nesprin-2; nuclear envelope spectrin repeat protein 2; nucleus & actin connecting element protein; protein NUANCE; synaptic nuclear envelope protein 2; syne-2 (SYNE2, KIAA1011, NUA)

Function: - multi-isomeric modular protein which forms a linking network between organelles & the actin cytoskeleton to maintain the subcellular spatial organization - component of SUN-protein-containing multivariate complexes - involved in the maintenance of nuclear organization & structural integrity - connects nuclei to the cytoskeleton by interacting with the nuclear envelope & with F-actin in the cytoplasm - required for centrosome migration to the apical cell surface during early ciliogenesis - interacts with F-actin via its N-terminal domain - interacts with EMD, LMNA & MKS3 Structure: - the KASH domain mediates the nuclear envelope targeting - belongs to the nesprin family - contains 1 actin-binding domain - contains 2 CH (calponin-homology) domains - contains 1 KASH domain - contains 13 LRR repeats (leucine-rich repeats) - contains 9 spectrin repeats Compartment: - nuclear outer membrane - single-pass type 4 membrane protein; cytoplasmic side (putative) - sarcoplasmic reticulum membrane - plasma membrane - cytoplasm, cytoskeleton - mitochondrion - nucleus, nucleoplasm - different isoform patterns are found in different compartments of the cell - isoforms having the C-terminal transmembrane span can be found in several organellar membranes like the a) nuclear envelope b) sarcoplasmic reticulum of myoblasts c) lamellipodia & focal adhesions at the plasma membrane - the largest part of the outer nuclear membrane-associated protein is cytoplasmic, while its C-terminal part is associated with the nuclear envelope, most probably the outer nuclear membrane - remains associated with the nuclear envelope during its breakdown in mitotic cells - shorter solubles isoforms can be found in the cytoplasm & within the nucleus Alternative splicing: - named isoforms=9 - isoforms produced by exon skipping that results in a frameshift Expression: - widely expressed - high expression in kidney, adult & fetal liver, stomach & placenta - weak expression in skeletal muscle & brain - isoform 5 is highly expressed in pancreas, skeletal muscle & heart Pathology: - defects in SYNE2 are the cause of Emery-Dreifuss muscular dystrophy type 5

General

leucine-rich repeat-containing protein (LRRC) nesprin

Properties

SIZE: entity length = 6885 aa MW = 796 kD COMPARTMENT: mitochondria cytoplasm nuclear membrane MOTIF: actin-binding site SITE: 1-286 FOR-BINDING-OF: F-actin MOTIF: calponin homology domain NAME: calponin homology domain SITE: 31-136 calponin homology domain NAME: calponin homology domain SITE: 181-286 coiled coil {233-255} leucine-rich repeat SITE: 300-323 MOTIF: leucine residue (SEVERAL) coiled coil {306-323} coiled coil {461-477} coiled coil {810-909} MOTIF: Ser phosphorylation site {S841} coiled coil {941-972} coiled coil {1008-1041} coiled coil {1194-1222} coiled coil {1299-1332} leucine-rich repeat SITE: 1329-1352 MOTIF: leucine residue (SEVERAL) coiled coil {1462-1494} coiled coil {1566-1602} coiled coil {1658-1708} coiled coil {1747-1771} coiled coil {1782-1804} coiled coil {1923-1965} coiled coil {2007-2035} coiled coil {2176-2205} coiled coil {2282-2369} MOTIF: leucine-rich repeat SITE: 2292-2319 MOTIF: leucine residue (SEVERAL) coiled coil {2422-2478} coiled coil {2589-2650} Ser phosphorylation site {S2655} coiled coil {2696-2717} coiled coil {2802-2835} coiled coil {2866-2975} MOTIF: leucine-rich repeat SITE: 2914-2937 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 3004-3027 MOTIF: leucine residue (SEVERAL) coiled coil {3014-3057} leucine-rich repeat SITE: 3052-3075 MOTIF: leucine residue (SEVERAL) coiled coil {3087-3132} coiled coil {3207-3241} leucine-rich repeat SITE: 3230-3253 MOTIF: leucine residue (SEVERAL) coiled coil {3297-3428} coiled coil {3464-3505} coiled coil {3553-3584} coiled coil {3655-3723} coiled coil {3778-3799} coiled coil {3853-3911} leucine-rich repeat SITE: 3947-3969 MOTIF: leucine residue (SEVERAL) coiled coil {3971-4069} Ser phosphorylation site {S4108} Ser phosphorylation site {S4110} Tyr phosphorylation site {Y4111} coiled coil {4272-4299} coiled coil {4307-4339} coiled coil {4493-4536} coiled coil {4636-4701} coiled coil {4831-4861} coiled coil {4911-4944} spectrin repeat {4944-5053} spectrin repeat {5054-5167} spectrin repeat {5170-5274} coiled coil {5308-5346} MOTIF: leucine-rich repeat SITE: 5308-5330 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 5409-5431 MOTIF: leucine residue (SEVERAL) coiled coil {5428-5445} coiled coil {5505-5529} spectrin repeat {5852-5914} spectrin repeat {5917-6019} spectrin repeat {6022-6133} spectrin repeat {6136-6242} MOTIF: leucine-rich repeat SITE: 6187-6210 MOTIF: leucine residue (SEVERAL) spectrin repeat {6245-6349} MOTIF: leucine-rich repeat SITE: 6287-6313 MOTIF: leucine residue (SEVERAL) Ser phosphorylation site {S6361} spectrin repeat {6551-6658} MOTIF: leucine-rich repeat SITE: 6584-6608 MOTIF: leucine residue (SEVERAL) coiled coil {6697-6770} KASH {6826-6885} MOTIF: transmembrane domain {6835-6855} Perinuclear space {6856-6885}

Database Correlations

OMIM correlations MORBIDMAP 608442 UniProt Q8WXH0 PFAM correlations Entrez Gene 23224 Kegg hsa:23224

References

UniProt :accession Q8WXH0