# TRAPPC14

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. C7orf43 has no other human alias, but in mice can be found as BC037034.

## Gene Locus

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

## mRNA
### Splice variants

MAP11 encodes 2 isoforms, the longest being C7orf43 isoform 1, which is 2585 base pairs long and has with 11 exons and 10 introns. C7orf43 isoform 1 encodes a protein that is 580 amino acids long and only has one polyadenylation site. 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.

### Tissue expression

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

### 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. There are several transcription factor binding sites located in this promoter, including binding sites for zinc fingers and Kruppel-like transcription factors. 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
### 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. 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. 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 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. 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. No C7orf43 orthologs can be found outside the animal kingdom. The following table lists representative C7orf43 orthologs across multiple animal classes.

#### Strict orthologs

| 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

| 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

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

### 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. An analysis using the PELE tool from SDSC Biology Workbench predicted mostly beta sheets and random coils that are conserved throughout the strict orthologs. 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. C7orf43 was found to interact with angiomotin-like protein 2 (AMOTL2), also known as Leman Coiled-Coil Protein (LCCP), a regulator of Hippo signaling. 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.
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). 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). 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. TFAP2C has also been shown to have an oncogenic role by promotion of cell proliferation and tumour growth in neuroblastoma.
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.