Affinage

CRCP

DNA-directed RNA polymerase III subunit RPC9 · UniProt O75575

Length
148 aa
Mass
16.9 kDa
Annotated
2026-06-09
69 papers in source corpus 8 papers cited in narrative 9 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CRCP encodes a dual-function intracellular protein that operates both as a signal-coupling component of the CGRP/adrenomedullin receptor and as a subunit of RNA polymerase III (PMID:10903324, PMID:12482973). As CGRP receptor component protein (RCP), it is required for CGRP- and adrenomedullin-stimulated cAMP signaling but is dispensable for ligand binding or receptor density; it physically associates with calcitonin receptor-like receptor (CRLR), so that a functional receptor requires CRLR, RAMP, and RCP together, with RCP linking the activated receptor to Gα-stimulatory downstream effectors (PMID:10903324). Independently, CRCP is the genuine human orthologue of yeast Pol III subunit C17/RPC17—it rescues Δrpc17 yeast, supports faithful transcription initiation in reconstituted Pol III, copurifies with human Pol III, and forms a Rpb4/Rpb7-like heterodimer with the C25/RPC25 subunit (PMID:12482973). The cellular abundance of RCP protein is controlled post-transcriptionally and sets tissue CGRP responsiveness: RCP protein but not mRNA tracks CGRP inhibitory efficacy in myometrium across parturition and the estrous/progesterone cycle (PMID:9322931, PMID:10712245), and complete cochlear CLR/RAMP1/RCP complex formation accompanies maturation of auditory nerve activity (PMID:27440744). Functionally, RCP knockdown modulates caveolin-1/ERK1/2-dependent vascular smooth muscle proliferation (PMID:29741760), and neural-specific loss of RCP preserves CGRP behavioral effects while abolishing the efficacy of gepant-class CGRP receptor antagonists (PMID:39484482).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1997 Medium

    Established that RCP protein abundance, rather than transcript level, gates the physiological efficacy of CGRP, introducing post-transcriptional control of an unknown signaling component.

    Evidence Western/Northern blot with isometric force measurements on mouse myometrial strips across parturition

    PMID:9322931

    Open questions at the time
    • Molecular function of RCP not yet defined at this stage
    • Mechanism of post-transcriptional regulation unidentified
    • Correlative link between protein level and contractility, not causal manipulation
  2. 1999 Medium

    Mapped RCP protein to the acrosomal region of spermatozoa and its loss on the acrosome reaction, and showed highest mRNA in testis, hinting at a reproductive role beyond smooth muscle.

    Evidence Northern blot and immunohistochemistry with multiple antisera plus induced acrosome reaction in murine sperm

    PMID:10067875

    Open questions at the time
    • Functional role in acrosomal physiology untested
    • No mechanistic link to a receptor or signaling pathway established here
    • Whether localization reflects receptor coupling or another activity unknown
  3. 2000 High

    Defined RCP molecularly as a coupling protein required for CGRP/adrenomedullin signal transduction but not ligand binding, and demonstrated direct physical interaction with the receptor CRLR.

    Evidence Stable antisense cell lines, cAMP and radioligand binding assays, and co-immunoprecipitation

    PMID:10903324

    Open questions at the time
    • Structural basis of the RCP–CRLR interaction unresolved
    • Identity of the Gα-coupling step downstream of RCP not detailed
    • Stoichiometry within the CRLR–RAMP–RCP complex undefined
  4. 2000 Medium

    Confirmed that hormonal modulation of CGRP sensitivity in myometrium operates through post-transcriptional control of RCP protein, reinforcing RCP abundance as a tunable rheostat of receptor responsiveness.

    Evidence Isometric force, Western/Northern blot, and ovariectomy with steroid replacement in mice

    PMID:10712245

    Open questions at the time
    • The post-transcriptional mechanism (translation vs stability) not identified
    • Direct demonstration that RCP level limits signaling output absent
    • Generalizability beyond myometrium unaddressed
  5. 2003 High

    Revealed an entirely separate function by showing CRCP is the bona fide human orthologue of Pol III subunit C17/RPC17, establishing it as a core transcription machinery component.

    Evidence Yeast Δrpc17 complementation, in vitro transcription of reconstituted Pol III, and mass spectrometry of purified human Pol III

    PMID:12482973

    Open questions at the time
    • Relationship, if any, between the Pol III role and the receptor-coupling role unknown
    • Whether the same protein pool serves both functions unresolved
    • Pol III gene targets dependent on this subunit not enumerated
  6. 2003 Medium

    Placed C17/CRCP architecturally within Pol III as a heterodimer partner of C25/RPC25, paralleling the Rpb4/Rpb7 stalk of Pol II.

    Evidence Genetic suppression screens, co-immunopurification, two-hybrid, and molecular modeling in yeast

    PMID:12482973

    Open questions at the time
    • Human C17–C25 interaction inferred from yeast, not directly shown
    • Functional consequence of the heterodimer for transcription initiation only partly resolved
    • No structure of the human subcomplex
  7. 2016 Medium

    Linked assembly of the complete cochlear CLR/RAMP1/RCP receptor complex to a developmental milestone, implicating RCP-dependent CGRP signaling in maturation of auditory nerve function.

    Evidence Auditory nerve recordings in CGRP knockout vs wild-type mice with developmental expression analysis of receptor components

    PMID:27440744

    Open questions at the time
    • Effect attributed to CGRP loss, not direct RCP deletion
    • Causal role of RCP timing not isolated from CLR/RAMP1
    • Mechanism connecting receptor coupling to nerve maturation unknown
  8. 2018 Medium

    Connected RCP to a caveolin-1/ERK1/2 axis governing pressure-induced vascular smooth muscle proliferation, broadening its signaling reach beyond cAMP coupling.

    Evidence siRNA knockdown with Western blot for p-ERK1/2, caveolin-1, and PCNA in a static pressure model in A10 VSMCs

    PMID:29741760

    Open questions at the time
    • Direct molecular partner mediating the caveolin-1/ERK link unidentified
    • Single cell-line model without in vivo confirmation
    • Relation to canonical CGRP receptor coupling unclear
  9. 2024 Medium

    Demonstrated in vivo that neural RCP biases CGRP receptor pharmacology: its loss spares agonist-driven behaviors but abolishes gepant-class antagonist efficacy, defining RCP as a determinant of antagonist responsiveness.

    Evidence Tamoxifen-inducible neural-specific RCP knockout mouse with behavioral assays and systemic CGRP/olcegepant challenge (preprint)

    PMID:39484482

    Open questions at the time
    • Preprint, not peer-reviewed
    • Molecular basis for the antagonist-specific pharmacology shift unresolved
    • Single lab with two behavioral readouts

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single small protein partitions between its role as a Pol III subunit and its role as a membrane-receptor signal-coupling protein, and whether these functions are coordinated, remains unresolved.
  • No study reconciles the nuclear Pol III and receptor-coupling pools
  • Structural basis of RCP–CRLR coupling and Gα activation undefined
  • Post-transcriptional regulatory mechanism setting RCP abundance unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0140110 transcription regulator activity 2 GO:0060089 molecular transducer activity 1
Localization
GO:0005634 nucleus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
CALCRLRPC25
Complex memberships
CGRP receptor complex (CRLR-RAMP-RCP)RNA Polymerase III

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 CGRP-RCP (CRCP) is required for CGRP- and adrenomedullin-mediated signal transduction but not for CGRP binding or receptor density: antisense suppression of RCP greatly reduced cAMP signaling without affecting ligand binding, demonstrating RCP acts as a coupling protein that links the CGRP receptor to downstream effectors rather than as a chaperone. RCP co-immunoprecipitated with calcitonin receptor-like receptor (CRLR), indicating direct physical interaction. A functional CGRP or adrenomedullin receptor complex thus requires at least three proteins: CRLR (receptor), RAMP (chaperone), and RCP (signal coupling). Stable antisense cell lines, cAMP signaling assays, radioligand binding assays, co-immunoprecipitation The Journal of biological chemistry High 10903324
2003 Human CGRP-RCP (CRCP) is the genuine orthologue of yeast RNA polymerase III subunit C17 (RPC17): CGRP-RCP functionally rescued a Δrpc17 yeast strain, and the purified mutant Pol III contained CGRP-RCP with decreased but faithful transcription initiation activity. CGRP-RCP was also identified by mass spectrometry in a highly purified human RNA Pol III preparation, indicating it is a bona fide subunit of human Pol III. Yeast complementation assay, in vitro transcription of reconstituted Pol III, mass spectrometry of purified human Pol III Molecular and cellular biology High 12482973
2003 In yeast, C17 (the CRCP orthologue) forms a heterodimer with C25 (RPC25) analogous to the Rpb4/Rpb7 subcomplex of RNA Pol II: genetic suppression screens and co-immunopurification/two-hybrid experiments established the C17–C25 interaction, and sequence/molecular modeling indicated structural similarity to the archaeal RpoE/RpoF heterodimer. Genetic suppression screens, co-immunopurification, two-hybrid assay, sequence analysis and molecular modeling Molecular and cellular biology Medium 12482973
1997 CGRP-RCP protein expression in mouse myometrium correlates with the biological efficacy of CGRP in inhibiting smooth muscle contractions: CGRP-RCP protein (but not mRNA) was greatly diminished at parturition, paralleling the loss of CGRP inhibitory activity, indicating post-transcriptional regulation of RCP protein abundance controls CGRP responsiveness. Isometric force measurements on myometrial strips, Northern blot, Western blot, cDNA cloning Endocrinology Medium 9322931
2000 CGRP-RCP protein levels (not mRNA) in mouse myometrium vary across the estrous cycle and in response to progesterone, correlating with changes in myometrial sensitivity to CGRP inhibition, demonstrating that regulation of CGRP-RCP does not occur at the transcriptional level. Isometric force measurements, Western blot, Northern blot, ovariectomy with steroid hormone treatment American journal of physiology. Cell physiology Medium 10712245
1999 CGRP-RCP protein is localized to the head (acrosomal) region of murine spermatozoa and is lost upon acrosome reaction, suggesting a role in reproduction linked to acrosomal function. Northern blot showed highest CGRP-RCP mRNA abundance in testis among human and mouse tissues. Northern blot, immunohistochemistry with multiple antisera including one against recombinant hCGRP-RCP, experimentally induced acrosome reaction Endocrinology Medium 10067875
2016 Maturation of suprathreshold auditory nerve activity in mice requires formation of a complete cochlear CGRP receptor complex (CLR/RAMP1/RCP): CGRP null mice lacked the developmental increase in sound-evoked nerve activity, and the increase in wild-type animals correlated temporally with completion of cochlear CGRP receptor complex formation (incomplete at 1 month, complete by 3 months). Auditory nerve recordings in wild-type and CGRP knockout mice, developmental immunohistochemistry/expression analysis of receptor complex components Physiological reports Medium 27440744
2018 RCP (CRCP) is involved in the caveolin-1/ERK1/2 signaling pathway in vascular smooth muscle cell (VSMC) proliferation induced by static pressure: siRNA-mediated knockdown of RCP increased VSMC proliferation and phospho-ERK1/2 expression under static pressure; RCP expression was upregulated by static pressure and inversely correlated with caveolin-1 levels. siRNA knockdown, Western blot for p-ERK1/2 and caveolin-1, PCNA expression, static pressure model in A10 VSMCs Journal of cellular physiology Medium 29741760
2024 Loss of RCP specifically in the nervous system (nestinRCP -/- mouse) does not abolish CGRP-mediated behavioral effects (sway, tail vasodilation) but prevents antagonism by the CGRP receptor antagonist olcegepant, indicating RCP mediates Gα-stimulatory pathway coupling and its loss biases receptor pharmacology such that gepant-class antagonists lose efficacy. Tamoxifen-inducible neural-specific RCP knockout mouse (nestinRCP -/-), behavioral assays (motion-induced thermoregulation, center of pressure), systemic CGRP and olcegepant injections bioRxivpreprint Medium 39484482

Source papers

Stage 0 corpus · 69 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 CGRP-RCP, a novel protein required for signal transduction at calcitonin gene-related peptide and adrenomedullin receptors. The Journal of biological chemistry 256 10903324
1997 The role of CED-3-related cysteine proteases in apoptosis of cerebellar granule cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 125 9236222
2004 Human respiratory tract cancer risks of inhaled formaldehyde: dose-response predictions derived from biologically-motivated computational modeling of a combined rodent and human dataset. Toxicological sciences : an official journal of the Society of Toxicology 80 15254341
2003 Biologically motivated computational modeling of formaldehyde carcinogenicity in the F344 rat. Toxicological sciences : an official journal of the Society of Toxicology 72 12857938
2017 PET/CT With 68Ga-DOTA-TATE for Diagnosis of Neuroendocrine: Differentiation in Patients With Castrate-Resistant Prostate Cancer. Clinical nuclear medicine 56 27775942
2016 Stromal factors involved in human prostate cancer development, progression and castration resistance. Journal of cancer research and clinical oncology 46 27787597
2002 Cyclosporine inhibition of P-glycoprotein in chronic myeloid leukemia blast phase. Blood 43 12176916
2012 Allogeneic stem cell transplantation for myeloproliferative neoplasm in blast phase. Leukemia research 38 22578777
2003 An Rpb4/Rpb7-like complex in yeast RNA polymerase III contains the orthologue of mammalian CGRP-RCP. Molecular and cellular biology 38 12482973
2020 Independence of HIF1a and androgen signaling pathways in prostate cancer. BMC cancer 33 32450824
1998 Heart failure: is there an energy deficit contributing to contractile dysfunction? Basic research in cardiology 31 9538931
1997 Inhibitory effect of calcitonin gene-related peptide on myometrial contractility is diminished at parturition. Endocrinology 31 9322931
2000 Immunological and inflammatory characterisation of three canine cell lines: K1, K6 and DH82. Veterinary immunology and immunopathology 30 10889296
2018 Down-Regulation of the Androgen Receptor by G-Quadruplex Ligands Sensitizes Castration-Resistant Prostate Cancer Cells to Enzalutamide. Journal of medicinal chemistry 29 30188709
2002 Regulation and function of the CGRP receptor complex in human granulopoiesis. Experimental hematology 28 11937264
2018 New NO- and H2S-releasing doxorubicins as targeted therapy against chemoresistance in castration-resistant prostate cancer: in vitro and in vivo evaluations. Investigational new drugs 25 29607467
2017 A prospective study of fungal biomarkers to improve management of invasive fungal diseases in a mixed specialty critical care unit. Journal of critical care 25 28384600
2010 Novel, potent anti-androgens of therapeutic potential: recent advances and promising developments. Future medicinal chemistry 24 21426013
1987 Pregnancy suppression in the bonnet monkey by active immunisation with chicken riboflavin carrier protein. Journal of reproductive immunology 24 3430484
2016 Maturation of suprathreshold auditory nerve activity involves cochlear CGRP-receptor complex formation. Physiological reports 22 27440744
2014 Methylation of migraine-related genes in different tissues of the rat. PloS one 22 24609082
2016 miRNA-30a functions as a tumor suppressor by downregulating cyclin E2 expression in castration-resistant prostate cancer. Molecular medicine reports 21 27431942
1973 The effect of scald injury upon the distribution of glucose between red cells and plasma and upon the turnover of glucose in red cells in the rat. British journal of experimental pathology 20 4726090
2008 Characterization of a balanced reciprocal translocation, rcp(9;11)(q27;q11) in cattle. Cytogenetic and genome research 19 18253034
2002 The graft-versus-leukaemia effect in haematopoietic stem cell transplantation using unrelated donors. Bone marrow transplantation 19 12439699
2021 Identification of sensory and motor nerve fascicles by immunofluorescence staining after peripheral nerve injury. Journal of translational medicine 18 33985539
2006 Recognition, co-internalization, and recycling of an avian riboflavin carrier protein in human placental trophoblasts. The Journal of pharmacology and experimental therapeutics 17 16399883
2000 Sensitivity of myometrium to CGRP varies during mouse estrous cycle and in response to progesterone. American journal of physiology. Cell physiology 17 10712245
2025 FOS-driven inflammatory CAFs promote colorectal cancer liver metastasis via the SFRP1-FGFR2-HIF1 axis. Theranostics 16 40225580
1995 Enhancing peptide antigenicity by helix stabilization. FEBS letters 15 7535246
2011 Genome-wide joint SNP and CNV analysis of aortic root diameter in African Americans: the HyperGEN study. BMC medical genomics 14 21223598
1999 Regional and cellular localization of calcitonin gene-related peptide-receptor component protein mRNA in the guinea-pig central nervous system. Brain research. Molecular brain research 14 10095096
1988 Isolation and partial characterisation of human riboflavin carrier protein and the estimation of its levels during human pregnancy. Journal of reproductive immunology 14 3418615
2004 Preliminary data suggest that mutations in the CgRP pathway are not involved in human sporadic cryptorchidism. Journal of endocrinological investigation 13 15636430
1994 Termination of pregnancy in mice following administration of antibodies to the pentadecapeptide 10-24 of chicken riboflavin carrier protein: identification of a bioneutralizing epitope of chicken riboflavin carrier protein. Vaccine 12 7517603
1996 Comparison of antibodies raised against the peptide 10-24 of chicken riboflavin carrier protein (cRCP) by classical and multiple antigen peptide (MAP) approaches. Journal of immunological methods 11 8621956
1999 Testes exhibit elevated expression of calcitonin gene-related peptide receptor component protein. Endocrinology 10 10067875
2023 Low-Energy Shock Wave Suppresses Prostatic Pain and Inflammation by Modulating Mitochondrial Dynamics Regulators on a Carrageenan-Induced Prostatitis Model in Rats. International journal of molecular sciences 8 36835316
2019 Clinical exome sequencing vs. usual care for hereditary colorectal cancer diagnosis: A pilot comparative effectiveness study. Contemporary clinical trials 8 31400517
1998 Identification and characterization of receptors for riboflavin carrier protein in the chicken oocyte. Role of the phosphopeptide in mediating receptor interaction. Biochimica et biophysica acta 8 9540794
2017 Complexation of a Globular Protein, β-Lactoglobulin, with an Anionic Surfactant in Aqueous Solution. Langmuir : the ACS journal of surfaces and colloids 7 28502171
2004 Effectiveness of twenty, twenty-five diazacholesterol, avian gonadotropin-releasing hormone, and chicken riboflavin carrier protein for inhibiting reproduction in Coturnix quail. Poultry science 7 14979575
2025 Genome-scale CRISPR/Cas9 screening reveals the role of PSMD4 in colibactin-mediated cell cycle arrest. mSphere 6 39918307
2024 Exploration and validation of ceRNA regulatory networks in colorectal cancer based on associations whole transcriptome sequencing. Scientific reports 6 39227669
2022 NK-cell dysfunction of acute myeloid leukemia in relation to the renin-angiotensin system and neurotransmitter genes. Open medicine (Warsaw, Poland) 6 36213442
2010 A cytogenetic study of breeding boars in Canada. Cytogenetic and genome research 6 20068298
1995 Immunohistochemical localization of riboflavin carrier protein in testicular cells of mammals. Indian journal of experimental biology 6 9135669
1988 Characterization of antibodies to chicken riboflavin carrier protein. Immunoneutralizing ability of antibodies to a sequence-specific region of the protein. The Biochemical journal 6 2460089
2023 The molecular mechanism for inhibiting the growth of nasopharyngeal carcinoma cells using polymethoxyflavonoids purified from pericarp of Citrus reticulata 'Chachi' via HSCCC. Frontiers in pharmacology 5 37180721
2007 Biochemical characterization of recombinant chicken Riboflavin carrier protein. Molecular and cellular biochemistry 5 17891525
1993 Studies on the delineation of the antigenic determinants of chicken riboflavin carrier protein (cRCP). Identification of a determinant in the region 10-24 of the protein. International journal of peptide and protein research 5 7679667
2020 Integrating transcriptome-wide association study and copy number variation study identifies candidate genes and pathways for diffuse non-Hodgkin's lymphoma. Cancer genetics 4 32179489
2020 Identification of an LPS-Induced Chemo-Attractive Peptide from Ciona robusta. Marine drugs 4 32290587
2007 Expression of calcitonin gene-related peptide-receptor component protein (CGRP-RCP) in human myometrium in differing physiological states and following misoprostol administration. American journal of perinatology 4 17853344
2019 Rates of Actionable Genetic Findings in Individuals with Colorectal Cancer or Polyps Ascertained from a Community Medical Setting. American journal of human genetics 3 31422818
1989 Effects of antibodies against chicken riboflavin carrier protein on fetal hepatic cell ultrastructure. American journal of reproductive immunology (New York, N.Y. : 1989) 3 2765133
2018 Involvement of CGRP-RCP in the caveolin-1/ERK1/2 signal pathway in the static pressure-induced proliferation of vascular smooth muscle cells. Journal of cellular physiology 2 29741760
1992 Enzyme-linked immunosorbent assay for riboflavin carrier protein and modified protein: application for epitope analysis. Indian journal of biochemistry & biophysics 2 1380947
2025 4-Vinylguaiacol in Citri Reticulatae 'Chachiensis' Pericarpium Volatile Oil: A Microbial-Mediated Aging Marker Enhances Glucose Metabolism. Foods (Basel, Switzerland) 1 41154025
2023 Characterization of Robertsonian and Reciprocal Translocations in Cattle through NGS. Animals : an open access journal from MDPI 1 37835624
2023 [Mechanism study on the effect of androgen antagonism in prostate cancer]. Zhonghua nan ke xue = National journal of andrology 1 38602755
2018 Microbiome dataset from Clara Cave and Empalme Sinkhole waters in Puerto Rico. Data in brief 1 30505899
2010 [Demethylation of the gamma-synuclein gene CpG island in colorectal cancer and its clinical significance]. Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 1 20577925
1993 Improved presentation of antigenic sites in enzyme-linked immunosorbent assay: antigenicity of reduced and carboxymethylated riboflavin carrier protein. Indian journal of biochemistry & biophysics 1 7506230
1993 [A case report of graft replacement of the ascending and transverse aorta without homologous red blood cell transfusion]. Kyobu geka. The Japanese journal of thoracic surgery 1 8361111
2026 Differential Metabolic and Transcriptional Responses of PBMCs to Blastocystis sp. Subtypes in Chemotherapy-Treated Colorectal Cancer Patients. Acta parasitologica 0 42154421
2024 Loss of Calcitonin Gene Related Receptor component protein (RCP) in nervous system can bias "gepant" antagonism. bioRxiv : the preprint server for biology 0 39484482
2000 Development and characterization of monoclonal antibodies to chicken riboflavin carrier protein. Hybridoma 0 11128028
1998 Immunoreactive riboflavin carrier protein concentration during ovulatory cycle in the common marmoset (Callithrix jachhus): role of estrogen. Indian journal of experimental biology 0 9717443

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