SYNE4_MOUSE
ID SYNE4_MOUSE Reviewed; 388 AA.
AC Q8CII8; Q6PH99; Q99J42;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Nesprin-4;
DE AltName: Full=KASH domain-containing protein 4;
DE Short=KASH4;
DE AltName: Full=Nuclear envelope spectrin repeat protein 4;
GN Name=Syne4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II, and FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP FUNCTION, INTERACTION WITH KIF5B AND KLC1, SUBCELLULAR LOCATION, TOPOLOGY,
RP DOMAIN, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=19164528; DOI=10.1073/pnas.0808602106;
RA Roux K.J., Crisp M.L., Liu Q., Kim D., Kozlov S., Stewart C.L., Burke B.;
RT "Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-
RT mediated cell polarization.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:2194-2199(2009).
RN [3]
RP DISRUPTION PHENOTYPE, POTENTIAL INTERACTION WITH SUN1, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23348741; DOI=10.1172/jci66911;
RA Horn H.F., Brownstein Z., Lenz D.R., Shivatzki S., Dror A.A.,
RA Dagan-Rosenfeld O., Friedman L.M., Roux K.J., Kozlov S., Jeang K.T.,
RA Frydman M., Burke B., Stewart C.L., Avraham K.B.;
RT "The LINC complex is essential for hearing.";
RL J. Clin. Invest. 123:740-750(2013).
CC -!- FUNCTION: As a component of the LINC (LInker of Nucleoskeleton and
CC Cytoskeleton) complex, involved in the connection between the nuclear
CC lamina and the cytoskeleton. The nucleocytoplasmic interactions
CC established by the LINC complex play an important role in the
CC transmission of mechanical forces across the nuclear envelope and in
CC nuclear movement and positioning (By similarity). Behaves as a kinesin
CC cargo, providing a functional binding site for kinesin-1 at the nuclear
CC envelope. Hence may contribute to the establishment of secretory
CC epithelial morphology, by promoting kinesin-dependent apical migration
CC of the centrosome and Golgi apparatus and basal localization of the
CC nucleus. {ECO:0000250, ECO:0000269|PubMed:19164528}.
CC -!- SUBUNIT: Core component of LINC complexes which are composed of inner
CC nuclear membrane SUN domain-containing proteins coupled to outer
CC nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-
CC containing proteins seem to bind each other promiscuously; however,
CC differentially expression of LINC complex constituents can give rise to
CC specific assemblies. Probably part of a SUN1-containing LINC complex.
CC Interacts with kinesins KIF5B and KLC1. {ECO:0000250,
CC ECO:0000269|PubMed:19164528}.
CC -!- INTERACTION:
CC Q8CII8; P33176: KIF5B; Xeno; NbExp=2; IntAct=EBI-15752280, EBI-355878;
CC -!- SUBCELLULAR LOCATION: Nucleus outer membrane
CC {ECO:0000269|PubMed:19164528, ECO:0000269|PubMed:23348741}; Single-pass
CC type IV membrane protein {ECO:0000269|PubMed:19164528,
CC ECO:0000269|PubMed:23348741}. Note=Localization at the nucleus outer
CC membrane location requires the presence of SUN1.
CC -!- TISSUE SPECIFICITY: Expressed in secretory epithelial cells, such as
CC those found in exocrine pancreas, bulbourethral gland, mammary gland
CC and salivary gland (at protein level). Also expressed in the cochlea,
CC where it is restricted primarily to the 3 rows of outer hair cells and
CC 1 row of inner hair cells (at protein level). Not detected in other
CC cells of the cochlea, including Deiter's cells and pillar cells, nor in
CC liver and kidney (at protein level). {ECO:0000269|PubMed:19164528,
CC ECO:0000269|PubMed:23348741}.
CC -!- DEVELOPMENTAL STAGE: In the cochlea, low expression at P0 and P15, then
CC rises significantly by P30 and remains steady. In the HC11 cell line
CC model, up-regulated during differentiation of mammary cells into milk-
CC secreting cells (at protein level). {ECO:0000269|PubMed:19164528}.
CC -!- DOMAIN: The KASH domain, which contains a transmembrane domain,
CC mediates the nuclear envelope targeting and is involved in the binding
CC to SUN1 and SUN2 through recognition of their SUN domains.
CC {ECO:0000269|PubMed:19164528}.
CC -!- PTM: The disulfid bond with SUN1 or SUN2 is required for stability of
CC the respective LINC complex under tensile forces.
CC {ECO:0000250|UniProtKB:Q8WXH0}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate and
CC look overtly normal. In the cochlea, outer hair cells form, but appear
CC to degenerate as hearing matures. Inner hair cells remain intact.
CC Hearing loss is already detected at P15 and progresses at all
CC frequencies by P60. {ECO:0000269|PubMed:23348741}.
CC -!- SIMILARITY: Belongs to the nesprin family. {ECO:0000305}.
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DR EMBL; BC004761; AAH04761.2; -; mRNA.
DR EMBL; BC023803; AAH23803.1; -; mRNA.
DR EMBL; BC056649; AAH56649.1; -; mRNA.
DR CCDS; CCDS21086.1; -.
DR RefSeq; NP_705805.1; NM_153577.2.
DR AlphaFoldDB; Q8CII8; -.
DR SMR; Q8CII8; -.
DR DIP; DIP-48702N; -.
DR IntAct; Q8CII8; 6.
DR STRING; 10090.ENSMUSP00000055874; -.
DR iPTMnet; Q8CII8; -.
DR PhosphoSitePlus; Q8CII8; -.
DR PaxDb; Q8CII8; -.
DR PRIDE; Q8CII8; -.
DR ProteomicsDB; 254707; -.
DR Antibodypedia; 34811; 103 antibodies from 18 providers.
DR DNASU; 233066; -.
DR Ensembl; ENSMUST00000054594; ENSMUSP00000055874; ENSMUSG00000019737.
DR GeneID; 233066; -.
DR KEGG; mmu:233066; -.
DR UCSC; uc009gec.1; mouse.
DR CTD; 163183; -.
DR MGI; MGI:2141950; Syne4.
DR VEuPathDB; HostDB:ENSMUSG00000019737; -.
DR eggNOG; ENOG502SZGW; Eukaryota.
DR GeneTree; ENSGT00510000049061; -.
DR HOGENOM; CLU_034166_1_0_1; -.
DR InParanoid; Q8CII8; -.
DR OMA; IRSEQAQ; -.
DR OrthoDB; 938875at2759; -.
DR PhylomeDB; Q8CII8; -.
DR BioGRID-ORCS; 233066; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Syne4; mouse.
DR PRO; PR:Q8CII8; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8CII8; protein.
DR Bgee; ENSMUSG00000019737; Expressed in metanephric proximal tubule and 183 other tissues.
DR ExpressionAtlas; Q8CII8; baseline and differential.
DR Genevisible; Q8CII8; MM.
DR GO; GO:0031309; C:integral component of nuclear outer membrane; IDA:UniProtKB.
DR GO; GO:0034993; C:meiotic nuclear membrane microtubule tethering complex; IEA:InterPro.
DR GO; GO:0045198; P:establishment of epithelial cell apical/basal polarity; IMP:UniProtKB.
DR InterPro; IPR012315; KASH.
DR InterPro; IPR030268; SYNE4.
DR PANTHER; PTHR21640; PTHR21640; 1.
DR Pfam; PF10541; KASH; 1.
DR SMART; SM01249; KASH; 1.
DR PROSITE; PS51049; KASH; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Membrane; Nucleus; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..388
FT /note="Nesprin-4"
FT /id="PRO_0000306265"
FT TOPO_DOM 1..339
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385"
FT TRANSMEM 340..360
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385"
FT TOPO_DOM 361..388
FT /note="Perinuclear space"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385"
FT DOMAIN 331..388
FT /note="KASH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385"
FT REGION 60..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 62..76
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 365
FT /note="Interchain (with C-577 in SUN2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8WXH0"
FT DISULFID 365
FT /note="Interchain (with C-759 in SUN1)"
FT /evidence="ECO:0000250|UniProtKB:Q8WXH0"
FT CONFLICT 56
FT /note="H -> Q (in Ref. 1; AAH04761/AAH56649)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="T -> I (in Ref. 1; AAH56649)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 388 AA; 42024 MW; D407808F62CB5498 CRC64;
MALVPPLGRE FPPEPVNCPL AAPRELDVVG GTICPAPEEE TSRPEQVQAS LGLPEHCMGE
LKSTESATSP SRLPLASSHE HQDGGKPCEH SDSGLEVLEA EQDSLHLCLL RLNFRLQDLE
RGLGSWTLAH NRIVQMQALQ AELRGAAERV DALLAFGEGL AERSEPRAWA SLEQVLRALG
THRDTIFQRL WQLQAQLISY SLVLEKANLL DQDLEVEGDS DGPAAGGVWG PWAPSTFPTP
AELEWDPAGD VGGLGPSGQK ISRIPGAPCE LCGYRGPQSS GQGLEDLLSL GLGHRKHLAA
HHRRRLRKPQ DRKRQVSPSL PDAMLEVDRG VPAPASKRPL TLFFLLLFLL LVGATLLLPL
SGVSCCSHAR LARTPYLVLS YVNGLPPI
