Coiled-coil domain containing protein 180 (CCDC180) is a protein that in humans is encoded by the CCDC180 gene. This protein is known to localize to the nucleus and is thought to be involved in regulation of transcription as are many proteins containing coiled-coil domains. As it is expressed most highly in the testes and is regulated by SRY and SOX transcription factors, it could be involved in sex determination.
Gene
Locus CCDC180 is located on chromosome 9 at the locus 9q22.33.
Common aliases CCDC180 is also known by the aliases KIAA1529, BDAG1 (Behçet's Disease Associated Gene 1), and C9orf174.
Gene features The CCDC180 gene is 71,221 bases long. It contains 37 exons and is oriented on the forward strand of the chromosome.
mRNA There are no known isoforms or alternative splicing variants of the CCDC180 mRNA.
Protein
General features CCDC180 contains 1,701 amino acids and has a molecular weight of 197.3 kDa. The isoelectric point (pI) is 5.74. The low pI is attributed to a relatively high concentration of glutamic acid when compared to other human proteins at 12.9%. CCDC180 also contains a relatively low concentration of glycine when compared to the average human protein at 3.5%.
Domains
CCDC180 contains two domains of unknown function (DUFs): DUF4455 and DUF4456. There are also two coiled-coil regions which overlap with the DUFs. There is a region of low complexity that is very rich in glutamic acid.
Secondary and tertiary structure The secondary structure of CCDC180 is predicted to be almost completely composed of alpha helices, with only a few predicted beta sheets. The tertiary structure is not completely characterized as yet, but a model predicted by the I-TASSER server at the University of Michigan is pictured.
Post-translational modifications CCDC180 is predicted to undergo a variety of post-translational modifications: Phosphorylation on serine, threonine, and tyrosine residues Tyrosine sulfation Sumoylation O-linked β-N-acetylglucosamine modification of a serine residue Modification Position ContextSerine Phosphorylation195KARESENTISerine Phosphorylation627LRQQSDKETSerine Phosphorylation680SSALSQYFFSerine Phosphorylation734RSEESISSGSerine Phosphorylation961NELDSELELSerine Phosphorylation1069VTQVSLRSFSerine Phosphorylation1087KLRYSNIEFSerine Phosphorylation1105GGNFSPKEISerine Phosphorylation1381QPENSGKKASerine Phosphorylation1396TSAGSFTPHSerine Phosphorylation1526KFFTSKVEISerine Phosphorylation1649LAGLSLKEESerine Phosphorylation1663IERGSRKWPThreonine Phosphorylation521WKAFTEEEAThreonine Phosphorylation1621DEVVTIDDVThreonine Phosphorylation1690SSISTTKTTTyrosine Phosphorylation345EKTSYLMRPTyrosine Phosphorylation650MKSRYECFHTyrosine Phosphorylation1141LENEYLDQATyrosine Phosphorylation1447AEEFYRKEKTyrosine Phosphorylation1485QANKYHNSCSumoylation89ERSVTLKSGRIPMMSumoylation137REKERAKREKARESSumoylation355DTWKALKKEALLQSSumoylation492VGALQGKVEEDLELSumoylation1590LAGLSLKEESEKPLSerine O-linked β-N-acetylglucosamine 1635KQKLSMLIRR
Subcellular localization CCDC180 is predicted to localize to the nucleus, and it contains four nuclear localization sequences.
Expression
CCDC180 is expressed ubiquitously at low levels throughout the body, and the highest expression is consistently seen to be in the testes. Other replicated tissues of high expression include the trachea and eye.
Regulation of expression
Transcriptional regulation Transcription of CCDC180 is predicted to be regulated by a 664 base pair promoter region, with the ID GXP_1829211. This prediction is supported by the transcripts GXT_23217882, GXT_24495001, GXT_24495002, and GXT_24495003. Transcription factors predicted to bind to this promoter region are described below. Ccaat-enhancer binding protein KRAB domain zinc finger protein 57 Krüppel-like C2H2 zinc finger factors Octamer binding protein SRY box 9 GLI zinc finger family RXR heterodimers SOX factors E-box binding factors Nerve growth factor-induced protein C Myc-associated zinc finger GC-binding factor 2 X-box binding protein 1 Histone nuclear factor P
Interacting proteins The following proteins have been shown to interact with CCDC180 in yeast two-hybrid assays. ProteinFunctionY box binding protein 1DNA and RNA binding, transcriptional and translational regulationMitotic checkpoint serine/threonine kinaseAssists in spindle assembly during mitosisB-cell CLL/Lymphoma 10Induces apoptosis and activates NF-κBNeuroblastoma RAS viral oncogene homologRegulates cell divisionErb-B2 receptor tyrosine kinase 2Stabilizes ligand binding in other EGF receptor family membersRetinoblastoma 1Negative regulation of cell cycle progressionProto-oncogene tyrosine-protein kinase SrcSignal transductionMutated in colorectal cancersNegative regulation of cell cycle progressionCatenin alpha 1Associates with cadherinsmutL homolog 1DNA repairPostmeitotic segregation increased 2DNA mismatch repairPhosphatase and tensin homologTumor suppressionProtein tyrosine phosphatase, non-receptor type 12Signal transductionMothers against decapentaplegic homolog 4Transcription regulationPlatelet-derived growth factor receptor-likeUnknown, possible tumor suppressionSerine/threonine kinase 11Regulates cell polarityCycline-dependent kinase inhibitor 2AStabilizes p53FolliculinUnknown, possible tumor suppressionDLC Rho GTPase activating proteinRegulates small GTP-binding proteinsmutL homolog 3DNA repair
Clinical significance A single-nucleotide polymorphism (SNP) in the gene that leads to a single amino acid change (S995C) has been shown in a genome-wide association study to be significantly associated with Behçet's disease, and this designation led to the alias Behcet's disease-associated gene 1 (BDAG1). The role of CCDC180 in the disease phenotype is unknown.
Homology There are no paralogs in humans for this gene, but there are orthologs in a wide variety of organisms, extending back to single-celled green algae. CCDC180 is not conserved in bacteria, archaea, plants, fungi, or protists. The following table includes a subset of species containing protein orthologs of CCDC180. It is not exhaustive, but it indicates the variety of species containing orthologs of CCDC180. Genus and speciesCommon nameDivergence from HumansAccession #Sequence Length% Identity% SimilarityHomo sapiensHuman -NP_065944.21701 - -Pan paniscusBonobo6.6 myaXP_008972301.1170399%99%Capra hircusGoat97.5 myaXP_013821462.1174670%83%Physeter cotodonSperm whale97.5 myaXP_007131156.1174472%84%Struthio camelusOstrich320.5 myaXP_009664045.1160539%58%Apteryx australisBrown kiwi320.5 myaXP_013797236.1160640%60%Alligator sinensisChinese alligator320.5 myaXP_006029881.1155840%59%Gekko japonicusGecko320.5 myaXP_015266758.1163840%58%Thamnophis sirtalisGarter snake320.5 myaXP_013926700.155641%56%Chelonia mydasGreen sea turtle320.5 myaXP_007061172.1163245%68%Salmo salarAtlantic salmon429.6 myaXP_014027541.1148838%54%Lepisosteus oculatusSpotted gar429.6 myaXP_015222467.1148040%59%Ciona intestinalisSea squirt733.0 myaXP_002123678.2157132%51%Branchiostoma floridaeLancelet733.0 myaXP_002609423.1151533%50%Saccoglossus kowalevskiiAcorn worm747.8 myaXP_002742433.1152333%53%Priapulida caudatusPriapulid worm847.0 myaXP_014672086.1129328%46%Crassostrea gigasPacific oyster847.0 myaXP_011430927.1114433%51%Lottia giganteaOwl limpet847.0 myaXP_009044533.188634%52%Lingula anatinaBrachiopod847.0 myaXP_013409374.1152335%53%Chlamydomonas reinhardtiiChlamydomonas1513.9 myaXP_001694909.1154420%40%Salpingoeca rosettaChoanoflagellate1724.7 myaXP_004997848.1151424%49%
Evolutionary history
CCDC180 is a relatively quickly-evolving gene compared to other well-known genes. There are no known family members, splice variants or isoforms, or evidence of gene duplications in the history of the gene.
References