HDGF_HUMAN
ID HDGF_HUMAN Reviewed; 240 AA.
AC P51858; B3KU21; D3DVC9; Q5SZ07; Q5SZ08; Q5SZ09;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Hepatoma-derived growth factor;
DE Short=HDGF;
DE AltName: Full=High mobility group protein 1-like 2;
DE Short=HMG-1L2;
GN Name=HDGF; Synonyms=HMG1L2;
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 [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 4-24, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Hepatoma;
RX PubMed=7929202; DOI=10.1016/s0021-9258(17)31509-0;
RA Nakamura H., Izumoto Y., Kambe H., Kuroda T., Mori T., Kawamura K.,
RA Yamamoto H., Kishimoto T.;
RT "Molecular cloning of complementary DNA for a novel human hepatoma-derived
RT growth factor. Its homology with high mobility group-1 protein.";
RL J. Biol. Chem. 269:25143-25149(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT LEU-201.
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=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 SUBCELLULAR LOCATION (ISOFORM 1), AND NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=11751870; DOI=10.1074/jbc.m111122200;
RA Kishima Y., Yamamoto H., Izumoto Y., Yoshida K., Enomoto H., Yamamoto M.,
RA Kuroda T., Ito H., Yoshizaki K., Nakamura H.;
RT "Hepatoma-derived growth factor stimulates cell growth after translocation
RT to the nucleus by nuclear localization signals.";
RL J. Biol. Chem. 277:10315-10322(2002).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=15302935; DOI=10.1073/pnas.0404720101;
RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J.,
RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
RT "Large-scale characterization of HeLa cell nuclear phosphoproteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132; SER-133 AND SER-165, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165 AND THR-200, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132 AND SER-133, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pituitary;
RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x;
RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
RT "Phosphoproteomic analysis of the human pituitary.";
RL Pituitary 9:109-120(2006).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND DNA-BINDING.
RX PubMed=17974029; DOI=10.1186/1471-2199-8-101;
RA Yang J., Everett A.D.;
RT "Hepatoma-derived growth factor binds DNA through the N-terminal PWWP
RT domain.";
RL BMC Mol. Biol. 8:101-101(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132 AND SER-133, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Prostate cancer;
RX PubMed=17487921; DOI=10.1002/elps.200600782;
RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
RT "Toward a global characterization of the phosphoproteome in prostate cancer
RT cells: identification of phosphoproteins in the LNCaP cell line.";
RL Electrophoresis 28:2027-2034(2007).
RN [13]
RP SUMOYLATION AT LYS-80.
RX PubMed=18331345; DOI=10.1111/j.1742-4658.2008.06303.x;
RA Thakar K., Niedenthal R., Okaz E., Franken S., Jakobs A., Gupta S.,
RA Kelm S., Dietz F.;
RT "SUMOylation of the hepatoma-derived growth factor negatively influences
RT its binding to chromatin.";
RL FEBS J. 275:1411-1426(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132; SER-133 AND SER-165, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using sequential
RT IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132 AND SER-133, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-200; SER-206 AND SER-239, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132; SER-133 AND SER-165, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132 AND SER-165, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-44, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133; SER-165; THR-200 AND
RP SER-239, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132; SER-133; SER-165;
RP THR-184 AND SER-239, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132; SER-133; SER-165;
RP THR-200 AND SER-202, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-80, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [30]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-80, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [31]
RP ALTERNATIVE SPLICING, FUNCTION, INTERACTION WITH ACTIN; DYNEIN; TUBULIN;
RP VIMENTIN; NCL AND YBX1, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=26845719; DOI=10.1515/hsz-2015-0273;
RA Nuesse J., Mirastschijski U., Waespy M., Oetjen J., Brandes N., Rebello O.,
RA Paroni F., Kelm S., Dietz F.;
RT "Two new isoforms of the human hepatoma-derived growth factor interact with
RT components of the cytoskeleton.";
RL Biol. Chem. 397:417-436(2016).
RN [32]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-165.
RX PubMed=27926477; DOI=10.1515/hsz-2016-0315;
RA Nuesse J., Blumrich E.M., Mirastschijski U., Kappelmann L., Kelm S.,
RA Dietz F.;
RT "Intra- or extra-exosomal secretion of HDGF isoforms: the extraordinary
RT function of the HDGF-A N-terminal peptide.";
RL Biol. Chem. 398:793-811(2017).
RN [33]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-80, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [34]
RP STRUCTURE BY NMR OF 1-100, SUBUNIT, AND DOMAIN.
RX PubMed=17270212; DOI=10.1016/j.jmb.2007.01.010;
RA Sue S.C., Lee W.T., Tien S.C., Lee S.C., Yu J.G., Wu W.J., Wu W.G.,
RA Huang T.-H.;
RT "PWWP module of human hepatoma-derived growth factor forms a domain-swapped
RT dimer with much higher affinity for heparin.";
RL J. Mol. Biol. 367:456-472(2007).
RN [35]
RP STRUCTURE BY NMR OF 1-100, FUNCTION, HEPARIN-BINDING SITES, AND DOMAIN.
RX PubMed=15491618; DOI=10.1016/j.jmb.2004.09.014;
RA Sue S.C., Chen J.Y., Lee S.C., Wu W.G., Huang T.-H.;
RT "Solution structure and heparin interaction of human hepatoma-derived
RT growth factor.";
RL J. Mol. Biol. 343:1365-1377(2004).
CC -!- FUNCTION: [Isoform 1]: Acts as a transcriptional repressor
CC (PubMed:17974029). Has mitogenic activity for fibroblasts
CC (PubMed:11751870, PubMed:26845719). Heparin-binding protein
CC (PubMed:15491618). {ECO:0000269|PubMed:11751870,
CC ECO:0000269|PubMed:15491618, ECO:0000269|PubMed:17974029,
CC ECO:0000269|PubMed:26845719}.
CC -!- FUNCTION: [Isoform 2]: Does not have mitogenic activity for fibroblasts
CC (PubMed:26845719). Does not bind heparin (PubMed:26845719).
CC {ECO:0000269|PubMed:26845719}.
CC -!- FUNCTION: [Isoform 3]: Has mitogenic activity for fibroblasts
CC (PubMed:26845719). Heparin-binding protein (PubMed:26845719).
CC {ECO:0000269|PubMed:26845719}.
CC -!- SUBUNIT: Monomer, and domain-swapped homodimer (PubMed:17270212).
CC {ECO:0000269|PubMed:17270212}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with nuclear proteins NCL and YBX1/YB1
CC (PubMed:26845719). {ECO:0000269|PubMed:26845719}.
CC -!- SUBUNIT: [Isoform 2]: Interacts with cytoskeletal proteins such as
CC actin, dynein, tubulin and vimentin (PubMed:26845719).
CC {ECO:0000269|PubMed:26845719}.
CC -!- SUBUNIT: [Isoform 3]: Interacts with cytoskeletal proteins such as
CC dynein and tubulin but does not interact with actin or vimentin
CC (PubMed:26845719). {ECO:0000269|PubMed:26845719}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000269|PubMed:11751870, ECO:0000269|PubMed:26845719}. Cytoplasm
CC {ECO:0000269|PubMed:11751870}. Secreted, extracellular exosome
CC {ECO:0000269|PubMed:27926477}. Note=Secreted by exosomes and is located
CC inside the exosome (PubMed:27926477). May also be secreted as free
CC protein via an as yet unknown pathway (PubMed:27926477).
CC {ECO:0000269|PubMed:27926477}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus
CC {ECO:0000269|PubMed:26845719}. Cytoplasm {ECO:0000269|PubMed:26845719}.
CC Secreted, extracellular exosome {ECO:0000269|PubMed:27926477}.
CC Note=Secreted by exosomes and is located on the outer exosome surface.
CC {ECO:0000269|PubMed:27926477}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Nucleus
CC {ECO:0000269|PubMed:26845719}. Cytoplasm {ECO:0000269|PubMed:26845719}.
CC Secreted, extracellular exosome {ECO:0000269|PubMed:27926477}.
CC Note=Secreted by exosomes and is located on the outer exosome surface.
CC {ECO:0000269|PubMed:27926477}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=HDFG-A {ECO:0000303|PubMed:26845719};
CC IsoId=P51858-1; Sequence=Displayed;
CC Name=2; Synonyms=HDGF-C {ECO:0000303|PubMed:26845719};
CC IsoId=P51858-2; Sequence=VSP_045620;
CC Name=3; Synonyms=HDGF-B {ECO:0000303|PubMed:26845719};
CC IsoId=P51858-3; Sequence=VSP_047328;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:7929202}.
CC -!- DOMAIN: The PWWP domain harbors the heparin-binding sites and is
CC responsible for DNA-binding, while the C-terminal region is essentially
CC unstructured. {ECO:0000269|PubMed:15491618,
CC ECO:0000269|PubMed:17270212}.
CC -!- DOMAIN: The N-terminal region does not contain a typical signal
CC sequence but is required for secretion (By similarity). It also
CC determines exosomal location (PubMed:26845719).
CC {ECO:0000250|UniProtKB:P51859, ECO:0000269|PubMed:26845719}.
CC -!- PTM: Sumoylated with SUMO1. Sumoylation prevents binding to chromatin.
CC {ECO:0000269|PubMed:18331345}.
CC -!- PTM: Phosphorylation at Ser-165 is likely to be required for secretion.
CC {ECO:0000250|UniProtKB:P51859}.
CC -!- SIMILARITY: Belongs to the HDGF family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D16431; BAA03903.1; -; mRNA.
DR EMBL; AK096411; BAG53283.1; -; mRNA.
DR EMBL; AL590666; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW52910.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52911.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52912.1; -; Genomic_DNA.
DR EMBL; BC018991; AAH18991.1; -; mRNA.
DR CCDS; CCDS1156.1; -. [P51858-1]
DR CCDS; CCDS44247.1; -. [P51858-3]
DR CCDS; CCDS44248.1; -. [P51858-2]
DR PIR; A55055; A55055.
DR RefSeq; NP_001119522.1; NM_001126050.1. [P51858-3]
DR RefSeq; NP_001119523.1; NM_001126051.1. [P51858-2]
DR RefSeq; NP_001306115.1; NM_001319186.1.
DR RefSeq; NP_001306116.1; NM_001319187.1.
DR RefSeq; NP_001306117.1; NM_001319188.1.
DR RefSeq; NP_004485.1; NM_004494.2. [P51858-1]
DR PDB; 1RI0; NMR; -; A=1-100.
DR PDB; 2NLU; NMR; -; A/B=1-100.
DR PDBsum; 1RI0; -.
DR PDBsum; 2NLU; -.
DR AlphaFoldDB; P51858; -.
DR BMRB; P51858; -.
DR SMR; P51858; -.
DR BioGRID; 109318; 248.
DR CORUM; P51858; -.
DR IntAct; P51858; 130.
DR MINT; P51858; -.
DR STRING; 9606.ENSP00000357189; -.
DR DrugBank; DB09130; Copper.
DR GlyGen; P51858; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P51858; -.
DR MetOSite; P51858; -.
DR PhosphoSitePlus; P51858; -.
DR SwissPalm; P51858; -.
DR BioMuta; HDGF; -.
DR DMDM; 1708157; -.
DR EPD; P51858; -.
DR jPOST; P51858; -.
DR MassIVE; P51858; -.
DR MaxQB; P51858; -.
DR PaxDb; P51858; -.
DR PeptideAtlas; P51858; -.
DR PRIDE; P51858; -.
DR ProteomicsDB; 56439; -. [P51858-1]
DR ProteomicsDB; 64044; -.
DR ProteomicsDB; 64045; -.
DR TopDownProteomics; P51858-1; -. [P51858-1]
DR TopDownProteomics; P51858-2; -. [P51858-2]
DR Antibodypedia; 34226; 368 antibodies from 38 providers.
DR DNASU; 3068; -.
DR Ensembl; ENST00000357325.10; ENSP00000349878.5; ENSG00000143321.19. [P51858-1]
DR Ensembl; ENST00000368206.5; ENSP00000357189.5; ENSG00000143321.19. [P51858-3]
DR Ensembl; ENST00000368209.9; ENSP00000357192.5; ENSG00000143321.19. [P51858-2]
DR Ensembl; ENST00000537739.5; ENSP00000443120.1; ENSG00000143321.19. [P51858-1]
DR GeneID; 3068; -.
DR KEGG; hsa:3068; -.
DR MANE-Select; ENST00000357325.10; ENSP00000349878.5; NM_004494.3; NP_004485.1.
DR UCSC; uc001fpy.5; human. [P51858-1]
DR CTD; 3068; -.
DR DisGeNET; 3068; -.
DR GeneCards; HDGF; -.
DR HGNC; HGNC:4856; HDGF.
DR HPA; ENSG00000143321; Low tissue specificity.
DR MIM; 600339; gene.
DR neXtProt; NX_P51858; -.
DR OpenTargets; ENSG00000143321; -.
DR PharmGKB; PA29234; -.
DR VEuPathDB; HostDB:ENSG00000143321; -.
DR eggNOG; KOG1904; Eukaryota.
DR GeneTree; ENSGT00940000157485; -.
DR HOGENOM; CLU_090867_0_0_1; -.
DR InParanoid; P51858; -.
DR OMA; RGRFVPQ; -.
DR OrthoDB; 530959at2759; -.
DR PhylomeDB; P51858; -.
DR TreeFam; TF105385; -.
DR PathwayCommons; P51858; -.
DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes.
DR SignaLink; P51858; -.
DR BioGRID-ORCS; 3068; 13 hits in 1082 CRISPR screens.
DR ChiTaRS; HDGF; human.
DR EvolutionaryTrace; P51858; -.
DR GeneWiki; Hepatoma-derived_growth_factor; -.
DR GenomeRNAi; 3068; -.
DR Pharos; P51858; Tbio.
DR PRO; PR:P51858; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P51858; protein.
DR Bgee; ENSG00000143321; Expressed in endometrium epithelium and 202 other tissues.
DR ExpressionAtlas; P51858; baseline and differential.
DR Genevisible; P51858; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0017053; C:transcription repressor complex; IDA:BHF-UCL.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:BHF-UCL.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:BHF-UCL.
DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB.
DR GO; GO:0098761; P:cellular response to interleukin-7; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0051781; P:positive regulation of cell division; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR CDD; cd05834; HDGF_related; 1.
DR IDEAL; IID00454; -.
DR InterPro; IPR035496; HDGF-rel_PWWP.
DR InterPro; IPR000313; PWWP_dom.
DR Pfam; PF00855; PWWP; 1.
DR SMART; SM00293; PWWP; 1.
DR PROSITE; PS50812; PWWP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; DNA-binding; Growth factor;
KW Heparin-binding; Isopeptide bond; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Secreted; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..240
FT /note="Hepatoma-derived growth factor"
FT /id="PRO_0000191700"
FT DOMAIN 12..69
FT /note="PWWP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00162"
FT REGION 69..240
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 75..80
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:11751870"
FT MOTIF 155..170
FT /note="Bipartite nuclear localization signal"
FT COMPBIAS 69..85
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 108..193
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 212..227
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 19
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000305"
FT BINDING 21
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000305"
FT BINDING 72
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000305"
FT BINDING 75
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000305"
FT BINDING 79
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000305"
FT BINDING 80
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000305"
FT MOD_RES 44
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 132
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16807684,
FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:17487921,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18318008,
FT ECO:0007744|PubMed:19367720, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16807684,
FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:17487921,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18318008,
FT ECO:0007744|PubMed:19367720, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15302935,
FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19367720, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 184
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHK7"
FT MOD_RES 200
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 206
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT DISULFID 12..108
FT /evidence="ECO:0000250|UniProtKB:P51859"
FT CROSSLNK 80
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT CROSSLNK 80
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..29
FT /note="MSRSNRQKEYKCGDLVFAKMKGYPHWPAR -> MEQRAGGNRVQTSTLNCAG
FT AAV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045620"
FT VAR_SEQ 1..29
FT /note="MSRSNRQKEYKCGDLVFAKMKGYPHWPAR -> MHPEGGQFVPQLLGHLLAT
FT KLKRFLLSKGGRRAQIPDVSRATPHT (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_047328"
FT VARIANT 201
FT /note="P -> L (in dbSNP:rs4399146)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_061209"
FT MUTAGEN 165
FT /note="S->A: Abolishes secretion and alters location of the
FT protein from inside the exosome to the exosomal surface."
FT /evidence="ECO:0000269|PubMed:27926477"
FT CONFLICT 206
FT /note="S -> P (in Ref. 2; BAG53283)"
FT /evidence="ECO:0000305"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:1RI0"
FT STRAND 15..20
FT /evidence="ECO:0007829|PDB:1RI0"
FT STRAND 23..31
FT /evidence="ECO:0007829|PDB:1RI0"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:1RI0"
FT STRAND 45..49
FT /evidence="ECO:0007829|PDB:1RI0"
FT TURN 50..53
FT /evidence="ECO:0007829|PDB:1RI0"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:1RI0"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:2NLU"
FT HELIX 66..72
FT /evidence="ECO:0007829|PDB:1RI0"
FT HELIX 80..90
FT /evidence="ECO:0007829|PDB:1RI0"
SQ SEQUENCE 240 AA; 26788 MW; DD60D9203BDD4B34 CRC64;
MSRSNRQKEY KCGDLVFAKM KGYPHWPARI DEMPEAAVKS TANKYQVFFF GTHETAFLGP
KDLFPYEESK EKFGKPNKRK GFSEGLWEIE NNPTVKASGY QSSQKKSCVE EPEPEPEAAE
GDGDKKGNAE GSSDEEGKLV IDEPAKEKNE KGALKRRAGD LLEDSPKRPK EAENPEGEEK
EAATLEVERP LPMEVEKNST PSEPGSGRGP PQEEEEEEDE EEEATKEDAE APGIRDHESL
