The reference OMIM entry for this protein is 603335

Dynein, axonemal, heavy chain 5; dnah5
Hl1

CLONING

Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The dynein heavy chains (DHCs) are responsible for force production and ATPase activity and contain a highly conserved catalytic domain with 4 P-loop consensus motifs involved in nucleotide binding (Chapelin et al. (1997)). Two major classes of dyneins, axonemal and cytoplasmic, have been identified. See 603297. By PCR of human lung cDNA with degenerate primers based on the sequences surrounding the first P-loop region, Vaughan et al. (1996) isolated partial cDNAs encoding DNAH1 (603332), DNAH5, DNAH6 (603336), DHAH9 (603330), DNAH12 (603340), and DNAH14 (603341). They referred to DNAH5 as HL1. Sequence analysis revealed that DNAH5 is an axonemal DHC and is homologous to rat DLP5. Olbrich et al. (2002) obtained a full-length DNAH5 cDNA by PCR amplification of overlapping fragments from testis and trachea libraries and by RACE analyses. The composite transcript contained an open reading frame of 13,872 nucleotides, encoding a deduced 4,624-amino acid protein. Northern blot analysis using a cDNA probe corresponding to mouse Dnah5, which shares 91% sequence identity to the human homolog, detected strong expression of a 14-kb transcript in lung and kidney and weaker expression in brain, heart, and testis. In situ hybridization to whole mouse embryos detected weak expression confined to the node from 7.0 to 8.25 dpc.

GENE FUNCTION

Ibanez-Tallon et al. (2003) reviewed the roles of cilia in normal development, the pathologic consequences caused by their dysfunction in mammals, the evolutionary relationships between cilia from lower and higher eukaryotes, the ciliary components required for assembly and motility, and the terminology of axonemal heavy chain dynein genes.

GENE STRUCTURE

Olbrich et al. (2002) determined that the DNAH5 genomic region comprises 79 exons and spans 250 kb. By sequencing EST clones, they found evidence of an alternative first exon.

MAPPING

By analysis of an interspecific backcross, Vaughan et al. (1996) mapped the mouse Dnahc5 gene to chromosome 15. Omran et al. (2000) studied a large consanguineous family of Arabic origin with primary ciliary dyskinesia (608644). Direct examination of the respiratory cilia revealed ciliary akinesia and electron microscopy of cilia showed absence of the outer dynein arms. Two of 4 affected individuals exhibited a situs inversus, typical for Kartagener syndrome (see 608644), due to randomization of the left/right body axis. Omran et al. (2000) performed a total genome scan with 340 highly polymorphic microsatellites and localized the locus for primary ciliary dyskinesia in this family to a region of homozygosity by descent on chromosome 5p15-p14, with a maximum parametric multipoint lod score of 3.51, flanked by markers D5S2095 and D5S502 within an interval of 20 cM sex-averaged genetic distance. Applying a PCR-based approach, Omran et al. (2000) identified a 1.5-kb partial cDNA of DNAH5 within the critical disease interval of this locus.

MOLECULAR GENETICS

Primary ciliary dyskinesia is characterized by recurrent infections of the respiratory tract due to reduced mucociliary clearance and by sperm immotility. Half of affected individuals have situs inversus (reversed organs), which results from randomization of left-right asymmetry. In individuals with primary ciliary dyskinesia-3 (CILD3; 608644) with randomi ... More on the omim web site

Subscribe to this protein entry history

July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 603335 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).