ANKMY1 explained

Ankyrin Repeat And MYND Domain Containing 1 (ANKMY1) is a protein that in humans is encoded by the ANKMY1 gene. Known aliases of ANKMY1 include Zinc Finger Myeloid, Nervy and DEAF-1 or ZMYND13.

Gene

The ANKMY1 gene is located on the minus strand of chromosome 2, at 2q37.3 .[1] The gene begins at base position 240,479,422 and ends at position 240,577,988. The coding sequence is 3424 nucleotides long and contains 17 exons.

mRNA Expression

ANKMY1 is ubiquitously expressed in most tissue types in the body.[2]

Protein

The ANKMY1 protein is 941 amino acids long and weighs approximately 105.5 kDa.[3] The pI is 6.3.

Domains and motifs

ANKMY1 protein contains three MORN domains, seven ANK repeats and a single MYND zinc finger toward the end of the protein.[4]

Structure

The ANKMY1 protein contains both beta sheets and alpha helices. The MORN domains are exclusively beta sheets and the alpha helices appear only in the ANK domain.

Subcellular location

Subcellular location of ANKMY1 protein was found to primarily be in the cytosol.[5] However, ANKMY1 contains nuclear export signals and evidence of nuclear transport indicating it is able to travel between both the nucleus and cytosol.[6]

Post-translational modifications

ANKMY1 protein contains 3 sulfonated Tyrosines at positions 153, 155 and 162.[7] There is also a N-Glycosylation sites at 163.[8] ANKMY1 contains several (87) phosphorylation sites throughout.[9]

Homology

Paralogs

No paralogs were found for the ANKMY1 gene.

Orthologs

ANKMY1 has numerous orthologs, strictly among vertebrates. The oldest known ortholog for ANKMY1 is the sea lamprey, an organism that diverged nearly 599 million years ago.

Genus and SpeciesCommon NameTaxonomic GroupMedian Date of Divergence (MYA)Accession #Sequence Length (aa)Sequence Identity to Human Protein (%)Sequence Similarity to Human Protein (%)
Homo SapiensHumanPrimates0NP_057636.2941100100
Mirounga angustirostrisNorthern Elephant SealPinnipedia94XP_0543618516883137
Vombatus ursinusCommon WombatDiprotodontia160XP_02771730010684761
Ornithorhynchus anatinusPlatypusMonotremata180XP_02893500510544861
Cygnus atratusBlack SwanAnseriformes318XP_0505709468193953
Pelecanus crispusDalmatian PelicanPelecaniformes319XP_0094812727414256
Apteryx rowiOkarito Brown KiwiApterygiformes319XP_0259399588283849
Gopherus evgoodeiGoodes Thronscrub TortoiseTestudines319XP_03043180610414456
Alligator mississippiensisAmerican AlligatorCrocodylia319XP_01445406610244456
Dermochelys coriaceaLeatherback Sea TurtleTestudines319XP_04334791510544356
Sphaerodactylus townsendiTownsend's Least GeckoSquamata319XP_04836279610464053
Notechis scutatusMainland Tiger SnakeSquamata319XP_0265246369903650
Bombina bombinaFire-bellied ToadSalientia352XP_0535674909423953
Hyla sardaSardinian Tree FrogAnura352XP_0564205359523549
Rhinatrema bivittatumTwo-lined CaecilianGymnophiona352XP_02947231612603245
Latimeria chalumnaeWest Indian Ocean CoelacanthCoelacanthiformes413XP_01435420412233548
Chiloscyllium plagiosumWhite-Spotted Bamboo SharkOrectolobiformes462XP_04355772510553751
Amblyraja radiataThorny SkateRajiformes465XP_03288741710173751
Petromyzon marinusSea LampreyPetromyzontiformes599XP_03283100712652838
Table 1. Orthologs of ANKMY1 in humans. Sorted first by estimated date of divergence, then by sequence identity to human protein. ANKMY1 is only found in vertebrates, not invertebrates.

Function

The specific MYND finger of ANKMY1 is specialized for protein-protein interactions. MORN repeats are also associated with linking, more specifically linking parasites and their hosts together.[10] ANKMY1's fast evolution rate coupled with its binding capabilities make it a good candidate for cellular defense. ANKMY1 was found to interact with several proteins within the cell (Table 2).

Interacting proteins

NameFunctionSubcellular Location
MKRN2 Opposite StrandN/AGolgi Apparatus
THAP Domain Containing 4N/AMostly cytoplasm, some nucleus
Zinc Finger Protein  227May be involved in transcriptional regulationNucleus
Zygote Arrest Protein 1N/ACytoplasm
FERM, ARHGEF and pleckstrin domain-containing protein 2Plays a role in TNFSF11-mediated osteoclast differentiation, especially in podosome rearrangement and reorganization of the actin cytoskeleton. Regulates the activation of ITGB3, integrin signaling and cell adhesionCytosol
Stress-associated endoplasmic reticulum protein 2May protect unfolded target proteins against degradation and facilitate correct glycosylationEndoplasmic Reticulum
Thymidylate kinaseCatalyzes the conversion of dTMP to dTDPCytosol/Nucleus
Serine/threonine-protein Kinase 25Targets to the Golgi apparatus where it appears to regulate protein transport events, cell adhesion, and polarity complexes important for cell migration.Golgi/Extracellular
Paired Box Protein Pax-9Transcription factor required for normal development of thymus, parathyroid glands, ultimobranchial bodies, teeth, skeletal elements of skull and larynx as well as distal limbsNucleus
Receptor Transporter Protein 5N/ACytosol
Table 2. Potential ANKMY1 protein-protein interactions drawn from the STRING database. [11] "N/A" indicates unknown function.

Clinical significance

Missense mutations commonly resulting in oncogenic growths were identified at various sites within the coding region.[12] Via text-mining a link between increased expression of the ANKMY1 gene and longer time periods of metastasis-free survival in Osteosarcoma patients.[13] [14] [15] ANKMY1 also shows elevated expression in the omental adipose tissue of obese children.[16]

Notes and References

  1. Web site: Homo sapiens ankyrin repeat and MYND domain containing 1 (ANKMY1), transcript variant 1, mRNA. April 18, 2022. NCBI Nucleotide.
  2. Web site: TMEM212 transmembrane protein 212 [Homo sapiens (human)] - Gene - NCBI]. www.ncbi.nlm.nih.gov.
  3. Web site: ANKMY1 Gene - GeneCards | ANKY1 Protein | ANKY1 Antibody.
  4. Web site: InterPro . 2023-12-06 . www.ebi.ac.uk.
  5. Web site: Subcellular - ANKMY1 - The Human Protein Atlas . 2023-12-15 . www.proteinatlas.org.
  6. Web site: PSORT II Prediction . 2023-12-15 . psort.hgc.jp.
  7. Web site: Expasy Sulfinator tool .
  8. Web site: NetNGlyc 1.0 - DTU Health Tech - Bioinformatic Services. services.healthtech.dtu.dk.
  9. Web site: NetPhos 3.1 - DTU Health Tech - Bioinformatic Services . 2023-12-15 . services.healthtech.dtu.dk.
  10. Sajko S, Grishkovskaya I, Kostan J, Graewert M, Setiawan K, Trübestein L, Niedermüller K, Gehin C, Sponga A, Puchinger M, Gavin AC, Leonard TA, Svergun DI, Smith TK, Morriswood B, Djinovic-Carugo K . 6 . Structures of three MORN repeat proteins and a re-evaluation of the proposed lipid-binding properties of MORN repeats . PLOS ONE . 15 . 12 . e0242677 . 2020-12-09 . 33296386 . 7725318 . 10.1371/journal.pone.0242677 . free . 2020PLoSO..1542677S .
  11. Web site: STRING: functional protein association networks . 2023-12-06 . string-db.org.
  12. Web site: PhosphoSitePlus . 2023-12-06 . www.phosphosite.org.
  13. Wang F, Qin G, Liu J, Wang X, Ye B . Integrated Genome-Wide Methylation and Expression Analyses Reveal Key Regulators in Osteosarcoma . Computational and Mathematical Methods in Medicine . 2020 . 7067649 . 2020 . 32855654 . 7443031 . 10.1155/2020/7067649 . free .
  14. Chen H, Xing K, He X . The dJ/dS Ratio Test Reveals Hundreds of Novel Putative Cancer Drivers . Molecular Biology and Evolution . 32 . 8 . 2181–2185 . August 2015 . 25873590 . 4833070 . 10.1093/molbev/msv083 .
  15. Turi M, Anilkumar Sithara A, Hofmanová L, Žihala D, Radhakrishnan D, Vdovin A, Knápková S, Ševčíková T, Chyra Z, Jelínek T, Šimíček M, Gullà A, Anderson KC, Hájek R, Hrdinka M . 6 . Transcriptome Analysis of Diffuse Large B-Cell Lymphoma Cells Inducibly Expressing MyD88 L265P Mutation Identifies Upregulated CD44, LGALS3, NFKBIZ, and BATF as Downstream Targets of Oncogenic NF-κB Signaling . International Journal of Molecular Sciences . 24 . 6 . March 2023 . 5623 . 36982699 . 10057398 . 10.3390/ijms24065623 . free .
  16. Web site: GDS3688 / 220280_s_at . 2023-12-15 . www.ncbi.nlm.nih.gov.