Affinage

ASIP

Agouti-signaling protein · UniProt P42127

Round 2 corrected
Length
132 aa
Mass
14.5 kDa
Annotated
2026-04-28
130 papers in source corpus 12 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASIP encodes a secreted paracrine signaling peptide that functions as an inverse agonist/antagonist of melanocortin-1 receptor (MC1R), blocking α-MSH-stimulated cAMP accumulation in melanocytes to shift pigment synthesis from eumelanin toward pheomelanin (PMID:7757071). Its spatial expression is governed by multiple promoters—including a hair-cycle-specific promoter controlling dorsoventral patterning and a ventral/distal promoter mediating countershading—whose disruption by deletions, retrotransposon insertions, or structural rearrangements causes loss-of-function melanism or gain-of-function pheomelanin-dominant phenotypes across vertebrates (PMID:31729778, PMID:18287407, PMID:28811591). In humans, a regulatory polymorphic SVA retrotransposon insertion that elevates skin ASIP expression is associated with lighter pigmentation and increased skin cancer risk under recent positive selection (PMID:39048794), while a tandem duplication placing ASIP under the ITCH promoter causes ubiquitous ectopic expression resulting in extreme childhood obesity, red hair, and hyperinsulinemia through pleiotropic melanocortin receptor antagonism (PMID:36536132).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1995 High

    Cloning of human ASIP and demonstration that it encodes a functional MC1R antagonist established the core molecular activity: blocking α-MSH-stimulated cAMP in melanocytes to promote pheomelanin synthesis.

    Evidence Transgenic mouse expression producing yellow coat; cell-based cAMP assay in mouse melanoma cells

    PMID:7757071

    Open questions at the time
    • No crystal structure of ASIP–MC1R interaction
    • Mechanism of receptor selectivity among melanocortin receptors not resolved
    • In vivo paracrine range and half-life of secreted ASIP protein unknown
  2. 2001 High

    Identification of a frameshift deletion in equine ASIP causing recessive black coat in multiple breeds demonstrated that coding-region loss-of-function mutations are sufficient to ablate pheomelanin-promoting activity across mammals.

    Evidence Genomic sequencing and breed-wide genotyping in 24 black horses across 9 breeds

    PMID:11353392

    Open questions at the time
    • No direct protein expression or binding data from the mutant allele
    • Potential modifier loci not assessed
  3. 2008 High

    Analysis of Japanese quail allelic series and upstream deletions revealed that ASIP activity is dosage-sensitive and that upstream regulatory rearrangements (including a >90-kb deletion fusing ASIP to the RALY promoter) can produce gain-of-function phenotypes by ectopic, tissue-wide expression, while a C-terminal frameshift disrupting disulfide bonds causes loss-of-function melanism.

    Evidence Allelism tests, RT-PCR, microarray, deletion mapping, and RACE in quail

    PMID:18287406 PMID:18287407

    Open questions at the time
    • Specific disulfide bonds critical for MC1R binding not mapped by mutagenesis
    • Downstream target SLC24A5 downregulation mechanism not characterized beyond correlation
  4. 2012 Medium

    Discovery that the conserved distal (ventral) ASIP promoter responds to estrogen in chicken feather follicles linked ASIP regulation to endocrine control and explained sexual plumage dichromatism, while independent ASIP coding mutations in leopard and Asian golden cat confirmed convergent loss-of-function melanism across felids.

    Evidence RT-PCR isoform analysis with estrogen treatment in chickens; coding-region sequencing and association analysis in felids

    PMID:22554923 PMID:23251368

    Open questions at the time
    • Estrogen response element in the distal promoter not mapped
    • Felid functional validation (protein assay or rescue) not performed
    • Role of additional melanocortin receptors in non-cutaneous tissues unexplored
  5. 2017 High

    CRISPR/Cas9-mediated disruption of ASIP in sheep produced graded coat-color phenotypes dependent on the specific indel and allele dosage, directly demonstrating that ASIP coding integrity and gene dosage control the spatial balance of eumelanin versus pheomelanin in vivo.

    Evidence CRISPR/Cas9 genome editing with phenotypic analysis of multiple lambs

    PMID:28811591

    Open questions at the time
    • No measurement of ASIP protein levels in edited animals
    • Interaction with other pigmentation pathway components (e.g., TYRP1, MC1R variants) not tested
  6. 2019 High

    Identification of promoter-region structural variants in rabbit (11-kb deletion at the hair-cycle-specific promoter) and quail (71-kb duplication creating an ITCH–ASIP fusion; 141-kb deletion removing 5′ repressor elements) established that distinct cis-regulatory elements independently control dorsal versus ventral ASIP expression and that 5′ sequences normally repress ASIP transcription.

    Evidence WGS deletion mapping in 49 rabbits; structural variant characterization and RT-PCR in quail

    PMID:30987584 PMID:31729778

    Open questions at the time
    • Identity and binding factors of the 5′ repressor elements not determined
    • Chromatin architecture at the ASIP locus not characterized
  7. 2022 High

    A heterozygous tandem duplication placing ASIP under the ITCH promoter in humans caused ubiquitous ectopic ASIP expression, resulting in extreme childhood obesity, red hair, and hyperinsulinemia—establishing ectopic ASIP as a monogenic cause of human obesity through pleiotropic melanocortin receptor antagonism.

    Evidence Genomic sequencing, iPSC differentiation to all germ layers and hypothalamic-like neurons, RT-PCR; replicated in 4 additional patients from a 1,745-individual cohort

    PMID:36536132

    Open questions at the time
    • Relative contribution of MC3R versus MC4R antagonism to the metabolic phenotype not dissected
    • ASIP protein levels and receptor occupancy in patient tissues not quantified
  8. 2024 High

    A polymorphic SVA retrotransposon insertion in an early ASIP intron was shown to increase skin ASIP expression 2.2-fold by eliminating nonproductive splicing from an older SVA insertion, linking ASIP expression level to lighter skin pigmentation and elevated skin cancer risk under recent positive selection in Europeans.

    Evidence UK Biobank GWAS (n=169,641), eQTL analysis, haplotype and extended haplotype homozygosity analysis

    PMID:39048794

    Open questions at the time
    • Functional validation of the nonproductive splicing rescue mechanism in experimental models not performed
    • Effect size on melanoma versus non-melanoma skin cancer not separated
    • Interaction with MC1R variant alleles on skin cancer risk not modeled

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution structural model of the ASIP–MC1R complex exists, the precise binding interface and receptor selectivity determinants remain undefined, and the identities of transcription factors occupying ASIP cis-regulatory elements (including the 5′ repressor and the estrogen-responsive distal promoter) are unresolved.
  • No ASIP–MC1R co-crystal or cryo-EM structure
  • Transcription factors binding ASIP regulatory elements not identified
  • Post-translational processing and secretion pathway of ASIP not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0048018 receptor ligand activity 2
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 2
Partners
MC1R

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Human ASIP (agouti signaling protein) encodes a 132-amino-acid paracrine signaling molecule; expression of ASIP in transgenic mice produces a yellow coat, and expression in cell culture blocks alpha-MSH-stimulated cAMP accumulation in mouse melanoma cells, establishing ASIP as a functional antagonist of the melanocortin-1 receptor (MC1R/extension locus). Transgenic mouse expression, cell-based cAMP assay in mouse melanoma cells Human molecular genetics High 7757071
2001 A frameshift 11-bp deletion in exon 2 of equine ASIP (ADEx2) is found homozygous in 24 black horses across 9 breeds and is completely associated with recessive black coat color, acting as a loss-of-function ASIP allele that abolishes pheomelanin-promoting signaling. Genomic sequencing, breed-wide genotyping, comparative genetics Mammalian genome High 11353392
2006 The recessive black coat color in Japanese quail caused by the *RB allele results from an 8-base deletion in the ASIP gene that causes a frameshift altering the last six amino acids (including a cysteine residue) and removing the stop codon, disrupting disulfide bond formation required for proper ASIP tertiary structure and its function as an alpha-MSH antagonist. Allelism test, sequencing, frameshift and structural analysis Genetics High 18287406
2008 The Japanese quail yellow mutation is caused by a >90-kb deletion upstream of the avian ASIP gene that encompasses coding sequences of RALY and EIF2B and places ASIP expression under control of the RALY promoter, producing a novel ASIP fusion transcript with upregulated expression in multiple tissues; downstream, SLC24A5 is the most downregulated gene in yellow quail feather buds, and ventral skin-specific ASIP isoforms are present in both quail and chicken, showing conservation of dorsoventral ASIP expression across vertebrates. Deletion mapping, RT-PCR, microarray analysis, RACE, comparative genomics Genetics High 18287407
2008 The black-and-tan phenotype in Japanese quail (*RB allele) shows allelism with the yellow locus, and the dominance hierarchy (fawn-2 > yellow > wild-type > recessive black) is consistent with graded levels of ASIP activity; loss of functional ASIP prevents antagonism of alpha-MSH at melanocortin receptors in follicular melanocytes, leading to eumelanin production. Allelism test, genetic crosses, sequencing Genetics Medium 18287406
2012 In leopard (Panthera pardus), melanism is caused by a nonsense mutation in the ASIP coding region predicted to completely ablate protein function; in Asian golden cat (Pardofelis temminckii), a different SNP causes a predicted loss-of-function amino acid change, demonstrating that independent ASIP coding mutations cause species-specific melanism in felids. Coding region sequencing, association analysis, functional prediction PloS one Medium 23251368
2012 The conserved distal promoter of the chicken ASIP gene drives class 1 ASIP mRNA expression specifically on the ventral side and in estrogen-responsive ornamental feathers, mediating countershading in chicks/females and estrogen-dependent sexual plumage dichromatism in males; estrogen treatment shifts male ASIP class 1 expression to the female pattern. RT-PCR analysis of tissue-specific isoforms, estrogen treatment experiments in chickens General and comparative endocrinology Medium 22554923
2017 CRISPR/Cas9-mediated disruption of sheep ASIP produces a variety of coat color patterns (badgerface black, brown with light ventral pigmentation, black-white spotted) depending on the type of indel introduced and the copy number of ASIP alleles modified, demonstrating that ASIP dosage and coding-sequence integrity directly control the spatial distribution of eumelanin vs. pheomelanin in sheep. CRISPR/Cas9 genome editing, sequencing of targeted indels, phenotypic analysis of lambs Scientific reports High 28811591
2019 The rabbit black-and-tan (at) allele is caused by an 11-kb deletion in the region of the hair cycle-specific ASIP promoter (homologous to the site of the retroviral insertion causing the mouse at allele), which selectively abolishes hair-cycle-specific ASIP expression and results in eumelanin production on the dorsal surface, establishing that the hair cycle-specific promoter controls dorsoventral pigment patterning. WGS-based comparative analysis, deletion mapping, genotype-phenotype association in 49 rabbits Animal genetics High 31729778
2019 In Japanese quail, the fawn-2/beige phenotype results from a 71-kb tandem duplication creating an ITCH-ASIP fusion gene that drives higher-than-expected ASIP transcription, while the yellow phenotype results from a 141-kb deletion; both mutations place ASIP expression under control of upstream gene promoters lacking normal 5' repressor elements, demonstrating that the 5' region of ASIP contains regulatory sequences that normally repress ASIP expression. Structural variant characterization by sequencing, RT-PCR, comparative genomics Genetics, selection, evolution : GSE Medium 30987584
2021 A structural rearrangement (ASIP-SV1) near the ASIP locus in Nellore cattle, involving a 1155-bp deletion followed by insertion of a transposable element, is associated with darker coat pigmentation by impairing recruitment of ASIP non-coding exons and reducing ASIP expression, thereby increasing eumelanin production. GWAS, whole-genome sequencing, Oxford Nanopore long-read sequencing, structural variant characterization Genetics, selection, evolution : GSE Medium 33910501
2022 A heterozygous tandem duplication at the ASIP locus places ASIP under control of the ITCH (itchy E3 ubiquitin protein ligase) promoter, causing ubiquitous ectopic ASIP expression in all germ layers and hypothalamic-like neurons, leading to extreme childhood obesity, overgrowth, red hair, and hyperinsulinemia in humans; the same mutation was identified in four additional patients from a cohort of 1,745, establishing ectopic ASIP expression as a monogenic cause of human obesity through its action as a melanocortin receptor antagonist affecting eating behavior, energy expenditure, adipocyte differentiation, and pigmentation. Genomic sequencing, iPSC differentiation, RT-PCR across germ layers, cohort rescreening Nature metabolism High 36536132
2024 A recent polymorphic 3.3-kb SVA retrotransposon insertion in an early intron of the human ASIP gene is strongly associated with lighter skin pigmentation and increased skin cancer risk in European populations; the insertion increases ASIP expression in skin 2.2-fold by eliminating nonproductive splicing caused by an older, human-specific, non-polymorphic SVA insertion 3.9 kb upstream that had previously caused ASIP hypofunction; extended haplotype homozygosity indicates recent positive selection of the insertion allele. UK Biobank GWAS (n=169,641), eQTL analysis, haplotype analysis, extended haplotype homozygosity Nature genetics High 39048794

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
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
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
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
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
1999 Identification of a novel aspartic protease (Asp 2) as beta-secretase. Molecular and cellular neurosciences 938 10656250
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2000 The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nature cell biology 761 10934474
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
1988 Cell attachment to thrombospondin: the role of ARG-GLY-ASP, calcium, and integrin receptors. The Journal of cell biology 450 2848850
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2005 Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules. Molecular & cellular proteomics : MCP 434 15951569
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
1998 An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3. The Journal of cell biology 424 9763423
2009 Germline genomic variants associated with childhood acute lymphoblastic leukemia. Nature genetics 388 19684603
2004 Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. Current biology : CB 386 15324660
2013 Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Science signaling 383 24255178
2005 Par-3 controls tight junction assembly through the Rac exchange factor Tiam1. Nature cell biology 382 15723052
2001 Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. The Journal of cell biology 378 11257119
1996 Generation and analysis of 280,000 human expressed sequence tags. Genome research 376 8889549
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2005 PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1. Nature cell biology 313 15723051
2001 The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). The EMBO journal 310 11447115
2006 A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell 302 16678097
2007 Numb controls integrin endocytosis for directional cell migration with aPKC and PAR-3. Developmental cell 292 17609107
2010 Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6. Nature cell biology 285 21170030
2017 Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proceedings of the National Academy of Sciences of the United States of America 282 28611215
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2001 Mutations in the agouti (ASIP), the extension (MC1R), and the brown (TYRP1) loci and their association to coat color phenotypes in horses (Equus caballus). Mammalian genome : official journal of the International Mammalian Genome Society 187 11353392
1998 His-Asp phosphotransfer signal transduction. Journal of biochemistry 174 9538242
1995 Structure and function of ASP, the human homolog of the mouse agouti gene. Human molecular genetics 159 7757071
2002 Involvement of ASIP/PAR-3 in the promotion of epithelial tight junction formation. Journal of cell science 141 12045219
2008 Human DNMT2 methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalytic mechanism. RNA (New York, N.Y.) 140 18567810
2001 The drosophila protein asp is involved in microtubule organization during spindle formation and cytokinesis. The Journal of cell biology 131 11352927
1998 Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period. Journal of lipid research 121 9555951
2001 Polo kinase and Asp are needed to promote the mitotic organizing activity of centrosomes. Nature cell biology 109 11283617
2000 Possible His to Asp phosphorelay signaling in an Arabidopsis two-component system. FEBS letters 106 10930573
1991 An Arg-Gly-Asp sequence within thrombin promotes endothelial cell adhesion. The Journal of cell biology 102 1988465
1999 Acylation stimulating protein (ASP), an adipocyte autocrine: new directions. Seminars in cell & developmental biology 91 10355026
2002 Association of ASIP/mPAR-3 with adherens junctions of mouse neuroepithelial cells. Developmental dynamics : an official publication of the American Association of Anatomists 83 12203721
2002 Acylation-stimulating protein (ASP) deficiency induces obesity resistance and increased energy expenditure in ob/ob mice. The Journal of biological chemistry 83 12244109
2005 Spindle pole organization in Drosophila S2 cells by dynein, abnormal spindle protein (Asp), and KLP10A. Molecular biology of the cell 80 15888542
2013 The microcephaly protein Asp regulates neuroepithelium morphogenesis by controlling the spatial distribution of myosin II. Nature cell biology 78 24142104
2008 Characterization of Japanese quail yellow as a genomic deletion upstream of the avian homolog of the mammalian ASIP (agouti) gene. Genetics 76 18287407
1992 The Ser-Arg-Tyr-Asp region of the major surface glycoprotein of Leishmania mimics the Arg-Gly-Asp-Ser cell attachment region of fibronectin. The Journal of biological chemistry 73 1629196
1997 Acylation-stimulating protein (ASP) regulates glucose transport in the rat L6 muscle cell line. Biochimica et biophysica acta 70 9059512
1998 His...Asp catalytic dyad of ribonuclease A: structure and function of the wild-type, D121N, and D121A enzymes. Biochemistry 68 9636030
2015 A tonoplast Glu/Asp/GABA exchanger that affects tomato fruit amino acid composition. The Plant journal : for cell and molecular biology 67 25602029
2001 STAT3 activation is required for Asp(816) mutant c-Kit induced tumorigenicity. Oncogene 66 11494148
1999 Acylation stimulating protein (ASP) deficiency alters postprandial and adipose tissue metabolism in male mice. The Journal of biological chemistry 64 10593909
1990 Site-directed mutagenesis of the conserved Asp-443 and Asp-498 carboxy-terminal residues of HIV-1 reverse transcriptase. Nucleic acids research 56 1699202
2012 Anti-diabetic activities of Acanthopanax senticosus polysaccharide (ASP) in combination with metformin. International journal of biological macromolecules 55 22326821
2006 Identification of an essential gene responsible for D-Asp incorporation in the Lactococcus lactis peptidoglycan crossbridge. Molecular microbiology 51 17083466
2018 Polymorphisms in MC1R and ASIP Genes are Associated with Coat Color Variation in the Arabian Camel. The Journal of heredity 50 29893870
1991 Locations of Arg-82, Asp-85, and Asp-96 in helix C of bacteriorhodopsin relative to the aqueous boundaries. Proceedings of the National Academy of Sciences of the United States of America 50 1656452
2021 Variants at the ASIP locus contribute to coat color darkening in Nellore cattle. Genetics, selection, evolution : GSE 49 33910501
1996 Roles of Glu 349 and Asp 352 in membrane insertion and translocation by diphtheria toxin. Protein science : a publication of the Protein Society 48 8845758
2002 Catalytic mechanism of S-adenosylhomocysteine hydrolase. Site-directed mutagenesis of Asp-130, Lys-185, Asp-189, and Asn-190. The Journal of biological chemistry 45 11927587
1993 Antiapoptotic effect of heterozygously expressed mutant RI (Ala336-->Asp) subunit of cAMP kinase I in a rat leukemia cell line. The Journal of biological chemistry 45 8385140
2008 Recessive black is allelic to the yellow plumage locus in Japanese quail and associated with a frameshift deletion in the ASIP gene. Genetics 44 18287406
2006 The mutation causing the black-and-tan pigmentation phenotype of Mangalitza pigs maps to the porcine ASIP locus but does not affect its coding sequence. Mammalian genome : official journal of the International Mammalian Genome Society 44 16416091
1994 Site-directed mutagenesis of the Asp-197 and Asp-202 residues in chitinase A1 of Bacillus circulans WL-12. Bioscience, biotechnology, and biochemistry 44 7765724
2023 Exploring Kinase Asp-Phe-Gly (DFG) Loop Conformational Stability with AlphaFold2-RAVE. Journal of chemical information and modeling 41 37981824
2009 Recombinant C3adesArg/acylation stimulating protein (ASP) is highly bioactive: a critical evaluation of C5L2 binding and 3T3-L1 adipocyte activation. Molecular immunology 41 19767107
2003 A single amino acid change (Asp 53 --> Ala53) converts Survivin from anti-apoptotic to pro-apoptotic. Molecular biology of the cell 41 14699067
2000 Meiotic maturation induces animal-vegetal asymmetric distribution of aPKC and ASIP/PAR-3 in Xenopus oocytes. Development (Cambridge, England) 41 11060229
2017 Alteration of sheep coat color pattern by disruption of ASIP gene via CRISPR Cas9. Scientific reports 40 28811591
2015 Microcephaly protein Asp focuses the minus ends of spindle microtubules at the pole and within the spindle. The Journal of cell biology 38 26644514
2000 His-Asp phosphorelay signaling: a communication avenue between plants and their environment. Plant molecular biology 35 10794527
2015 The HIV-1 antisense protein (ASP) induces CD8 T cell responses during chronic infection. Retrovirology 33 25809376
2008 Differences in the expression of the ASIP gene are involved in the recessive black coat colour pattern in sheep: evidence from the rare Xalda sheep breed. Animal genetics 32 18384465
1998 Plasma acylation stimulating protein (ASP) as a predictor of impaired cellular biological response to ASP in patients with hyperapoB. European journal of clinical investigation 32 9767372
1994 The adipsin-ASP pathway and regulation of adipocyte function. Annals of medicine 32 7695862
2001 Involvement of the Arg-Asp-His catalytic triad in enzymatic cleavage of the phosphodiester bond. Biochemistry 31 11331006
2013 Elevated fetal adipsin/acylation-stimulating protein (ASP) in obese pregnancy: novel placental secretion via Hofbauer cells. The Journal of clinical endocrinology and metabolism 30 23956345
2005 Glu-Q-tRNA(Asp) synthetase coded by the yadB gene, a new paralog of aminoacyl-tRNA synthetase that glutamylates tRNA(Asp) anticodon. Biochimie 30 16164993
2019 Polymorphism in MC1R, TYR and ASIP genes in different colored feather chickens. 3 Biotech 29 31065503
2014 Inherited variation at MC1R and ASIP and association with melanoma-specific survival. International journal of cancer 29 25382380
2010 Influence of Lβ-, Dα- and Dβ-Asp isomers of the Asp-76 residue on the properties of αA-crystallin 70-88 peptide. Amino acids 28 20437187
2006 A polymorphism in the agouti signalling protein (ASIP) is associated with decreased levels of mRNA. Pigment cell research 28 16704456
2022 Aberrant expression of agouti signaling protein (ASIP) as a cause of monogenic severe childhood obesity. Nature metabolism 27 36536132
2016 Inhibitors of Arg-Gly-Asp-Binding Integrins Reduce Development of Pancreatic Fibrosis in Mice. Cellular and molecular gastroenterology and hepatology 27 28174730
2007 Loss of partitioning-defective-3/isotype-specific interacting protein (par-3/ASIP) in the elongating spermatid of RA175 (IGSF4A/SynCAM)-deficient mice. The American journal of pathology 27 18055550
2001 Acylation stimulating protein (ASP) acute effects on postprandial lipemia and food intake in rodents. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 26 11360154
2012 Conserved distal promoter of the agouti signaling protein (ASIP) gene controls sexual dichromatism in chickens. General and comparative endocrinology 25 22554923
2012 How the leopard hides its spots: ASIP mutations and melanism in wild cats. PloS one 25 23251368
2007 The ASP receptor C5L2 is regulated by metabolic hormones associated with insulin resistance. Biochemistry and cell biology = Biochimie et biologie cellulaire 25 17464341
1999 [Cytotoxic activity and cytokine gene induction of Asp-hemolysin to murine macrophages]. Nihon Ishinkin Gakkai zasshi = Japanese journal of medical mycology 25 10536308
2016 The MC1R and ASIP Coat Color Loci May Impact Behavior in the Horse. The Journal of heredity 24 26884605
2000 High sensitivity bioassay of paralytic (PSP) and amnesic (ASP) algal toxins based on the fluorimetric detection of [Ca(2+)](i) in rat cortical primary cultures. Toxicon : official journal of the International Society on Toxinology 24 10736481
1996 Perturbed interaction between residues 85 and 204 in Tyr-185-->Phe and Asp-85-->Glu bacteriorhodopsins. Biophysical journal 24 8968608
1985 The structure of yeast tRNA(Asp). A model for tRNA interacting with messenger RNA. Journal of biomolecular structure & dynamics 24 3917033
2014 Molecular cloning and functional characterization of porcine DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41). Developmental and comparative immunology 23 25086295
2012 Variants at chromosome 20 (ASIP locus) and melanoma risk. International journal of cancer 23 22628150
2002 A family of activation associated secreted protein (ASP) homologues of Cooperia punctata. Research in veterinary science 22 12443689
2019 Two new structural mutations in the 5' region of the ASIP gene cause diluted feather color phenotypes in Japanese quail. Genetics, selection, evolution : GSE 21 30987584
2012 MC1R, ASIP, TYR, and TYRP1 gene variants in a population-based series of multiple primary melanomas. Genes, chromosomes & cancer 21 22447455
2016 Isomerization of Asp residues plays an important role in αA-crystallin dissociation. The FEBS journal 20 26700637
2012 Isomerization of Asp-Asp motif in model peptides and a monoclonal antibody Fab fragment. Journal of pharmaceutical sciences 20 23280575
2001 Down-regulated expression of atypical PKC-binding domain deleted asip isoforms in human hepatocellular carcinomas. Cell research 20 11642408
2020 Venomics of the asp viper Vipera aspis aspis from France. Journal of proteomics 19 32087377
2011 Loss of ASP but not ROPN1 reduces mammalian ciliary motility. Cytoskeleton (Hoboken, N.J.) 19 22021175
2006 Investigation of the role of the agouti signaling protein gene (ASIP) in coat color evolution in primates. Mammalian genome : official journal of the International Mammalian Genome Society 19 17143587
2019 Detection of antisense protein (ASP) RNA transcripts in individuals infected with human immunodeficiency virus type 1 (HIV-1). The Journal of general virology 18 30896385
2019 Site-specific analysis of the Asp- and Glu-ADP-ribosylated proteome by quantitative mass spectrometry. Methods in enzymology 18 31606080
1999 Fibrinogen Matsumoto III: a variant with gamma275 Arg-->Cys (CGC-->TGC)--comparison of fibrin polymerization properties with those of Matsumoto I (gamma364 Asp-->His) and Matsumoto II (gamma308 Asn-->Lys). Thrombosis and haemostasis 18 10365751
1999 A critical evaluation of the putative role of C3adesArg (ASP) in lipid metabolism and hyperapobetalipoproteinemia. Molecular immunology 18 10698341
2020 An Independent Locus Upstream of ASIP Controls Variation in the Shade of the Bay Coat Colour in Horses. Genes 17 32486210
2019 LPS-induced inflammation delays the transportation of ASP+ due to down-regulation of OCTN1/2 in alveolar epithelial cells. Journal of drug targeting 17 31591905
2010 Genetic variation within coat color genes of MC1R and ASIP in Chinese brownish red Tibetan pigs. Animal science journal = Nihon chikusan Gakkaiho 17 21108681
1991 Resonance Raman spectra of bacteriorhodopsin mutants with substitutions at Asp-85, Asp-96, and Arg-82. Photochemistry and photobiology 17 2062880
2022 Anticancer Properties of N,N-dibenzylasparagine as an Asparagine (Asp) analog, Using Colon Cancer Caco-2 Cell Line. Asian Pacific journal of cancer prevention : APJCP 16 35901362
2022 Deciphering the Alphabet of Disorder-Glu and Asp Act Differently on Local but Not Global Properties. Biomolecules 16 36291634
2017 Sequential activities of Dynein, Mud and Asp in centrosome-spindle coupling maintain centrosome number upon mitosis. Journal of cell science 16 28864767
2024 A sequence of SVA retrotransposon insertions in ASIP shaped human pigmentation. Nature genetics 15 39048794
2022 Anti-Inflammatory and Mineralization Effects of an ASP/PLGA-ASP/ACP/PLLA-PLGA Composite Membrane as a Dental Pulp Capping Agent. Journal of functional biomaterials 15 35997444
2019 Mutations in ASIP and MC1R: dominant black and recessive black alleles segregate in native Swedish sheep populations. Animal genetics 15 31475378
2018 Genetic Variation in Coat Colour Genes MC1R and ASIP Provides Insights Into Domestication and Management of South American Camelids. Frontiers in genetics 15 30483307
1999 Arg-gly-Asp (RGD) peptides and peptidomimetics as therapeutics: relevance for renal diseases. Experimental nephrology 15 10213871
2023 Horizontal gene transfer underlies the painful stings of asp caterpillars (Lepidoptera: Megalopygidae). Proceedings of the National Academy of Sciences of the United States of America 14 37428925
2020 A Pilot Study of the Humoral Response Against the AntiSense Protein (ASP) in HIV-1-Infected Patients. Frontiers in microbiology 14 32117090
2020 Australian snakebite myotoxicity (ASP-23). Clinical toxicology (Philadelphia, Pa.) 14 33156703
2019 Synergy between MC1R and ASIP for coat color in horses (Equus caballus)1. Journal of animal science 14 30785190
2019 A deletion spanning the promoter and first exon of the hair cycle-specific ASIP transcript isoform in black and tan rabbits. Animal genetics 14 31729778