SMC4
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Structural maintenance of chromosomes protein 4 (SMC-4) also known as chromosome-associated polypeptide C (CAP-C) or XCAP-C homolog is a protein that in humans is encoded by the SMC4 gene.[5][6][7] SMC-4 is a core subunit of condensin I and II, large protein complexes involved in high order chromosome organization,[8] including condensation and segregation.[9] SMC-4 protein is commonly associated with the SMC-2 protein, another protein complex within the SMC protein family. SMC-4 dimerizes with SMC-2, creating the flexible and dynamic structure of the condensin holocomplex.[8] An over-expression of the SMC-4 protein is shown to impact carcinogenesis.[10][11][9]
Structure and interactions
The primary 5 domain structure of SMC proteins is highly conserved among species. The basic structure of SMC proteins are characterized by a non-helical hinge group, separated by two anti-parallel α-helical coiled-coil domains, along with two Amino-terminal globular domains containing ATP hydrolytic sites, or nucleotide-binding motifs located at the C-terminus and N-terminus called the Walker A and Walker B motifs.[12]
In
In the condensin holocomplex, a protein subunit called kleisin joins the C-terminus and N-terminus ATPase end domains of both SMC-4 and SMC-2 proteins. when the condensin holocomplex is bound with ATP at these end domains, the condensin will assume a "closed" conformation state.[8] SMC-4 is a dynamic and flexible protein, allowing different domain components to occasionally interact with others. This is speculated to be involved in the mechanical ability of the complex when associated with chromosomes.[8] In budding yeast, these interactions may result in open "O" appearances, or collapsed B-shaped states as a result of its dynamic ability.[13]
Clinical significance
The SMC-4 protein is associated with abnormal cell and tumor growth, and involved with migration and invasion. In general, the presence of over-expressed SMC-4 proteins is thought to be correlated with carcinogenesis.[10]
It is found that an over-expression or down-regulation of the SMC-4 protein alters TGFβ/Smad signaling pathways in glioma cells. SMC-4-transduced glioma cells showed activation of the TGFβ/Smad signaling pathway which was not present in SMC-4 silenced glioma cells. This pathway was shown to be correlated with an "aggressive" behavioral phenotype in glioma cells. An over-expression of SMC-4 can induce a higher rate of proliferation, and ultimately increased invasive capability. A down-regulation of SMC-4 reduced this quality.[10]
The SMC-4 protein is involved with normal lung development however, adenocarcinoma lung tissue shows an over-expression of SMC-4. additionally, SMC-4 may act as independent prognostic factor for carcinogenesis and lung adenocarcinoma.[9]
Studies suggest that over-expression of the SMC-4 protein in human liver tissue may be correlated with progression of hepatocellular carcinoma.[11]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000113810 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034349 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: SMC4 structural maintenance of chromosomes 4".
- PMID 10319587.
- PMID 9789013.
- ^ PMID 26904946.
- ^ PMID 27687868.
- ^ PMID 28287612.
- ^ PMID 24980149.
- S2CID 45664625.
- S2CID 222146992.
Further reading
- Hirano T (February 2002). "The ABCs of SMC proteins: two-armed ATPases for chromosome condensation, cohesion, and repair". Genes & Development. 16 (4): 399–414. PMID 11850403.
- Ball AR, Yokomori K (2001). "The structural maintenance of chromosomes (SMC) family of proteins in mammals". Chromosome Research. 9 (2): 85–96. S2CID 23761326.
- Ham MF, Takakuwa T, Rahadiani N, Tresnasari K, Nakajima H, Aozasa K (July 2007). "Condensin mutations and abnormal chromosomal structures in pyothorax-associated lymphoma". Cancer Science. 98 (7): 1041–1047. S2CID 25888221.
- Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R (April 2006). "Phosphoproteome analysis of the human mitotic spindle". Proceedings of the National Academy of Sciences of the United States of America. 103 (14): 5391–5396. PMID 16565220.
- Geiman TM, Sankpal UT, Robertson AK, Chen Y, Mazumdar M, Heale JT, et al. (2004). "Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery". Nucleic Acids Research. 32 (9): 2716–2729. PMID 15148359.
- Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–435. PMID 11230166.
- Kimura K, Cuvier O, Hirano T (February 2001). "Chromosome condensation by a human condensin complex in Xenopus egg extracts". The Journal of Biological Chemistry. 276 (8): 5417–5420. PMID 11136719.
- Schmiesing JA, Gregson HC, Zhou S, Yokomori K (September 2000). "A human condensin complex containing hCAP-C-hCAP-E and CNAP1, a homolog of Xenopus XCAP-D2, colocalizes with phosphorylated histone H3 during the early stage of mitotic chromosome condensation". Molecular and Cellular Biology. 20 (18): 6996–7006. PMID 10958694.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. PMID 9373149.
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. PMID 8125298.
External links
- SMC4 human gene location in the UCSC Genome Browser.
- SMC4 human gene details in the UCSC Genome Browser.
- PDBe-KB provides an overview of all the structure information available in the PDB for Human Structural maintenance of chromosomes protein 4 (SMC4)
- PDBe-KB provides an overview of all the structure information available in the PDB for Mouse Structural maintenance of chromosomes protein 4 (SMC4)