Proteins of the neuroblastoma breakpoint family (NBPF) contain a highly conserved domain of unknown function, which is known as NBPF, also known as Olduvai [ (PUBMED:16079250) ] or DUF1220 [ (PUBMED:19850849) ]. The NBPF/DUF1220 domain is present in multiple copies in NBPF proteins and once, with lower homology, in mammalian myomegalin, a protein localised in the Golgi/centrosomal area which functions as an anchor to localise components of the cyclic adenosine monophosphate-dependent pathway to this region. The implications of the resemblance of NBPF proteins to myomegalin remain obscure.
NBPF domains are typically built of two exons [ (PUBMED:16079250) (PUBMED:16946073) ]. The number of NBPF repeat copies is highly expanded in humans, reduced in African great apes, further reduced in orangutan and Old World monkeys, single-copy in nonprimate mammals, and absent in nonmammalian species. The NBPF domain that is found as a singly copy in nonprimate mammals is the likely ancestral domain. Studies suggest an association between NBPF/DUF1220 copy number and brain size, and more specifically neocortex volume [ (PUBMED:26112965) ]. An association has been established between DUF1220 subtype CON1 copy number and autism severity [ (PUBMED:25758905) ], and between subtype CON2 copy number and cognitive function [ (PUBMED:25287832) ].
Family alignment:
There are 2459 DUF1220 domains in 1036 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing DUF1220 domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with DUF1220 domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing DUF1220 domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
DUF1220 domains, cognitive disease, and human brain evolution.
Cold Spring Harb Symp Quant Biol. 2009; 74: 375-82
Display abstract
We have established that human genome sequences encoding a novel protein domain, DUF1220, show a dramatically elevated copy number in the human lineage (>200copies in humans vs. 1 in mouse/rat) and may be important to human evolutionaryadaptation. Copy-number variations (CNVs) in the 1q21.1 region, where mostDUF1220 sequences map, have now been implicated in numerous diseases associatedwith cognitive dysfunction, including autism, autism spectrum disorder, mentalretardation, schizophrenia, microcephaly, and macrocephaly. We report here thatthese disease-related 1q21.1 CNVs either encompass or are directly flanked byDUF1220 sequences and exhibit a dosage-related correlation with human brain size.Microcephaly-producing 1q21.1 CNVs are deletions, whereas macrocephaly-producing 1q21.1 CNVs are duplications. Similarly, 1q21.1 deletions and smaller brain size are linked with schizophrenia, whereas 1q21.1 duplications and larger brain size are associated with autism. Interestingly, these two diseases are thought to bephenotypic opposites. These data suggest a model which proposes that (1) DUF1220 domain copy number may be involved in influencing human brain size and (2) theevolutionary advantage of rapidly increasing DUF1220 copy number in the humanlineage has resulted in favoring retention of the high genomic instability of the1q21.1 region, which, in turn, has precipitated a spectrum of recurrent humanbrain and developmental disorders.
Links (links to other resources describing this domain)
