ID   HNF4G_HUMAN             Reviewed;         408 AA.
AC   Q14541; Q7Z2V9; Q9UH81; Q9UIS6;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2007, sequence version 3.
DT   27-MAR-2024, entry version 219.
DE   RecName: Full=Hepatocyte nuclear factor 4-gamma;
DE            Short=HNF-4-gamma;
DE   AltName: Full=Nuclear receptor subfamily 2 group A member 2;
GN   Name=HNF4G; Synonyms=NR2A2;
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).
RC   TISSUE=Kidney;
RX   PubMed=8622695; DOI=10.1128/mcb.16.3.925;
RA   Drewes T., Senkel S., Holewa B., Ryffel G.U.;
RT   "Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and
RT   differentially expressed genes.";
RL   Mol. Cell. Biol. 16:925-931(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANT ILE-190.
RX   PubMed=10512380; DOI=10.2337/diabetes.48.10.2099;
RA   Plengvidhya N., Antonellis A., Wogan L.T., Poleev A., Borgschulze M.,
RA   Warram J.H., Ryffel G.U., Krolewski A.S., Doria A.;
RT   "Hepatocyte nuclear factor-4gamma: cDNA sequence, gene organization, and
RT   mutation screening in early-onset autosomal-dominant type 2 diabetes.";
RL   Diabetes 48:2099-2102(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16421571; DOI=10.1038/nature04406;
RA   Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA   Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA   Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA   Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA   Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA   Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA   Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA   Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA   Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA   O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA   Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA   Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA   Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA   Platzer M., Shimizu N., Lander E.S.;
RT   "DNA sequence and analysis of human chromosome 8.";
RL   Nature 439:331-335(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 103-328.
RX   PubMed=12220494; DOI=10.1016/s0969-2126(02)00829-8;
RA   Wisely G.B., Miller A.B., Davis R.G., Thornquest A.D. Jr., Johnson R.,
RA   Spitzer T., Sefler A., Shearer B., Moore J.T., Miller A.B., Willson T.M.,
RA   Williams S.P.;
RT   "Hepatocyte nuclear factor 4 is a transcription factor that constitutively
RT   binds fatty acids.";
RL   Structure 10:1225-1234(2002).
CC   -!- FUNCTION: Transcription factor. Has a lower transcription activation
CC       potential than HNF4-alpha.
CC   -!- INTERACTION:
CC       Q14541-2; Q9UEG4: ZNF629; NbExp=3; IntAct=EBI-18543805, EBI-9977294;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q14541-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q14541-2; Sequence=VSP_037691;
CC   -!- TISSUE SPECIFICITY: Expressed in pancreas, kidney, small intestine and
CC       testis. Weakly expressed in colon. Not expressed in liver, skeletal
CC       muscle, lung, placenta, brain, heart, peripheral blood, ovary,
CC       prostate, thymus and spleen.
CC   -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC       subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAE11875.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Hepatocyte nuclear factors entry;
CC       URL="https://en.wikipedia.org/wiki/Hepatocyte_nuclear_factors";
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DR   EMBL; Z49826; CAA89990.2; -; mRNA.
DR   EMBL; BX571750; CAE11875.1; ALT_INIT; mRNA.
DR   EMBL; AF133504; AAF00110.1; -; Genomic_DNA.
DR   EMBL; AF133496; AAF00110.1; JOINED; Genomic_DNA.
DR   EMBL; AF133497; AAF00110.1; JOINED; Genomic_DNA.
DR   EMBL; AF133498; AAF00110.1; JOINED; Genomic_DNA.
DR   EMBL; AF133499; AAF00110.1; JOINED; Genomic_DNA.
DR   EMBL; AF133500; AAF00110.1; JOINED; Genomic_DNA.
DR   EMBL; AF133501; AAF00110.1; JOINED; Genomic_DNA.
DR   EMBL; AF133502; AAF00110.1; JOINED; Genomic_DNA.
DR   EMBL; AF133503; AAF00110.1; JOINED; Genomic_DNA.
DR   EMBL; AF207953; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC105009; AAI05010.1; -; mRNA.
DR   EMBL; BC105011; AAI05012.1; -; mRNA.
DR   CCDS; CCDS83303.1; -. [Q14541-1]
DR   PIR; JC6095; JC6095.
DR   RefSeq; NP_001317490.1; NM_001330561.1. [Q14541-1]
DR   RefSeq; NP_004124.4; NM_004133.4.
DR   RefSeq; XP_016868862.1; XM_017013373.1. [Q14541-1]
DR   RefSeq; XP_016868863.1; XM_017013374.1. [Q14541-1]
DR   RefSeq; XP_016868864.1; XM_017013375.1. [Q14541-1]
DR   RefSeq; XP_016868865.1; XM_017013376.1. [Q14541-1]
DR   PDB; 1LV2; X-ray; 2.70 A; A=103-328.
DR   PDBsum; 1LV2; -.
DR   AlphaFoldDB; Q14541; -.
DR   SMR; Q14541; -.
DR   BioGRID; 109416; 17.
DR   IntAct; Q14541; 3.
DR   STRING; 9606.ENSP00000501146; -.
DR   ChEMBL; CHEMBL1961786; -.
DR   DrugBank; DB03796; Palmitic Acid.
DR   iPTMnet; Q14541; -.
DR   PhosphoSitePlus; Q14541; -.
DR   BioMuta; HNF4G; -.
DR   DMDM; 160110004; -.
DR   jPOST; Q14541; -.
DR   MassIVE; Q14541; -.
DR   MaxQB; Q14541; -.
DR   PaxDb; 9606-ENSP00000379701; -.
DR   PeptideAtlas; Q14541; -.
DR   ProteomicsDB; 60035; -. [Q14541-1]
DR   ProteomicsDB; 60036; -. [Q14541-2]
DR   Antibodypedia; 1695; 204 antibodies from 28 providers.
DR   DNASU; 3174; -.
DR   Ensembl; ENST00000354370.5; ENSP00000346339.1; ENSG00000164749.13. [Q14541-1]
DR   Ensembl; ENST00000674002.1; ENSP00000501146.1; ENSG00000164749.13. [Q14541-2]
DR   GeneID; 3174; -.
DR   KEGG; hsa:3174; -.
DR   UCSC; uc003yaq.4; human. [Q14541-1]
DR   AGR; HGNC:5026; -.
DR   CTD; 3174; -.
DR   DisGeNET; 3174; -.
DR   GeneCards; HNF4G; -.
DR   HGNC; HGNC:5026; HNF4G.
DR   HPA; ENSG00000164749; Tissue enriched (intestine).
DR   MIM; 605966; gene.
DR   neXtProt; NX_Q14541; -.
DR   OpenTargets; ENSG00000164749; -.
DR   PharmGKB; PA29351; -.
DR   VEuPathDB; HostDB:ENSG00000164749; -.
DR   eggNOG; KOG4215; Eukaryota.
DR   GeneTree; ENSGT00940000158224; -.
DR   HOGENOM; CLU_007368_5_2_1; -.
DR   InParanoid; Q14541; -.
DR   OrthoDB; 5400963at2759; -.
DR   PhylomeDB; Q14541; -.
DR   TreeFam; TF352097; -.
DR   PathwayCommons; Q14541; -.
DR   Reactome; R-HSA-210745; Regulation of gene expression in beta cells.
DR   Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR   SignaLink; Q14541; -.
DR   SIGNOR; Q14541; -.
DR   BioGRID-ORCS; 3174; 20 hits in 1175 CRISPR screens.
DR   ChiTaRS; HNF4G; human.
DR   EvolutionaryTrace; Q14541; -.
DR   GeneWiki; Hepatocyte_nuclear_factor_4_gamma; -.
DR   GenomeRNAi; 3174; -.
DR   Pharos; Q14541; Tbio.
DR   PRO; PR:Q14541; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; Q14541; Protein.
DR   Bgee; ENSG00000164749; Expressed in jejunal mucosa and 93 other cell types or tissues.
DR   ExpressionAtlas; Q14541; baseline and differential.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR   GO; GO:0072686; C:mitotic spindle; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR   GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   CDD; cd06960; NR_DBD_HNF4A; 1.
DR   CDD; cd06931; NR_LBD_HNF4_like; 1.
DR   Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1.
DR   Gene3D; 1.10.565.10; Retinoid X Receptor; 1.
DR   IDEAL; IID00077; -.
DR   InterPro; IPR049636; HNF4-like_DBD.
DR   InterPro; IPR049635; HNF4_LBD.
DR   InterPro; IPR035500; NHR-like_dom_sf.
DR   InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR   InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR   InterPro; IPR001628; Znf_hrmn_rcpt.
DR   InterPro; IPR013088; Znf_NHR/GATA.
DR   PANTHER; PTHR24083:SF42; HEPATOCYTE NUCLEAR FACTOR 4-GAMMA; 1.
DR   PANTHER; PTHR24083; NUCLEAR HORMONE RECEPTOR; 1.
DR   Pfam; PF00104; Hormone_recep; 1.
DR   Pfam; PF00105; zf-C4; 1.
DR   PRINTS; PR01282; COUPTNFACTOR.
DR   PRINTS; PR00398; STRDHORMONER.
DR   PRINTS; PR00047; STROIDFINGER.
DR   SMART; SM00430; HOLI; 1.
DR   SMART; SM00399; ZnF_C4; 1.
DR   SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1.
DR   SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1.
DR   PROSITE; PS51843; NR_LBD; 1.
DR   PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR   PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
DR   Genevisible; Q14541; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; DNA-binding; Metal-binding; Nucleus;
KW   Phosphoprotein; Receptor; Reference proteome; Transcription;
KW   Transcription regulation; Zinc; Zinc-finger.
FT   CHAIN           1..408
FT                   /note="Hepatocyte nuclear factor 4-gamma"
FT                   /id="PRO_0000053562"
FT   DOMAIN          99..328
FT                   /note="NR LBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT   DNA_BIND        9..84
FT                   /note="Nuclear receptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         12..32
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         48..72
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   REGION          368..390
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         94
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P22449"
FT   MOD_RES         370
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P49698"
FT   MOD_RES         373
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P49698"
FT   MOD_RES         377
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49698"
FT   VAR_SEQ         1
FT                   /note="M -> MDMANYSEVLDPTYTTLEFETMQILYNSSDSSAPETSM (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_037691"
FT   VARIANT         190
FT                   /note="M -> I (in dbSNP:rs1805098)"
FT                   /evidence="ECO:0000269|PubMed:10512380"
FT                   /id="VAR_009704"
FT   CONFLICT        28
FT                   /note="S -> T (in Ref. 1; CAA89990 and 3; AAF00110)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        45
FT                   /note="V -> I (in Ref. 1; CAA89990 and 3; AAF00110)"
FT                   /evidence="ECO:0000305"
FT   HELIX           103..116
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   HELIX           136..155
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   HELIX           158..161
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   HELIX           167..174
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   HELIX           176..188
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   STRAND          191..196
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   STRAND          202..204
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   TURN            210..212
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   HELIX           213..222
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   HELIX           224..230
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   HELIX           234..245
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   HELIX           256..275
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   STRAND          277..280
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   TURN            281..283
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   HELIX           284..289
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   HELIX           292..311
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   HELIX           319..324
FT                   /evidence="ECO:0007829|PDB:1LV2"
FT   TURN            325..327
FT                   /evidence="ECO:0007829|PDB:1LV2"
SQ   SEQUENCE   408 AA;  45877 MW;  C75410E10251AE9F CRC64;
     MNTTDNGVNC LCAICGDRAT GKHYGASSCD GCKGFFRRSI RKSHVYSCRF SRQCVVDKDK
     RNQCRYCRLR KCFRAGMKKE AVQNERDRIS TRRSTFDGSN IPSINTLAQA EVRSRQISVS
     SPGSSTDINV KKIASIGDVC ESMKQQLLVL VEWAKYIPAF CELPLDDQVA LLRAHAGEHL
     LLGATKRSMM YKDILLLGNN YVIHRNSCEV EISRVANRVL DELVRPFQEI QIDDNEYACL
     KAIVFFDPDA KGLSDPVKIK NMRFQVQIGL EDYINDRQYD SRGRFGELLL LLPTLQSITW
     QMIEQIQFVK LFGMVKIDNL LQEMLLGGAS NDGSHLHHPM HPHLSQDPLT GQTILLGPMS
     TLVHADQIST PETPLPSPPQ GSGQEQYKIA ANQASVISHQ HLSKQKQL
//