Affinage

TAC4

Tachykinin-4 · UniProt Q86UU9

Round 2 corrected
Length
113 aa
Mass
12.3 kDa
Annotated
2026-04-28
45 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAC4 encodes preprotachykinin-C, the precursor of hemokinin-1 (HK-1) and endokinins A–D, which function as high-affinity NK1 receptor agonists (with additional NK2/NK3 activity) predominantly in non-neuronal peripheral tissues including hematopoietic, immune, airway, vascular, and reproductive cells (PMID:11062498, PMID:12383518, PMID:12716968). In the immune system, HK-1 acts as an autocrine survival factor for B cell precursors while exerting inhibitory feedback on pro-B cell expansion, and drives Th17 polarization via monocyte-derived IL-1β, IL-23, and TNF-like 1A through NK1 receptor signaling (PMID:20660792, PMID:21368235). TAC4 transcription is controlled by a TATA-less promoter with NFκB-dependent induction in immune cells, and the N-terminal domain of human HK-1 confers biased agonism at NK1 receptors, selectively engaging Gs over Gq to differentially modulate ERK1/2 and NF-κB signaling (PMID:19081134, PMID:21168392). Beyond hematopoiesis, TAC4-derived peptides mediate airway and vascular smooth muscle contraction, promote angiogenesis via NK1/ERK1/2/eNOS/VEGF signaling, regulate sperm motility, and facilitate melanoma cell migration through MMP-2/MT1-MMP upregulation (PMID:20929541, PMID:22554585, PMID:17437961, PMID:27458061).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2000 High

    The discovery of TAC4 (Pptc) and its product HK-1 established that a non-neuronal tachykinin gene exists with a dedicated role in hematopoiesis, resolving how B cell precursors receive tachykinin survival signals in the absence of neuronal substance P expression.

    Evidence Molecular cloning of TAC4, in vitro B cell proliferation/survival assays, in vivo NK1 antagonist administration with flow cytometric analysis of bone marrow and spleen B cell compartments

    PMID:11062498

    Open questions at the time
    • Mechanism by which HK-1 promotes B cell precursor survival (downstream intracellular signaling) was not defined
    • Whether HK-1 acts on B cells directly or via stromal intermediaries was not resolved
  2. 2002 High

    Receptor pharmacology studies demonstrated that HK-1 and the human TAC4 products bind NK1 receptors with affinity comparable to substance P and also activate NK2 and NK3 receptors, establishing the receptor selectivity profile of this new tachykinin family.

    Evidence Radioligand competition binding at NK1/NK2/NK3 receptors, functional organ bioassays (rat bladder, rabbit pulmonary artery, guinea pig ileum), in vivo cardiovascular pharmacology with selective NK1 antagonist blockade

    PMID:11786503 PMID:12383518

    Open questions at the time
    • Whether different TAC4 splice products have distinct receptor selectivity profiles was not yet addressed
    • Signaling bias among G-protein pathways at NK1 was unknown
  3. 2003 High

    Identification of endokinins A–D from four alternative TAC4 mRNAs revealed that the human gene produces a diverse set of tachykinin peptides with divergent receptor activities — EKA/B acting as potent NK1 agonists and EKC/D having a novel C-terminal motif with low receptor potency — expanding the functional repertoire beyond a single HK-1 peptide.

    Evidence cDNA cloning of four human TAC4 splice variants, RT-PCR tissue expression profiling, radioligand binding, in vivo hemodynamic measurements in rats

    PMID:12716968

    Open questions at the time
    • Tissue-specific splice variant regulation was not characterized
    • Whether EKC/D have a dedicated receptor or function remained unknown
  4. 2007 High

    Structure-activity analysis of EKC/D revealed that it acts as a functional antagonist of substance P in spinal pain processing, with the C-terminal leucine residue being critical — resolving the paradox of why TAC4 encodes peptides with weak agonist activity and demonstrating that a single gene can produce both agonists and antagonists at tachykinin receptors.

    Evidence Intrathecal peptide and analog administration, behavioral assays, c-Fos immunohistochemistry, leucine-to-methionine substitution mutagenesis

    PMID:17655832

    Open questions at the time
    • Molecular mechanism of EKC/D antagonism (competitive vs. allosteric) at the receptor level was not determined
    • Relevance of EKC/D antagonism outside the spinal cord was untested
  5. 2008 Medium

    Characterization of the TAC4 promoter revealed a TATA-less architecture with NFκB-dependent transcriptional induction, explaining the immune-cell-enriched expression pattern that distinguishes TAC4 from neuronal tachykinin genes.

    Evidence 5' RACE, promoter-reporter assays, NFκB pathway manipulation in a T cell line

    PMID:19081134

    Open questions at the time
    • Additional transcription factors regulating tissue-specific TAC4 expression were not identified
    • Chromatin-level regulation and epigenetic control were not examined
  6. 2010 High

    TAC4 knockout mice revealed that HK-1 has an unexpected inhibitory role in pro-B cell expansion — TAC4-/- mice accumulated fraction B pro-B cells — refining the initial model from pure survival factor to a dual role as a survival signal for pre-B cells and a negative regulator of pro-B cell proliferation.

    Evidence TAC4-/- mice, flow cytometric bone marrow analysis, in vitro bone marrow and sorted pro-B cell cultures with exogenous HK-1 addition

    PMID:20660792

    Open questions at the time
    • Receptor and signaling pathway mediating pro-B cell inhibition were not identified
    • Whether the knockout phenotype has functional immunological consequences (e.g., antibody responses) was not tested
  7. 2010 High

    Systematic truncation and structure-activity studies demonstrated that the N-terminal domain of human HK-1 confers biased agonism at NK1 receptors, preferentially engaging Gs/cAMP over Gq/Ca2+ signaling and modulating ERK1/2 phosphorylation and NF-κB activation, providing a molecular basis for functional selectivity among TAC4-derived peptides.

    Evidence Peptide truncation series, cAMP and intracellular Ca2+ assays, ERK1/2 phosphorylation, NF-κB reporter assay, receptor internalization assay in NK1-expressing cells

    PMID:21168392

    Open questions at the time
    • Structural basis of biased agonism (receptor conformation) was not resolved
    • In vivo consequences of biased signaling in immune or vascular contexts were not tested
  8. 2011 High

    HK-1 was shown to drive Th17 cell differentiation through an indirect monocyte-dependent mechanism involving NK1 receptor–triggered IL-1β, IL-23, and TNF-like 1A production, establishing TAC4-derived peptides as regulators of adaptive immune polarization beyond their known innate/B cell roles.

    Evidence Human PBMC co-culture, cytokine neutralization experiments, monocyte depletion, flow cytometry and ELISA across multiple donors

    PMID:21368235

    Open questions at the time
    • Whether HK-1-driven Th17 polarization operates in vivo in autoimmune or inflammatory contexts was not demonstrated
    • Relative contribution of HK-1 versus substance P to Th17 generation in tissues was not defined
  9. 2012 Medium

    TAC4-encoded hemokinins were established as pro-angiogenic factors acting through NK1 receptors to activate ERK1/2, stimulate eNOS/NO production, and upregulate VEGF expression — extending the functional scope of TAC4 products from immune regulation to vascular biology.

    Evidence HUVEC proliferation, migration, adhesion, tube formation assays; chick embryo CAM model; NK1/NK2 antagonists; ERK1/2, eNOS, and VEGF Western blotting

    PMID:22554585

    Open questions at the time
    • In vivo angiogenic role in mammalian pathological contexts (tumor angiogenesis, wound healing) was not tested
    • Whether this pathway operates independently of VEGF receptor signaling was unclear
  10. 2016 Medium

    The functional repertoire of TAC4 products was further extended to include promotion of melanoma cell migration via NK1 receptor–dependent upregulation of MMP-2 and MT1-MMP through PKC/PKA and MAPK cascades, and regulation of human ovarian granulosa cell function through reciprocal signaling with the kisspeptin system.

    Evidence Melanoma cell migration assays with NK1 antagonist and kinase inhibitors; primary human granulosa cell RT-PCR, Western blot, and Ca2+ assays with kisspeptin/SP co-treatment

    PMID:27146034 PMID:27458061

    Open questions at the time
    • In vivo relevance of HK-1-driven melanoma metastasis was not established
    • Molecular mechanism linking TAC4 and kisspeptin signaling was not fully resolved
  11. 2021 Medium

    Circulating HK-1 was found to desensitize MRGPRX2 on mast cells without inducing receptor internalization, providing a mechanism by which TAC4 products modulate innate immune responses by cross-regulating a non-tachykinin receptor.

    Evidence Serum HK-1 ELISA, primary skin mast cell histamine release assays, MRGPRX2 shRNA knockdown, receptor internalization assay

    PMID:34090787

    Open questions at the time
    • Mechanism of MRGPRX2 desensitization (competitive binding vs. allosteric modulation) was not resolved
    • In vivo relevance of this HK-1/MRGPRX2 axis in allergic or inflammatory disease was not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural basis for HK-1's biased agonism at NK1 receptors, the in vivo significance of TAC4 products in adaptive immunity and cancer metastasis, the precise mechanism of EKC/D antagonism, and whether TAC4-derived peptides have dedicated non-NK receptors.
  • No crystal structure or cryo-EM structure of HK-1 bound to NK1R
  • In vivo role of TAC4 in tumor angiogenesis and metastasis lacks genetic evidence
  • Potential non-NK receptor targets for EKC/D remain unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 8 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 6
Pathway
R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 2
Partners
MRGPRX2TACR1TACR2TACR3

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 A new preprotachykinin gene (Pptc/TAC4) encodes hemokinin-1 (HK-1), a tachykinin peptide primarily expressed in hematopoietic cells (unlike neuronal Ppta/Pptb). HK-1 stimulated proliferation of IL-7-expanded B cell precursors and promoted survival of bone marrow B lineage cells, whereas substance P had no effect on these cells. In vivo administration of a tachykinin receptor antagonist specifically reduced the pre-B cell compartment (B220lowCD43) in bone marrow and newly generated B cells in spleen, establishing HK-1 as an autocrine survival factor for B cell precursors. Molecular cloning, in vitro B cell proliferation/survival assays, in vivo antagonist administration with flow cytometric readouts Nature immunology High 11062498
2002 Human and rat orthologs of PPT-C (TAC4) were isolated and characterized. Human PPT-C can generate full-length HK-1 and a truncated form HK-1(4-11) due to a monobasic rather than dibasic N-terminal cleavage site. Both human and mouse HK-1 bind the NK1 receptor with high affinity (comparable to substance P) and act as agonists at NK1, NK2, and NK3 receptors, with strongest selectivity for NK1. PCR expression analysis, radioligand binding assays, functional receptor assays in transfected cells Gene High 12383518
2002 Hemokinin-1 (HEK-1) is a full agonist at tachykinin NK1, NK2, and NK3 receptors. It inhibits [3H]-substance P binding to the human NK1 receptor with Ki=0.175 nM (comparable to SP Ki=0.13 nM), while its affinity for NK2 is markedly lower (Ki=560 nM). In vivo, intravenous HK-1 produces dose-related decreases in blood pressure and salivary secretion in anaesthetized animals, effects fully blocked by the selective NK1 antagonist SR 140333. Radioligand binding, isolated organ bioassays (rat urinary bladder, rabbit pulmonary artery, guinea pig ileum), in vivo pharmacology with selective antagonists British journal of pharmacology High 11786503
2003 Four human tachykinins encoded by the TAC4 gene — endokinins A, B, C, and D (EKA-D) — were identified from four alternative mRNAs (alpha, beta, gamma, delta). TAC4 expression was detected primarily in adrenal gland and placenta. EKA/B 10-mers displayed equivalent affinity for NK1, NK2, and NK3 receptors as substance P, whereas EKC/D (possessing a novel FQGLL-NH2 motif instead of FXGLM) had low potency. EKA/B produced the same hemodynamic effects as SP in rats (fall in mean arterial blood pressure, tachycardia, mesenteric vasoconstriction, hindquarter vasodilatation), establishing EKA/B as endocrine/paracrine agonists at peripheral SP receptors. cDNA cloning, RT-PCR tissue expression, radioligand binding, in vivo hemodynamic measurements in rats Proceedings of the National Academy of Sciences of the United States of America High 12716968
2003 Centrally administered HK-1 acts as a functional agonist at NK1 receptors in the CNS. HK-1 competed with substance P for binding to mouse and human NK1 receptors and induced calcium release in CHO cells transfected with human NK1 receptor. In vivo, intracerebroventricular HK-1 induced foot-tapping (gerbils) and scratching (mice) behaviors identical to those induced by substance P or NK1 agonist GR-73632; these were blocked by the selective NK1 antagonist MK-869. Radioligand competition binding, intracellular calcium release assay in transfected CHO cells, in vivo behavioral pharmacology with selective antagonist Neuropharmacology High 12842130
2004 The TAC4 gene encodes multiple species-divergent tachykinin peptides: hemokinin-1 (HK-1) in mouse and rat, endokinin-1 (EK-1) in rabbit, and EKA, EKB, human HK-1 (hHK-1), and hHK(4-11) in humans, plus three orphan tachykinin gene-related peptides (EK-2 in rabbit; EKC and EKD in humans). All TAC4-encoded tachykinins exhibit remarkable selectivity and potency for the NK1 receptor similar to substance P, establishing them as the endogenous peripheral SP-like agonists in tissues where SP is not expressed. Comparative genomic and peptide sequence analysis, receptor pharmacology review integrating published data Cellular and molecular life sciences : CMLS Medium 15224188
2006 TAC4-encoded endokinin peptides EKA/B and EKC/D have distinct roles in spinal pain processing. Intrathecal EKA/B (common C-terminal decapeptide) evoked scratching behavior and thermal hyperalgesia in rats via the NK1 receptor, whereas EKC/D (common C-terminal duodecapeptide) did not. These effects of EKA/B were blocked by NK1 receptor antagonists, placing EKA/B as NK1 agonists in spinal nociception. Intrathecal administration, behavioral assays (scratching, paw withdrawal latency), NK1 receptor antagonist pharmacology in rats Neuroscience letters Medium 17101218
2007 EKC/D (C-terminal duodecapeptide common to endokinins C and D, TAC4 products) acts as an antagonist of substance P in rat spinal pain processing. EKC/D pretreatment prevented EKA/B- and SP-induced scratching behavior and thermal hyperalgesia. The antagonistic effect depends on leucine at the carboxyl-terminus of EKC/D: replacing leucine with methionine ([Met12]-EKC/D) abolished inhibition and instead caused thermal hyperalgesia. Intrathecal administration of peptides and analogs, behavioral assays (scratching, thermal hyperalgesia), c-Fos immunohistochemistry in spinal cord, structure-activity mutagenesis (leucine-to-methionine substitution) Brain research High 17655832
2007 TAC4 mRNA (encoding hHK-1) is expressed in human spermatozoa, and hHK-1 along with other tachykinins produces concentration-dependent increases in sperm progressive motility. These effects are antagonized by selective NK1, NK2, and NK3 receptor antagonists, and immunocytochemistry confirmed expression of all three tachykinin receptor proteins in spermatozoa at distinct subcellular localizations. RT-PCR, Western blotting, immunocytochemistry, WHO-guideline motility analysis with selective receptor antagonists Human reproduction (Oxford, England) Medium 17437961
2008 TAC4 gene transcription is initiated from multiple start sites through a TATA-less promoter, a mechanism distinct from the substance P promoter. The 5' non-coding region is conserved across species. NFκB was identified as a transcription factor that drives increased TAC4 transcription upon PMA stimulation in a T cell line, providing a molecular basis for HK-1's immune cell-specific expression. Promoter analysis, 5' RACE, reporter assays, NFκB pathway manipulation in T cell line Neuropeptides Medium 19081134
2010 TAC4-/- mice show an accumulation of CD19+CD117+HSA+BP.1- 'fraction B' pro-B cells in bone marrow, with normal pre-B, immature, and mature B cell numbers. In vitro cultures from TAC4-/- bone marrow or sorted pro-B cells generated significantly more pro-B cells than controls. Exogenous HK-1 added to long-term and intermediate-term reconstituting stem cell cultures significantly decreased de novo generated pro-B cells, establishing an inhibitory role for HK-1 in pro-B cell development. Gene knockout (TAC4-/-), flow cytometry, in vitro bone marrow cultures with exogenous peptide addition Blood High 20660792
2010 hHK-1 expression and TAC4 mRNA were detected in human bronchi (including airway macrophages). Exogenous hHK-1 caused contractile responses in human bronchi primarily through NK2 receptors, with unmasked NK1 receptor involvement (subject to rapid desensitization) when NK2 is blocked. In guinea pig trachea, hHK-1 contraction was mainly NK1-mediated. Endokinins A/B had similar effects; endokinins C/D were inactive. RT-PCR, enzyme immunoassay, isolated tissue pharmacology (human bronchi, guinea pig trachea) with selective NK1/NK2 receptor antagonists Respiratory research Medium 20929541
2010 The N-terminal domain of hHK-1 confers functional selectivity at the NK1 receptor: hHK-1 and its C-terminal fragments independently activate Gs (adenylate cyclase/cAMP) and Gq (intracellular Ca2+ release) pathways, with a relative bias toward Gq over Gs. Residues T1, K3, and Q6 in the N-terminus of hHK-1 contribute specifically to Gs/adenylate cyclase activation without affecting Gq-mediated calcium release. Stepwise N-terminal truncation progressively decreased ERK1/2 phosphorylation and NF-κB activity without affecting NK1 receptor desensitization or internalization. Peptide truncation structure-activity analysis, cAMP assay, intracellular Ca2+ measurement, ERK1/2 phosphorylation, NF-κB reporter assay, receptor internalization assay Biochemical pharmacology High 21168392
2011 HK-1 (encoded by TAC4) and substance P promote differentiation of human memory CD4+ T cells into Th17 cells by acting on monocytes via NK1 receptors: both peptides triggered IL-1β, IL-6, TNF-α production, upregulated IL-23, and enhanced TNF-like 1A expression on monocyte surfaces. Neutralization experiments demonstrated that IL-1β, IL-23, and TNF-like 1A are required intermediaries for HK-1-induced Th17 generation. Neurokinins A and B had no effect, identifying this as a specific property of SP/HK-1. In vitro human PBMC culture system, cytokine neutralization experiments, flow cytometry, ELISA, monocyte depletion assays Journal of immunology (Baltimore, Md. : 1950) High 21368235
2012 Hemokinins (rat/mouse HK-1, human HK-1, hHK(4-11)) dose-dependently stimulated proliferation, migration, adhesion, and tube formation of human umbilical vein endothelial cells (HUVECs), and exhibited in vivo angiogenic activity in the chick embryo chorioallantoic membrane model. These angiogenic effects were inhibited by selective NK1 (but not NK2) receptor antagonist. Mechanistically, HKs activated ERK1/2 phosphorylation, stimulated nitric oxide production, and upregulated eNOS and VEGF expression in HUVECs. HUVEC proliferation, migration, adhesion, and tube formation assays; chick embryo CAM model; NK1/NK2 selective antagonists; ERK1/2 phosphorylation; NO production assay; Western blotting for eNOS and VEGF The international journal of biochemistry & cell biology Medium 22554585
2016 TAC4-encoded HK-1 and its receptor NK1R-Tr (truncated isoform) are expressed in human mural granulosa cells (MGCs) and cumulus cells. Kisspeptin treatment modulated HK-1, NK3R, and KISS1R mRNA expression in these cells, and substance P regulated kisspeptin mRNA levels and attenuated kisspeptin-induced intracellular Ca2+ responses, revealing a reciprocal interaction between the tachykinin and kisspeptin systems in regulating human ovarian granulosa cell function. RT-PCR, quantitative RT-PCR, immunocytochemistry, Western blotting, intracellular Ca2+ measurement in primary human granulosa cells Biology of reproduction Medium 27146034
2016 hHK-1 promotes migration of melanoma cells via NK1 receptor activation. NK1 receptor expression correlated with melanoma metastatic potential. hHK-1 treatment upregulated MMP-2 and MT1-MMP expression in A375 and B16F10 melanoma cells and induced phosphorylation of ERK1/2, JNK, and p38 via PKC and PKA pathways; an NK1 receptor antagonist (L732138) blocked migration. Cell migration assay, NK1 receptor antagonist pharmacology, Western blotting for MMP-2/MT1-MMP and kinase phosphorylation, kinase inhibitor dissection Peptides Medium 27458061
2020 Human HK-1 (encoded by TAC4) stimulates production and release of multiple inflammatory cytokines and chemokines (MCP-1, MIP-1α, MIP-1β, RANTES, TNF-α, IL-1β, IL-6) from human colonic mucosal explants. These effects were mediated through both NK1 and NK2 tachykinin receptors, as separate NK1 (SR140333) and NK2 (SR48968) antagonists each partially inhibited the responses, distinguishing hHK-1's receptor usage profile from that of substance P (which did not affect MCP-1 or RANTES). Human colonic mucosal explant system, Procarta multiplex cytokine assay, QuantiGene mRNA assay, selective NK1/NK2 receptor antagonists Neuropeptides Medium 32600668
2021 In teleost (grass carp), TAC4 encodes two mature peptides: HK1 (containing a mutant VFGLM motif) and HK2 (containing canonical FXGLM motif). HK2 activated all 6 grass carp neurokinin receptors with highest activity at NK2R, whereas HK1 showed very weak activation of each NKR. In grass carp pituitary cells, HK2 induced prolactin, somatolactin α, and other neuropeptide mRNA expression via NK2R and NK3R through cAMP/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMKII cascades. A phenylalanine-to-valine substitution in the signature motif of HK1 accounts for its weak agonistic activity. cDNA cloning, receptor activation assays (all 6 NKR isoforms), pituitary cell culture with peptide treatment and receptor-selective antagonists, signaling pathway inhibitors, RT-qPCR for pituitary gene expression International journal of molecular sciences Medium 34884698
2021 In healthy subjects, serum HK-1 (encoded by TAC4) is present at high concentrations that can desensitize MRGPRX2 on mast cells, thereby preventing mast cell degranulation by substance P. HK-1 induced histamine release from skin-derived mast cells with an EC50 12-fold higher than SP (5056 nM vs 426 nM). Brief pre-incubation of mast cells with HK-1 at 3-10 µM significantly reduced subsequent histamine release by SP without causing MRGPRX2 internalization, suggesting a competitive or allosteric desensitization mechanism distinct from receptor internalization. ELISA for serum HK-1, histamine release assay from primary skin-derived mast cells, lentiviral shRNA knockdown of MRGPRX2, receptor internalization assay Allergology international : official journal of the Japanese Society of Allergology Medium 34090787

Source papers

Stage 0 corpus · 45 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
2021 Mapping the human genetic architecture of COVID-19. Nature 734 34237774
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2000 Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis. Nature immunology 241 11062498
2000 Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. Proceedings of the National Academy of Sciences of the United States of America 135 10737800
2002 Identification, localization and receptor characterization of novel mammalian substance P-like peptides. Gene 134 12383518
2004 Hemokinins and endokinins. Cellular and molecular life sciences : CMLS 133 15224188
2003 Characterization of the endokinins: human tachykinins with cardiovascular activity. Proceedings of the National Academy of Sciences of the United States of America 121 12716968
2002 Pharmacological profile of the novel mammalian tachykinin, hemokinin 1. British journal of pharmacology 87 11786503
2011 The tachykinins substance P and hemokinin-1 favor the generation of human memory Th17 cells by inducing IL-1β, IL-23, and TNF-like 1A expression by monocytes. Journal of immunology (Baltimore, Md. : 1950) 85 21368235
2014 Cr(VI) reduction and Cr(III) immobilization by Acinetobacter sp. HK-1 with the assistance of a novel quinone/graphene oxide composite. Environmental science & technology 80 25296002
2003 Centrally administered hemokinin-1 (HK-1), a neurokinin NK1 receptor agonist, produces substance P-like behavioral effects in mice and gerbils. Neuropharmacology 69 12842130
2020 TAC4 controls tiller angle by regulating the endogenous auxin content and distribution in rice. Plant biotechnology journal 48 32628357
2012 Mapping of clinical and expression quantitative trait loci in a sex-dependent effect of host susceptibility to mouse-adapted influenza H3N2/HK/1/68. Journal of immunology (Baltimore, Md. : 1950) 45 22427645
2007 A role for tachykinins in the regulation of human sperm motility. Human reproduction (Oxford, England) 44 17437961
2006 Characterization of the gene structures, precursor processing and pharmacology of the endokinin peptides. Vascular pharmacology 41 16931167
2002 Recombinant adenovirus encoding the HA gene from swine H3N2 influenza virus partially protects mice from challenge with heterologous virus: A/HK/1/68 (H3N2). Archives of virology 36 12417948
2011 Distinct differences in tachykinin gene expression in ulcerative colitis, Crohn's disease and diverticular disease: a role for hemokinin-1? Neurogastroenterology and motility 25 21342363
2014 Evaluation of in vitro efficacy for decolorization and degradation of commercial azo dye RB-B by Morganella sp. HK-1 isolated from dye contaminated industrial landfill. Chemosphere 23 24480425
2007 Leucine at the carboxyl-terminal of endokinins C and D contributes to elicitation of the antagonistic effect on substance P in rat pain processing. Brain research 21 17655832
2001 Downeast anemia (dea), a new mouse model of severe nonspherocytic hemolytic anemia caused by hexokinase (HK(1)) deficiency. Blood cells, molecules & diseases 21 11783948
2010 Targeted deletion of the tachykinin 4 gene (TAC4-/-) influences the early stages of B lymphocyte development. Blood 20 20660792
2006 Intrathecal administration of the common carboxyl-terminal decapeptide in endokinin A and endokinin B evokes scratching behavior and thermal hyperalgesia in the rat. Neuroscience letters 20 17101218
2010 Expression and function of human hemokinin-1 in human and guinea pig airways. Respiratory research 18 20929541
2016 Expression of Tachykinins and Tachykinin Receptors and Interaction with Kisspeptin in Human Granulosa and Cumulus Cells. Biology of reproduction 17 27146034
2012 Hemokinins modulate endothelium function and promote angiogenesis through neurokinin-1 receptor. The international journal of biochemistry & cell biology 17 22554585
2010 The N-terminal domain of human hemokinin-1 influences functional selectivity property for tachykinin receptor neurokinin-1. Biochemical pharmacology 16 21168392
2008 Regulatory mechanisms in the differential expression of Hemokinin-1. Neuropeptides 13 19081134
2016 Altered expression of the tachykinins substance P/neurokinin A/hemokinin-1 and their preferred neurokinin 1/neurokinin 2 receptors in uterine leiomyomata. Fertility and sterility 10 27456549
1981 Evidence of gene dosage effect for HK 1 in the red cells of a patient with trisomy 10pter leads to p13. Annales de genetique 10 6971618
2016 Human hemokinin-1 promotes migration of melanoma cells and increases MMP-2 and MT1-MMP expression by activating tumor cell NK1 receptors. Peptides 9 27458061
2021 Serum level of hemokinin-1 is significantly lower in patients with chronic spontaneous urticaria than in healthy subjects. Allergology international : official journal of the Japanese Society of Allergology 8 34090787
2006 The neuropeptide genes TAC1, TAC3, TAC4, VIP and PACAP(ADCYAP1), and susceptibility to multiple sclerosis. Journal of neuroimmunology 8 17175032
2022 BRITTLE CULM17, a Novel Allele of TAC4, Affects the Mechanical Properties of Rice Plants. International journal of molecular sciences 7 35628116
2020 Hemokinin-1 and substance P stimulate production of inflammatory cytokines and chemokines in human colonic mucosa via both NK1 and NK2 tachykinin receptors. Neuropeptides 7 32600668
2024 PARP-1 inhibitor alleviates cerebral ischemia/reperfusion injury by reducing PARylation of HK-1 and LDH in mice. European journal of pharmacology 6 38346469
2023 Insecticidal Effect of the Entomopathogenic Fungus Lecanicillium araneicola HK-1 in Aphis craccivora (Hemiptera: Aphididae). Insects 6 37999059
2018 In vitro cytotoxicity evaluation of thiourea derivatives bearing Salix sp. constituent against HK-1 cell lines. Natural product research 5 30507306
2010 Common variants of the neuropeptide expressing tachykinin genes and susceptibility to asthma: a case-control study. Journal of neuroimmunology 4 20580442
2021 Novel Pituitary Actions of TAC4 Gene Products in Teleost. International journal of molecular sciences 3 34884698
2025 Characterization of Lactiplantibacillus paraplantarum HK-1 and GABA Synthesis Under Simulated Gastrointestinal Conditions. Foods (Basel, Switzerland) 1 41097514
2024 Genetic association of novel SNPs in HK-1 (rs201626997) and HK-3 (rs143604141) with type 2 diabetes mellitus in Bangladeshi population. Gene 0 38527673
2024 Mast Cells and Their Related Gene HK-1 are Closely Associated with Discogenic Low Back Pain: A Bioinformatics and Clinical Sample Study. Journal of pain research 0 38618297
2022 The deletion of HK-1 gene affects the bacterial virulence of Pseudomonas stutzeri LH-42. PloS one 0 36445858
2007 [Construction and sequencing of full-length cDNA clone of swine vesicular disease virus strain HK'1/70]. Bing du xue bao = Chinese journal of virology 0 17886721