ID   HLF_HUMAN               Reviewed;         295 AA.
AC   Q16534; A8K1X8; Q6FHS9;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   24-JAN-2024, entry version 197.
DE   RecName: Full=Hepatic leukemia factor;
GN   Name=HLF;
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), AND CHROMOSOMAL TRANSLOCATION WITH
RP   TCF3.
RC   TISSUE=Hepatoma;
RX   PubMed=1516826; DOI=10.1101/gad.6.9.1608;
RA   Hunger S.P., Ohyashiki K., Toyama K., Cleary M.L.;
RT   "Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties
RT   following fusion to E2A in t(17;19) acute lymphoblastic leukemia.";
RL   Genes Dev. 6:1608-1620(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHROMOSOMAL TRANSLOCATION WITH
RP   TCF3.
RC   TISSUE=Hepatoma;
RX   PubMed=1386162; DOI=10.1126/science.1386162;
RA   Inaba T., Roberts W.M., Shapiro L.H., Jolly K.W., Raimondi S.C.,
RA   Smith S.D., Look A.T.;
RT   "Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-
RT   lineage leukemia.";
RL   Science 257:531-534(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Hippocampus, and Testis;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA   Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA   Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA   LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA   Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA   Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA   Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT   human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton 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   [7]
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).
CC   -!- SUBUNIT: Binds DNA specifically as homodimer or heterodimer with other
CC       PAR factors.
CC   -!- INTERACTION:
CC       Q16534; Q16520: BATF; NbExp=2; IntAct=EBI-2798854, EBI-749503;
CC       Q16534; Q9NR55: BATF3; NbExp=2; IntAct=EBI-2798854, EBI-10312707;
CC       Q16534; Q10586: DBP; NbExp=3; IntAct=EBI-2798854, EBI-3908088;
CC       Q16534; P35638: DDIT3; NbExp=3; IntAct=EBI-2798854, EBI-742651;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q16534-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q16534-2; Sequence=VSP_053852;
CC   -!- TISSUE SPECIFICITY: Highly expressed in liver; lower levels in lung and
CC       kidney.
CC   -!- INDUCTION: Accumulates according to a robust circadian rhythm.
CC       {ECO:0000250}.
CC   -!- DISEASE: Note=A chromosomal aberration involving HLF is a cause of pre-
CC       B-cell acute lymphoblastic leukemia (B-ALL). Translocation
CC       t(17;19)(q22;p13.3) with TCF3.
CC   -!- SIMILARITY: Belongs to the bZIP family. PAR subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA58445.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/47/HLF";
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DR   EMBL; M95585; AAA52675.1; -; mRNA.
DR   EMBL; M95586; AAA58445.1; ALT_INIT; mRNA.
DR   EMBL; X68985; CAA48777.1; -; mRNA.
DR   EMBL; AK290043; BAF82732.1; -; mRNA.
DR   EMBL; AK315079; BAG37547.1; -; mRNA.
DR   EMBL; CR541672; CAG46473.1; -; mRNA.
DR   EMBL; AC007638; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471109; EAW94544.1; -; Genomic_DNA.
DR   EMBL; BC036093; AAH36093.1; -; mRNA.
DR   CCDS; CCDS11585.1; -. [Q16534-1]
DR   CCDS; CCDS82164.1; -. [Q16534-2]
DR   PIR; A44064; A44064.
DR   RefSeq; NP_001317304.1; NM_001330375.1. [Q16534-2]
DR   RefSeq; NP_002117.1; NM_002126.4. [Q16534-1]
DR   AlphaFoldDB; Q16534; -.
DR   SMR; Q16534; -.
DR   BioGRID; 109376; 10.
DR   ComplexPortal; CPX-7011; bZIP transcription factor complex, BATF-HLF.
DR   ComplexPortal; CPX-7081; bZIP transcription factor complex, BATF2-HLF.
DR   ComplexPortal; CPX-7107; bZIP transcription factor complex, BATF3-HLF.
DR   CORUM; Q16534; -.
DR   IntAct; Q16534; 34.
DR   STRING; 9606.ENSP00000226067; -.
DR   iPTMnet; Q16534; -.
DR   PhosphoSitePlus; Q16534; -.
DR   BioMuta; HLF; -.
DR   DMDM; 6919907; -.
DR   MassIVE; Q16534; -.
DR   PaxDb; 9606-ENSP00000226067; -.
DR   PeptideAtlas; Q16534; -.
DR   ProteomicsDB; 1850; -.
DR   ProteomicsDB; 60897; -. [Q16534-1]
DR   Antibodypedia; 30848; 204 antibodies from 27 providers.
DR   DNASU; 3131; -.
DR   Ensembl; ENST00000226067.10; ENSP00000226067.5; ENSG00000108924.14. [Q16534-1]
DR   Ensembl; ENST00000430986.6; ENSP00000402496.2; ENSG00000108924.14. [Q16534-2]
DR   Ensembl; ENST00000573945.5; ENSP00000460296.1; ENSG00000108924.14. [Q16534-2]
DR   Ensembl; ENST00000575345.5; ENSP00000460572.1; ENSG00000108924.14. [Q16534-2]
DR   GeneID; 3131; -.
DR   KEGG; hsa:3131; -.
DR   MANE-Select; ENST00000226067.10; ENSP00000226067.5; NM_002126.5; NP_002117.1.
DR   UCSC; uc002iug.2; human. [Q16534-1]
DR   AGR; HGNC:4977; -.
DR   CTD; 3131; -.
DR   DisGeNET; 3131; -.
DR   GeneCards; HLF; -.
DR   HGNC; HGNC:4977; HLF.
DR   HPA; ENSG00000108924; Tissue enhanced (liver).
DR   MalaCards; HLF; -.
DR   MIM; 142385; gene.
DR   neXtProt; NX_Q16534; -.
DR   OpenTargets; ENSG00000108924; -.
DR   Orphanet; 641375; B-lymphoblastic leukemia/lymphoma with t(17;19).
DR   PharmGKB; PA29311; -.
DR   VEuPathDB; HostDB:ENSG00000108924; -.
DR   eggNOG; KOG3119; Eukaryota.
DR   GeneTree; ENSGT00940000156555; -.
DR   InParanoid; Q16534; -.
DR   OMA; HDHSPHQ; -.
DR   OrthoDB; 5354784at2759; -.
DR   PhylomeDB; Q16534; -.
DR   TreeFam; TF315869; -.
DR   PathwayCommons; Q16534; -.
DR   SignaLink; Q16534; -.
DR   SIGNOR; Q16534; -.
DR   BioGRID-ORCS; 3131; 11 hits in 1166 CRISPR screens.
DR   ChiTaRS; HLF; human.
DR   GeneWiki; HLF_(gene); -.
DR   GenomeRNAi; 3131; -.
DR   Pharos; Q16534; Tbio.
DR   PRO; PR:Q16534; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q16534; Protein.
DR   Bgee; ENSG00000108924; Expressed in calcaneal tendon and 198 other cell types or tissues.
DR   ExpressionAtlas; Q16534; baseline and differential.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:ComplexPortal.
DR   GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR   GO; GO:0003690; F:double-stranded DNA binding; TAS:ProtInc.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IMP:NTNU_SB.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
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   GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR   GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
DR   CDD; cd14695; bZIP_HLF; 1.
DR   Gene3D; 1.20.5.170; -; 1.
DR   InterPro; IPR004827; bZIP.
DR   InterPro; IPR046347; bZIP_sf.
DR   InterPro; IPR040223; PAR_bZIP.
DR   PANTHER; PTHR11988:SF28; HEPATIC LEUKEMIA FACTOR; 1.
DR   PANTHER; PTHR11988; THYROTROPH EMBRYONIC FACTOR RELATED; 1.
DR   Pfam; PF07716; bZIP_2; 1.
DR   SMART; SM00338; BRLZ; 1.
DR   SUPFAM; SSF57959; Leucine zipper domain; 1.
DR   PROSITE; PS50217; BZIP; 1.
DR   Genevisible; Q16534; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Biological rhythms; Chromosomal rearrangement;
KW   DNA-binding; Nucleus; Proto-oncogene; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..295
FT                   /note="Hepatic leukemia factor"
FT                   /id="PRO_0000076510"
FT   DOMAIN          225..288
FT                   /note="bZIP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT   REGION          37..70
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          93..167
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          227..247
FT                   /note="Basic motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT   REGION          248..255
FT                   /note="Leucine-zipper"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT   COMPBIAS        37..54
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        152..166
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..85
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_053852"
FT   VARIANT         253
FT                   /note="I -> F (in fusion protein; decreases DNA-binding
FT                   activity)"
FT                   /id="VAR_008515"
SQ   SEQUENCE   295 AA;  33199 MW;  80572A727BBB5635 CRC64;
     MEKMSRPLPL NPTFIPPPYG VLRSLLENPL KLPLHHEDAF SKDKDKEKKL DDESNSPTVP
     QSAFLGPTLW DKTLPYDGDT FQLEYMDLEE FLSENGIPPS PSQHDHSPHP PGLQPASSAA
     PSVMDLSSRA SAPLHPGIPS PNCMQSPIRP GQLLPANRNT PSPIDPDTIQ VPVGYEPDPA
     DLALSSIPGQ EMFDPRKRKF SEEELKPQPM IKKARKVFIP DDLKDDKYWA RRRKNNMAAK
     RSRDARRLKE NQIAIRASFL EKENSALRQE VADLRKELGK CKNILAKYEA RHGPL
//