MAP11

MAP11 (Microtubule-associated protein 11) is a protein that in human is encoded by the gene MAP11. It was previously referred to by the generic name C7orf43.[1] C7orf43 has no other human alias, but in mice can be found as BC037034.[2]

MAP11
Identifiers
Aliases
External IDsGeneCards:
Orthologs
SpeciesHumanMouse
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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Gene Locus

In humans, MAP11 is located in the long arm of human chromosome 7 (7q22.1), and is on the negative (antisense) strand.[1] Genes located around C7orf43 include GAL3ST4, LAMTOR4, GPC2.[1] In humans, C7orf43 has 9 detected common single-nucleotide polymorphisms (SNPs), all of which are located in non-coding regions and thus do not affect amino acid sequence.[3]

Gene neighbourhood of C7orf43 in human chromosome 7

mRNA

Splice variants

Primary transcript of C7orf43 isoform 1, showing 11 exons and 10 introns (NCBI Aceview:C7orf43)

MAP11 encodes 2 isoforms, the longest being C7orf43 isoform 1, which is 2585 base pairs long and has with 11 exons and 10 introns.[1] C7orf43 isoform 1 encodes a protein that is 580 amino acids long and only has one polyadenylation site.[1] C7orf43 isoform 2 is 2085 base pairs long and encodes a protein of 311 amino acids. Two additional isoforms has been reported on several occasions, encoding for proteins with 199 and 206 amino acids.[4]

Tissue expression

MAP11 has a widespread moderate expression with tissue to tissue variability in humans and across mammalian species.[5][6] The mouse C7orf43 ortholog has been shown to be ubiquitously expressed in the brain,[7] as well as in the mouse embryonic central nervous system.[8]

Regulations

MAP11 has one promoter region upstream of its transcription site, as predicted by Genomatix. This promoter is 657 base pairs long and is located at position 99756182 to 99756838 in the negative strand of chromosome 7.[9] There are several transcription factor binding sites located in this promoter, including binding sites for zinc fingers and Kruppel-like transcription factors.[10] The top 20 transcription binding sites as predicted by the ElDorado from Genomatix is listed in the following table.

Detailed Family InformationDetailed Matrix InformationStart PositionEnd PositionAnchor PositionStrandMatrix Similarity ScoreSequence
Brachyury gene, mesoderm developmental factorT-box transcription factor TBX20617645631+1agcagccggAGGTgtcgggaccctctgga
C2H2 zinc finger transcription factors 2KRAB-containing zinc finger protein 300596618607+1ccggccgCCCCagccgggcgcag
Fork head domain factorsAlternative splicing variant of FOXP1, activated in ESCs375345-1aaaaaaaAACAaccctt
Pleomorphic adenoma genePleomorphic adenoma gene 1411433422-1gaGGGGgcggggtcccgctgctc
Pleomorphic adenoma genePleomorphic adenoma gene 1464486475-1gaGGGGgcgtggccgccgaggcc
RNA polymerase II transcription factor II BTranscription factor II B (TFIIB) recognition element197203200+1ccgCGCC
TGF-beta induced apoptosis proteinsCysteine-serine-rich nuclear protein 1 (AXUD1, AXIN1 up-regulated 1)737976-1AGAGtga
GC-Box factors SP1/GCStimulating protein 1, ubiquitous zinc finger transcription factor418434426-0.998ggaggGGGCggggtccc
Human and murine ETS1 factorsEts variant 3486506496-0.996gagaaacaGGAAgcggaaggg
Krueppel like transcription factorsGut-enriched Krueppel-like factor / KLF4469485477-0.994agggggcGTGGccgccg
Two-handed zinc finger homeodomain transcription factorsAREB6 (Atp1a1 regulatory element binding factor 6)495507501+0.994ttcctGTTTctct
Zinc finger transcription factor RU49, zinc finger proliferation 1 - Zipro1Zinc finger transcription factor RU49 (zinc finger proliferation 1 - Zipro 1). RU49 exhibits a strong preference for binding to tandem repeats of the minimal RU49 consensus binding site.522528525+0.994cAGTAcc
Krueppel like transcription factorsCore promoter-binding protein (CPBP) with 3 Krueppel-type zinc fingers (KLF6, ZF9)418434426-0.992ggagGGGGcggggtccc
C2H2 zinc finger transcription factors 7Zinc finger protein 263, ZKSCAN12 (zinc finger protein with KRAB and SCAN domains 12)425439432+0.99cgccccCTCCtccac
C2H2 zinc finger transcription factors 6Zinc finger and BTB domain containing 7, Proto-oncogene FBI-1, Pokémon (secondary DNA binding preference)252264258-0.989caaGACCaccctg
Krueppel like transcription factorsKruppel-like factor 7 (ubiquitous, UKLF)416432424-0.989agggGGCGgggtcccgc
GC-Box factors SP1/GCSp4 transcription factor471487479-0.986ggagggGGCGtggccgc
Krueppel like transcription factorsGut-enriched Krueppel-like factor137153145+0.986gggctcAAAGgatcctc
Krueppel like transcription factorsKrueppel-like factor 2 (lung) (LKLF)641657649-0.986cgctaGGGTgggtccag
Human and murine ETS1 factorsEts variant 162616-0.984ttctcccaGGAAgattctcca

Protein

Composition and Domains

The human protein MAP11 has an isoelectric point of 8.94. MAP11 also has a glycine-rich region spanning amino acids 54 through 134.[11] Analysis using the SAPS tool from the SDSC Biology Workbench showed this glycine-rich region to not be conserved in terms of specific glycine residue positions, but is well conserved in overall glycine content in mammals and reptiles, although not in bony fishes.[12][13] C7orf43 is mostly uncharged, and this neutral charge distribution is conserved in mammals and reptiles, but bony fishes have at least one negative charge cluster [12][13] C7orf43 is predicted to have no signal peptide in its first 70 amino acid residues. However, it is predicted to have a vacuolar targeting motif starting at residue 258 in the human protein.[14] This vacuolar targeting motif is shown to be conserved throughout mammals, reptiles, birds, amphibians, and bony fishes.

Evolutionary history

The MAP11 protein has no paralogs in humans. However, C7orf43 orthologs can be found to be highly conserved in mammals, reptiles, and several species of bony fishes. C7orf43 is also conserved in birds, although several bird species lack parts of the N-terminus.[15] No C7orf43 orthologs can be found outside the animal kingdom.[15] The following table lists representative C7orf43 orthologs across multiple animal classes.

Strict orthologs

No.SpeciesCommon NameDate of Divergence (MYA)Accession No.E-valueLength (aa)Identity (%)Similarity (%)
1Homo sapiensHuman-NP_060745.30.0580100100
2Pan troglodytesCommon Chimpanzee6.3XP_0094520320.058099100
3Macaca mulattaMacaque29.0XP_0011022380.05809999
4Cavia porcellusGuinea pig92.3XP_0034700510.05809898
5Sus scrofaWild boar94.2XP_0031243860.05809899
6Odobenus rosmarus divergensWalrus94.2XP_0043990750.05809898
7Tursiops truncatesCommon bottlenose dolphin94.2XP_0043151990.05829293
8Echinops telfairiLesser hedgehog tenrec98.7XP_0047056440.05819597
9Dasypus novemcinctusNine-banded armadillo104.2XP_0044572340.05809798
10Monodelphis domesticaGray short-tailed opossum162.6XP_0013670970.05688992
11Chrysemys picta belliiPainted turtle296.0XP_0081759740.05727683
12Alligator mississippiensisAmerican alligator296.0XP_0062663840.05827582
13Pelodiscus sinensisChinese softshell turtle296.0XP_0061273250.05697381
14Xenopus tropicalisWestern clawed frog371.2NP_0011215230.05806474
15Oncorhynchus mykissRainbow trout400.1CDQ848780.05816475
16Danio rerioZebrafish400.1XP_0013393290.05956374
17Oryzias latipesJapanese rice fish400.1XP_0040768070.06096270
18Takifugu rubripesPufferfish400.1XP_0039708220.06186171

Distant orthologs

No.SpeciesCommon NameDate of Divergence (MYA)Accession No.E-valueLength (aa)Identity (%)Similarity (%)
1Nipponia NipponCrested ibis296.0XP_0094723390.05038088
2Charadrius vociferousKilldeer296.0XP_0098927470.04568290
3Pseudopodoces humilisGround tit296.0XP_0055334260.06006676
4Latimeria chalumnaeWest Indian Ocean coelacanth414.9XP_0060116123E-1774296575
5Branchiostoma floridaeFlorida lancelet713.2XP_0025929729E-675573246
6Strongylocentrotus purpuratusPurple sea urchin742.9XP_0037274193E-467253551
7Aplysia californicaCalifornia sea slug782.7XP_0051130154E-216922539
8Nematostella vectensisStarlet sea anemone855.3XP_0016327064E-194942439
9Trichoplax adhaerens--XP_0021088095E-156452441

Post-translational modifications

C7orf43 has three phosphorylated sites, Ser 517, Thr 541 and, Ser 546.[11] All three sites are relatively well-conserved throughout mammals, reptiles, birds, amphibians, and bony fishes. The protein has no predicted N-myristoylation, as it has no N-terminal glycine.[16] However, C7orf43 is predicted to have one N-acetylation on a serine residue at the N-terminus.[17]

Secondary structure

The secondary structure of C7orf43 is yet to be determined. However, C7orf43 is predicted to have no transmembrane domain and to eventually be secreted from the cell.[18][19] An analysis using the PELE tool from SDSC Biology Workbench predicted mostly beta sheets and random coils that are conserved throughout the strict orthologs.[13] Similarly conserved alpha helix motifs have been predicted, one near the N-terminus and one near the C-terminus.

Clinical significance

While no studies have focused on the characterization of C7orf43, several large-scale screenings have revealed information related to C7orf43 function. A study using FLAG affinity purification mass spectrometry (AP-MS) to profile protein interactions in the Hippo signaling pathway identified C7orf43 as one of the interacting proteins.[20] C7orf43 was found to interact with angiomotin-like protein 2 (AMOTL2), also known as Leman Coiled-Coil Protein (LCCP), a regulator of Hippo signaling.[20][21] AMOTL2 is also known to be an inhibitor of Wnt signaling, a pathway with known associations to cancer development, and to be a factor for angiogenesis, a process essential to tumour maintenance and metastasis.[21]

Several studies have linked C7orf43 to carcinomic events. Other studies have also linked C7orf43 to carcinomic events. A large-scale yeast two-hybrid experiment identified C7orf43 to be interacting with transmembrane protein 50A (TMEM50A), also known as cervical cancer gene 9 or small membrane protein 1 (SMP1).[22][23][24] While the exact function of TMEM50A is unknown, it has been associated with cervical cancer.

C7orf43 has also been identified as a target gene of the transcription factor AP-2 gamma (TFAP2C).[25] TFAP2C has been shown to be involved in the development, differentiation, and oncogenesis of mammary tissues. Specifically, TFAP2C has a role in breast carcinoma through its regulatory effect to ESR1 and ERBB2, both of which are receptors whose aberrations have been associated with breast carcinomas.[25][26] TFAP2C has also been shown to have an oncogenic role by promotion of cell proliferation and tumour growth in neuroblastoma.[27][28]

Through its location in the q arm of chromosome 7, C7orf43 has been linked to various diseases. Several diseases have been described as having deletions in the q arm of chromosome 7, among them are myeloid disorders, including acute myelogenous leukemia and myelodysplasia.[29]


References

  1. "C7orf43 chromosome 7 open reading frame 43 [ Homo sapiens (human) ]". NCBI Gene. Retrieved 9 May 2015.
  2. "BC037034 cDNA sequence BC037034 [ Mus musculus (house mouse) ]". NCBI Gene. Retrieved 9 May 2015.
  3. "C7orf43 UCSC Genome Browser". UCSC Genome Browser. Retrieved 1 May 2015.
  4. "Q8WVR3 -CG043_HUMAN". UniProt. Retrieved 8 May 2015.
  5. "C7orf43-Large-scale analysis of the human transcriptome (HG-U133A)". NCBI GEO Profiles. Retrieved 2 April 2015.
  6. "C7orf43-Multiple normal tissues". NCBI GEO Profiles. Retrieved 2 April 2015.
  7. "BC037034-sagittal". Allen Brain Atlas. Retrieved 2 April 2015.
  8. "BC037034 expression". GenePaint. Retrieved 2 April 2015.
  9. "C7orf43 promoter GXP_116482". Genomatix. Retrieved 5 April 2015.
  10. "C7orf43-promoter binding sites". Genomatix. Retrieved 5 April 2015.
  11. "Uncharacterized protein C7orf43 [Homo sapiens]". NCBI Protein. Retrieved 8 May 2015.
  12. Brendel, V.; Bucher, P.; Nourbakhsh, I.R.; Blaisdell, B.E. & Karlin, S. (1992). "Methods and algorithms for statistical analysis of protein sequences". SAPS (Statistical Analysis of PS). Proc. Natl. Acad. Sci. U.S.A. 89 (6): 2002–2006. Bibcode:1992PNAS...89.2002B. doi:10.1073/pnas.89.6.2002. PMC 48584. PMID 1549558. Retrieved 2015-04-26.
  13. "SDSC Biology Workbench". Department of Bioengineering. University of California Sand Diego. Retrieved 1 May 2015.
  14. Nakai, K; Horton, P (January 1999). "PSORT: a program for detecting sorting signals in proteins and predicting their subcellular localization". Trends in Biochemical Sciences. 24 (1): 34–6. doi:10.1016/s0968-0004(98)01336-x. PMID 10087920.
  15. "BLAST: Basic Local Alignment Search Tool". Conserved Domain Database. National Center for Biotechnology Information. Retrieved 2015-03-01.
  16. "Myristoylator". ExPASy Bioinformatics Resource Portal. Retrieved 9 May 2015.
  17. "NetAcet 1.0 Server". CBS. Retrieved 9 May 2015.
  18. "Transmembrane Topology". Phobius. Stockholm Bioinformatics Centre. Retrieved 1 May 2015.
  19. "SOSUI". Classification and Secondary Structure Prediction of Membrane Proteins. Mitaku Group.
  20. Couzens, A. L.; Knight, J. D. R.; Kean, M. J.; Teo, G.; Weiss, A.; Dunham, W. H.; Lin, Z.-Y.; Bagshaw, R. D.; Sicheri, F.; Pawson, T.; Wrana, J. L.; Choi, H.; Gingras, A.-C. (19 November 2013). "Protein Interaction Network of the Mammalian Hippo Pathway Reveals Mechanisms of Kinase-Phosphatase Interactions". Science Signaling. 6 (302): rs15. doi:10.1126/scisignal.2004712. PMID 24255178. S2CID 206672249.
  21. "Q9Y2J4 - AMOL2_HUMAN". UniProt. Retrieved 30 April 2015.
  22. Stelzl, Ulrich; Worm, Uwe; Lalowski, Maciej; Haenig, Christian; Brembeck, Felix H.; Goehler, Heike; Stroedicke, Martin; Zenkner, Martina; Schoenherr, Anke; Koeppen, Susanne; Timm, Jan; Mintzlaff, Sascha; Abraham, Claudia; Bock, Nicole; Kietzmann, Silvia; Goedde, Astrid; Toksöz, Engin; Droege, Anja; Krobitsch, Sylvia; Korn, Bernhard; Birchmeier, Walter; Lehrach, Hans; Wanker, Erich E. (September 2005). "A Human Protein-Protein Interaction Network: A Resource for Annotating the Proteome". Cell. 122 (6): 957–968. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923.
  23. "Q7RU07 - Q7RU07_HUMAN". UniProt. Retrieved 8 May 2015.
  24. "TMEM50A transmembrane protein 50A [ Homo sapiens (human) ]". NCBI Gene. Retrieved 9 May 2015.
  25. Woodfield, George W.; Chen, Yizhen; Bair, Thomas B.; Domann, Frederick E.; Weigel, Ronald J. (October 2010). "Identification of primary gene targets of TFAP2C in hormone responsive breast carcinoma cells". Genes, Chromosomes and Cancer. 49 (10): 948–962. doi:10.1002/gcc.20807. PMC 2928401. PMID 20629094.
  26. Ailan, He; Xiangwen, Xiao; Daolong, Ren; Lu, Gan; Xiaofeng, Ding; Xi, Qiao; Xingwang, Hu; Rushi, Liu; Jian, Zhang; Shuanglin, Xiang (2009). "Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells". BMC Cancer. 9 (1): 279. doi:10.1186/1471-2407-9-279. PMC 3224728. PMID 19671168.
  27. Gao, Shun-Li; Wang, Li-Zhong; Liu, Hai-Ying; Liu, Dan-Li; Xie, Li-Ming; Zhang, Zhi-Wei (15 June 2014). "miR-200a Inhibits Tumor Proliferation by Targeting AP-2γ in Neuroblastoma Cells". Asian Pacific Journal of Cancer Prevention. 15 (11): 4671–4676. doi:10.7314/APJCP.2014.15.11.4671. PMID 24969902.
  28. Begon, D. Y. (25 April 2005). "Yin Yang 1 Cooperates with Activator Protein 2 to Stimulate ERBB2 Gene Expression in Mammary Cancer Cells". Journal of Biological Chemistry. 280 (26): 24428–24434. doi:10.1074/jbc.M503790200. PMID 15870067.
  29. Březinová, Jana; Zemanová, Zuzana; Ransdorfová, Šárka; Pavlištová, Lenka; Babická, Libuše; Houšková, Lucie; Melicherčíková, Jela; Šišková, Magda; Čermák, Jaroslav; Michalová, Kyra (February 2007). "Structural aberrations of chromosome 7 revealed by a combination of molecular cytogenetic techniques in myeloid malignancies". Cancer Genetics and Cytogenetics. 173 (1): 10–16. doi:10.1016/j.cancergencyto.2006.09.003. PMID 17284364.

Further reading

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