SOGA2

MTCL1
Identifiers
Aliases	MTCL1, CCDC165, KIAA0802, SOGA2, microtubule crosslinking factor 1
External IDs	OMIM: 615766; MGI: 1915867; HomoloGene: 41017; GeneCards: MTCL1; OMA:MTCL1 - orthologs
Gene location (Human) Chr. Chromosome 18 (human) Band 18p11.22 Start 8,705,661 bp End 8,832,778 bp
Gene location (Mouse) Chr. Chromosome 17 (mouse) Band 17|17 E1.1 Start 66,643,977 bp End 66,756,745 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cerebellar cortex cerebellar hemisphere right hemisphere of cerebellum cerebellar vermis middle temporal gyrus muscle layer of sigmoid colon hair follicle Brodmann area 23 primary visual cortex retinal pigment epithelium Top expressed in neural layer of retina cerebellar vermis lobe of cerebellum trigeminal ganglion retinal pigment epithelium olfactory tubercle spinal ganglia lumbar spinal ganglion primary motor cortex pituitary gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity protein binding microtubule binding RNA binding Cellular component apical plasma membrane plasma membrane membrane cytoplasm midbody spindle pole cytoskeleton lateral plasma membrane extracellular space apicolateral plasma membrane microtubule bundle Biological process regulation of autophagy microtubule bundle formation establishment or maintenance of epithelial cell apical/basal polarity positive regulation of protein targeting to membrane Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23255 68617 Ensembl ENSG00000168502 ENSMUSG00000052105 UniProt Q9Y4B5 Q3UHU5 RefSeq (mRNA) NM_015210 NM_001114098 NM_172963 RefSeq (protein) NP_056025 NP_001365134 NP_001365135 NP_001365136 NP_001107570 NP_766551 Location (UCSC) Chr 18: 8.71 – 8.83 Mb Chr 17: 66.64 – 66.76 Mb PubMed search
Wikidata
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SOGA2, also known as Suppressor of glucose autophagy associated 2 or CCDC165, is a protein that in humans is encoded by the SOGA2 gene. SOGA2 has two human paralogs, SOGA1 and SOGA3. In humans, the gene coding sequence is 151,349 base pairs long, with an mRNA of 6092 base pairs, and a protein sequence of 1586 amino acids. The SOGA2 gene is conserved in gorilla, baboon, galago, rat, mouse, cat, and more. There is distant conservation seen in organisms such as zebra finches and anoles. SOGA2 is ubiquitously expressed in humans, with especially high expression in brain (especially the cerebellum and hippocampus), colon, pituitary gland, small intestine, spinal cord, testis and fetal brain.

Gene

Locus

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

Homology and Evolution

Paralogs

There are two main paralogs to SOGA2: human protein SOGA1 and human protein SOGA3. SOGA1 has been shown to be involved in suppression of glucose by autophagy. 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.

protein name	accession number	sequence length (aa)	sequence identity to human protein	notes
SOGA3	NP_001012279.1	947	58%	conserved in ~500 N-terminal aa
SOGA1 isoform 2	NP_954650.2	1016 aa	65%	conserved in first ~900 aa
SOGA1 isoform 1	NP_542194.2	1661	41%	conserved across the length of sequence except ~950-1150

Orthologs

Many orthologs have been identified in Eukaryotes.

common name	protein name	divergence from human lineage (MYA)	accession number	sequence length (aa)	sequence identity to human protein	protein domain differences
gorilla	protein SOGA2	8.8	XP_004059220.1	1586	99%
baboon	protein SOGA2	29	XP_003914218	1587	98%
galago	protein SOGA3	74	XP_003801047.1	1583	88%	DUF4201 not present
rat	CCDC165	92.3	XP_237548.6	2060	81%	DUF4201 not present
mouse	SOGA2	92.3	NP_001107570.1	1893	80%
house cat	protein SOGA2	94.2	XP_003995077.1	1700	84%	DUF4201 not present
cow	CCDC166	94.2	XP_581047.5	1525	74%	DUF4201 not present
African Elephant	CCDC167-like	98.7	XP_003406836.1	1544	73%
zebra Finch	protein SOGA2	296	XP_002193121.1	1598	69%	DUF4201 not present
Red JungleFowl	CCDC165	296	XP_423729.3	1600	70%	DUF4201 not present
Carolina anole	uncharacterized protein KIAA0802-like	296	XP_003225723.1	1839	67%	DUF4201 not present

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

Distant Homologs

common name	protein name	divergence from human lineage (MYA)	accession number	sequence length (aa)	sequence identity to human protein	protein domain differences
Tropical Clawed Frog	uncharacterized protein C20orf117-like	371.2	XP_002942331.1	1584	39%
purple sea urchin	uncharacterized protein LOC578090	742.9	XP_783370.2	1587	47%	DUF4201 not present
body louse	Centromeric protein E, putative	782.7	XP_002429877.1	2086	30%	no shared domains
southern house mosquito	conserved hypothetical protein	782.7	XP_001843754.1	1878	32%	no shared domains
porkworm	surface antigen repeat family protein	937.5	XP_003380263.1	2030	36%	no shared domains

Homologous Domains

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

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.

Protein

Protein internal composition

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).

Primary structure and isoforms

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

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

Domains and motifs

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. It also contains two copies of Domain of Unknown Function 3166 (DUF3166): one from aa 140-235 and one from aa 269-364.

Post-translational modifications

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.
• Sulfination at tyrosines 14 and 1249.
• Phosphorylation at a number of sites, highlighted in the following graphic:

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

Secondary structure

The consensus of the prediction software PELE, GOR4, 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

Tertiary structure

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 and NCBI structure.

SOGA2's 3d structure predicted by Phyre2. 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.

Gene expression

Promoter

The promoter for human SOGA2 is below.

The promoter of the human SOGA2 gene.

Gene expression data

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. 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. 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.

Transcript variants

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.

Function

Possible transcription factors

Possible transcription factors for human SOGA2 include:

• 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

Interactions

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.

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

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.

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

Clinical significance

SOGA2 has no currently known disease associations or mutations.

Further reading

• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Brajenovic M, Joberty G, Küster B, et al. (2004). "Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network". J. Biol. Chem. 279 (13): 12804–11. doi:10.1074/jbc.M312171200. PMID 14676191.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Nusbaum C, Zody MC, Borowsky ML, et al. (2005). "DNA sequence and analysis of human chromosome 18". Nature. 437 (7058): 551–5. Bibcode:2005Natur.437..551N. doi:10.1038/nature03983. PMID 16177791.
• Nousiainen M, Silljé HH, Sauer G, et al. (2006). "Phosphoproteome analysis of the human mitotic spindle". Proc. Natl. Acad. Sci. U.S.A. 103 (14): 5391–6. Bibcode:2006PNAS..103.5391N. doi:10.1073/pnas.0507066103. PMC 1459365. PMID 16565220.
• Beausoleil SA, Villén J, Gerber SA, et al. (2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nat. Biotechnol. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243. S2CID 14294292.
• Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.