Affinage

RLF

Zinc finger protein Rlf · UniProt Q13129

Round 2 corrected
Length
1914 aa
Mass
218.0 kDa
Annotated
2026-04-28
71 papers in source corpus 13 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RLF is a large zinc finger protein that functions as a Ras-regulated guanine nucleotide exchange factor (GEF) for RalA and RalB, coupling Ras and R-Ras signaling to Ral-dependent cellular processes including exocytosis, proliferation, and transcriptional activation. Its C-terminal Ras-binding domain adopts a ubiquitin superfold that recognizes GTP-loaded Ras and Rap1A (PMID:8710374, PMID:9753431), while its central CDC25-homology domain catalyzes nucleotide exchange on Ral with selectivity determined by specific interface residues resolved crystallographically (PMID:26687416, PMID:23891840). R-Ras recruits RLF to endosomes where it locally activates RalA to promote calcium-triggered exocytosis (PMID:17344481), and loss of RLF in mice causes cardiac defects resembling left ventricular non-compaction through attenuated JAGGED1/NOTCH signaling (PMID:27930960). The RLF locus on chromosome 1p32 undergoes intrachromosomal rearrangement with MYCL in small-cell lung cancer, producing a fusion oncoprotein that accelerates tumor proliferation and metastasis (PMID:1649386, PMID:34344693).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1991 High

    Identification of RLF as a gene physically linked to L-MYC on chromosome 1p32, fused to L-MYC in SCLC, established it as a locus of recurrent somatic rearrangement in lung cancer.

    Evidence Somatic cell hybrid mapping, PFGE, Southern blotting, and molecular cloning of chimeric fusion gene in SCLC cell lines

    PMID:1649386

    Open questions at the time
    • Whether the fusion drives oncogenesis or merely deregulates L-MYC expression was unresolved
    • Full-length RLF protein function unknown
  2. 1995 High

    Cloning of full-length RLF cDNA revealed a 1914 amino acid protein with sixteen Zn-15-related zinc fingers, broadly expressed in fetal and adult tissues, and showed that the RLF-LMYC fusion's transforming ability was indistinguishable from L-MYC alone, suggesting deregulated expression rather than a neomorphic protein.

    Evidence Full-length cDNA sequencing, Northern blotting, focus formation assay comparing fusion versus wild-type L-MYC

    PMID:8545128

    Open questions at the time
    • Biochemical function of the zinc finger domains uncharacterized
    • No pathway context for RLF protein
  3. 1996 High

    Discovery that RLF contains a CDC25-homology domain and a C-terminal Ras-binding domain that selectively associates with GTP-bound Ras and Rap1A placed it within the RalGDS family of Ras effectors.

    Evidence Yeast two-hybrid screen, in vitro pull-down assays with recombinant proteins, Kd measurements

    PMID:8710374

    Open questions at the time
    • GEF activity toward Ral was inferred but not directly demonstrated
    • Physiological role of dual Ras/Rap binding unclear
  4. 1997 High

    Demonstration that RLF functions as a bona fide GEF for Ral downstream of active Ras, stimulating c-fos promoter activity and serum-independent proliferation via a MEK-independent pathway, established the Ras→RLF→Ral signaling axis.

    Evidence Co-IP with Ras effector-domain mutants, Ral activation assays, c-fos/SRE reporter, PD98059 MEK inhibition, NIH 3T3 growth assays

    PMID:9362489

    Open questions at the time
    • Downstream effectors of Ral in this context not identified
    • Contribution relative to RalGDS and Rgl1 not defined
  5. 1997 High

    NMR structure of the RLF Ras-binding domain revealed a ubiquitin superfold and mapped the Ras-binding interface, explaining its dual specificity for Ras and Rap1A—unlike Raf-RBD or RalGDS-RBD which show preferential binding.

    Evidence NMR spectroscopy (3D structure), chemical shift perturbation mapping; mutagenesis of K687 confirmed interface residue

    PMID:9299525 PMID:9753431

    Open questions at the time
    • No full-length structural information
    • How dual Ras/Rap specificity is exploited physiologically unknown
  6. 2003 Medium

    Identification of CNK2A as a binding partner of the RLF GEF domain suggested a scaffold-mediated integration point between MAPK and Ral signaling pathways.

    Evidence Co-immunoprecipitation and deletion mapping in mammalian cells

    PMID:14597674

    Open questions at the time
    • Interaction based on single Co-IP without reciprocal validation
    • Functional consequence of CNK2-RLF interaction not demonstrated
    • No in vivo confirmation
  7. 2007 High

    Localization of RLF to early and recycling endosomes via R-Ras recruitment, where it drives local RalA activation to promote calcium-triggered exocytosis, defined a spatially organized R-Ras→RLF→RalA signaling module on endomembranes.

    Evidence FRET-based activity probes for R-Ras and RalA, shRNA knockdown, R-Ras GAP overexpression, PC12 exocytosis assay

    PMID:17344481

    Open questions at the time
    • Whether endosomal localization applies to all cell types unknown
    • Cargo specificity of RLF-dependent exocytosis not defined
  8. 2013 High

    Crystal structure of the RLF catalytic module (REM + CDC25-HD) revealed an extended 'flagpole' β-sheet that stabilizes domain orientation, with a unique proline-rich sequence mediating selective SH3 domain interactions through conformational pre-selection.

    Evidence X-ray crystallography, SH3 domain binding assays, affinity measurements

    PMID:23891840

    Open questions at the time
    • Identity and biological relevance of SH3-containing partners in vivo not established
    • Flagpole function in signaling output not tested
  9. 2015 High

    Crystal structures of RLF in complex with Ral captured two conformational intermediates of nucleotide exchange, elucidating the catalytic mechanism and the molecular basis of RLF's selectivity for RalA/RalB over other Ras-family GTPases.

    Evidence X-ray crystallography (two crystal forms), mutagenesis of selectivity determinants, in vitro exchange assays

    PMID:26687416

    Open questions at the time
    • How catalytic rate is modulated by upstream Ras binding in the full-length protein is unknown
    • No structure of a ternary Ras–RLF–Ral complex
  10. 2016 Medium

    Loss-of-function analysis in mice revealed that RLF is required for normal cardiac chamber formation; Rlf-null embryos develop left ventricular non-compaction-like defects associated with attenuated JAGGED1 expression and defective NOTCH signaling, implicating RLF as an epigenetic or transcriptional regulator in heart development.

    Evidence ENU mutagenesis generating two independent Rlf-null alleles, histological analysis, in situ hybridization, RNA-seq of mutant hearts

    PMID:27930960

    Open questions at the time
    • Whether the cardiac phenotype is mediated by RLF's GEF activity, zinc finger transcriptional function, or both is unknown
    • Direct biochemical link between RLF and JAGGED1 regulation not established
    • No human genetic disease association reported
  11. 2021 High

    CRISPR/Cas9-engineered Rlf-Mycl fusion in a mouse model demonstrated that RLF-MYCL is a bona fide oncogenic driver in SCLC—not merely deregulated L-MYC expression—accelerating proliferation, increasing metastasis, and recapitulating human RLF-MYCL tumor transcriptomes.

    Evidence CRISPR/Cas9 somatic knock-in mouse model, quantitative proliferation and metastasis analysis, RNA-seq profiling matched to human SCLC datasets

    PMID:34344693

    Open questions at the time
    • Which domains of the RLF portion contribute to neomorphic oncogenic activity not determined
    • Therapeutic vulnerability of RLF-MYCL tumors not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include whether RLF's zinc finger domains confer independent transcription-regulatory activity, how GEF and zinc finger functions are coordinated in vivo, whether the cardiac developmental role is GEF-dependent, and what therapeutic targets the RLF-MYCL fusion exposes in SCLC.
  • No biochemical characterization of zinc finger domains' DNA/chromatin binding
  • No structure of full-length RLF or ternary Ras–RLF–Ral complex
  • Whether RLF mutations cause human cardiac disease is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005768 endosome 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 2 R-HSA-1266738 Developmental Biology 1
Partners
CNKSR2KRASMYCLRALARALBRAP1ARRAS

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 RLF (RalGDS-like factor) was identified as a novel protein containing a Cdc25-homology domain (~30% identity with RalGDS) and a C-terminal Ras-binding domain. In vitro binding studies showed the C-terminal 91 amino acid region of Rlf directly associates with GTP-bound Ras and Rap1A (Kd ~0.6 µM and ~0.4 µM, respectively) but not with their GDP-bound forms, defining Rlf as a putative effector for Ras and Rap1A. Yeast two-hybrid screen, in vitro binding assays (pull-down with recombinant proteins), deletion mapping Oncogene High 8710374
1997 Rlf functions as a guanine nucleotide exchange factor (GEF) for the small GTPase Ral. Co-expression with active Ras mutants showed Rlf associates in vivo with RasV12 and the effector-domain mutant RasV12G37 but not with RasV12E38 or RasV12C40. Active Ras stimulates Rlf-induced Ral activation, and a membrane-targeted constitutively active form (Rlf-CAAX) activates both Ral and the c-fos promoter independently of MEK, inducing NIH 3T3 cell proliferation under low-serum conditions. Co-immunoprecipitation in vivo, Ral activation assay, reporter gene assay (c-fos promoter/SRE), dominant-negative Ras, MEK inhibitor (PD98059), NIH 3T3 proliferation assay The EMBO journal High 9362489
1997 The Ras-binding domain (RBD) of Rlf adopts a ubiquitin superfold (βαβββαβ topology) structurally similar to RalGDS-RBD, as determined by NMR. Unlike Raf-RBD and RalGDS-RBD (which prefer Ras or Rap respectively), Rlf-RBD binds both Ras and Rap1A with similar affinity. Chemical shift mapping identified the Ras-binding interface and revealed a binding mode similar to the Rap·Raf-RBD complex. NMR spectroscopy (3D structure determination), chemical shift perturbation mapping Biochemistry High 9753431
1997 The minimal Ras-binding domain of Rlf was mapped to residues 657–778 by N- and C-terminal deletions. Rlf-RBD shows different Ras mutant binding characteristics compared to Raf-1 RBD. Alanine substitution of a conserved lysine (K687) in the predicted binding interface significantly reduced affinity for Ras-GTP, confirming its role in Ras interaction. ELISA-based binding assay with Ras mutants, deletion mutagenesis, alanine substitution mutagenesis Biochemical and biophysical research communications Medium 9299525
1991 The RLF gene on chromosome 1p32 is physically linked to L-MYC (separated by <800 kb), and intrachromosomal rearrangements fuse the first exon of RLF to L-MYC in small-cell lung cancer (SCLC) cell lines with amplified L-MYC, producing a chimeric RLF-L-MYC fusion protein. Independent rearrangements producing identical fusion proteins suggest a selected role for the fusion in SCLC development. Somatic cell hybrid mapping, pulsed-field gel electrophoresis (PFGE), Southern blotting, molecular cloning of fusion gene Molecular and cellular biology High 1649386
1995 The full-length RLF cDNA encodes a 1914 amino acid protein containing sixteen widely spaced zinc finger motifs related to the Zn-15 transcription factor. RLF is widely expressed in fetal and adult tissues. The zinc fingers are not included in the 79 amino acid N-terminal region involved in RLF-L-MYC fusions, and the transforming ability of the RLF-L-MYC fusion is indistinguishable from normal L-MYC, suggesting RLF rearrangements serve to deregulate L-MYC expression. Full-length cDNA cloning and sequencing, Northern blotting, comparison of transforming activity (focus formation assay) Oncogene High 8545128
1994 Expression of an rlf/L-myc minigene (recapitulating the SCLC rearrangement under rlf promoter control) in embryonic stem (ES) cells did not increase proliferation rate but severely impaired embryoid body formation and outgrowth/differentiation of cells from embryoid bodies. High-copy transgenic embryos failed to develop, suggesting the RLF-L-MYC fusion protein blocks early differentiation. Stable transfection of ES cells, embryoid body assay, transgenic mouse generation Oncogene Medium 7970711
2003 The human CNK2A protein (homologue of Drosophila CNK) interacts with Rlf through the GEF (CDC25-homology) domain of Rlf. CNK2 also interacts with Raf, suggesting it may integrate signals between MAPK and Ral pathways. CNK2 is found in membrane and cytoplasmic fractions, with full-length CNK2 localizing to the lateral plasma membrane in MDCK cells. Co-immunoprecipitation, domain mapping (deletion constructs), subcellular fractionation, immunofluorescence localization FASEB journal Medium 14597674
2007 Rgl2/Rlf (the RalGDS family GEF) accumulates on early and recycling endosomes where R-Ras activity is high. R-Ras recruits Rgl2/Rlf to endosomes, resulting in high local RalA activity. shRNA-mediated suppression of R-Ras reduced endosomal RalA activity and suppressed calcium-triggered exocytosis in PC12 cells, placing Rgl2/Rlf downstream of R-Ras on endosomes and upstream of RalA in the exocytosis pathway. FRET-based activity probes for R-Ras and RalA, shRNA knockdown, R-Ras GAP overexpression, exocytosis assay (PC12 cells), immunofluorescence/subcellular fractionation Molecular biology of the cell High 17344481
2013 The crystal structure of the catalytic module of Rlf (REM + CDC25-homology domains) was determined. The structure features an extended three-stranded β-sheet called the 'flagpole,' a conserved element in the RalGDS family that stabilizes the REM domain orientation relative to the CDC25-HD. A proline-rich sequence in the flagpole is unique to Rlf and mediates interactions with SH3 domain-containing proteins via conformational pre-selection, contributing to SH3 domain selectivity. X-ray crystallography, identification of SH3 domain interactors, binding affinity measurements Journal of structural biology High 23891840
2015 The crystal structure of Rlf in complex with the small G-protein Ral was determined in two different crystal forms representing different conformational intermediates of the nucleotide exchange reaction. The structure elucidated the catalytic mechanism of CDC25-HD-mediated nucleotide exchange and identified selectivity determinants at the Rlf·Ral binding interface. Mutagenesis of selectivity determinants confirmed the basis for Rlf's specificity for RalA and RalB over other Ras-family GTPases. X-ray crystallography (two crystal forms), recombinant protein exchange activity assays, site-directed mutagenesis of selectivity determinants Journal of structural biology High 26687416
2016 Loss of RLF (Rearranged L-Myc Fusion zinc finger protein) in Rlf null mutant mice (generated by ENU mutagenesis) causes heart defects resembling Left Ventricular Non-Compaction (LVNC) at high penetrance (E11.5–E14.5). RLF is expressed in endocardium, epicardium, and transiently in cardiomyocytes. RNA-seq of Rlf mutant hearts revealed attenuated JAGGED1 expression and defective NOTCH pathway signaling as likely contributors, consistent with RLF acting as an epigenetic modifier that maintains correct gene regulatory networks during heart development. ENU mutagenesis (two independent alleles), timed mating histological analysis, in situ hybridization, RNA-seq of mutant hearts Differentiation; research in biological diversity Medium 27930960
2021 The in-frame RLF-MYCL gene fusion drives oncogenesis in small-cell lung cancer (SCLC). Using CRISPR/Cas9 somatic editing to generate a Rlf-Mycl mouse model, the fusion was shown to accelerate SCLC transformation and proliferation, and to increase metastatic dissemination and diversity of metastatic sites. Gene expression profiles of mouse Rlf-Mycl tumors resembled human RLF-MYCL SCLC, establishing RLF-MYCL as the first demonstrated fusion oncogenic driver in SCLC. CRISPR/Cas9 somatic genome editing (knock-in mouse model), tumor growth and metastasis quantification, RNA-seq gene expression profiling, comparison to human SCLC datasets Cancer discovery High 34344693

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2004 Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nature biotechnology 916 15592455
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1995 Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature 688 7659163
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1994 Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells. Nature 575 8022486
1999 Cryptorchidism in mice mutant for Insl3. Nature genetics 547 10391220
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2001 Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin. Nature cell biology 392 11175741
2002 INSL3/Leydig insulin-like peptide activates the LGR8 receptor important in testis descent. The Journal of biological chemistry 316 12114498
2004 The DNA sequence and biology of human chromosome 19. Nature 271 15057824
1994 Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes. Proceedings of the National Academy of Sciences of the United States of America 265 8022790
2013 Induction of IL-17 and nonclassical T-cell activation by HIV-Tat protein. Proceedings of the National Academy of Sciences of the United States of America 235 23898208
2002 H3 relaxin is a specific ligand for LGR7 and activates the receptor by interacting with both the ectodomain and the exoloop 2. The Journal of biological chemistry 228 12506116
1993 Cloning of a cDNA for a novel insulin-like peptide of the testicular Leydig cells. The Journal of biological chemistry 198 8253799
2005 Insulin-like factor 3 serum levels in 135 normal men and 85 men with testicular disorders: relationship to the luteinizing hormone-testosterone axis. The Journal of clinical endocrinology and metabolism 147 15755855
1997 Stimulation of gene induction and cell growth by the Ras effector Rlf. The EMBO journal 142 9362489
2004 A novel circulating hormone of testis origin in humans. The Journal of clinical endocrinology and metabolism 129 15579743
1997 The RLF-M component of the replication licensing system forms complexes containing all six MCM/P1 polypeptides. The EMBO journal 121 9214646
1996 RalGDS-like factor (Rlf) is a novel Ras and Rap 1A-associating protein. Oncogene 117 8710374
2009 Biology of insulin-like factor 3 in human reproduction. Human reproduction update 112 19329805
2008 Mutations in the insulin-like factor 3 receptor are associated with osteoporosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 112 18433302
2002 Reproductive biology of the relaxin-like factor (RLF/INSL3). Biology of reproduction 112 12193374
1997 Structural and functional basis for JAK3-deficient severe combined immunodeficiency. Blood 111 9354668
2006 Peripheral INSL3 concentrations decline with age in a large population of Australian men. International journal of andrology 104 17014531
2007 Insulin-like factor 3 levels in cord blood and serum from children: effects of age, postnatal hypothalamic-pituitary-gonadal axis activation, and cryptorchidism. The Journal of clinical endocrinology and metabolism 100 17666478
2003 The INSL3-LGR8/GREAT ligand-receptor pair in human cryptorchidism. The Journal of clinical endocrinology and metabolism 100 12970298
2008 Genetic alterations associated with cryptorchidism. JAMA 98 19017913
2003 Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation. Blood 98 14615376
2004 Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein science : a publication of the Protein Society 92 15340161
2010 Family-based analysis of candidate genes for polycystic ovary syndrome. The Journal of clinical endocrinology and metabolism 91 20200332
2005 Multiple binding sites revealed by interaction of relaxin family peptides with native and chimeric relaxin family peptide receptors 1 and 2 (LGR7 and LGR8). The Journal of pharmacology and experimental therapeutics 90 15649866
2002 Geminin becomes activated as an inhibitor of Cdt1/RLF-B following nuclear import. Current biology : CB 88 11967157
2000 A common polymorphism in the human relaxin-like factor (RLF) gene: no relationship with cryptorchidism. Pediatric research 60 10759163
1999 Structure and expression of the rat relaxin-like factor (RLF) gene. Molecular reproduction and development 55 10542371
1999 Relaxin-like factor (RLF): a new specific marker for Leydig cells in the ovary. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 53 10202675
1999 Tryptophan B27 in the relaxin-like factor (RLF) is crucial for RLF receptor-binding. Biochemistry 52 10074360
2003 Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 50 14597674
2001 Relaxin-like factor (RLF) serum concentrations and gubernaculum RLF receptor display in relation to pre- and neonatal development of rats. Reproduction (Cambridge, England) 49 11732985
2007 R-Ras regulates exocytosis by Rgl2/Rlf-mediated activation of RalA on endosomes. Molecular biology of the cell 45 17344481
2000 Relaxin-like factor (RLF) is differentially expressed in the normal and neoplastic human mammary gland. Cancer 40 11147585
1997 Biology of the relaxin-like factor (RLF). Reviews of reproduction 40 9414476
2021 Rlf-Mycl Gene Fusion Drives Tumorigenesis and Metastasis in a Mouse Model of Small Cell Lung Cancer. Cancer discovery 37 34344693
1999 The RLF-B component of the replication licensing system is distinct from Cdc6 and functions after Cdc6 binds to chromatin. Current biology : CB 33 10074431
2012 Relaxin-like factor (RLF)/insulin-like peptide 3 (INSL3) is secreted from testicular Leydig cells as a monomeric protein comprising three domains B-C-A with full biological activity in boars. The Biochemical journal 31 21899516
2002 The expression of the RLF/INSL3 gene is reduced in Leydig cells of the aging rat testis. Experimental gerontology 30 12559415
2006 The mode of interaction of the relaxin-like factor (RLF) with the leucine-rich repeat G protein-activated receptor 8. The Journal of biological chemistry 29 16844694
1991 Intrachromosomal rearrangements fusing L-myc and rlf in small-cell lung cancer. Molecular and cellular biology 29 1649386
1998 Structure determination of the Ras-binding domain of the Ral-specific guanine nucleotide exchange factor Rlf. Biochemistry 28 9753431
2010 RLF, a cytochrome b(5)-like heme/steroid binding domain protein, controls lateral root formation independently of ARF7/19-mediated auxin signaling in Arabidopsis thaliana. The Plant journal : for cell and molecular biology 23 20230485
2000 Relaxin-like factor (RLF) mRNA expression in the fallow deer. Molecular and cellular endocrinology 21 10687860
1999 Molecular cloning and localization of caprine relaxin-like factor (RLF) mRNA within the goat testis. Molecular reproduction and development 18 10331451
1995 The rearranged L-myc fusion gene (RLF) encodes a Zn-15 related zinc finger protein. Oncogene 17 8545128
1992 Rearrangement and co-amplification of L-myc and rlf in primary lung cancer. Oncogene 14 1312699
2012 Replacement of disulfides by amide bonds in the relaxin-like factor (RLF/INSL3) reveals a role for the A11-B10 link in transmembrane signaling. Biochemistry 11 22574850
2007 Structure of the transmembrane signal initiation site of the relaxin-like factor (RLF/INSL3). Biochemistry 10 17676766
1994 Expression of a rlf/L-myc minigene inhibits differentiation of embryonic stem cells and embroid body formation. Oncogene 8 7970711
2022 RLF-LPI: An ensemble learning framework using sequence information for predicting lncRNA-protein interaction based on AE-ResLSTM and fuzzy decision. Mathematical biosciences and engineering : MBE 7 35430839
2015 Restriction-ligation-free (RLF) cloning: a high-throughput cloning method by in vivo homologous recombination of PCR products. Genetics and molecular research : GMR 7 26505379
2013 Expression and localization of RLF/ INSL3 receptor RXFP2 in boar testes. Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia 7 24640564
2010 Partial cDNA sequence of a relaxin-like factor (RLF) receptor, LGR8 and possible existence of the RLF ligand-receptor system in goat testes. Animal science journal = Nihon chikusan Gakkaiho 7 21108688
2016 Loss of Rearranged L-Myc Fusion (RLF) results in defects in heart development in the mouse. Differentiation; research in biological diversity 6 27930960
2015 The structure of the Guanine Nucleotide Exchange Factor Rlf in complex with the small G-protein Ral identifies conformational intermediates of the exchange reaction and the basis for the selectivity. Journal of structural biology 6 26687416
1997 Characterization of the Ras binding domain of the RalGDS-related protein, RLF. Biochemical and biophysical research communications 5 9299525
2025 Metabolic-immune crosstalk in myocardial infarction: RLF and SMCHD1 identified as causal therapeutic targets via integrated lactylation-MR analysis. Frontiers in cell and developmental biology 1 41158309
2013 The guanine nucleotide exchange factor Rlf interacts with SH3 domain-containing proteins via a binding site with a preselected conformation. Journal of structural biology 1 23891840
1991 myc, max, and a novel rlf-L-myc fusion protein in small-cell lung cancer. Princess Takamatsu symposia 1 1668890
2025 Evolutionary-conserved RLF, a cytochrome b5-like heme-binding protein, regulates organ development in Marchantia polymorpha. The New phytologist 0 40413697