SOGA2

The SOGA2 gene is located from 8717369 - 8832775 on the short arm of chromosome 18 (18p11.22).[11]

There are two main paralogs to SOGA2: human protein SOGA1 and human protein SOGA3.[9] SOGA1 has been shown to be involved in suppression of glucose by autophagy.[12] The rate at which orthologs diverge from SOGA2 human(measured by % identity) places the approximate duplication event of SOGA1 from SOGA2 at ~254.1 MYA and the duplication event of SOGA3 from SOGA2 ~329.1 MYA.

Many orthologs have been identified in Eukaryotes.[9]

A graph of sequence identity to human SOGA2 as a function of time of divergence of human SOGA2 orthologs.

SOGA2 is conserved farthest back in its N-terminal region, where it contains its three domains of unknown function.[13]

A comparison of multiple sequence alignment of the N-terminal regions vs. C-terminal regions of distantly related SOGA2 orthologs. Here it is demonstrated that the N-terminal region is well conserved in organisms like the clawed frog (FROG_SOGA2) but the C-terminal region is not. Location 19 is an example of one of the 7 Leucine residue that is conserved across all orthologs.

SOGA2 is rich in glycine (ratio r of SOGA2 composition to average human protein is 1.723), glutamate (r = 1.647), and arginine (r = 1.357). It also has a lower than usual composition of tyrosine (r = 0.3406), isoleucine (r = 0.4430), phenylalanine (r = 0.5808), and valine (r = 0.6161).[14][15]

SOGA2 has 4 isoforms: Q9Y4B5-1, Q9Y4B5-2, Q9Y4B5-3, Q9Y4B5-4.[16]

A graphic depicting the 4 different isoforms of SOGA2. Isoform 1 is canonical. Modification Key: * E → ELRGPPVLPEQSVSIEELQGQLVQAARLHQEETETFTNKIHK **Q → QNCCGYPRINIEEETLGFTRLPAGSTVKTLKSLGLQRLE *** NQTVLLTAPWGL → ELPCSALAPS...LHGLSQYNSL

SOGA2 contains Domain of Unknown Function 4201 (DUF4201) from aa 16-235. This domain is specific to the Coiled Coil Domain Containing family of proteins in eukaryotes.[17] It also contains two copies of Domain of Unknown Function 3166 (DUF3166): one from aa 140-235 and one from aa 269-364.[11]

SOGA2 is expected to undergo a number of post-translational modifications. Modifications of human SOGA2 that are shared by orthologs include:

• Sumoylation at amino acids 87, 152, 235, 392, and 1379.[18]
• Sulfination at tyrosines 14 and 1249.[19]
• Phosphorylation at a number of sites, highlighted in the following graphic:

Phosphorylation sites in SOGA2 predicted by netPhos.[20] Highlighted sites are conserved as far back as African clawed frogs.

The consensus of the prediction software PELE,[21] GOR4,[22] and SOSUICoil is that the secondary structure of SOGA2 is dominated by alpha helices with interspersed regions of random coil. GOR4 indicated that SOGA2 is dominated by alpha-helices; it predicted a mere 5.61% of residues in an extended strand (parallel or antiparallel Beta-sheet) conformation, as opposed to 47.79% alpha helix and 46.6% random coils.

Secondary structure of human SOGA2 predicted by the GOR4 tool. h corresponds to alpha helices, c corresponds to random coils, and e corresponds to extended strand

[23]

SOGA2 shares sequence features in its highly conserved N-terminal region. This homology allows prediction of its tertiary structure on the basis of homology to published 3d structures via Phyre2[24] and NCBI structure.[25]

SOGA2's 3d structure predicted by Phyre2.[24] Structure is based on the crystal structure of tropomyosin at 7 angstrom resolution, with 12% identity. 283 residues match, in the CCDC containing N-terminal region.

1I84 S, Heavy Meromyosin Subfragment Of Chicken Gizzard Smooth Muscle Myosin With Regulatory Light Chain In The Dephosphorylated State 3d structure. Highlighted region is conserved in SOGA2.[25]

The promoter for human SOGA2 is below.

The promoter of the human SOGA2 gene.

The EST profile shows that, in humans, SOGA2 is highly expressed in many sites throughout the body, including bone, brain, ear, eye, and many others.[26] There are a large number of transcripts in liver cancer samples. Human microarray data show that SOGA2 is moderately expressed, with especially high expression in brain (especially the cerebellum and hippocampus), colon, pituitary gland, small intestine, spinal cord, testis and fetal brain.[10] Brain-tissue-specific microarray data show that SOGA2 has high expression throughout the posterior lobe of the cerebellar hemispheres and posterial lobe of the vermis in the mouse brain. There is low expression in most other areas of the brain.[27]

In humans, the SOGA2 gene produces 17 different transcripts, 8 of which form a protein product (one undergoes nonsense mediated decay). The main transcript in humans is transcript ID ENST00000359865, or SOGA2-001.[28]

Possible transcription factors for human SOGA2 include:[29]

• Modulator recognition factor 2
• cAMP-responsive element binding protein 1
• alternative splicing variant of FOXP1
• MDS1/EVI1-like gene 1
• Ikaros 2, possible regulator of lymphocyte differentiation

Protein complex co-immunoprecipitation (Co-IP) experiments revealed interacting proteins such as cell death regulators, ATP-binding cassette (ABC) transporters and protein kinase A binding proteins.[30]

The 540 interacting proteins include ABCF1, ACTB, ACTL6A, BCLAF1, BCLAF1, CHEK1, and MAGEE2.[30]

K-nearest neighbor analysis by wolf pSort indicates that in humans, SOGA2 is focused mainly in the nucleus, cytoplasm, and the cytonuclear space. There is a small chance that it is localizes to the golgi.[31]

A number of protein interactants were also identified via the STRING database, including MARK2, MARK4, and PPP2R2B.