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TRAPPC14

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TRAPPC14
Identifiers
AliasesTRAPPC14, trafficking protein particle complex subunit 14, microtubule associated protein 11, chromosome 7 open reading frame 43, C7orf43, MCPH25, MAP11
External IDsOMIM: 618350; MGI: 2385896; HomoloGene: 10106; GeneCards: TRAPPC14; OMA:TRAPPC14 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

55262

231807

Ensembl

ENSG00000146826

ENSMUSG00000036948

UniProt

Q8WVR3

Q3UTZ3

RefSeq (mRNA)

NM_018275
NM_001303470

NM_153161

RefSeq (protein)

NP_001290399
NP_060745

NP_694801

Location (UCSC)Chr 7: 100.15 – 100.16 MbChr 5: 138.26 – 138.26 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

TRAPPC14 (trafficking protein particle complex subunit 14) also known as MAP11 (microtubule-associated protein 11) is a protein that in human is encoded by the gene TRAPPC14. It was previously referred to by the generic name C7orf43.[5] C7orf43 has no other human alias, but in mice can be found as BC037034.[6]

Gene Locus

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In humans, MAP11 is located in the long arm of human chromosome 7 (7q22.1), and is on the negative (antisense) strand.[5] Genes located around C7orf43 include GAL3ST4, LAMTOR4, GPC2.[5] 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.[7]

Gene neighbourhood of C7orf43 in human chromosome 7

mRNA

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Splice variants

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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.[5] C7orf43 isoform 1 encodes a protein that is 580 amino acids long and only has one polyadenylation site.[5] 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.[8]

Tissue expression

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MAP11 has a widespread moderate expression with tissue to tissue variability in humans and across mammalian species.[9][10] The mouse C7orf43 ortholog has been shown to be ubiquitously expressed in the brain,[11] as well as in the mouse embryonic central nervous system.[12]

Regulations

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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.[13] There are several transcription factor binding sites located in this promoter, including binding sites for zinc fingers and Kruppel-like transcription factors.[14] The top 20 transcription binding sites as predicted by the ElDorado from Genomatix is listed in the following table.

Detailed Family Information Detailed Matrix Information Start Position End Position Anchor Position Strand Matrix Similarity Score Sequence
Brachyury gene, mesoderm developmental factor T-box transcription factor TBX20 617 645 631 + 1 agcagccggAGGTgtcgggaccctctgga
C2H2 zinc finger transcription factors 2 KRAB-containing zinc finger protein 300 596 618 607 + 1 ccggccgCCCCagccgggcgcag
Fork head domain factors Alternative splicing variant of FOXP1, activated in ESCs 37 53 45 - 1 aaaaaaaAACAaccctt
Pleomorphic adenoma gene Pleomorphic adenoma gene 1 411 433 422 - 1 gaGGGGgcggggtcccgctgctc
Pleomorphic adenoma gene Pleomorphic adenoma gene 1 464 486 475 - 1 gaGGGGgcgtggccgccgaggcc
RNA polymerase II transcription factor II B Transcription factor II B (TFIIB) recognition element 197 203 200 + 1 ccgCGCC
TGF-beta induced apoptosis proteins Cysteine-serine-rich nuclear protein 1 (AXUD1, AXIN1 up-regulated 1) 73 79 76 - 1 AGAGtga
GC-Box factors SP1/GC Stimulating protein 1, ubiquitous zinc finger transcription factor 418 434 426 - 0.998 ggaggGGGCggggtccc
Human and murine ETS1 factors Ets variant 3 486 506 496 - 0.996 gagaaacaGGAAgcggaaggg
Krueppel like transcription factors Gut-enriched Krueppel-like factor / KLF4 469 485 477 - 0.994 agggggcGTGGccgccg
Two-handed zinc finger homeodomain transcription factors AREB6 (Atp1a1 regulatory element binding factor 6) 495 507 501 + 0.994 ttcctGTTTctct
Zinc finger transcription factor RU49, zinc finger proliferation 1 - Zipro1 Zinc 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. 522 528 525 + 0.994 cAGTAcc
Krueppel like transcription factors Core promoter-binding protein (CPBP) with 3 Krueppel-type zinc fingers (KLF6, ZF9) 418 434 426 - 0.992 ggagGGGGcggggtccc
C2H2 zinc finger transcription factors 7 Zinc finger protein 263, ZKSCAN12 (zinc finger protein with KRAB and SCAN domains 12) 425 439 432 + 0.99 cgccccCTCCtccac
C2H2 zinc finger transcription factors 6 Zinc finger and BTB domain containing 7, Proto-oncogene FBI-1, Pokémon (secondary DNA binding preference) 252 264 258 - 0.989 caaGACCaccctg
Krueppel like transcription factors Kruppel-like factor 7 (ubiquitous, UKLF) 416 432 424 - 0.989 agggGGCGgggtcccgc
GC-Box factors SP1/GC Sp4 transcription factor 471 487 479 - 0.986 ggagggGGCGtggccgc
Krueppel like transcription factors Gut-enriched Krueppel-like factor 137 153 145 + 0.986 gggctcAAAGgatcctc
Krueppel like transcription factors Krueppel-like factor 2 (lung) (LKLF) 641 657 649 - 0.986 cgctaGGGTgggtccag
Human and murine ETS1 factors Ets variant 1 6 26 16 - 0.984 ttctcccaGGAAgattctcca

Protein

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Composition and Domains

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The human protein MAP11 has an isoelectric point of 8.94. MAP11 also has a glycine-rich region spanning amino acids 54 through 134.[15] 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.[16][17] 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 [16][17] 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.[18] This vacuolar targeting motif is shown to be conserved throughout mammals, reptiles, birds, amphibians, and bony fishes.

Evolutionary history

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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.[19] No C7orf43 orthologs can be found outside the animal kingdom.[19] The following table lists representative C7orf43 orthologs across multiple animal classes.

Strict orthologs

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No. Species Common Name Date of Divergence (MYA) Accession No. E-value Length (aa) Identity (%) Similarity (%)
1 Homo sapiens Human - NP_060745.3 0.0 580 100 100
2 Pan troglodytes Common Chimpanzee 6.3 XP_009452032 0.0 580 99 100
3 Macaca mulatta Macaque 29.0 XP_001102238 0.0 580 99 99
4 Cavia porcellus Guinea pig 92.3 XP_003470051 0.0 580 98 98
5 Sus scrofa Wild boar 94.2 XP_003124386 0.0 580 98 99
6 Odobenus rosmarus divergens Walrus 94.2 XP_004399075 0.0 580 98 98
7 Tursiops truncates Common bottlenose dolphin 94.2 XP_004315199 0.0 582 92 93
8 Echinops telfairi Lesser hedgehog tenrec 98.7 XP_004705644 0.0 581 95 97
9 Dasypus novemcinctus Nine-banded armadillo 104.2 XP_004457234 0.0 580 97 98
10 Monodelphis domestica Gray short-tailed opossum 162.6 XP_001367097 0.0 568 89 92
11 Chrysemys picta bellii Painted turtle 296.0 XP_008175974 0.0 572 76 83
12 Alligator mississippiensis American alligator 296.0 XP_006266384 0.0 582 75 82
13 Pelodiscus sinensis Chinese softshell turtle 296.0 XP_006127325 0.0 569 73 81
14 Xenopus tropicalis Western clawed frog 371.2 NP_001121523 0.0 580 64 74
15 Oncorhynchus mykiss Rainbow trout 400.1 CDQ84878 0.0 581 64 75
16 Danio rerio Zebrafish 400.1 XP_001339329 0.0 595 63 74
17 Oryzias latipes Japanese rice fish 400.1 XP_004076807 0.0 609 62 70
18 Takifugu rubripes Pufferfish 400.1 XP_003970822 0.0 618 61 71

Distant orthologs

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No. Species Common Name Date of Divergence (MYA) Accession No. E-value Length (aa) Identity (%) Similarity (%)
1 Nipponia Nippon Crested ibis 296.0 XP_009472339 0.0 503 80 88
2 Charadrius vociferous Killdeer 296.0 XP_009892747 0.0 456 82 90
3 Pseudopodoces humilis Ground tit 296.0 XP_005533426 0.0 600 66 76
4 Latimeria chalumnae West Indian Ocean coelacanth 414.9 XP_006011612 3E-177 429 65 75
5 Branchiostoma floridae Florida lancelet 713.2 XP_002592972 9E-67 557 32 46
6 Strongylocentrotus purpuratus Purple sea urchin 742.9 XP_003727419 3E-46 725 35 51
7 Aplysia californica California sea slug 782.7 XP_005113015 4E-21 692 25 39
8 Nematostella vectensis Starlet sea anemone 855.3 XP_001632706 4E-19 494 24 39
9 Trichoplax adhaerens - - XP_002108809 5E-15 645 24 41

Post-translational modifications

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C7orf43 has three phosphorylated sites, Ser 517, Thr 541 and, Ser 546.[15] 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.[20] However, C7orf43 is predicted to have one N-acetylation on a serine residue at the N-terminus.[21]

Secondary structure

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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.[22][23] An analysis using the PELE tool from SDSC Biology Workbench predicted mostly beta sheets and random coils that are conserved throughout the strict orthologs.[17] Similarly conserved alpha helix motifs have been predicted, one near the N-terminus and one near the C-terminus.

Clinical significance

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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.[24] C7orf43 was found to interact with angiomotin-like protein 2 (AMOTL2), also known as Leman Coiled-Coil Protein (LCCP), a regulator of Hippo signaling.[24][25] 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.[25]

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).[26][27][28] 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).[29] 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.[29][30] TFAP2C has also been shown to have an oncogenic role by promotion of cell proliferation and tumour growth in neuroblastoma.[31][32]

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.[33]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000146826 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000036948 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d e "C7orf43 chromosome 7 open reading frame 43 [ Homo sapiens (human) ]". NCBI Gene. Retrieved 9 May 2015.
  6. ^ "BC037034 cDNA sequence BC037034 [ Mus musculus (house mouse) ]". NCBI Gene. Retrieved 9 May 2015.
  7. ^ "C7orf43 UCSC Genome Browser". UCSC Genome Browser. Retrieved 1 May 2015.
  8. ^ "Q8WVR3 -CG043_HUMAN". UniProt. Retrieved 8 May 2015.
  9. ^ "C7orf43-Large-scale analysis of the human transcriptome (HG-U133A)". NCBI GEO Profiles. Retrieved 2 April 2015.
  10. ^ "C7orf43-Multiple normal tissues". NCBI GEO Profiles. Retrieved 2 April 2015.
  11. ^ "BC037034-sagittal". Allen Brain Atlas. Retrieved 2 April 2015.
  12. ^ "BC037034 expression". GenePaint. Retrieved 2 April 2015.
  13. ^ "C7orf43 promoter GXP_116482". Genomatix. Retrieved 5 April 2015.
  14. ^ "C7orf43-promoter binding sites". Genomatix. Retrieved 5 April 2015.
  15. ^ a b "Uncharacterized protein C7orf43 [Homo sapiens]". NCBI Protein. Retrieved 8 May 2015.
  16. ^ a b Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S (March 1992). "Methods and algorithms for statistical analysis of protein sequences". Proceedings of the National Academy of Sciences of the United States of America. 89 (6). Proc. Natl. Acad. Sci. U.S.A.: 2002–2006. Bibcode:1992PNAS...89.2002B. doi:10.1073/pnas.89.6.2002. PMC 48584. PMID 1549558.
  17. ^ a b c "SDSC Biology Workbench". Department of Bioengineering. University of California San Diego. Retrieved 1 May 2015.
  18. ^ 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): 34–36. doi:10.1016/s0968-0004(98)01336-x. PMID 10087920.
  19. ^ a b "BLAST: Basic Local Alignment Search Tool". Conserved Domain Database. National Center for Biotechnology Information. Retrieved 2015-03-01.
  20. ^ "Myristoylator". ExPASy Bioinformatics Resource Portal. Retrieved 9 May 2015.
  21. ^ "NetAcet 1.0 Server". CBS. Retrieved 9 May 2015.
  22. ^ "Transmembrane Topology". Phobius. Stockholm Bioinformatics Centre. Retrieved 1 May 2015.
  23. ^ "SOSUI". Classification and Secondary Structure Prediction of Membrane Proteins. Mitaku Group.
  24. ^ a b Couzens AL, Knight JD, Kean MJ, Teo G, Weiss A, Dunham WH, et al. (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.
  25. ^ a b "Q9Y2J4 - AMOL2_HUMAN". UniProt. Retrieved 30 April 2015.
  26. ^ Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, et al. (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.
  27. ^ "Q7RU07 - Q7RU07_HUMAN". UniProt. Retrieved 8 May 2015.
  28. ^ "TMEM50A transmembrane protein 50A [ Homo sapiens (human) ]". NCBI Gene. Retrieved 9 May 2015.
  29. ^ a b Woodfield GW, Chen Y, Bair TB, Domann FE, Weigel RJ (October 2010). "Identification of primary gene targets of TFAP2C in hormone responsive breast carcinoma cells". Genes, Chromosomes & Cancer. 49 (10): 948–962. doi:10.1002/gcc.20807. PMC 2928401. PMID 20629094.
  30. ^ Ailan H, Xiangwen X, Daolong R, Lu G, Xiaofeng D, Xi Q, et al. (August 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.
  31. ^ Gao SL, Wang LZ, Liu HY, Liu DL, Xie LM, Zhang ZW (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.
  32. ^ Begon DY, Delacroix L, Vernimmen D, Jackers P, Winkler R (July 2005). "Yin Yang 1 cooperates with activator protein 2 to stimulate ERBB2 gene expression in mammary cancer cells". The Journal of Biological Chemistry. 280 (26): 24428–24434. doi:10.1074/jbc.M503790200. PMID 15870067.
  33. ^ Brezinová J, Zemanová Z, Ransdorfová S, Pavlistová L, Babická L, Housková L, et al. (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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