SMARCAL1

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 is a protein that in humans is encoded by the SMARCAL1 gene.[5][6][7]

SMARCAL1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4MQV
Identifiers
Aliases	SMARCAL1, HARP, HHARP, SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1
External IDs	OMIM: 606622 MGI: 1859183 HomoloGene: 8558 GeneCards: SMARCAL1
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q35 Start 216,412,414 bp[1] End 216,483,053 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 C3|1 36.72 cM Start 72,583,251 bp[2] End 72,633,134 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • nucleotide binding • DNA-dependent ATPase activity • GO:0001948 protein binding • hydrolase activity • ATP binding • GO:0008026 helicase activity • annealing helicase activity Cellular component • site of double-strand break • DNA replication factor A complex • cell nucleus • nucleoplasm • nuclear replication fork Biological process • regulation of transcription from RNA polymerase II promoter • DNA metabolic process • cellular response to DNA damage stimulus • DNA strand renaturation • t-circle formation • DNA repair • replication fork processing • DNA rewinding • replication fork protection Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	50485	54380
Ensembl	ENSG00000138375	ENSMUSG00000039354
UniProt	Q9NZC9	Q8BJL0
RefSeq (mRNA)	NM_001127207 NM_014140	NM_018817
RefSeq (protein)	NP_001120679 NP_054859	NP_061287
Location (UCSC)	Chr 2: 216.41 – 216.48 Mb	Chr 1: 72.58 – 72.63 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The SMARCAL1 protein convert RPA-bound, single stranded DNA into double-stranded DNA, an enzyme activity termed "annealing helicase".[8]

The encoded protein shows sequence similarity to the E. coli RNA polymerase-binding protein HepA. Mutations in this gene are a cause of Schimke immunoosseous dysplasia (SIOD), an autosomal recessive disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction, and T-cell immunodeficiency.[7]

Model organisms

Smarcal1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Homozygous Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Heart weight	Normal
Brain histopathology	Abnormal
All tests and analysis from[9][10]

Model organisms have been used in the study of SMARCAL1 function. A conditional knockout mouse line, called Smarcal1^{tm1a(EUCOMM)Wtsi}[11][12] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[13][14][15]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty tests were carried out and one significant phenotype was observed: homozygous mutant mice had abnormal brain histopathology, including an enlarged hippocampus and a thickened hippocampus stratum oriens.[9]

References

1. GRCh38: Ensembl release 89: ENSG00000138375 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000039354 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Muthuswami R, Truman PA, Mesner LD, Hockensmith JW (Mar 2000). "A eukaryotic SWI2/SNF2 domain, an exquisite detector of double-stranded to single-stranded DNA transition elements". The Journal of Biological Chemistry. 275 (11): 7648–55. doi:10.1074/jbc.275.11.7648. PMID 10713074.
6. Coleman MA, Eisen JA, Mohrenweiser HW (May 2000). "Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse". Genomics. 65 (3): 274–82. CiteSeerX 10.1.1.186.4879. doi:10.1006/geno.2000.6174. PMID 10857751.
7. "Entrez Gene: SMARCAL1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a-like 1".
8. Yusufzai T, Kadonaga JT (Oct 2008). "HARP is an ATP-driven annealing helicase". Science. 322 (5902): 748–50. doi:10.1126/science.1161233. PMC 2587503. PMID 18974355. Lay summary – ScienceDaily (2008-11-02).
9. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
10. Mouse Resources Portal, Wellcome Trust Sanger Institute.
11. "International Knockout Mouse Consortium".
12. "Mouse Genome Informatics".
13. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
14. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
15. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
16. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Boerkoel CF, Takashima H, John J, Yan J, Stankiewicz P, Rosenbarker L, André JL, Bogdanovic R, Burguet A, Cockfield S, Cordeiro I, Fründ S, Illies F, Joseph M, Kaitila I, Lama G, Loirat C, McLeod DR, Milford DV, Petty EM, Rodrigo F, Saraiva JM, Schmidt B, Smith GC, Spranger J, Stein A, Thiele H, Tizard J, Weksberg R, Lupski JR, Stockton DW (Feb 2002). "Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia". Nature Genetics. 30 (2): 215–20. doi:10.1038/ng821. PMID 11799392. S2CID 8954897.
• Lou S, Lamfers P, McGuire N, Boerkoel CF (Dec 2002). "Longevity in Schimke immuno-osseous dysplasia". Journal of Medical Genetics. 39 (12): 922–5. doi:10.1136/jmg.39.12.922. PMC 1757210. PMID 12471207.
• Bökenkamp A, deJong M, van Wijk JA, Block D, van Hagen JM, Ludwig M (Dec 2005). "R561C missense mutation in the SMARCAL1 gene associated with mild Schimke immuno-osseous dysplasia". Pediatric Nephrology. 20 (12): 1724–8. doi:10.1007/s00467-005-2047-x. PMID 16237566. S2CID 35371382.
• Clewing JM, Antalfy BC, Lücke T, Najafian B, Marwedel KM, Hori A, Powel RM, Do AF, Najera L, SantaCruz K, Hicks MJ, Armstrong DL, Boerkoel CF (Feb 2007). "Schimke immuno-osseous dysplasia: a clinicopathological correlation". Journal of Medical Genetics. 44 (2): 122–30. doi:10.1136/jmg.2006.044313. PMC 2598061. PMID 16840568.

External links

• GeneReviews/NCBI/NIH/UW entry on Schimke Immunoosseous Dysplasia