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von Hippel-Lindau disease tumor suppressor (Protein G7) (pVHL)

 VHL_HUMAN               Reviewed;         213 AA.
P40337; B2RE45; Q13599; Q6PDA9;
01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
15-DEC-1998, sequence version 2.
22-NOV-2017, entry version 206.
RecName: Full=von Hippel-Lindau disease tumor suppressor;
AltName: Full=Protein G7;
AltName: Full=pVHL;
Name=VHL;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANTS VHLD
ILE-75 DEL AND ARG-82--84-VAL DEL, AND ALTERNATIVE SPLICING (ISOFORM
2).
PubMed=8493574; DOI=10.1126/science.8493574;
Latif F., Tory K., Gnarra J., Yao M., Duh F.-M., Orcutt M.L.,
Stackhouse T., Kuzmin I., Modi W., Geil L., Schmidt L., Zhou F.,
Li H., Wei M.H., Chen F., Glenn G., Choyke P., Walther M.M., Weng Y.,
Duan D.-S.R., Dean M., Glavac D., Richards F.M., Crossey P.A.,
Ferguson-Smith M.A., le Paslier D., Chumakov I., Cohen D.,
Chinault A.C., Maher E.R., Linehan W.M., Zbar B., Lerman M.I.;
"Identification of the von Hippel-Lindau disease tumor suppressor
gene.";
Science 260:1317-1320(1993).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16641997; DOI=10.1038/nature04728;
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
Gibbs R.A.;
"The DNA sequence, annotation and analysis of human chromosome 3.";
Nature 440:1194-1198(2006).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
TYR-110.
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 33-67 AND 156-213, AND VARIANT
PRO-163.
TISSUE=Renal cell carcinoma;
Wenzel M.;
Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
[7]
DEVELOPMENTAL STAGE, AND ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
PubMed=8733131; DOI=10.1093/hmg/5.5.639;
Richards F.M., Schofield P.N., Fleming S., Maher E.R.;
"Expression of the von Hippel-Lindau disease tumour suppressor gene
during human embryogenesis.";
Hum. Mol. Genet. 5:639-644(1996).
[8]
INTERACTION WITH CUL2.
PubMed=9122164; DOI=10.1073/pnas.94.6.2156;
Pause A., Lee S., Worrel R., Chen D.Y.T., Burgess W.H., Linehan W.M.,
Klausner R.D.;
"The von Hippel-Lindau tumor-suppressor gene product forms a stable
complex with human CUL-2, a member of the Cdc53 family of proteins.";
Proc. Natl. Acad. Sci. U.S.A. 94:2156-2161(1997).
[9]
ALTERNATIVE SPLICING (ISOFORM 3).
PubMed=9671762; DOI=10.1073/pnas.95.15.8817;
Schoenfeld A., Davidowitz E.J., Burk R.D.;
"A second major native von Hippel-Lindau gene product, initiated from
an internal translation start site, functions as a tumor suppressor.";
Proc. Natl. Acad. Sci. U.S.A. 95:8817-8822(1998).
[10]
INTERACTION WITH ELONGIN BC COMPLEX.
PubMed=7660130; DOI=10.1126/science.7660130;
Kibel A., Iliopoulos O., DeCaprio J.A., Kaelin W.G. Jr.;
"Binding of the von Hippel-Lindau tumor suppressor protein to Elongin
B and C.";
Science 269:1444-1446(1995).
[11]
FUNCTION (ISOFORM 3), AND SUBCELLULAR LOCATION.
PubMed=9751722; DOI=10.1073/pnas.95.20.11661;
Iliopoulos O., Ohh M., Kaelin W.G. Jr.;
"pVHL19 is a biologically active product of the von Hippel-Lindau gene
arising from internal translation initiation.";
Proc. Natl. Acad. Sci. U.S.A. 95:11661-11666(1998).
[12]
INTERACTION WITH CHAPERONES, AND VARIANT VHLD PRO-158.
PubMed=10635329; DOI=10.1016/S1097-2765(00)80233-6;
Feldman D.E., Thulasiraman V., Ferreyra R.G., Frydman J.;
"Formation of the VHL-elongin BC tumor suppressor complex is mediated
by the chaperonin TRiC.";
Mol. Cell 4:1051-1061(1999).
[13]
INTERACTION WITH HIF1A, FUNCTION, CHARACTERIZATION OF VARIANT PHE-162,
AND MUTAGENESIS OF TYR-98.
PubMed=10944113; DOI=10.1093/emboj/19.16.4298;
Tanimoto K., Makino Y., Pereira T., Poellinger L.;
"Mechanism of regulation of the hypoxia-inducible factor-1 alpha by
the von Hippel-Lindau tumor suppressor protein.";
EMBO J. 19:4298-4309(2000).
[14]
IDENTIFICATION IN E3 UBIQUITIN-PROTEIN LIGASE COMPLEXES.
PubMed=11384984; DOI=10.1074/jbc.M103093200;
Kamura T., Burian D., Yan Q., Schmidt S.L., Lane W.S., Querido E.,
Branton P.E., Shilatifard A., Conaway R.C., Conaway J.W.;
"Muf1, a novel elongin BC-interacting leucine-rich repeat protein that
can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase.";
J. Biol. Chem. 276:29748-29753(2001).
[15]
INTERACTION WITH HIF1AN; HIF1A AND HISTONE DEACETYLASES.
TISSUE=Brain;
PubMed=11641274; DOI=10.1101/gad.924501;
Mahon P.C., Hirota K., Semenza G.L.;
"FIH-1: a novel protein that interacts with HIF-1alpha and VHL to
mediate repression of HIF-1 transcriptional activity.";
Genes Dev. 15:2675-2686(2001).
[16]
INTERACTION WITH USP33.
PubMed=11739384; DOI=10.1074/jbc.M108269200;
Li Z., Na X., Wang D., Schoen S.R., Messing E.M., Wu G.;
"Ubiquitination of a novel deubiquitinating enzyme requires direct
binding to von Hippel-Lindau tumor suppressor protein.";
J. Biol. Chem. 277:4656-4662(2002).
[17]
INTERACTION WITH JADE1.
PubMed=12169691; DOI=10.1074/jbc.M205040200;
Zhou M.I., Wang H., Ross J.J., Kuzmin I., Xu C., Cohen H.T.;
"The von Hippel-Lindau tumor suppressor stabilizes novel plant
homeodomain protein Jade-1.";
J. Biol. Chem. 277:39887-39898(2002).
[18]
INTERACTION WITH RNF139.
PubMed=12032852; DOI=10.1038/sj.onc.1205437;
Gemmill R.M., Bemis L.T., Lee J.P., Sozen M.A., Baron A., Zeng C.,
Erickson P.F., Hooper J.E., Drabkin H.A.;
"The TRC8 hereditary kidney cancer gene suppresses growth and
functions with VHL in a common pathway.";
Oncogene 21:3507-3516(2002).
[19]
FUNCTION, AND INTERACTION WITH HIF1A.
PubMed=17981124; DOI=10.1016/j.cell.2007.08.045;
Cheng J., Kang X., Zhang S., Yeh E.T.H.;
"SUMO-specific protease 1 is essential for stabilization of HIF1alpha
during hypoxia.";
Cell 131:584-595(2007).
[20]
INTERACTION WITH EPAS1.
PubMed=19208626; DOI=10.1074/jbc.M808737200;
Furlow P.W., Percy M.J., Sutherland S., Bierl C., McMullin M.F.,
Master S.R., Lappin T.R., Lee F.S.;
"Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical
role for residues C-terminal to the hydroxylacceptor proline.";
J. Biol. Chem. 284:9050-9058(2009).
[21]
INTERACTION WITH ADRB2, SUBCELLULAR LOCATION, AND FUNCTION.
PubMed=19584355; DOI=10.1126/scisignal.2000444;
Xie L., Xiao K., Whalen E.J., Forrester M.T., Freeman R.S., Fong G.,
Gygi S.P., Lefkowitz R.J., Stamler J.S.;
"Oxygen-regulated beta(2)-adrenergic receptor hydroxylation by EGLN3
and ubiquitylation by pVHL.";
Sci. Signal. 2:RA33-RA33(2009).
[22]
INTERACTION WITH LIMD1; AJUBA AND WTIP, AND IDENTIFICATION IN A
COMPLEX WITH LIMD1; EGLN1/PHD2; ELOB AND CUL2.
PubMed=22286099; DOI=10.1038/ncb2424;
Foxler D.E., Bridge K.S., James V., Webb T.M., Mee M., Wong S.C.,
Feng Y., Constantin-Teodosiu D., Petursdottir T.E., Bjornsson J.,
Ingvarsson S., Ratcliffe P.J., Longmore G.D., Sharp T.V.;
"The LIMD1 protein bridges an association between the prolyl
hydroxylases and VHL to repress HIF-1 activity.";
Nat. Cell Biol. 14:201-208(2012).
[23]
X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 54-213 IN COMPLEX WITH
556-575 OF HIF1A; ELOB AND ELOC.
PubMed=12004076; DOI=10.1126/science.1073440;
Min J.-H., Yang H., Ivan M., Gertler F., Kaelin W.G. Jr.,
Pavletich N.P.;
"Structure of an HIF-1alpha-pVHL complex: hydroxyproline recognition
in signaling.";
Science 296:1886-1889(2002).
[24]
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 52-213 IN COMPLEX WITH
549-582 OF HIF1A; 17-112 OF ELOB AND ELOC.
PubMed=12050673; DOI=10.1038/nature00767;
Hon W.-C., Wilson M.I., Harlos K., Claridge T.D.W., Schofield C.J.,
Pugh C.W., Maxwell P.H., Ratcliffe P.J., Stuart D.I., Jones E.Y.;
"Structural basis for the recognition of hydroxyproline in HIF-1 alpha
by pVHL.";
Nature 417:975-978(2002).
[25]
X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 54-213 IN COMPLEX WITH 17-112
OF ELOB AND ELOC.
PubMed=10205047; DOI=10.1126/science.284.5413.455;
Stebbins C.E., Kaelin W.G. Jr., Pavletich N.P.;
"Structure of the VHL-ElonginC-ElonginB complex: implications for VHL
tumor suppressor function.";
Science 284:455-461(1999).
[26]
VARIANT HEMANGIOBLASTOMA PHE-135.
PubMed=8069849;
Kanno H., Kondo K., Ito S., Yamamoto I., Fujii S., Torigoe S.,
Sakai N., Hosaka M., Shuin T., Yao M.;
"Somatic mutations of the von Hippel-Lindau tumor suppressor gene in
sporadic central nervous system hemangioblastomas.";
Cancer Res. 54:4845-4847(1994).
[27]
VARIANTS IN LUNG CANCER.
PubMed=8183553;
Sekido Y., Bader S., Latif F., Gnarra J.R., Gazdar A.F., Linehan W.M.,
Zbar B., Lerman M.I., Minna J.D.;
"Molecular analysis of the von Hippel-Lindau disease tumor suppressor
gene in human lung cancer cell lines.";
Oncogene 9:1599-1604(1994).
[28]
VARIANTS VHLD.
PubMed=7987306; DOI=10.1093/hmg/3.8.1303;
Crossey P.A., Richards F.M., Foster K., Green J.S., Prowse A.,
Latif F., Lerman M.I., Zbar B., Affara N.A., Ferguson-Smith M.A.,
Maher E.R.;
"Identification of intragenic mutations in the von Hippel-Lindau
disease tumour suppressor gene and correlation with disease
phenotype.";
Hum. Mol. Genet. 3:1303-1308(1994).
[29]
VARIANTS VHLD.
PubMed=7728151; DOI=10.1002/humu.1380050109;
Chen F., Kishida T., Yao M., Hustad T., Glavac D., Dean M.,
Gnarra J.R., Orcutt M.L., Duh F.-M., Glenn G., Green J.S., Hsia Y.E.,
Lamiell J., Li H., Wei M.H., Schmidt L., Tory K., Kuzmin I.,
Stackhouse T., Latif F., Linehan W.M., Lerman M.I., Zbar B.;
"Germline mutations in the von Hippel-Lindau disease tumor suppressor
gene: correlations with phenotype.";
Hum. Mutat. 5:66-75(1995).
[30]
VARIANTS VHLD.
PubMed=8634692;
Kondo K., Sakai N., Kaneko S., Kobayashi K., Hosaka M., Ito S.,
Fujii S., Yamamoto I., Kim I., Miyagami M., Shidara N., Shinohara N.,
Koyanagi T., Kato N., Yamanaka H., Kuratu J., Fujioka M., Nakatsu H.,
Shimazaki J., Yoshida J., Sugita K., Hirao Y., Okajima E.,
Tanigawa T., Sato S., Fujino H., Nagata M., Kanayama H., Kagawa S.,
Yamashima T., Furuta T., Saito Y., Kanno H., Yao M., Shuin T.;
"Germline mutations in the von Hippel-Lindau disease (VHL) gene in
Japanese VHL. Clinical Research Group for VHL in Japan.";
Hum. Mol. Genet. 4:2233-2237(1995).
[31]
VARIANTS VHLD LEU-84 AND TRP-167.
PubMed=8592333; DOI=10.1136/jmg.32.11.885;
Crossey P.A., Eng C., Ginalska-Malinowska M., Lennard T.W.J.,
Wheeler D.C., Ponder B.A.J., Maher E.R.;
"Molecular genetic diagnosis of von Hippel-Lindau disease in familial
phaeochromocytoma.";
J. Med. Genet. 32:885-886(1995).
[32]
VARIANTS VHLD SER-114; SER-119; GLU-143 AND ARG-164.
PubMed=8825918; DOI=10.1136/jmg.32.12.934;
Eng C., Crossey P.A., Mulligan L.M., Healey C.S., Houghton C.,
Prowse A., Chew S.L., Dahia P.L.M., O'Riordan J.L.H., Toledo S.P.A.,
Smith D.P., Maher E.R., Ponder B.A.J.;
"Mutations in the RET proto-oncogene and the von Hippel-Lindau disease
tumour suppressor gene in sporadic and syndromic phaeochromocytomas.";
J. Med. Genet. 32:934-937(1995).
[33]
VARIANTS VHLD PRO-96; VAL-116; ARG-118; PHE-166; ASP-170 AND GLU-186
DEL.
PubMed=8730290; DOI=10.1136/jmg.33.4.328;
Maher E.R., Webster A.R., Richards F.M., Green J.S., Crossey P.A.,
Payne S.J., Moore A.T.;
"Phenotypic expression in von Hippel-Lindau disease: correlations with
germline VHL gene mutations.";
J. Med. Genet. 33:328-332(1996).
[34]
VARIANTS VHLD LEU-65; TRP-65; GLY-74; PHE-76 DEL; ILE-76; HIS-78;
SER-78; THR-78; ARG-80; ASN-80; ILE-80; SER-81; ALA-86; LEU-86;
ARG-88; SER-88; PRO-89; ARG-101; ARG-111; ASN-111; CYS-114; TYR-115;
CYS-117; PRO-118; GLY-121; LEU-130; PRO-158; VAL-158; PRO-161;
ARG-162; PHE-162; TYR-162; TRP-162; ARG-164; GLN-167; TRP-167;
GLY-170; PRO-178; VAL-180; ARG-184; PRO-184; LYS-186; GLN-188 AND
TRP-200.
PubMed=8956040;
DOI=10.1002/(SICI)1098-1004(1996)8:4<348::AID-HUMU8>3.0.CO;2-3;
Zbar B., Kishida T., Chen F., Schmidt L., Maher E.R., Richards F.M.,
Crossey P.A., Webster A.R., Affara N.A., Ferguson-Smith M.A.,
Brauch H., Glavac D., Neumann H.P.H., Tisherman S., Mulvihill J.J.,
Gross D.J., Shuin T., Whaley J., Seizinger B., Kley N., Olschwang S.,
Boisson C., Richard S., Lips C.H.M., Linehan W.M., Lerman M.I.;
"Germline mutations in the von Hippel-Lindau disease (VHL) gene in
families from North America, Europe, and Japan.";
Hum. Mutat. 8:348-357(1996).
[35]
VARIANTS VHLD PRO-38; LEU-76 AND PHE-162.
PubMed=9452032;
Li C., Weber G., Ekman P., Lagercrantz J., Norlen B.J.,
Aakerstroem G., Nordenskjoeld M., Bergerheim U.S.R.;
"Germline mutations detected in the von Hippel-Lindau disease tumor
suppressor gene by Southern blot and direct genomic DNA sequencing.";
Hum. Mutat. Suppl. 1:S31-S33(1998).
[36]
VARIANT VHLD THR-149.
PubMed=9452106;
Mandich P., Montera M., Bellone E., Trojani A., Daniele S., Ajmar F.;
"Three novel mutations in the von Hippel-Lindau tumour suppressor gene
in Italian patients.";
Hum. Mutat. Suppl. 1:S268-S270(1998).
[37]
VARIANT VHLD TRP-68.
PubMed=10627136;
DOI=10.1002/(SICI)1098-1004(1998)12:1<71::AID-HUMU14>3.0.CO;2-A;
Martin R., Hockey A., Walpole I., Goldblatt J.;
"Variable penetrance of familial pheochromocytoma associated with the
von Hippel-Lindau gene mutation, S68W.";
Hum. Mutat. 12:71-71(1998).
[38]
VARIANTS VHLD TRP-65; SER-76; SER-81; ARG-86; ARG-88; GLY-101;
PRO-107; ASN-111; CYS-117; THR-131; PHE-162; GLY-167; ASP-175; PRO-184
AND LYS-186.
PubMed=9829911;
DOI=10.1002/(SICI)1098-1004(1998)12:6<417::AID-HUMU8>3.0.CO;2-K;
Stolle C., Glenn G., Zbar B., Humphrey J.S., Choyke P., Walther M.,
Pack S., Hurley K., Andrey C., Klausner R., Linehan W.M.;
"Improved detection of germline mutations in the von Hippel-Lindau
disease tumor suppressor gene.";
Hum. Mutat. 12:417-423(1998).
[39]
VARIANTS VHLD LYS-52; LEU-65; LYS-70; ASN-80; ARG-80; SER-86; SER-88;
LEU-91; ALA-104; PRO-105; GLN-115; CYS-117; PRO-118; LEU-130; LYS-131;
SER-136; ASP-156; CYS-156; ILE-157; PRO-158; GLN-161; TRP-162;
PHE-166; GLN-167; TRP-167; GLY-170; PRO-188 AND TRP-200.
PubMed=9829912;
DOI=10.1002/(SICI)1098-1004(1998)12:6<424::AID-HUMU9>3.0.CO;2-H;
Olschwang S., Richard S., Boisson C., Giraud S., Laurent-Puig P.,
Resche F., Thomas G.;
"Germline mutation profile of the VHL gene in von Hippel-Lindau
disease and in sporadic hemangioblastoma.";
Hum. Mutat. 12:424-430(1998).
[40]
VARIANTS PHEOCHROMOCYTOMA LEU-25; PRO-63; PRO-64 AND THR-147.
PubMed=9663592;
DOI=10.1002/(SICI)1097-0215(19980729)77:3<337::AID-IJC5>3.0.CO;2-P;
van der Harst E., de Krijger R.R., Dinjens W.N.M., Weeks L.E.,
Bonjer H.J., Bruining H.A., Lamberts S.W.J., Koper J.W.;
"Germline mutations in the vhl gene in patients presenting with
phaeochromocytomas.";
Int. J. Cancer 77:337-340(1998).
[41]
VARIANTS VHLD CYS-93; GLY-155 AND ILE-157.
Murigia M.;
Unpublished observations (MAY-1999).
[42]
VARIANT VHLD ASN-112.
PubMed=10533030;
DOI=10.1002/(SICI)1096-8628(19991119)87:2<163::AID-AJMG7>3.0.CO;2-A;
Bradley J.F., Collins D.L., Schimke R.N., Parrott H.N., Rothberg P.G.;
"Two distinct phenotypes caused by two different missense mutations in
the same codon of the VHL gene.";
Am. J. Med. Genet. 87:163-167(1999).
[43]
VARIANTS VHLD.
PubMed=10408776;
DOI=10.1002/(SICI)1098-1004(1999)13:6<464::AID-HUMU6>3.0.CO;2-A;
Gallou C., Joly D., Mejean A., Staroz F., Martin N., Tarlet G.,
Orfanelli M.T., Bouvier R., Droz D., Chretien Y., Marechal J.M.,
Richard S., Junien C., Beroud C.;
"Mutations of the VHL gene in sporadic renal cell carcinoma:
definition of a risk factor for VHL patients to develop an RCC.";
Hum. Mutat. 13:464-475(1999).
[44]
VARIANT RCC PRO-163, AND CHARACTERIZATION OF VARIANT RCC PRO-163.
PubMed=11986208; DOI=10.1182/blood.V99.10.3562;
Wiesener M.S., Seyfarth M., Warnecke C., Juergensen J.S.,
Rosenberger C., Morgan N.V., Maher E.R., Frei U., Eckardt K.-U.;
"Paraneoplastic erythrocytosis associated with an inactivating point
mutation of the von Hippel-Lindau gene in a renal cell carcinoma.";
Blood 99:3562-3565(2002).
[45]
VARIANTS PHEOCHROMOCYTOMA ALA-65; TRP-68; ASN-80; SER-93; CYS-93;
HIS-98; GLY-107; LEU-119; ILE-122; CYS-136; ASN-156; CYS-156; GLN-161;
PRO-161; TRP-167; GLN-167; VAL-188 AND GLN-198.
PubMed=12000816; DOI=10.1056/NEJMoa020152;
The Freiburg-Warsaw-Columbus pheochromocytoma study group;
Neumann H.P.H., Bausch B., McWhinney S.R., Bender B.U., Gimm O.,
Franke G., Schipper J., Klisch J., Altehoefer C., Zerres K.,
Januszewicz A., Smith W.M., Munk R., Manz T., Glaesker S., Apel T.W.,
Treier M., Reineke M., Walz M.K., Hoang-Vu C., Brauckhoff M.,
Klein-Franke A., Klose P., Schmidt H., Maier-Woelfle M.,
Peczkowska M., Szmigielski C., Eng C.;
"Germ-line mutations in nonsyndromic pheochromocytoma.";
N. Engl. J. Med. 346:1459-1466(2002).
[46]
VARIANTS ECYT2 VAL-188; ASP-191; SER-192 AND TRP-200.
PubMed=12844285; DOI=10.1086/377108;
Pastore Y.D., Jedlickova K., Guan Y., Liu E., Fahner J., Hasle H.,
Prchal J.F., Prchal J.T.;
"Mutations of von Hippel-Lindau tumor-suppressor gene and congenital
polycythemia.";
Am. J. Hum. Genet. 73:412-419(2003).
[47]
VARIANTS PHEOCHROMOCYTOMA LEU-25 AND CYS-156.
PubMed=14500403;
Gimenez-Roqueplo A.-P., Favier J., Rustin P., Rieubland C.,
Crespin M., Nau V., Khau Van Kien P., Corvol P., Plouin P.-F.,
Jeunemaitre X.;
"Mutations in the SDHB gene are associated with extra-adrenal and/or
malignant phaeochromocytomas.";
Cancer Res. 63:5615-5621(2003).
[48]
ERRATUM.
Pastore Y.D., Jedlickova K., Guan Y., Liu E., Fahner J., Hasle H.,
Prchal J.F., Prchal J.T.;
Am. J. Hum. Genet. 74:598-598(2004).
[49]
VARIANTS ECYT2 TYR-126; LEU-130 AND TRP-200.
PubMed=12393546; DOI=10.1182/blood-2002-06-1843;
Pastore Y.D., Jelinek J., Ang S., Guan Y., Liu E., Jedlickova K.,
Krishnamurti L., Prchal J.T.;
"Mutations in the VHL gene in sporadic apparently congenital
polycythemia.";
Blood 101:1591-1595(2003).
[50]
VARIANT VHLD LEU-84.
PubMed=16502427; DOI=10.1002/ajmg.a.31116;
Abbott M.-A., Nathanson K.L., Nightingale S., Maher E.R.,
Greenstein R.M.;
"The von Hippel-Lindau (VHL) germline mutation V84L manifests as
early-onset bilateral pheochromocytoma.";
Am. J. Med. Genet. A 140:685-690(2006).
[51]
VARIANTS [LARGE SCALE ANALYSIS] LEU-25 AND SER-86.
PubMed=17344846; DOI=10.1038/nature05610;
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
-!- FUNCTION: Involved in the ubiquitination and subsequent
proteasomal degradation via the von Hippel-Lindau ubiquitination
complex. Seems to act as a target recruitment subunit in the E3
ubiquitin ligase complex and recruits hydroxylated hypoxia-
inducible factor (HIF) under normoxic conditions. Involved in
transcriptional repression through interaction with HIF1A, HIF1AN
and histone deacetylases. Ubiquitinates, in an oxygen-responsive
manner, ADRB2. {ECO:0000269|PubMed:10944113,
ECO:0000269|PubMed:17981124, ECO:0000269|PubMed:19584355}.
-!- PATHWAY: Protein modification; protein ubiquitination.
-!- SUBUNIT: Component of the VCB (VHL-Elongin BC-CUL2) complex; this
complex acts as a ubiquitin-ligase E3 and directs proteasome-
dependent degradation of targeted proteins. Interacts with CUL2;
this interaction is dependent on the integrity of the trimeric VBC
complex. Interacts (via the beta domain) with HIF1A (via the NTAD
domain); this interaction mediates degradation of HIF1A in
normoxia and, in hypoxia, prevents ubiquitination and degradation
of HIF1A by mediating hypoxia-induced translocation to the
nucleus, a process which requires a hypoxia-dependent regulatory
signal. Interacts with ADRB2; the interaction, in normoxia, is
dependent on hydroxylation of ADRB2 and the subsequent VCB-
mediated ubiquitination and degradation of ADRB2. Under hypoxia,
hydroxylation, interaction with VHL, ubiquitination and subsequent
degradation of ADRB2 are dramatically decreased. Interacts with
RNF139, USP33 and JADE1. Found in a complex composed of LIMD1,
VHL, EGLN1/PHD2, ELOB and CUL2. Isoform 1 and isoform 3 interact
with LIMD1 (via LIM zinc-binding 2), AJUBA (via LIM domains) and
WTIP (via LIM domains). Interacts with EPAS1. Interacts with
CARD9. {ECO:0000269|PubMed:10205047, ECO:0000269|PubMed:10635329,
ECO:0000269|PubMed:10944113, ECO:0000269|PubMed:11384984,
ECO:0000269|PubMed:11641274, ECO:0000269|PubMed:11739384,
ECO:0000269|PubMed:12004076, ECO:0000269|PubMed:12032852,
ECO:0000269|PubMed:12050673, ECO:0000269|PubMed:12169691,
ECO:0000269|PubMed:17981124, ECO:0000269|PubMed:19208626,
ECO:0000269|PubMed:19584355, ECO:0000269|PubMed:22286099,
ECO:0000269|PubMed:7660130, ECO:0000269|PubMed:9122164}.
-!- INTERACTION:
Q13617:CUL2; NbExp=13; IntAct=EBI-301246, EBI-456179;
O75912:DGKI; NbExp=3; IntAct=EBI-301270, EBI-1765520;
P02751:FN1; NbExp=2; IntAct=EBI-301246, EBI-1220319;
Q9UM11:FZR1; NbExp=2; IntAct=EBI-3504450, EBI-724997;
P08151:GLI1; NbExp=2; IntAct=EBI-301270, EBI-308084;
Q16665:HIF1A; NbExp=18; IntAct=EBI-301246, EBI-447269;
Q61221:Hif1a (xeno); NbExp=2; IntAct=EBI-301246, EBI-298954;
P14866:HNRNPL; NbExp=2; IntAct=EBI-301246, EBI-719024;
Q99750:MDFI; NbExp=3; IntAct=EBI-12157263, EBI-724076;
Q05513:PRKCZ; NbExp=3; IntAct=EBI-301246, EBI-295351;
Q99873:PRMT1; NbExp=2; IntAct=EBI-301246, EBI-78738;
P63244:RACK1; NbExp=9; IntAct=EBI-301246, EBI-296739;
Q15311:RALBP1; NbExp=3; IntAct=EBI-301270, EBI-749285;
Q8WU17:RNF139; NbExp=2; IntAct=EBI-301246, EBI-1551681;
P21980:TGM2; NbExp=10; IntAct=EBI-301246, EBI-727668;
-!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasm. Membrane; Peripheral
membrane protein. Nucleus. Note=Found predominantly in the
cytoplasm and with less amounts nuclear or membrane-associated.
Colocalizes with ADRB2 at the cell membrane.
-!- SUBCELLULAR LOCATION: Isoform 3: Cytoplasm. Nucleus. Note=Equally
distributed between the nucleus and the cytoplasm but not
membrane-associated.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing, Alternative initiation; Named isoforms=3;
Name=1; Synonyms=VHL30, VHLp24(MPR);
IsoId=P40337-1; Sequence=Displayed;
Note=Major isoform.;
Name=2;
IsoId=P40337-2; Sequence=VSP_004488;
Name=3; Synonyms=VHL19, VHLp18(MEA);
IsoId=P40337-3; Sequence=VSP_007740;
Note=Produced by alternative initiation at Met-54 of isoform 1.;
-!- TISSUE SPECIFICITY: Expressed in the adult and fetal brain and
kidney.
-!- DEVELOPMENTAL STAGE: At 4-10 weeks pc, strong expression in the
developing central nervous system, kidneys, testis and lung.
Differentially expressed within renal tubules.
{ECO:0000269|PubMed:8733131}.
-!- DOMAIN: The Elongin BC complex binding domain is also known as BC-
box with the consensus [APST]-L-x(3)-C-x(3)-[AILV].
-!- DISEASE: Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-
producing tumor of chromaffin tissue of the adrenal medulla or
sympathetic paraganglia. The cardinal symptom, reflecting the
increased secretion of epinephrine and norepinephrine, is
hypertension, which may be persistent or intermittent.
{ECO:0000269|PubMed:12000816, ECO:0000269|PubMed:14500403,
ECO:0000269|PubMed:9663592}. Note=Disease susceptibility is
associated with variations affecting the gene represented in this
entry.
-!- DISEASE: von Hippel-Lindau disease (VHLD) [MIM:193300]: VHLD is a
dominantly inherited familial cancer syndrome predisposing to a
variety of malignant and benign neoplasms, most frequently
retinal, cerebellar and spinal hemangioblastoma, renal cell
carcinoma (RCC), pheochromocytoma, and pancreatic tumors. VHL type
1 is without pheochromocytoma, type 2 is with pheochromocytoma.
VHL type 2 is further subdivided into types 2A (pheochromocytoma,
retinal angioma, and hemangioblastomas without renal cell
carcinoma and pancreatic cyst) and 2B (pheochromocytoma, retinal
angioma, and hemangioblastomas with renal cell carcinoma and
pancreatic cyst). {ECO:0000269|PubMed:10408776,
ECO:0000269|PubMed:10533030, ECO:0000269|PubMed:10627136,
ECO:0000269|PubMed:10635329, ECO:0000269|PubMed:16502427,
ECO:0000269|PubMed:7728151, ECO:0000269|PubMed:7987306,
ECO:0000269|PubMed:8493574, ECO:0000269|PubMed:8592333,
ECO:0000269|PubMed:8634692, ECO:0000269|PubMed:8730290,
ECO:0000269|PubMed:8825918, ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9452032, ECO:0000269|PubMed:9452106,
ECO:0000269|PubMed:9829911, ECO:0000269|PubMed:9829912,
ECO:0000269|Ref.41}. Note=The disease is caused by mutations
affecting the gene represented in this entry.
-!- DISEASE: Erythrocytosis, familial, 2 (ECYT2) [MIM:263400]: An
autosomal recessive disorder characterized by an increase in serum
red blood cell mass, hypersensitivity of erythroid progenitors to
erythropoietin, increased erythropoietin serum levels, and normal
oxygen affinity. Patients with ECYT2 carry a high risk for
peripheral thrombosis and cerebrovascular events.
{ECO:0000269|PubMed:12393546, ECO:0000269|PubMed:12844285}.
Note=The disease is caused by mutations affecting the gene
represented in this entry.
-!- DISEASE: Renal cell carcinoma (RCC) [MIM:144700]: Renal cell
carcinoma is a heterogeneous group of sporadic or hereditary
carcinoma derived from cells of the proximal renal tubular
epithelium. It is subclassified into clear cell renal carcinoma
(non-papillary carcinoma), papillary renal cell carcinoma,
chromophobe renal cell carcinoma, collecting duct carcinoma with
medullary carcinoma of the kidney, and unclassified renal cell
carcinoma. Clear cell renal cell carcinoma is the most common
subtype. {ECO:0000269|PubMed:11986208}. Note=The disease is caused
by mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the VHL family. {ECO:0000305}.
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/VHLID132.html";
-----------------------------------------------------------------------
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EMBL; AF010238; AAB64200.1; -; Genomic_DNA.
EMBL; L15409; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; AK315799; BAG38142.1; -; mRNA.
EMBL; AC034193; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471055; EAW64064.1; -; Genomic_DNA.
EMBL; BC058831; AAH58831.1; -; mRNA.
EMBL; U54612; AAA98614.1; -; Genomic_DNA.
EMBL; X96489; CAA65343.1; -; Genomic_DNA.
CCDS; CCDS2597.1; -. [P40337-1]
CCDS; CCDS2598.1; -. [P40337-2]
PIR; I38926; I38926.
RefSeq; NP_000542.1; NM_000551.3. [P40337-1]
RefSeq; NP_937799.1; NM_198156.2. [P40337-2]
UniGene; Hs.517792; -.
PDB; 1LM8; X-ray; 1.85 A; V=54-213.
PDB; 1LQB; X-ray; 2.00 A; C=54-213.
PDB; 1VCB; X-ray; 2.70 A; C/F/I/L=54-213.
PDB; 3ZRC; X-ray; 2.90 A; C/F/I/L=54-213.
PDB; 3ZRF; X-ray; 2.80 A; C/F/I/L=54-213.
PDB; 3ZTC; X-ray; 2.65 A; C/F/I/L=54-213.
PDB; 3ZTD; X-ray; 2.79 A; C/F/I/L=54-213.
PDB; 3ZUN; X-ray; 2.50 A; C/F/I/L=54-213.
PDB; 4AJY; X-ray; 1.73 A; V=54-213.
PDB; 4AWJ; X-ray; 2.50 A; C/F/I/L=54-213.
PDB; 4B95; X-ray; 2.80 A; C/F/I/L=54-213.
PDB; 4B9K; X-ray; 2.00 A; C/F/I/L=54-213.
PDB; 4BKS; X-ray; 2.20 A; C/F/I/L=54-213.
PDB; 4BKT; X-ray; 2.35 A; C/F/I/L=54-213.
PDB; 4W9C; X-ray; 2.20 A; C/F/I/L=54-213.
PDB; 4W9D; X-ray; 2.20 A; C/F/I/L=54-213.
PDB; 4W9E; X-ray; 2.60 A; C/F/I/L=54-213.
PDB; 4W9F; X-ray; 2.10 A; C/F/I/L=54-213.
PDB; 4W9G; X-ray; 2.70 A; C/F/I/L=54-213.
PDB; 4W9H; X-ray; 2.10 A; C/F/I/L=54-213.
PDB; 4W9I; X-ray; 2.40 A; C/F/I/L=54-213.
PDB; 4W9J; X-ray; 2.20 A; C/F/I/L=54-213.
PDB; 4W9K; X-ray; 2.10 A; C/F/I/L=54-213.
PDB; 4W9L; X-ray; 2.20 A; C/F/I/L=54-213.
PDB; 4WQO; X-ray; 3.20 A; A=1-213.
PDB; 5LLI; X-ray; 2.40 A; C/F/I/L=54-213.
PDB; 5N4W; X-ray; 3.90 A; V=54-213.
PDB; 5NVV; X-ray; 2.10 A; C/F/I/L=54-213.
PDB; 5NVW; X-ray; 2.20 A; C/F/I/L=54-213.
PDB; 5NVX; X-ray; 2.20 A; C/F/I/L=54-213.
PDB; 5NVY; X-ray; 2.90 A; C/F/I/L=54-213.
PDB; 5NVZ; X-ray; 2.70 A; C/F/I/L=54-213.
PDB; 5NW0; X-ray; 2.30 A; C/F/I/L=54-213.
PDB; 5NW1; X-ray; 2.10 A; C/F/I/L=54-213.
PDB; 5NW2; X-ray; 2.20 A; C/F/I/L=54-213.
PDB; 5T35; X-ray; 2.70 A; D/H=54-213.
PDBsum; 1LM8; -.
PDBsum; 1LQB; -.
PDBsum; 1VCB; -.
PDBsum; 3ZRC; -.
PDBsum; 3ZRF; -.
PDBsum; 3ZTC; -.
PDBsum; 3ZTD; -.
PDBsum; 3ZUN; -.
PDBsum; 4AJY; -.
PDBsum; 4AWJ; -.
PDBsum; 4B95; -.
PDBsum; 4B9K; -.
PDBsum; 4BKS; -.
PDBsum; 4BKT; -.
PDBsum; 4W9C; -.
PDBsum; 4W9D; -.
PDBsum; 4W9E; -.
PDBsum; 4W9F; -.
PDBsum; 4W9G; -.
PDBsum; 4W9H; -.
PDBsum; 4W9I; -.
PDBsum; 4W9J; -.
PDBsum; 4W9K; -.
PDBsum; 4W9L; -.
PDBsum; 4WQO; -.
PDBsum; 5LLI; -.
PDBsum; 5N4W; -.
PDBsum; 5NVV; -.
PDBsum; 5NVW; -.
PDBsum; 5NVX; -.
PDBsum; 5NVY; -.
PDBsum; 5NVZ; -.
PDBsum; 5NW0; -.
PDBsum; 5NW1; -.
PDBsum; 5NW2; -.
PDBsum; 5T35; -.
DisProt; DP00287; -.
ProteinModelPortal; P40337; -.
SMR; P40337; -.
BioGrid; 113269; 357.
CORUM; P40337; -.
DIP; DIP-32585N; -.
IntAct; P40337; 48.
MINT; MINT-133223; -.
STRING; 9606.ENSP00000256474; -.
BindingDB; P40337; -.
ChEMBL; CHEMBL3108660; -.
iPTMnet; P40337; -.
PhosphoSitePlus; P40337; -.
BioMuta; VHL; -.
DMDM; 4033778; -.
EPD; P40337; -.
MaxQB; P40337; -.
PaxDb; P40337; -.
PeptideAtlas; P40337; -.
PRIDE; P40337; -.
DNASU; 7428; -.
Ensembl; ENST00000256474; ENSP00000256474; ENSG00000134086. [P40337-1]
Ensembl; ENST00000345392; ENSP00000344757; ENSG00000134086. [P40337-2]
GeneID; 7428; -.
KEGG; hsa:7428; -.
UCSC; uc003bvc.4; human. [P40337-1]
CTD; 7428; -.
DisGeNET; 7428; -.
EuPathDB; HostDB:ENSG00000134086.7; -.
GeneCards; VHL; -.
GeneReviews; VHL; -.
HGNC; HGNC:12687; VHL.
HPA; CAB005430; -.
HPA; HPA031631; -.
HPA; HPA031632; -.
MalaCards; VHL; -.
MIM; 144700; phenotype.
MIM; 171300; phenotype.
MIM; 193300; phenotype.
MIM; 263400; phenotype.
MIM; 608537; gene.
neXtProt; NX_P40337; -.
OpenTargets; ENSG00000134086; -.
Orphanet; 238557; Chuvash erythrocytosis.
Orphanet; 892; Von Hippel-Lindau disease.
PharmGKB; PA37307; -.
eggNOG; KOG4710; Eukaryota.
eggNOG; ENOG4111PRU; LUCA.
GeneTree; ENSGT00390000014353; -.
HOGENOM; HOG000030904; -.
HOVERGEN; HBG044781; -.
InParanoid; P40337; -.
KO; K03871; -.
OMA; YWIDYQG; -.
OrthoDB; EOG091G0NHA; -.
PhylomeDB; P40337; -.
TreeFam; TF318985; -.
Reactome; R-HSA-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
Reactome; R-HSA-8951664; Neddylation.
Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
SIGNOR; P40337; -.
UniPathway; UPA00143; -.
ChiTaRS; VHL; human.
EvolutionaryTrace; P40337; -.
GeneWiki; Von_Hippel%E2%80%93Lindau_tumor_suppressor; -.
GenomeRNAi; 7428; -.
PRO; PR:P40337; -.
Proteomes; UP000005640; Chromosome 3.
Bgee; ENSG00000134086; -.
CleanEx; HS_VHL; -.
ExpressionAtlas; P40337; baseline and differential.
Genevisible; P40337; HS.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0005783; C:endoplasmic reticulum; NAS:UniProtKB.
GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
GO; GO:0005739; C:mitochondrion; NAS:UniProtKB.
GO; GO:0005654; C:nucleoplasm; IDA:HPA.
GO; GO:0005634; C:nucleus; TAS:ProtInc.
GO; GO:0030891; C:VCB complex; IBA:GO_Central.
GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:ParkinsonsUK-UCL.
GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:Reactome.
GO; GO:0000902; P:cell morphogenesis; NAS:UniProtKB.
GO; GO:0043066; P:negative regulation of apoptotic process; NAS:UniProtKB.
GO; GO:0008285; P:negative regulation of cell proliferation; IMP:CAFA.
GO; GO:0010629; P:negative regulation of gene expression; IMP:CAFA.
GO; GO:0046426; P:negative regulation of JAK-STAT cascade; IMP:CAFA.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
GO; GO:0061428; P:negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; IDA:UniProtKB.
GO; GO:0045597; P:positive regulation of cell differentiation; NAS:UniProtKB.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
GO; GO:0050821; P:protein stabilization; NAS:UniProtKB.
GO; GO:0016567; P:protein ubiquitination; IDA:ParkinsonsUK-UCL.
GO; GO:0006508; P:proteolysis; TAS:ProtInc.
GO; GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome.
GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:BHF-UCL.
CDD; cd05468; pVHL; 1.
Gene3D; 1.10.750.10; -; 1.
Gene3D; 2.60.40.780; -; 1.
InterPro; IPR002714; VHL.
InterPro; IPR024048; VHL_alpha_dom.
InterPro; IPR037139; VHL_alpha_dom_sf.
InterPro; IPR024053; VHL_beta_dom.
InterPro; IPR037140; VHL_beta_dom_sf.
InterPro; IPR036208; VHL_sf.
InterPro; IPR022772; VHL_tumour_suppress_b/a_dom.
PANTHER; PTHR15160:SF1; PTHR15160:SF1; 1.
Pfam; PF01847; VHL; 1.
Pfam; PF17211; VHL_C; 1.
SUPFAM; SSF49468; SSF49468; 1.
1: Evidence at protein level;
3D-structure; Alternative initiation; Alternative splicing;
Complete proteome; Congenital erythrocytosis; Cytoplasm;
Disease mutation; Membrane; Nucleus; Polymorphism; Reference proteome;
Repeat; Tumor suppressor; Ubl conjugation pathway.
CHAIN 1 213 von Hippel-Lindau disease tumor
suppressor.
/FTId=PRO_0000065809.
REPEAT 14 18 1.
REPEAT 19 23 2.
REPEAT 24 28 3.
REPEAT 29 33 4.
REPEAT 34 38 5.
REPEAT 39 43 6.
REPEAT 44 48 7.
REPEAT 49 53 8.
REGION 14 53 8 X 5 AA tandem repeats of G-[PAVG]-E-E-
[DAYSLE].
REGION 100 155 Involved in binding to CCT complex.
REGION 157 166 Interaction with Elongin BC complex.
VAR_SEQ 1 53 Missing (in isoform 3). {ECO:0000305}.
/FTId=VSP_007740.
VAR_SEQ 114 154 Missing (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_004488.
VARIANT 25 25 P -> L (in pheochromocytoma;
dbSNP:rs35460768).
{ECO:0000269|PubMed:14500403,
ECO:0000269|PubMed:17344846,
ECO:0000269|PubMed:9663592}.
/FTId=VAR_034562.
VARIANT 38 38 S -> P (in VHLD; type II).
{ECO:0000269|PubMed:9452032}.
/FTId=VAR_005670.
VARIANT 52 52 E -> K (in VHLD; type I;
dbSNP:rs373068386).
{ECO:0000269|PubMed:9829912}.
/FTId=VAR_005671.
VARIANT 63 63 L -> P (in pheochromocytoma;
dbSNP:rs104893827).
{ECO:0000269|PubMed:9663592}.
/FTId=VAR_034987.
VARIANT 64 64 R -> P (in pheochromocytoma;
dbSNP:rs104893826).
{ECO:0000269|PubMed:9663592}.
/FTId=VAR_034988.
VARIANT 65 65 S -> A (in pheochromocytoma;
dbSNP:rs869025616).
{ECO:0000269|PubMed:12000816}.
/FTId=VAR_034989.
VARIANT 65 65 S -> L (in VHLD; type I;
dbSNP:rs5030826).
{ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005672.
VARIANT 65 65 S -> W (in VHLD; type I;
dbSNP:rs5030826).
{ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829911}.
/FTId=VAR_005673.
VARIANT 66 73 Missing (in VHLD; type I).
/FTId=VAR_005674.
VARIANT 68 68 S -> W (in pheochromocytoma and VHLD;
type II). {ECO:0000269|PubMed:10627136,
ECO:0000269|PubMed:12000816}.
/FTId=VAR_005675.
VARIANT 70 70 E -> K (in VHLD; type I;
dbSNP:rs5030802).
{ECO:0000269|PubMed:9829912}.
/FTId=VAR_005676.
VARIANT 74 74 V -> G (in VHLD; type I-II;
dbSNP:rs5030803).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005677.
VARIANT 75 75 Missing (in VHLD).
{ECO:0000269|PubMed:8493574}.
/FTId=VAR_034990.
VARIANT 76 76 F -> I (in VHLD; type I).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005679.
VARIANT 76 76 F -> L (in VHLD; type I).
{ECO:0000269|PubMed:9452032}.
/FTId=VAR_005680.
VARIANT 76 76 F -> S (in VHLD; type I;
dbSNP:rs730882033).
{ECO:0000269|PubMed:9829911}.
/FTId=VAR_005681.
VARIANT 76 76 Missing (in VHLD; type I; common
mutation). {ECO:0000269|PubMed:8956040}.
/FTId=VAR_005678.
VARIANT 78 78 N -> H (in VHLD; type I).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005682.
VARIANT 78 78 N -> S (in VHLD; type I; common mutation;
dbSNP:rs5030804).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005683.
VARIANT 78 78 N -> T (in VHLD; type I).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005684.
VARIANT 79 79 R -> P (in VHLD).
/FTId=VAR_005685.
VARIANT 80 80 S -> I (in VHLD; type I;
dbSNP:rs5030805).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005686.
VARIANT 80 80 S -> N (in pheochromocytoma and VHLD;
type I; dbSNP:rs5030805).
{ECO:0000269|PubMed:12000816,
ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005688.
VARIANT 80 80 S -> R (in VHLD; type I).
{ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005687.
VARIANT 81 81 P -> S (in VHLD; type I;
dbSNP:rs5030806).
{ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829911}.
/FTId=VAR_005689.
VARIANT 82 84 Missing (in VHLD).
/FTId=VAR_005691.
VARIANT 82 82 R -> P (in VHLD; type I;
dbSNP:rs794726890).
/FTId=VAR_005690.
VARIANT 84 84 V -> L (in VHLD; type II and type 2C;
dbSNP:rs5030827).
{ECO:0000269|PubMed:16502427,
ECO:0000269|PubMed:8592333}.
/FTId=VAR_005692.
VARIANT 86 86 P -> A (in VHLD; type I;
dbSNP:rs398123481).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005693.
VARIANT 86 86 P -> H (in VHLD).
/FTId=VAR_008097.
VARIANT 86 86 P -> L (in VHLD; type I;
dbSNP:rs730882034).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005694.
VARIANT 86 86 P -> R (in VHLD; type I).
{ECO:0000269|PubMed:9829911}.
/FTId=VAR_005695.
VARIANT 86 86 P -> S (in VHLD; dbSNP:rs398123481).
{ECO:0000269|PubMed:17344846,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005696.
VARIANT 88 88 W -> R (in VHLD; type I).
{ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829911}.
/FTId=VAR_005697.
VARIANT 88 88 W -> S (in VHLD; type I;
dbSNP:rs119103277).
{ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005698.
VARIANT 89 89 L -> H (in lung cancer; dbSNP:rs5030807).
/FTId=VAR_005699.
VARIANT 89 89 L -> P (in VHLD; type I;
dbSNP:rs5030807).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005700.
VARIANT 91 91 F -> L (in cerebellar hemangioblastoma).
{ECO:0000269|PubMed:9829912}.
/FTId=VAR_005701.
VARIANT 92 97 Missing (in VHLD; type I).
/FTId=VAR_005702.
VARIANT 93 93 G -> C (in pheochromocytoma and VHLD;
type II; dbSNP:rs5030808).
{ECO:0000269|PubMed:12000816,
ECO:0000269|Ref.41}.
/FTId=VAR_005703.
VARIANT 93 93 G -> D (in VHLD).
/FTId=VAR_005704.
VARIANT 93 93 G -> S (in pheochromocytoma and VHLD;
type II; dbSNP:rs5030808).
{ECO:0000269|PubMed:12000816}.
/FTId=VAR_005705.
VARIANT 96 96 Q -> P (in VHLD; type I).
{ECO:0000269|PubMed:8730290}.
/FTId=VAR_005706.
VARIANT 98 98 Y -> H (in pheochromocytoma and VHLD;
type II; dbSNP:rs5030809).
{ECO:0000269|PubMed:12000816}.
/FTId=VAR_005707.
VARIANT 101 101 L -> G (in VHLD; type I; requires 2
nucleotide substitutions).
{ECO:0000269|PubMed:9829911}.
/FTId=VAR_005708.
VARIANT 101 101 L -> R (in VHLD; type I).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005709.
VARIANT 104 104 G -> A (in cerebellar hemangioblastoma).
{ECO:0000269|PubMed:9829912}.
/FTId=VAR_005710.
VARIANT 105 105 T -> P (in VHLD; type I).
{ECO:0000269|PubMed:9829912}.
/FTId=VAR_005711.
VARIANT 106 106 G -> D (in lung cancer).
/FTId=VAR_005712.
VARIANT 107 107 R -> G (in pheochromocytoma;
dbSNP:rs397516440).
{ECO:0000269|PubMed:12000816}.
/FTId=VAR_034991.
VARIANT 107 107 R -> P (in VHLD; type I;
dbSNP:rs193922609).
{ECO:0000269|PubMed:9829911}.
/FTId=VAR_005713.
VARIANT 110 110 H -> Y (in dbSNP:rs17855706).
{ECO:0000269|PubMed:15489334}.
/FTId=VAR_055087.
VARIANT 111 111 S -> C (in VHLD; type II).
/FTId=VAR_005714.
VARIANT 111 111 S -> N (in VHLD; type I;
dbSNP:rs869025631).
{ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829911}.
/FTId=VAR_005715.
VARIANT 111 111 S -> R (in VHLD; type I;
dbSNP:rs765978945).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005716.
VARIANT 112 112 Y -> H (in VHLD; type IIA;
dbSNP:rs104893824).
/FTId=VAR_005717.
VARIANT 112 112 Y -> N (in VHLD; dbSNP:rs104893824).
{ECO:0000269|PubMed:10533030}.
/FTId=VAR_034992.
VARIANT 114 114 G -> C (in VHLD; type II).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005718.
VARIANT 114 114 G -> R (in VHLD; type I-II;
dbSNP:rs869025636).
/FTId=VAR_005719.
VARIANT 114 114 G -> S (in VHLD; type II).
{ECO:0000269|PubMed:8825918}.
/FTId=VAR_005720.
VARIANT 115 115 H -> Q (in VHLD; type II).
{ECO:0000269|PubMed:9829912}.
/FTId=VAR_005723.
VARIANT 115 115 H -> R (in VHLD; type II;
dbSNP:rs5030812).
/FTId=VAR_008098.
VARIANT 115 115 H -> Y (in VHLD; type I;
dbSNP:rs5030811).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005722.
VARIANT 116 116 L -> V (in VHLD).
{ECO:0000269|PubMed:8730290}.
/FTId=VAR_005724.
VARIANT 117 117 W -> C (in VHLD; type I;
dbSNP:rs727504215).
{ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829911,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005725.
VARIANT 118 118 L -> P (in VHLD; type I;
dbSNP:rs5030830).
{ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005726.
VARIANT 118 118 L -> R (in VHLD).
{ECO:0000269|PubMed:8730290}.
/FTId=VAR_005727.
VARIANT 119 119 F -> L (in pheochromocytoma and VHLD;
type II). {ECO:0000269|PubMed:12000816}.
/FTId=VAR_005728.
VARIANT 119 119 F -> S (in VHLD; type II).
{ECO:0000269|PubMed:8825918}.
/FTId=VAR_005729.
VARIANT 121 121 D -> G (in VHLD; type I;
dbSNP:rs5030832).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005730.
VARIANT 122 122 A -> I (in pheochromocytoma; requires 2
nucleotide substitutions).
{ECO:0000269|PubMed:12000816}.
/FTId=VAR_034993.
VARIANT 126 126 D -> Y (in ECYT2; dbSNP:rs104893831).
{ECO:0000269|PubMed:12393546}.
/FTId=VAR_034994.
VARIANT 128 128 L -> F (in VHLD; type II).
/FTId=VAR_005731.
VARIANT 129 129 L -> LE (in VHLD).
/FTId=VAR_005732.
VARIANT 130 130 V -> L (in ECYT2 and VHLD; type I;
dbSNP:rs104893830).
{ECO:0000269|PubMed:12393546,
ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005733.
VARIANT 131 131 N -> K (in VHLD; type I).
{ECO:0000269|PubMed:9829912}.
/FTId=VAR_005734.
VARIANT 131 131 N -> T (in VHLD; type I).
{ECO:0000269|PubMed:9829911}.
/FTId=VAR_005735.
VARIANT 135 135 L -> F (in hemangioblastoma;
dbSNP:rs119103278).
{ECO:0000269|PubMed:8069849}.
/FTId=VAR_034995.
VARIANT 136 136 F -> C (in pheochromocytoma and VHLD;
type II; dbSNP:rs5030833).
{ECO:0000269|PubMed:12000816}.
/FTId=VAR_005737.
VARIANT 136 136 F -> S (in VHLD; dbSNP:rs5030833).
{ECO:0000269|PubMed:9829912}.
/FTId=VAR_005736.
VARIANT 136 136 F -> Y (in VHLD).
/FTId=VAR_008099.
VARIANT 143 143 D -> E (in VHLD; type II).
{ECO:0000269|PubMed:8825918}.
/FTId=VAR_005738.
VARIANT 145 145 Q -> H (in VHLD; dbSNP:rs771727849).
/FTId=VAR_008100.
VARIANT 147 147 I -> T (in pheochromocytoma).
{ECO:0000269|PubMed:9663592}.
/FTId=VAR_034996.
VARIANT 148 148 Missing (in VHLD; type I).
/FTId=VAR_005739.
VARIANT 149 149 A -> T (in VHLD; type II;
dbSNP:rs587780077).
{ECO:0000269|PubMed:9452106}.
/FTId=VAR_005740.
VARIANT 154 154 P -> L (in VHLD; type II).
/FTId=VAR_005741.
VARIANT 155 155 V -> G (in VHLD; type II).
{ECO:0000269|Ref.41}.
/FTId=VAR_005742.
VARIANT 155 155 V -> M (in VHLD; with RCC;
dbSNP:rs869025659).
/FTId=VAR_008101.
VARIANT 156 156 Y -> C (in pheochromocytoma and VHLD;
type I; dbSNP:rs397516441).
{ECO:0000269|PubMed:12000816,
ECO:0000269|PubMed:14500403,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005743.
VARIANT 156 156 Y -> D (in VHLD; type I).
{ECO:0000269|PubMed:9829912}.
/FTId=VAR_005744.
VARIANT 156 156 Y -> N (in pheochromocytoma).
{ECO:0000269|PubMed:12000816}.
/FTId=VAR_034997.
VARIANT 157 157 T -> I (in VHLD; type II;
dbSNP:rs869025660).
{ECO:0000269|PubMed:9829912,
ECO:0000269|Ref.41}.
/FTId=VAR_005746.
VARIANT 157 157 T -> TF (in VHLD; type I).
/FTId=VAR_005747.
VARIANT 158 158 L -> P (in VHLD; type I-II; abolishes
release from chaperonin complex and the
interaction with Elongin BC complex;
dbSNP:rs121913346).
{ECO:0000269|PubMed:10635329,
ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005748.
VARIANT 158 158 L -> V (in VHLD; type I).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005749.
VARIANT 159 159 K -> E (in VHLD; type II).
/FTId=VAR_005750.
VARIANT 161 161 R -> G (in VHLD; type II;
dbSNP:rs5030818).
/FTId=VAR_005753.
VARIANT 161 161 R -> P (in pheochromocytoma and VHLD;
type I). {ECO:0000269|PubMed:12000816,
ECO:0000269|PubMed:8956040}.
/FTId=VAR_005752.
VARIANT 161 161 R -> Q (in pheochromocytoma and VHLD;
type II; dbSNP:rs730882035).
{ECO:0000269|PubMed:12000816,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005751.
VARIANT 162 162 C -> F (in VHLD; type I; No effect on
interaction with HIF1A nor on HIF1A
degradation; dbSNP:rs397516444).
{ECO:0000269|PubMed:10944113,
ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9452032,
ECO:0000269|PubMed:9829911}.
/FTId=VAR_005754.
VARIANT 162 162 C -> R (in VHLD; type I).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005755.
VARIANT 162 162 C -> W (in VHLD; type I-II;
dbSNP:rs869025662).
{ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005756.
VARIANT 162 162 C -> Y (in VHLD; type I).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005757.
VARIANT 163 163 L -> P (in RCC; with paraneoplastic
erythrocytosis; inhibits binding to
HIF1AN; dbSNP:rs28940297).
{ECO:0000269|PubMed:11986208,
ECO:0000269|Ref.6}.
/FTId=VAR_034998.
VARIANT 164 164 Q -> H (in VHLD).
/FTId=VAR_008102.
VARIANT 164 164 Q -> R (in VHLD; type II;
dbSNP:rs267607170).
{ECO:0000269|PubMed:8825918,
ECO:0000269|PubMed:8956040}.
/FTId=VAR_005758.
VARIANT 166 166 V -> D (in VHLD; with RCC).
/FTId=VAR_008103.
VARIANT 166 166 V -> F (in VHLD; type IIA;
dbSNP:rs104893825).
{ECO:0000269|PubMed:8730290,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005759.
VARIANT 167 167 R -> G (in VHLD; type I-II;
dbSNP:rs5030820).
{ECO:0000269|PubMed:9829911}.
/FTId=VAR_005760.
VARIANT 167 167 R -> Q (in pheochromocytoma and VHLD;
type II; common mutation;
dbSNP:rs5030821).
{ECO:0000269|PubMed:12000816,
ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005761.
VARIANT 167 167 R -> W (in pheochromocytoma and VHLD;
type II; common mutation;
dbSNP:rs5030820).
{ECO:0000269|PubMed:12000816,
ECO:0000269|PubMed:8592333,
ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005762.
VARIANT 170 170 V -> D (in VHLD; type II).
{ECO:0000269|PubMed:8730290}.
/FTId=VAR_005763.
VARIANT 170 170 V -> F (in VHLD; type II).
/FTId=VAR_005764.
VARIANT 170 170 V -> G (in VHLD; type I).
{ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005765.
VARIANT 175 175 Y -> D (in VHLD; type I).
{ECO:0000269|PubMed:9829911}.
/FTId=VAR_005766.
VARIANT 176 176 R -> W (in VHLD).
/FTId=VAR_008104.
VARIANT 177 177 R -> RLRVKPE (in VHLD; type I).
/FTId=VAR_005767.
VARIANT 178 178 L -> P (in VHLD; type I-II; common
mutation). {ECO:0000269|PubMed:8956040}.
/FTId=VAR_005768.
VARIANT 178 178 L -> Q (in VHLD; type II;
dbSNP:rs5030822).
/FTId=VAR_005769.
VARIANT 180 180 I -> V (in VHLD; type I;
dbSNP:rs377715747).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005770.
VARIANT 184 184 L -> P (in VHLD; type I).
{ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829911}.
/FTId=VAR_005772.
VARIANT 184 184 L -> R (in VHLD; type I).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005771.
VARIANT 186 186 E -> K (in VHLD; type I;
dbSNP:rs367545984).
{ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829911}.
/FTId=VAR_005773.
VARIANT 186 186 Missing (in VHLD).
{ECO:0000269|PubMed:8730290}.
/FTId=VAR_005774.
VARIANT 188 188 L -> P (in VHLD; type I-II).
{ECO:0000269|PubMed:9829912}.
/FTId=VAR_005775.
VARIANT 188 188 L -> Q (in VHLD; type I).
{ECO:0000269|PubMed:8956040}.
/FTId=VAR_005776.
VARIANT 188 188 L -> V (in ECYT2, pheochromocytoma and
VHLD; type IIA; dbSNP:rs5030824).
{ECO:0000269|PubMed:12000816,
ECO:0000269|PubMed:12844285}.
/FTId=VAR_005777.
VARIANT 191 191 H -> D (in ECYT2; dbSNP:rs28940301).
{ECO:0000269|PubMed:12844285}.
/FTId=VAR_034999.
VARIANT 192 192 P -> S (in ECYT2; dbSNP:rs28940300).
{ECO:0000269|PubMed:12844285}.
/FTId=VAR_035000.
VARIANT 198 198 L -> Q (in pheochromocytoma).
{ECO:0000269|PubMed:12000816}.
/FTId=VAR_035001.
VARIANT 198 198 L -> R (in ECYT2 and VHLD; type II).
/FTId=VAR_005778.
VARIANT 200 200 R -> W (in ECYT2 and VHLD; type I;
dbSNP:rs28940298).
{ECO:0000269|PubMed:12393546,
ECO:0000269|PubMed:12844285,
ECO:0000269|PubMed:8956040,
ECO:0000269|PubMed:9829912}.
/FTId=VAR_005779.
MUTAGEN 98 98 Y->N: No interaction with HIF1A. No HIF1A
degradation.
{ECO:0000269|PubMed:10944113}.
STRAND 71 78 {ECO:0000244|PDB:4AJY}.
STRAND 80 82 {ECO:0000244|PDB:4AJY}.
STRAND 84 89 {ECO:0000244|PDB:4AJY}.
STRAND 91 93 {ECO:0000244|PDB:3ZTC}.
STRAND 95 97 {ECO:0000244|PDB:4AJY}.
STRAND 105 112 {ECO:0000244|PDB:4AJY}.
STRAND 116 121 {ECO:0000244|PDB:4AJY}.
TURN 122 124 {ECO:0000244|PDB:4AJY}.
STRAND 127 130 {ECO:0000244|PDB:3ZTD}.
STRAND 142 144 {ECO:0000244|PDB:1LQB}.
STRAND 147 152 {ECO:0000244|PDB:4AJY}.
HELIX 158 169 {ECO:0000244|PDB:4AJY}.
HELIX 172 177 {ECO:0000244|PDB:4AJY}.
STRAND 178 180 {ECO:0000244|PDB:4B9K}.
HELIX 183 189 {ECO:0000244|PDB:4AJY}.
HELIX 194 206 {ECO:0000244|PDB:4AJY}.
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


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