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 . 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.

Protein The ANKMY1 protein is 941 amino acids long and weighs approximately 105.5 kDa. 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.

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. However, ANKMY1 contains nuclear export signals and evidence of nuclear transport indicating it is able to travel between both the nucleus and cytosol.

Post-translational modifications ANKMY1 protein contains 3 sulfonated Tyrosines at positions 153, 155 and 162. There is also a N-Glycosylation sites at 163. ANKMY1 contains several (87) phosphorylation sites throughout.

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_057636.2941100100Mirounga angustirostrisNorthern Elephant SealPinnipedia94XP_0543618516883137Vombatus ursinusCommon WombatDiprotodontia160XP_02771730010684761Ornithorhynchus anatinusPlatypusMonotremata180XP_02893500510544861Cygnus atratusBlack SwanAnseriformes318XP_0505709468193953Pelecanus crispusDalmatian PelicanPelecaniformes319XP_0094812727414256Apteryx rowiOkarito Brown KiwiApterygiformes319XP_0259399588283849Gopherus evgoodeiGoodes Thronscrub TortoiseTestudines319XP_03043180610414456Alligator mississippiensisAmerican AlligatorCrocodylia319XP_01445406610244456Dermochelys coriaceaLeatherback Sea TurtleTestudines319XP_04334791510544356Sphaerodactylus townsendiTownsend's Least GeckoSquamata319XP_04836279610464053Notechis scutatusMainland tiger snakeSquamata319XP_0265246369903650Bombina bombinaFire-bellied ToadSalientia352XP_0535674909423953Hyla sardaSardinian Tree FrogAnura352XP_0564205359523549Rhinatrema bivittatumTwo-lined CaecilianGymnophiona352XP_02947231612603245Latimeria chalumnaeWest Indian Ocean CoelacanthCoelacanthiformes413XP_01435420412233548Chiloscyllium plagiosumWhite-Spotted Bamboo SharkOrectolobiformes462XP_04355772510553751Amblyraja radiataThorny SkateRajiformes465XP_03288741710173751Petromyzon 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. 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 Name Function Subcellular LocationMKRN2 Opposite StrandN/AGolgi Apparatus THAP Domain Containing 4N/AMostly cytoplasm, some nucleusZinc Finger Protein  227May be involved in transcriptional regulationNucleusZygote Arrest Protein 1N/ACytoplasmFERM, 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 adhesionCytosolStress-associated endoplasmic reticulum protein 2May protect unfolded target proteins against degradation and facilitate correct glycosylationEndoplasmic ReticulumThymidylate kinaseCatalyzes the conversion of dTMP to dTDPCytosol/NucleusSerine/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/ExtracellularPaired 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 limbsNucleusReceptor Transporter Protein 5N/ACytosol Table 2. Potential ANKMY1 protein-protein interactions drawn from the STRING database. "N/A" indicates unknown function.

Clinical significance

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

References