HDGF_RAT
ID HDGF_RAT Reviewed; 237 AA.
AC Q8VHK7; Q923W3;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2004, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Hepatoma-derived growth factor;
DE Short=HDGF;
GN Name=Hdgf;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Hepatic stellate cell;
RA Matsui H., Kawada N., Yokoya F., Takahara Y.;
RT "Isolation of rat HDGF from hepatic stellate cells.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yu L.;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [4]
RP PROTEIN SEQUENCE OF 45-61 AND 139-146, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA Lubec G., Diao W.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132 AND SER-133, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16396499; DOI=10.1021/pr0503073;
RA Moser K., White F.M.;
RT "Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-
RT MS/MS.";
RL J. Proteome Res. 5:98-104(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132; SER-133; SER-165;
RP SER-199; THR-200; SER-202 AND SER-206, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [8]
RP STRUCTURE BY NMR OF 1-110.
RX PubMed=16384999; DOI=10.1110/ps.051751706;
RA Lukasik S.M., Cierpicki T., Borloz M., Grembecka J., Everett A.,
RA Bushweller J.H.;
RT "High resolution structure of the HDGF PWWP domain: a potential DNA binding
RT domain.";
RL Protein Sci. 15:314-323(2006).
CC -!- FUNCTION: Acts as a transcriptional repressor (By similarity). Has
CC mitogenic activity for fibroblasts (By similarity). Heparin-binding
CC protein (By similarity). {ECO:0000250|UniProtKB:P51858}.
CC -!- SUBUNIT: Monomer, and domain-swapped homodimer (By similarity).
CC Interacts with nuclear proteins NCL and YBX1/YB1 (By similarity).
CC {ECO:0000250|UniProtKB:P51858}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P51858}. Cytoplasm
CC {ECO:0000250|UniProtKB:P51858}. Secreted, extracellular exosome
CC {ECO:0000250|UniProtKB:P51858}. Note=Secreted by exosomes and is
CC located inside the exosome (By similarity). May also be secreted as
CC free protein via an as yet unknown pathway (By similarity).
CC {ECO:0000250|UniProtKB:P51858}.
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:0000250|UniProtKB:P51858}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:P51858, ECO:0000250|UniProtKB:P51859}.
CC -!- PTM: Sumoylated with SUMO1. Sumoylation prevents binding to chromatin.
CC {ECO:0000250|UniProtKB:P51858}.
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}.
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DR EMBL; AF448810; AAL47132.1; -; mRNA.
DR EMBL; AF389348; AAK72966.1; -; mRNA.
DR EMBL; BC070943; AAH70943.1; -; mRNA.
DR RefSeq; NP_446159.1; NM_053707.2.
DR PDB; 2B8A; NMR; -; A=1-110.
DR PDB; 5XSK; X-ray; 2.84 A; A/B=1-100.
DR PDB; 5XSL; X-ray; 3.30 A; A=1-100.
DR PDBsum; 2B8A; -.
DR PDBsum; 5XSK; -.
DR PDBsum; 5XSL; -.
DR AlphaFoldDB; Q8VHK7; -.
DR BMRB; Q8VHK7; -.
DR SMR; Q8VHK7; -.
DR STRING; 10116.ENSRNOP00000017234; -.
DR iPTMnet; Q8VHK7; -.
DR PhosphoSitePlus; Q8VHK7; -.
DR jPOST; Q8VHK7; -.
DR PaxDb; Q8VHK7; -.
DR PRIDE; Q8VHK7; -.
DR Ensembl; ENSRNOT00000103162; ENSRNOP00000088839; ENSRNOG00000042261.
DR GeneID; 114499; -.
DR KEGG; rno:114499; -.
DR UCSC; RGD:70961; rat.
DR CTD; 3068; -.
DR RGD; 70961; Hdgf.
DR eggNOG; KOG1904; Eukaryota.
DR GeneTree; ENSGT00940000157485; -.
DR InParanoid; Q8VHK7; -.
DR OrthoDB; 530959at2759; -.
DR PhylomeDB; Q8VHK7; -.
DR EvolutionaryTrace; Q8VHK7; -.
DR PRO; PR:Q8VHK7; -.
DR Proteomes; UP000002494; Chromosome 2.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0017053; C:transcription repressor complex; ISO:RGD.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
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; ISS:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
DR GO; GO:0001222; F:transcription corepressor binding; ISO:RGD.
DR GO; GO:0015631; F:tubulin binding; ISO:RGD.
DR GO; GO:0098761; P:cellular response to interleukin-7; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0034504; P:protein localization to nucleus; IDA:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd05834; HDGF_related; 1.
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; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; DNA-binding; Growth factor; Heparin-binding;
KW Isopeptide bond; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Secreted; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..237
FT /note="Hepatoma-derived growth factor"
FT /id="PRO_0000191702"
FT DOMAIN 12..69
FT /note="PWWP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00162"
FT REGION 69..237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 75..80
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 155..170
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250"
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 209..223
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:0000250"
FT BINDING 21
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250"
FT BINDING 72
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250"
FT BINDING 75
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250"
FT BINDING 79
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250"
FT BINDING 80
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250"
FT MOD_RES 44
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51858"
FT MOD_RES 132
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16396499,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16396499,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 200
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 206
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 236
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51858"
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 /evidence="ECO:0000250"
FT CROSSLNK 80
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P51858"
FT CONFLICT 231
FT /note="V -> I (in Ref. 1; AAL47132)"
FT /evidence="ECO:0000305"
FT STRAND 15..18
FT /evidence="ECO:0007829|PDB:5XSK"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:5XSK"
FT HELIX 35..39
FT /evidence="ECO:0007829|PDB:5XSK"
FT TURN 40..43
FT /evidence="ECO:0007829|PDB:5XSK"
FT STRAND 45..49
FT /evidence="ECO:0007829|PDB:5XSK"
FT TURN 50..52
FT /evidence="ECO:0007829|PDB:5XSK"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:5XSK"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:5XSK"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:5XSK"
FT HELIX 70..73
FT /evidence="ECO:0007829|PDB:5XSK"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:2B8A"
FT HELIX 82..91
FT /evidence="ECO:0007829|PDB:5XSK"
SQ SEQUENCE 237 AA; 26488 MW; C120F798BD40D360 CRC64;
MSRSNRQKEY KCGDLVFAKM KGYPHWPARI DEMPEAAVKS TANKYQVFFF GTHETAFLGP
KDLFPYEESK EKFGKPNKRK GFSEGLWEIE NNPTVKASGY QSSQKKSCAE EPEVEPEAHE
GDGDKKGNAE GSSDEEGKLV IDEPAKEKNE KGMLKRRAGD MLEDSPKRPK ESGDHEEEEK
EIAALEGERP LPVEMEKNST PSEPDSGQGP PPEEEEGEEE AAKEEAEAQG VRDHESL
