Adipose-secreted signaling protein is a protein that in humans is encoded by the gene ADISSP (previously C20orf27). It is expressed in the majority of the human tissues. One study on this protein revealed its role in regulating cell cycle, apoptosis, and tumorigenesis via promoting the activation of NFĸB pathway.
Gene Adipose-secreted signaling protein has other aliases, UPF0687 Protein C20orf27, Chromosome 20 Open Reading Frame 27, Hypothetical Protein LOC54976, C20orf27, and FLJ20550. It is located on the minus strand at 20p13. It consists of 7 exons and 12 introns. This most updated annotation shows that gene ADISSP starts at 3,753,499 bp to 3,768,388 bp on Chromosome 20.
Transcription
Known isoforms The ADISSP gene has 5 transcript isoforms, ADISSP transcript variant 1, ADISSP transcript variant 2, ADISSP transcript variant 3, and ADISSP transcript variant 4.
Transcript variant 1 encodes for the longest protein isoform, with a size of 1327 bases and 6 exons.
Transcript variant 2 maintains the reading frames and 6 exons compared to transcript variant 1, but it has an alternative spliced site in the coding region. It has a size of 1252 bases.
Transcription variant 3 has a size of 1706 bases and 6 exons. This variant has an alternative spliced site in the coding region and differs in the 5' UTR, but it still maintains the reading frame seen in transcript variant 1. Despite their differences in size, variant 2 and variant 3 encodes the same protein isoform and this second protein isoform is shorted than the protein isoform encoded by transcript variant 1.
Transcript variant 4 has a size of 1457 bases with 6 exons. Compared to variant 1, it uses an alternative 5'-most exon and an alternative splice site. Because of the presence of an upstream ORF that is predicted to interfere with translation of this variant, the transcription variant 4 does not encode any protein.
The information on transcript variant X1 comes from GRCh38.p13 Primary Assembly. This variant has a size of 1195 bases, and the number of exons in this variant remains unknown.
Proteins
Physical features
The human gene ADISSP has three known isoforms.
Isoform 1 has 199 amino acid residues and a domain named DUF4517. Isoform 2 has 174 amino acid residues, and isoform X1 has 154 amino acid residues. All three isoforms contain the same domain DUF4517. The function of domain DUF4517 requires future research.
The predicted isoelectric point of unmodified protein ADISSP is 6.89.ExPASy Bioinformatics Resource Portal entry on Compute pl/Mw tool https://web.expasy.org/compute_pi/. Retrieved 2020-7-31.
The percentage of each amino acid residue is about its average percentage among human proteins.EMBL-EBI (European Bioinformatics Institute) entry on Statistical Analysis of Protein Sequences (SAPS) tool https://www.ebi.ac.uk/Tools/seqstats/saps/. Retrieved 2020-7-31. Overall, the positively charged amino acid residues in human protein ADISSP outnumbers the negatively charged amino acid residues. Protein ADISSP has no high scoring hydrophobic regions, no highly charged regions, and no transmembrane regions.
Post-translation modifications The predicted molecular weight of ADISSP is 21.6 kDa. A Western Blot binding pattern on protein ADISSP with its polyclonal antibody reveals that the experimental molecular weight of protein ADISSP is about 22 kDa. This suggests that there are relatively few post-translation modifications on protein ADISSP.
There is no predicted signal peptide or cleavage site.
There are many predicted phosphorylation sites along the sequence of protein ADISSP, including four sites for protein kinase A (PKA), two sites for protein kinase C (PKC), three sites for casein kinase 2 (CKII), one site for ribosomal S6 kinase (RSK), one site for cGMP-dependent protein kinase or Protein Kinase G (PKG), and one site for ataxia-telangiectasia mutated (ATM) serine/threonine protein kinase.ExPASy Bioinformatics Resource Portal entry on NetPhos 3.1 Serve. http://www.cbs.dtu.dk/services/NetPhos/. Retrieved 2020-7-31.
Protein ADISSP is predicted to have other post-translation modification sites including five palmitoylation sites,GSS-Palm. Prediction of Palmitoylation Site. http://csspalm.biocuckoo.org/. Retrie ved on 2020-7-31. one c-mannosylation site,NetCGlyc 1.0. Neural network predictions of C-mannosylation sites in mammalian proteins. http://www.cbs.dtu.dk/services/NetCGlyc/. Retrieved on 2020-7-31. and two sumoylation sites.GPS-SUMO. Prediction of SUMOylation Sites & SUMO-binding Motifs. http://sumosp.biocuckoo.org/ Retrieved on 2020-7-31.
Structure Three stretches of beta sheet from amino acid 62 to 67, 76 to 87, and 92 to 100 are predicted with the highest confidence using CFSSPCFSSP: Chou and Fasman Secondary Structure Prediction server. http://www.biogem.org/tool/chou-fasman/. Retrieved 2020-8-01. and Phyre2.Phyre2: Protein Homology/analogY Recognition Engine V 2.0. http://www.sbg.bio.ic.ac.uk/~phyre2/html/page.cgi?id=index. Retrieved on 2020-8-01. A model predicted by I-TASSERI-TASSER (Iterative Threading ASSEmbly Refinement. A server for protein structure & function prediction. anglab.ccmb.med.umich.edu/I-TASSER/. Retrieved on 2020-8-01. shows that the tertiary structure of human protein ADISSP is a combination of many beta sheets. This confirms the predictions made by CFSSP and Phyre2.
Subcellular Localization This protein is expected to be found in cytosol and nucleus, but not in nuclei.ThermoFisher entry on C20orf27 Polyclonal Antobody. Retrieved on 2020-08-02. Additional computational analysis predicts that this protein is most likely to be in cytosol.PSORT: a portal to protein subcellular localization resources . Retrieved on 2020-8-02.
Expression Protein ADISSP is expressed ubiquitously throughout different human tissues. Microarray-assessed tissue expression pattern suggests caudate nucleus has the highest expression of protein ADISSP.NCBI (National Center for Biotechnology Information) GEO Profile entry on C20orf27 gene https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS596:50314_i_at. Retrieved on 2020-8-01.
Other than caudate nucleus, protein ADISSP expression measure ranks at the top 25% among 100 proteins in pons, fetal brain, BM- CD105+ endothelial, BM- CD34+, bone marrow, adipocyte, uterus corpus, 721 BLymphoblast, PB- CD56+NK cells, BM- CD33+ myeloid, colorectal adenocarcinoma, leukemia chronic Myelogenous K-562, leukemia lymphoblastic (MOLT-4), and leukemia promyelocytic-HL-60.
In situ hybridization data has shown that the expression of ADISSP in airway epithelial cells (AECs) can be correlated to chronic lung diseases.NCBI (National Center for Biotechnology Information) GEO Profile entry on C20orf27 gene. Retrieved on 2020-8-01. After AECs are treated with IL-13, which is a cytokine expressed by CD4 T helper cells, AECs begin to secrete excess mucous, and excess mucous secretion in the airway is a mark of chronic lung diseases.
Regulation of expression
Gene level expression
There are three promoter regions in gene ADISSP.
Five transcription factors that bind to the promoter region of gene ADISSPSPP (The Signaling Pathway Project) transcription factors report on C20orf27 gene. Retrieved on 2020-8-01. have been discovered, including MITF, JUN, ZNF282, FOXA1, and TCF7L2.
Using genomatix, more transcription factor binding sites are predicted. Transcription binding matrix, like EGR/nerve growth factor induced protein C & related factors, GC-Box factors SP1/GC, Krueppel like transcription factors, Myc associated zinc fingers, vertebrate homologues of enhancer of split complex, E-box binding factors, E2F-myc activator/cell cycle regulator, and BED subclass of zinc-finger proteins, are predicted to give the highest matrix similarity.
Transcript level regulation
Predicted miRNA binding sites in 3' end of ADISSP mRNA which sequences are also conserved evolutionarily are hsa-miR-7856-5p, hsa-miR-671-5p, hsa-miR-4768, hsa-miR-6791-3p, hsa-miR-6829-3p, hsa-miR-548d-3p, hsa-miR-548-3p, hsa-miR-548z, and hsa-miR-548h-3p.miRDB. Online database for miRNA targeting prediction and functional annotations. Retrieved on 2020-8-01.
The formation of three stem loops is conserved in different predicted models.The mfold web server. Web server for nucleic acid folding and hybridization prediction. Retrieved on 2020-8-01. The three stem loops start from the 5' end of ADISSP mRNA base 1 to base 27, base 56 to base 74, and base 116 to base 130.
The mRNA of ADISSP has about 23 predicted mRNA binding protein binding sites which sequences are also conserved in evolution.RBPmap: mapping binding sites of RNA binding proteins. Retrieved on 2020-8-02. The names of these mRNA binding proteins are BRUNOL5, BRUNOL6, PCBP2, TARDBP, MBNL1, CUG-BP, PCBP3, PTBP1, RBM5, SRSF1, HNRNPH2, FMR1, HNRNPF, LIN28A, CPEB4, HNRNPC, HNRNPCL1, HNRNPM, HuR, RALY, PABPC1, PABPC4, SART3, and SRSF10.
Function and clinical significance
Interacting proteins Interactors of protein ADISSP found in Y2H screen are replicase polyprotein 1ab from coronavirus, RAIYL, PHKB, FERMT2 from human. The function of replicase polyprotein 1ab is transcribing and replicating viral RNAs, and it contains the proteinases responsible for the cleavages of the polyprotein. The function of RAIYL, PHKB, and FERMT2 remain unknown.
Other interactors that discovered by pull-down assays include PPP1CA, PPP1CB, PPP1CC, PPP1R7, PSME3, RBFOX2, and DMWD. Interactors PPP1CA, PPP1CB, PPP1CC, and PPP1R7 have similar functions. They involve in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. PSME3 facilitates the MDM2-p53/TP53 interaction which promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53, limiting its accumulation and resulting in inhibited apoptosis after DNA damage, and might play a role in cell cycle regulation. RBFOX2 regulates alternative splicing events by binding to 5'-UGCAUGU-3' elements. The function of DMWD is unknown.
The above evidence suggests protein ADISSP plays a role in cell cycle regulation, cell proliferation and differentiation, and cell survival.
Clinical significance Human protein ADISSP and its variants have not been discovered to be associated with any diseases or disorders.
Homology and evolution history
Paralogs There are no known paralogs.
Orthologs There are about 281+ known orthologs for this gene, ranging from primates to invertebrates.
The closest related orthologs are selected from primates and mammals, and the sequence similarity ranks from 75% to 100%. The moderately related orthologs are selected from fishes and birds, and the sequence similarity ranks from 55% to 75%. The most distantly related orthologs are selected from invertebrates and trichoplax, and the sequence similarity ranks from 40% to 55%. The conserved amino acids are bold in the conceptional translation diagram.