Biology:CCDC180

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Short description: Protein-coding gene in humans


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Coiled-coil domain containing protein 180 (CCDC180) is a protein that in humans is encoded by the CCDC180 gene.[1] 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

The location of CCDC180 on human chromosome 9 within locus 9q22.33 is marked with a line.

Locus

CCDC180 is located on chromosome 9 at the locus 9q22.33.[1]

Common aliases

CCDC180 is also known by the aliases KIAA1529, BDAG1 (Behçet's Disease Associated Gene 1), and C9orf174.[1]

Gene features

The CCDC180 gene is 71,221 bases long. It contains 37 exons and is oriented on the forward strand of the chromosome.[2]

mRNA

There are no known isoforms or alternative splicing variants of the CCDC180 mRNA.[2]

Protein

General features

CCDC180 contains 1,701 amino acids[3] 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%.[4]

Domains

Here are shown the major domains present within the protein CCDC180: Domains of Unknown Function 4455 and 4456, two coiled-coil domains, and a glutamic acid rich domain.

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.

A model of CCDC180 secondary and tertiary structure predicted by the University of Michigan I-TASSER server[5]

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.[6] 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.

Translation of the mRNA and protein sequence for the human protein CCDC180, including domains, secondary structure, exon splice sites, and post-translation modification sites

Post-translational modifications

CCDC180 is predicted to undergo a variety of post-translational modifications:

Modification Position Context
Serine Phosphorylation 195 KARESENTI
Serine Phosphorylation 627 LRQQSDKET
Serine Phosphorylation 680 SSALSQYFF
Serine Phosphorylation 734 RSEESISSG
Serine Phosphorylation 961 NELDSELEL
Serine Phosphorylation 1069 VTQVSLRSF
Serine Phosphorylation 1087 KLRYSNIEF
Serine Phosphorylation 1105 GGNFSPKEI
Serine Phosphorylation 1381 QPENSGKKA
Serine Phosphorylation 1396 TSAGSFTPH
Serine Phosphorylation 1526 KFFTSKVEI
Serine Phosphorylation 1649 LAGLSLKEE
Serine Phosphorylation 1663 IERGSRKWP
Threonine Phosphorylation 521 WKAFTEEEA
Threonine Phosphorylation 1621 DEVVTIDDV
Threonine Phosphorylation 1690 SSISTTKTT
Tyrosine Phosphorylation 345 EKTSYLMRP
Tyrosine Phosphorylation 650 MKSRYECFH
Tyrosine Phosphorylation 1141 LENEYLDQA
Tyrosine Phosphorylation 1447 AEEFYRKEK
Tyrosine Phosphorylation 1485 QANKYHNSC
Sumoylation 89 ERSVTLKSGRIPMM
Sumoylation 137 REKERAKREKARES
Sumoylation 355 DTWKALKKEALLQS
Sumoylation 492 VGALQGKVEEDLEL
Sumoylation 1590 LAGLSLKEESEKPL
Serine O-linked β-N-acetylglucosamine 1635 KQKLSMLIRR

Subcellular localization

CCDC180 is predicted to localize to the nucleus, and it contains four nuclear localization sequences.[11]

Expression

GEO Profile for the expression of the human protein CCDC180 in normal tissues[12]

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.[12][13]

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.[14]

Interacting proteins

The following proteins have been shown to interact with CCDC180 in yeast two-hybrid assays.[15]

Protein Function
Y box binding protein 1 DNA and RNA binding, transcriptional and translational regulation[16]
Mitotic checkpoint serine/threonine kinase Assists in spindle assembly during mitosis[17]
B-cell CLL/Lymphoma 10 Induces apoptosis and activates NF-κB[18]
Neuroblastoma RAS viral oncogene homolog Regulates cell division[19]
Erb-B2 receptor tyrosine kinase 2 Stabilizes ligand binding in other EGF receptor family members[20]
Retinoblastoma 1 Negative regulation of cell cycle progression[21]
Proto-oncogene tyrosine-protein kinase Src Signal transduction[22]
Mutated in colorectal cancers Negative regulation of cell cycle progression[23]
Catenin alpha 1 Associates with cadherins[24]
mutL homolog 1 DNA repair[25]
Postmeitotic segregation increased 2 DNA mismatch repair[26]
Phosphatase and tensin homolog Tumor suppression[27]
Protein tyrosine phosphatase, non-receptor type 12 Signal transduction[28]
Mothers against decapentaplegic homolog 4 Transcription regulation[29]
Platelet-derived growth factor receptor-like Unknown, possible tumor suppression[29]
Serine/threonine kinase 11 Regulates cell polarity[30]
Cycline-dependent kinase inhibitor 2A Stabilizes p53[31]
Folliculin Unknown, possible tumor suppression[32]
DLC Rho GTPase activating protein Regulates small GTP-binding proteins[33]
mutL homolog 3 DNA repair[34]

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).[35] 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 Species Common Name Divergence from

Humans[36]

Accession # Sequence

Length

% Identity % Similarity
Homo sapiens Human - NP_065944.2 1701 - -
Pan paniscus Bonobo 6.6 mya XP_008972301.1 1703 99% 99%
Capra hircus Goat 97.5 mya XP_013821462.1 1746 70% 83%
Physeter cotodon Sperm whale 97.5 mya XP_007131156.1 1744 72% 84%
Struthio camelus Ostrich 320.5 mya XP_009664045.1 1605 39% 58%
Apteryx australis Brown kiwi 320.5 mya XP_013797236.1 1606 40% 60%
Alligator sinensis Chinese alligator 320.5 mya XP_006029881.1 1558 40% 59%
Gekko japonicus Gecko 320.5 mya XP_015266758.1 1638 40% 58%
Thamnophis sirtalis Garter snake 320.5 mya XP_013926700.1 556 41% 56%
Chelonia mydas Green sea turtle 320.5 mya XP_007061172.1 1632 45% 68%
Salmo salar Atlantic salmon 429.6 mya XP_014027541.1 1488 38% 54%
Lepisosteus oculatus Spotted gar 429.6 mya XP_015222467.1 1480 40% 59%
Ciona intestinalis Sea squirt 733.0 mya XP_002123678.2 1571 32% 51%
Branchiostoma floridae Lancelet 733.0 mya XP_002609423.1 1515 33% 50%
Saccoglossus kowalevskii Acorn worm 747.8 mya XP_002742433.1 1523 33% 53%
Priapulida caudatus Priapulid worm 847.0 mya XP_014672086.1 1293 28% 46%
Crassostrea gigas Pacific oyster 847.0 mya XP_011430927.1 1144 33% 51%
Lottia gigantea Owl limpet 847.0 mya XP_009044533.1 886 34% 52%
Lingula anatina Brachiopod 847.0 mya XP_013409374.1 1523 35% 53%
Chlamydomonas reinhardtii Chlamydomonas 1513.9 mya XP_001694909.1 1544 20% 40%
Salpingoeca rosetta Choanoflagellate 1724.7 mya XP_004997848.1 1514 24% 49%

Evolutionary history

The amino acid changes per 100 (m) in a selection of orthologs of CCDC180 versus time of divergence of the species from human in millions of years. This is compared to Cytochrom C and Fibrinogen to indicate the relatively high speed of evolution of the CCDC180 protein.

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

  1. ↑ 1.0 1.1 1.2 "www.genecards.org/cgi-bin/carddisp.pl?gene=CCDC180&keywords=CCDC180". https://www.genecards.org/cgi-bin/carddisp.pl?gene=CCDC180&keywords=CCDC180. 
  2. ↑ 2.0 2.1 "CCDC180 coiled-coil domain containing 180 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene?cmd=retrieve&dopt=full_report&list_uids=100499483. 
  3. ↑ "coiled-coil domain-containing protein 180 [Homo sapiens - Protein - NCBI"]. https://www.ncbi.nlm.nih.gov/protein/NP_065944.2. 
  4. ↑ "SDSC Biology Workbench". http://workbench.sdsc.edu/CGI/BW.cgi#!. [yes|permanent dead link|dead link}}]
  5. ↑ "I-TASSER results". http://zhanglab.ccmb.med.umich.edu/I-TASSER/output/S272827/. 
  6. ↑ Kelley, Lawrence. "PHYRE2 Protein Fold Recognition Server". http://www.sbg.bio.ic.ac.uk/~phyre2/html/page.cgi?id=index. 
  7. ↑ "NetPhos 2.0 Server". http://www.cbs.dtu.dk/services/NetPhos/. 
  8. ↑ "ExPASy - Sulfinator tool". http://web.expasy.org/sulfinator/. 
  9. ↑ "SUMOplot™ Analysis Program | Abgent". http://www.abgent.com/sumoplot. 
  10. ↑ "YinOYang 1.2 Server". http://www.cbs.dtu.dk/services/YinOYang/. 
  11. ↑ "PSORT II Prediction". http://psort.hgc.jp/form2.html. 
  12. ↑ 12.0 12.1 "Home - GEO Profiles - NCBI". https://www.ncbi.nlm.nih.gov/geoprofiles. 
  13. ↑ "Home - EST - NCBI". https://www.ncbi.nlm.nih.gov/nucest. 
  14. ↑ "Genomatix: Gene2Promoter Result". https://www.genomatix.de/cgi-bin/c2p/c2p.pl?s=0a653e40d5231dcb1bc88685daa9e08f;TASK=c2p;SHOW=result.html. [yes|permanent dead link|dead link}}]
  15. ↑ IntAct. "www.ebi.ac.uk/intact/". http://www.ebi.ac.uk/intact/. 
  16. ↑ "www.genecards.org/cgi-bin/carddisp.pl?gene=YBX1". https://www.genecards.org/cgi-bin/carddisp.pl?gene=YBX1. 
  17. ↑ "BUB1 - Mitotic checkpoint serine/threonine-protein kinase BUB1 - Homo sapiens (Human) - BUB1 gene & protein". https://www.uniprot.org/uniprot/O43683. 
  18. ↑ "www.genecards.org/cgi-bin/carddisp.pl?gene=BCL10". https://www.genecards.org/cgi-bin/carddisp.pl?gene=BCL10. 
  19. ↑ Reference, Genetics Home. "NRAS". https://ghr.nlm.nih.gov/gene/NRAS. 
  20. ↑ "www.genecards.org/cgi-bin/carddisp.pl?gene=ERBB2". https://www.genecards.org/cgi-bin/carddisp.pl?gene=ERBB2. 
  21. ↑ "www.genecards.org/cgi-bin/carddisp.pl?gene=RB1". https://www.genecards.org/cgi-bin/carddisp.pl?gene=RB1. 
  22. ↑ "SRC - Proto-oncogene tyrosine-protein kinase Src - Homo sapiens (Human) - SRC gene & protein". https://www.uniprot.org/uniprot/P12931. 
  23. ↑ "www.genecards.org/cgi-bin/carddisp.pl?gene=MCC". https://www.genecards.org/cgi-bin/carddisp.pl?gene=MCC. 
  24. ↑ "www.genecards.org/cgi-bin/carddisp.pl?gene=CTNNA1". https://www.genecards.org/cgi-bin/carddisp.pl?gene=CTNNA1. 
  25. ↑ Reference, Genetics Home. "MLH1". https://ghr.nlm.nih.gov/gene/MLH1. 
  26. ↑ "www.genecards.org/cgi-bin/carddisp.pl?gene=PMS2". https://www.genecards.org/cgi-bin/carddisp.pl?gene=PMS2. 
  27. ↑ "PTEN phosphatase and tensin homolog [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/5728. 
  28. ↑ "PTPN12 protein tyrosine phosphatase, non-receptor type 12 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/5782. 
  29. ↑ 29.0 29.1 "www.genecards.org/cgi-bin/carddisp.pl?gene=SMAD4". https://www.genecards.org/cgi-bin/carddisp.pl?gene=SMAD4. 
  30. ↑ "STK11 serine/threonine kinase 11 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/6794. 
  31. ↑ "www.genecards.org/cgi-bin/carddisp.pl?gene=CDKN2A". https://www.genecards.org/cgi-bin/carddisp.pl?gene=CDKN2A. 
  32. ↑ "www.genecards.org/cgi-bin/carddisp.pl?gene=FLCN". https://www.genecards.org/cgi-bin/carddisp.pl?gene=FLCN. 
  33. ↑ "www.genecards.org/cgi-bin/carddisp.pl?gene=DLC1". https://www.genecards.org/cgi-bin/carddisp.pl?gene=DLC1. 
  34. ↑ "www.genecards.org/cgi-bin/carddisp.pl?gene=MLH3". https://www.genecards.org/cgi-bin/carddisp.pl?gene=MLH3. 
  35. ↑ "Candidate gene/loci studies in cleft lip/palate and dental anomalies finds novel susceptibility genes for clefts". Genetics in Medicine 10 (9): 668–74. September 2008. doi:10.1097/GIM.0b013e3181833793. PMID 18978678. 
  36. ↑ "TimeTree :: The Timescale of Life". http://www.timetree.org. 



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