HLTF_RABIT
ID HLTF_RABIT Reviewed; 1005 AA.
AC Q95216; Q95217;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Helicase-like transcription factor;
DE EC=2.3.2.27;
DE EC=3.6.4.-;
DE AltName: Full=RING-type E3 ubiquitin transferase HLTF {ECO:0000305};
DE AltName: Full=RUSH-1;
DE AltName: Full=SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 3;
DE AltName: Full=Sucrose nonfermenting protein 2-like 3;
GN Name=HLTF; Synonyms=RUSH1, SMARCA3;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INDUCTION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=New Zealand white; TISSUE=Endometrium;
RX PubMed=8923460; DOI=10.1210/mend.10.11.8923460;
RA Hayward-Lester A., Hewetson A., Beale E.G., Oefner P.J., Doris P.A.,
RA Chilton B.S.;
RT "Cloning, characterization, and steroid-dependent posttranscriptional
RT processing of RUSH-1 alpha and beta, two uteroglobin promoter-binding
RT proteins.";
RL Mol. Endocrinol. 10:1335-1349(1996).
RN [2]
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=9370258; DOI=10.1016/s0378-1119(97)00305-3;
RA Robinson C.A., Hayward-Lester A., Hewetson A., Oefner P.J., Doris P.A.,
RA Chilton B.S.;
RT "Quantification of alternatively spliced RUSH mRNA isoforms by QRT-PCR and
RT IP-RP-HPLC analysis: a new approach to measuring regulated splicing
RT efficiency.";
RL Gene 198:1-4(1997).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=10859255; DOI=10.1095/biolreprod63.1.156;
RA Rendon A., Hewetson A., Chilton B.S., Lee V.H.;
RT "Expression of RUSH transcription factors in developing and adult rabbit
RT gonads.";
RL Biol. Reprod. 63:156-164(2000).
RN [4]
RP FUNCTION, AND INTERACTION WITH ATP11B.
RX PubMed=11058586; DOI=10.1074/jbc.m004231200;
RA Mansharamani M., Hewetson A., Chilton B.S.;
RT "Cloning and characterization of an atypical type IV P-type ATPase that
RT binds to the RING motif of RUSH transcription factors.";
RL J. Biol. Chem. 276:3641-3649(2001).
RN [5]
RP DNA-BINDING, INTERACTION WITH GATA4, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=12198246; DOI=10.1210/me.2002-0064;
RA Hewetson A., Hendrix E.C., Mansharamani M., Lee V.H., Chilton B.S.;
RT "Identification of the RUSH consensus-binding site by cyclic amplification
RT and selection of targets: demonstration that RUSH mediates the ability of
RT prolactin to augment progesterone-dependent gene expression.";
RL Mol. Endocrinol. 16:2101-2112(2002).
RN [6]
RP DNA-BINDING, AND FUNCTION.
RX PubMed=12890680; DOI=10.1074/jbc.m303921200;
RA Hewetson A., Chilton B.S.;
RT "An Sp1-NF-Y/progesterone receptor DNA binding-dependent mechanism
RT regulates progesterone-induced transcriptional activation of the rabbit
RT RUSH/SMARCA3 gene.";
RL J. Biol. Chem. 278:40177-40185(2003).
RN [7]
RP INTERACTION WITH EGR1, PHOSPHORYLATION, AND FUNCTION.
RX PubMed=15306550; DOI=10.1095/biolreprod.104.031435;
RA Hewetson A., Moore S.L., Chilton B.S.;
RT "Prolactin signals through RUSH/SMARCA3 in the absence of a physical
RT association with Stat5a.";
RL Biol. Reprod. 71:1907-1912(2004).
RN [8]
RP FUNCTION.
RX PubMed=18631131; DOI=10.1042/bst0360632;
RA Chilton B.S., Hewetson A.;
RT "Progesterone regulation of RUSH/SMARCA3/HLTF includes DNA looping.";
RL Biochem. Soc. Trans. 36:632-636(2008).
RN [9]
RP INTERACTION WITH ATP11B, AND MUTAGENESIS OF PRO-767; VAL-768; ILE-769;
RP HIS-771; ALA-792 AND LYS-793.
RX PubMed=18584949; DOI=10.1016/j.mce.2008.05.007;
RA Hewetson A., Wright-Pastusek A.E., Helmer R.A., Wesley K.A., Chilton B.S.;
RT "Conservation of inter-protein binding sites in RUSH and RFBP, an ATP11B
RT isoform.";
RL Mol. Cell. Endocrinol. 292:79-86(2008).
RN [10]
RP INTERACTION WITH EGR1 AND REL, DNA-BINDING, SUBCELLULAR LOCATION, AND
RP FUNCTION.
RX PubMed=18174357; DOI=10.1210/me.2007-0432;
RA Hewetson A., Chilton B.S.;
RT "Progesterone-dependent deoxyribonucleic acid looping between RUSH/SMARCA3
RT and Egr-1 mediates repression by c-Rel.";
RL Mol. Endocrinol. 22:813-822(2008).
RN [11]
RP SUBCELLULAR LOCATION, INDUCTION, AND PHOSPHORYLATION BY JAK2.
RX PubMed=20562009; DOI=10.1016/j.mce.2010.05.010;
RA Helmer R.A., Panchoo M., Dertien J.S., Bhakta S.M., Hewetson A.,
RA Chilton B.S.;
RT "Prolactin-induced Jak2 phosphorylation of RUSH: a key element in Jak/RUSH
RT signaling.";
RL Mol. Cell. Endocrinol. 325:143-149(2010).
RN [12]
RP FUNCTION IN SCGB1A1 PROMOTER BINDING, AND PHOSPHORYLATION AT TYR-195.
RX PubMed=21457752; DOI=10.1016/j.mce.2011.03.009;
RA Helmer R.A., Dertien J.S., Chilton B.S.;
RT "Prolactin induces Jak2 phosphorylation of RUSHY195.";
RL Mol. Cell. Endocrinol. 338:79-83(2011).
CC -!- FUNCTION: Has both helicase and E3 ubiquitin ligase activities.
CC Possesses intrinsic ATP-dependent nucleosome-remodeling activity. This
CC activity may be required for transcriptional activation or repression
CC of specific target promoters (By similarity). These may include the
CC SERPINE1, to which this protein can bind directly. Mediates repression
CC by c-Rel through a DNA-looping mechanism. Plays a role in error-free
CC postreplication repair (PRR) of damaged DNA and maintains genomic
CC stability through acting as a ubiquitin ligase for 'Lys-63'-linked
CC polyubiquitination of chromatin-bound PCNA (By similarity).
CC Transcriptional regulator that mediates the ability of prolactin to
CC augment progesterone-dependent transcription of the SCGB1A1/uteroglobin
CC gene through a bipartite progesterone receptor half-site/overlapping Y-
CC box combination (-38/-26) where progesterone activation is attenuated
CC by nuclear factor Y binding. Regulation also involves two GC-rich
CC sequences in the proximal promoter (positions -162/+90) and a
CC RUSH/SMARCA3 site (positions -616/-611) in the 5'-untranslated region.
CC {ECO:0000250, ECO:0000269|PubMed:11058586, ECO:0000269|PubMed:12890680,
CC ECO:0000269|PubMed:15306550, ECO:0000269|PubMed:18174357,
CC ECO:0000269|PubMed:18631131, ECO:0000269|PubMed:21457752}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with SP1 and SP3 independently of DNA; the
CC interaction with these transcriptional factors may be required for
CC basal transcription of target genes (By similarity). Interacts (via the
CC RING-finger) with isoform RFBP of ATP11B. Progesterone-dependent
CC isoform 1 interacts with EGR1; the interaction requires prior binding
CC to DNA and represses c-Rel via a DNA looping mechanism. Interacts with
CC GATA4. Interacts with PCNA; the interaction promotes polyubiquitination
CC of PCNA through association with the UBE2B-RAD18 and UBE2V2-UBE2N
CC ubiquitin ligase complexes. Interacts with RAD18, SHPRH, UBE2V2 and
CC UBE2N (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleolus. Nucleus,
CC nucleoplasm. Note=Cytoplasmic and nuclear localization in the presence
CC of prolactin. Nuclear localization is stimulated by progesterone.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=RUSH 1-alpha;
CC IsoId=Q95216-1; Sequence=Displayed;
CC Name=2; Synonyms=RUSH 1-beta;
CC IsoId=Q95216-2; Sequence=VSP_012923, VSP_012924;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed preferentially in bladder,
CC cervix, diaphragm, duodenum, epididymis, heart, kidney, liver, lung,
CC ovary (granulosa cells), prostate, spleen, testis (predominantly in the
CC Sertoli cells of the seminiferous tubules) and vagina. Isoform 2 is
CC expressed preferentially in lactating mammary gland and uterine
CC endometrium. {ECO:0000269|PubMed:10859255, ECO:0000269|PubMed:12198246,
CC ECO:0000269|PubMed:8923460, ECO:0000269|PubMed:9370258}.
CC -!- INDUCTION: Isoform RUSH 1-alpha expression is increased by progesterone
CC and decreased by estradiol. Progesterone induction is increased in the
CC presence of prolactin. Isoform RUSH 1-beta/RFBP expression is increased
CC by estrogen and decreased by progesterone.
CC {ECO:0000269|PubMed:12198246, ECO:0000269|PubMed:20562009,
CC ECO:0000269|PubMed:8923460}.
CC -!- PTM: Phosphorylated on serine, threonine, and tyrosine residues. Tyr-
CC 195 phosphorylation is catalyzed by JAK2 in response to prolactin
CC treatment. It is required for DNA binding.
CC {ECO:0000269|PubMed:15306550, ECO:0000269|PubMed:20562009,
CC ECO:0000269|PubMed:21457752}.
CC -!- MISCELLANEOUS: [Isoform 1]: Major isoform in progesterone-dominant
CC endometrium.
CC -!- MISCELLANEOUS: [Isoform 2]: Truncated, estrogen-dependent isoform.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the SNF2/RAD54 helicase family. RAD16 subfamily.
CC {ECO:0000305}.
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DR EMBL; U66564; AAC18656.1; -; mRNA.
DR EMBL; U66565; AAC48693.1; -; mRNA.
DR RefSeq; NP_001075845.1; NM_001082376.1. [Q95216-2]
DR RefSeq; NP_001108200.1; NM_001114728.1. [Q95216-1]
DR AlphaFoldDB; Q95216; -.
DR SMR; Q95216; -.
DR STRING; 9986.ENSOCUP00000003055; -.
DR iPTMnet; Q95216; -.
DR PRIDE; Q95216; -.
DR GeneID; 100009232; -.
DR KEGG; ocu:100009232; -.
DR CTD; 6596; -.
DR eggNOG; KOG1001; Eukaryota.
DR InParanoid; Q95216; -.
DR OrthoDB; 132523at2759; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0140658; F:ATP-dependent chromatin remodeler activity; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0004386; F:helicase activity; IEA:UniProtKB-KW.
DR GO; GO:0016818; F:hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides; IEA:InterPro.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.40.50.10810; -; 2.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR014905; HIRAN.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR038718; SNF2-like_sf.
DR InterPro; IPR000330; SNF2_N.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF08797; HIRAN; 1.
DR Pfam; PF00176; SNF2-rel_dom; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SMART; SM00910; HIRAN; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; ATP-binding; Chromatin regulator;
KW Cytoplasm; DNA-binding; Helicase; Hydrolase; Isopeptide bond;
KW Metal-binding; Methylation; Multifunctional enzyme; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..1005
FT /note="Helicase-like transcription factor"
FT /id="PRO_0000056186"
FT DOMAIN 427..603
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 834..999
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DNA_BIND 38..287
FT /evidence="ECO:0000250"
FT ZN_FING 757..798
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 325..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 767..772
FT /note="Required for interaction with the RFBP isoform of
FT ATP11B"
FT REGION 791..796
FT /note="Required for interaction with the RFBP isoform of
FT ATP11B"
FT REGION 922..1005
FT /note="Interaction with SP1 and SP3"
FT /evidence="ECO:0000250"
FT MOTIF 554..557
FT /note="DEGH box"
FT COMPBIAS 325..368
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 369..385
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 294..301
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOD_RES 27
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q14527"
FT MOD_RES 195
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000269|PubMed:21457752"
FT MOD_RES 395
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14527"
FT MOD_RES 396
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14527"
FT MOD_RES 398
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14527"
FT MOD_RES 733
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14527"
FT CROSSLNK 112
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q14527"
FT CROSSLNK 211
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q14527"
FT VAR_SEQ 832..836
FT /note="INALM -> RFLSC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8923460"
FT /id="VSP_012923"
FT VAR_SEQ 837..1005
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8923460"
FT /id="VSP_012924"
FT MUTAGEN 767
FT /note="P->S,T: Abolishes binding to the RFBP isoform of
FT ATP11B."
FT /evidence="ECO:0000269|PubMed:18584949"
FT MUTAGEN 768
FT /note="V->R: Abolishes binding to the RFBP isoform of
FT ATP11B."
FT /evidence="ECO:0000269|PubMed:18584949"
FT MUTAGEN 769
FT /note="I->M,P: Abolishes binding to the RFBP isoform of
FT ATP11B."
FT /evidence="ECO:0000269|PubMed:18584949"
FT MUTAGEN 771
FT /note="H->D,K: Abolishes binding to the RFBP isoform of
FT ATP11B."
FT /evidence="ECO:0000269|PubMed:18584949"
FT MUTAGEN 792
FT /note="A->Q: Abolishes binding to the RFBP isoform of
FT ATP11B."
FT /evidence="ECO:0000269|PubMed:18584949"
FT MUTAGEN 793
FT /note="K->P: Abolishes binding to the RFBP isoform of
FT ATP11B."
FT /evidence="ECO:0000269|PubMed:18584949"
SQ SEQUENCE 1005 AA; 113582 MW; C741E7117D6BD807 CRC64;
MSWMFKRDPV WKYLQTVQYG VHGNFSRLSY PTFFPRFEFQ DIIPPDDFLT SDEELDSVLF
GTLRGHVVGL RYYTGVVNNN EMVALQREPN NPYDKNAIKV NNVNGNQVGY LKKELAAALA
YIMDNKLAQI EGVVPYGANN AFTMPLQMTF WGKEENRKAV LDQLKKHGFK LGPAPKTLGF
SLESGWGSGR AGPSYSMPVH AAIQMTTEQL KTEFDKLFED LKEDDKTQEM EPAEAVETPL
LPHQKQALAW MVSRENSREL PPFWELRNDL YYNTITNFSE KDQPENVHGG ILADDMGLGK
TLTAIAVILT NFHDGKPLPV ERMKKNQVKK ECNSSESDKP GRKDTIKKTD GLSKEGSRYS
EEPSISDVKK NKYSMSELSS SQPKRKKIAV QYIESSDSEE IEISELPQKM KGKLKNVQSE
TKRVKVGPSK IKEDTAFACA LTSSASTTTK KILKKGASAQ RVQRKLMFEE RPRTTLIICP
LSVLSNWIDQ FGQHIKSDVH LNFYVYYGPD RIRDPALLSK QDIVLTTYNI LTHDYGTKGD
SPLHSIRWLR VILDEGHAIR NPNAQQTKAV LDLEAERRWV LTGTPIQNSL KDLWSLLSFL
KLKPFVDREW WHRTIQRPVT MGDEGGLRRL QSLIKNITLR RTKTSKIKGK PVLELPERPV
FIQHITLSDE ERKIYQSVKS EGKATIGRYF NEGTVLAHYA DVLGLLLRLR QICCHTHLLT
NTVSSSGPSG NDTPEELRKK LIKKMKLILS SGSDEECAIC LDSLTVPVIT HCAHVFCKPC
ICQCIQNEQP HAKCPLCRND IHGDNLLECP PEELACDSEK KSNMEWTSSS KINALMHALI
DLRTKNPNIK SLVVSQFTTF LSLIETPLKA SGFVFTRLDG SMAQKKRVES IQCFQNTEAG
SPTIMLLSLK AGGVGLNLCA ASRVFLMDPA WNPAAEDQRF DRCHRLGQKQ EVIITKFIVK
DSVEENMLKI QNTKRELAAG AFGTKKNANE MKQAKINEIR TLIDL
