KIDINS220 explained
Kinase D-interacting substrate of 220 kDa or ARMS (ankyrin repeat-rich membrane spanning) is a scaffold protein that in humans is encoded by the KIDINS220 gene.[1] [2] [3]
It is a downstream target of neuronal signaling events initiated by neutrophins and ephrins. Additionally, it was shown to have important roles in the immune system by interacting with the B-cell and T-cell receptor.[4] [5]
Molecular biology
The gene is located on the short arm of chromosome 2 (2p25.1) on the Crick strand. It is 116,550 bases in length. It encodes a transmembrane protein that is preferentially expressed in the nervous system. The protein acts as a receptor for the CRKL-C3G complex. Binding this complex results in Rap1-dependent sustained ERK activation. This, in turn, interacts with several pathways the effects of which are under active investigation.
Clinical importance
Heterozygous mutations of this gene have been suggested as a cause of a syndrome consisting of spastic paraplegia, intellectual disability, nystagmus and obesity. Knock out mice with homozygous mutations have non-viable offspring with enlarged cerebral ventricles. A consanginous couple has been reported who suffered from repeated miscarriages in whom homozygous mutations of this gene were found.[6] Post mortem showed enlarged cerebral ventricles and contracted limbs.
Further reading
- Kong H, Boulter J, Weber JL, Lai C, Chao MV . An evolutionarily conserved transmembrane protein that is a novel downstream target of neurotrophin and ephrin receptors . The Journal of Neuroscience . 21 . 1 . 176–85 . January 2001 . 11150334 . 10.1523/JNEUROSCI.21-01-00176.2001. 6762419 .
- Riol-Blanco L, Iglesias T, Sánchez-Sánchez N, de la Rosa G, Sánchez-Ruiloba L, Cabrera-Poch N, Torres A, Longo I, García-Bordas J, Longo N, Tejedor A, Sánchez-Mateos P, Rodríguez-Fernández JL . The neuronal protein Kidins220 localizes in a raft compartment at the leading edge of motile immature dendritic cells . European Journal of Immunology . 34 . 1 . 108–18 . January 2004 . 14971036 . 10.1002/eji.200324640 . 26864345 . free .
- Arévalo JC, Yano H, Teng KK, Chao MV . A unique pathway for sustained neurotrophin signaling through an ankyrin-rich membrane-spanning protein . The EMBO Journal . 23 . 12 . 2358–68 . June 2004 . 15167895 . 423292 . 10.1038/sj.emboj.7600253 .
- Chang MS, Arevalo JC, Chao MV . Ternary complex with Trk, p75, and an ankyrin-rich membrane spanning protein . Journal of Neuroscience Research . 78 . 2 . 186–92 . October 2004 . 15378608 . 10.1002/jnr.20262 . 39296669 .
- Bracale A, Cesca F, Neubrand VE, Newsome TP, Way M, Schiavo G . Kidins220/ARMS is transported by a kinesin-1-based mechanism likely to be involved in neuronal differentiation . Molecular Biology of the Cell . 18 . 1 . 142–52 . January 2007 . 17079733 . 1751333 . 10.1091/mbc.E06-05-0453 .
Notes and References
- Iglesias T, Cabrera-Poch N, Mitchell MP, Naven TJ, Rozengurt E, Schiavo G . Identification and cloning of Kidins220, a novel neuronal substrate of protein kinase D . The Journal of Biological Chemistry . 275 . 51 . 40048–56 . December 2000 . 10998417 . 10.1074/jbc.M005261200 . free .
- Nagase T, Ishikawa K, Kikuno R, Hirosawa M, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 6 . 5 . 337–45 . October 1999 . 10574462 . 10.1093/dnares/6.5.337 . free .
- Web site: Entrez Gene: KIDINS220 kinase D-interacting substance of 220 kDa .
- Fiala GJ, Janowska I, Prutek F, Hobeika E, Satapathy A, Sprenger A, Plum T, Seidl M, Dengjel J, Reth M, Cesca F, Brummer T, Minguet S, Schamel WW . Kidins220/ARMS binds to the B cell antigen receptor and regulates B cell development and activation . en . The Journal of Experimental Medicine . 212 . 10 . 1693–708 . September 2015 . 26324445 . 4577850 . 10.1084/jem.20141271 .
- Deswal S, Meyer A, Fiala GJ, Eisenhardt AE, Schmitt LC, Salek M, Brummer T, Acuto O, Schamel WW . Kidins220/ARMS associates with B-Raf and the TCR, promoting sustained Erk signaling in T cells . en . Journal of Immunology . 190 . 5 . 1927–35 . March 2013 . 23359496 . 10.4049/jimmunol.1200653 . free .
- Mero IL, Mørk HH, Sheng Y, Blomhoff A, Opheim GL, Erichsen A, Vigeland MD, Selmer KK (2017) Homozygous KIDINS220 loss-of-function variants in fetuses with cerebral ventriculomegaly and limb contractures. Hum Mol Genet 26(19):3792-3796