="VAR_005775"
FT VARIANT 188
FT /note="L -> Q (in VHLD; type I; dbSNP:rs1559429824)"
FT /evidence="ECO:0000269|PubMed:8956040"
FT /id="VAR_005776"
FT VARIANT 188
FT /note="L -> V (in ECYT2, pheochromocytoma and VHLD; type
FT IIA; dbSNP:rs5030824)"
FT /evidence="ECO:0000269|PubMed:12000816,
FT ECO:0000269|PubMed:12844285"
FT /id="VAR_005777"
FT VARIANT 191
FT /note="H -> D (in ECYT2; dbSNP:rs28940301)"
FT /evidence="ECO:0000269|PubMed:12844285"
FT /id="VAR_034999"
FT VARIANT 192
FT /note="P -> S (in ECYT2; dbSNP:rs28940300)"
FT /evidence="ECO:0000269|PubMed:12844285"
FT /id="VAR_035000"
FT VARIANT 198
FT /note="L -> Q (in pheochromocytoma)"
FT /evidence="ECO:0000269|PubMed:12000816"
FT /id="VAR_035001"
FT VARIANT 198
FT /note="L -> R (in ECYT2 and VHLD; type II)"
FT /id="VAR_005778"
FT VARIANT 200
FT /note="R -> W (in ECYT2 and VHLD; type I;
FT dbSNP:rs28940298)"
FT /evidence="ECO:0000269|PubMed:12393546,
FT ECO:0000269|PubMed:12844285, ECO:0000269|PubMed:8956040,
FT ECO:0000269|PubMed:9829912"
FT /id="VAR_005779"
FT MUTAGEN 98
FT /note="Y->N: No interaction with HIF1A. No HIF1A
FT degradation."
FT /evidence="ECO:0000269|PubMed:10944113"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:6HAY"
FT STRAND 71..78
FT /evidence="ECO:0007829|PDB:7JTO"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:7JTO"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:7JTO"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:3ZTC"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:7JTO"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:7JTO"
FT STRAND 116..121
FT /evidence="ECO:0007829|PDB:7JTO"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:7JTO"
FT STRAND 129..134
FT /evidence="ECO:0007829|PDB:6GMX"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:6GFX"
FT STRAND 147..152
FT /evidence="ECO:0007829|PDB:7JTO"
FT HELIX 158..169
FT /evidence="ECO:0007829|PDB:7JTO"
FT HELIX 172..177
FT /evidence="ECO:0007829|PDB:7JTO"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:7JTO"
FT HELIX 182..189
FT /evidence="ECO:0007829|PDB:7JTO"
FT HELIX 194..204
FT /evidence="ECO:0007829|PDB:7JTO"
SQ SEQUENCE 213 AA; 24153 MW; BA5D6765FBC16EA7 CRC64;
MPRRAENWDE AEVGAEEAGV EEYGPEEDGG EESGAEESGP EESGPEELGA EEEMEAGRPR
PVLRSVNSRE PSQVIFCNRS PRVVLPVWLN FDGEPQPYPT LPPGTGRRIH SYRGHLWLFR
DAGTHDGLLV NQTELFVPSL NVDGQPIFAN ITLPVYTLKE RCLQVVRSLV KPENYRRLDI
VRSLYEDLED HPNVQKDLER LTQERIAHQR MGD
