SYNE3_MOUSE
ID SYNE3_MOUSE Reviewed; 975 AA.
AC Q4FZC9; Q8BMM1; Q8C117;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Nesprin-3;
DE AltName: Full=KASH domain-containing protein 3;
DE Short=KASH3;
DE AltName: Full=Nuclear envelope spectrin repeat protein 3;
GN Name=Syne3;
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] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 691-975 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Head, and Pituitary;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
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 [3]
RP INTERACTION WITH PLEC, FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=16330710; DOI=10.1083/jcb.200506083;
RA Wilhelmsen K., Litjens S.H.M., Kuikman I., Tshimbalanga N., Janssen H.,
RA van den Bout I., Raymond K., Sonnenberg A.;
RT "Nesprin-3, a novel outer nuclear membrane protein, associates with the
RT cytoskeletal linker protein plectin.";
RL J. Cell Biol. 171:799-810(2005).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=18396275; DOI=10.1016/j.yexcr.2008.02.022;
RA Stewart-Hutchinson P.J., Hale C.M., Wirtz D., Hodzic D.;
RT "Structural requirements for the assembly of LINC complexes and their
RT function in cellular mechanical stiffness.";
RL Exp. Cell Res. 314:1892-1905(2008).
RN [5]
RP INTERACTION WITH DST.
RX PubMed=18638474; DOI=10.1016/j.yexcr.2008.06.021;
RA Young K.G., Kothary R.;
RT "Dystonin/Bpag1 is a necessary endoplasmic reticulum/nuclear envelope
RT protein in sensory neurons.";
RL Exp. Cell Res. 314:2750-2761(2008).
RN [6]
RP INTERACTION WITH TOR1A, AND SUBCELLULAR LOCATION.
RX PubMed=18827015; DOI=10.1242/jcs.029454;
RA Nery F.C., Zeng J., Niland B.P., Hewett J., Farley J., Irimia D., Li Y.,
RA Wiche G., Sonnenberg A., Breakefield X.O.;
RT "TorsinA binds the KASH domain of nesprins and participates in linkage
RT between nuclear envelope and cytoskeleton.";
RL J. Cell Sci. 121:3476-3486(2008).
RN [7]
RP INTERACTION WITH SYNE1.
RX PubMed=22518138; DOI=10.1155/2012/736524;
RA Taranum S., Sur I., Muller R., Lu W., Rashmi R.N., Munck M., Neumann S.,
RA Karakesisoglou I., Noegel A.A.;
RT "Cytoskeletal interactions at the nuclear envelope mediated by nesprins.";
RL Int. J. Cell Biol. 2012:736524-736524(2012).
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. Probable anchoring protein which
CC tethers the nucleus to the cytoskeleton by binding PLEC which can
CC associate with the intermediate filament system. Plays a role in the
CC regulation of aortic epithelial cell morphology, and is required for
CC flow-induced centrosome polarization and directional migration in
CC aortic endothelial cells (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:16330710}.
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. Interacts with SUN1 and SUN2; probably forming
CC respective LINC complexes. Interacts with PLEC (via actin-binding
CC domain). Interacts with DST. Interacts with SYNE1. Interacts (via KASH
CC domain) with TOR1A (ATP-bound); the interaction is required for SYNE3
CC nuclear envelope localization. {ECO:0000269|PubMed:16330710,
CC ECO:0000269|PubMed:18638474, ECO:0000269|PubMed:18827015,
CC ECO:0000269|PubMed:22518138}.
CC -!- SUBCELLULAR LOCATION: Nucleus outer membrane; Single-pass type IV
CC membrane protein. Nucleus envelope. Rough endoplasmic reticulum.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q4FZC9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q4FZC9-2; Sequence=VSP_023979, VSP_023980;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:16330710}.
CC -!- DOMAIN: The KASH domain is involved in the binding to SUN1 and SUN2
CC through recognition of their SUN domains. {ECO:0000250}.
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 -!- SIMILARITY: Belongs to the nesprin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC26351.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK029216; BAC26351.1; ALT_FRAME; mRNA.
DR EMBL; AK030542; BAC27012.1; -; mRNA.
DR EMBL; BC099694; AAH99694.1; -; mRNA.
DR CCDS; CCDS36542.1; -. [Q4FZC9-1]
DR CCDS; CCDS36543.1; -. [Q4FZC9-2]
DR RefSeq; NP_001036164.1; NM_001042699.2. [Q4FZC9-1]
DR RefSeq; NP_766088.2; NM_172500.3. [Q4FZC9-2]
DR RefSeq; XP_006515715.2; XM_006515652.3. [Q4FZC9-1]
DR RefSeq; XP_006515716.1; XM_006515653.2. [Q4FZC9-1]
DR RefSeq; XP_006515717.1; XM_006515654.3. [Q4FZC9-1]
DR AlphaFoldDB; Q4FZC9; -.
DR SMR; Q4FZC9; -.
DR IntAct; Q4FZC9; 2.
DR STRING; 10090.ENSMUSP00000093090; -.
DR iPTMnet; Q4FZC9; -.
DR PhosphoSitePlus; Q4FZC9; -.
DR SwissPalm; Q4FZC9; -.
DR EPD; Q4FZC9; -.
DR MaxQB; Q4FZC9; -.
DR PaxDb; Q4FZC9; -.
DR PeptideAtlas; Q4FZC9; -.
DR PRIDE; Q4FZC9; -.
DR ProteomicsDB; 263183; -. [Q4FZC9-1]
DR ProteomicsDB; 263184; -. [Q4FZC9-2]
DR Antibodypedia; 54248; 161 antibodies from 28 providers.
DR Ensembl; ENSMUST00000067005; ENSMUSP00000065771; ENSMUSG00000054150. [Q4FZC9-2]
DR Ensembl; ENSMUST00000095439; ENSMUSP00000093090; ENSMUSG00000054150. [Q4FZC9-1]
DR Ensembl; ENSMUST00000109927; ENSMUSP00000105553; ENSMUSG00000054150. [Q4FZC9-2]
DR GeneID; 212073; -.
DR KEGG; mmu:212073; -.
DR UCSC; uc007oxr.2; mouse. [Q4FZC9-1]
DR UCSC; uc007oxs.2; mouse. [Q4FZC9-2]
DR CTD; 161176; -.
DR MGI; MGI:2442408; Syne3.
DR VEuPathDB; HostDB:ENSMUSG00000054150; -.
DR eggNOG; ENOG502QQSI; Eukaryota.
DR GeneTree; ENSGT00440000039367; -.
DR HOGENOM; CLU_012764_0_0_1; -.
DR InParanoid; Q4FZC9; -.
DR OMA; KICRLEP; -.
DR OrthoDB; 87219at2759; -.
DR PhylomeDB; Q4FZC9; -.
DR TreeFam; TF331132; -.
DR BioGRID-ORCS; 212073; 4 hits in 72 CRISPR screens.
DR PRO; PR:Q4FZC9; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q4FZC9; protein.
DR Bgee; ENSMUSG00000054150; Expressed in retinal neural layer and 73 other tissues.
DR Genevisible; Q4FZC9; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0034993; C:meiotic nuclear membrane microtubule tethering complex; IDA:MGI.
DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005640; C:nuclear outer membrane; IDA:UniProtKB.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0051015; F:actin filament binding; ISS:UniProtKB.
DR GO; GO:0140444; F:cytoskeleton-nuclear membrane anchor activity; ISO:MGI.
DR GO; GO:0007010; P:cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0090150; P:establishment of protein localization to membrane; ISS:UniProtKB.
DR GO; GO:0007097; P:nuclear migration; IBA:GO_Central.
DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
DR InterPro; IPR012315; KASH.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR002017; Spectrin_repeat.
DR InterPro; IPR030267; SYNE3.
DR PANTHER; PTHR47535:SF2; PTHR47535:SF2; 1.
DR Pfam; PF10541; KASH; 1.
DR Pfam; PF00435; Spectrin; 2.
DR SMART; SM01249; KASH; 1.
DR SMART; SM00150; SPEC; 3.
DR PROSITE; PS51049; KASH; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Endoplasmic reticulum; Membrane;
KW Nucleus; Reference proteome; Repeat; Transmembrane; Transmembrane helix.
FT CHAIN 1..975
FT /note="Nesprin-3"
FT /id="PRO_0000281121"
FT TOPO_DOM 1..925
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385"
FT TRANSMEM 926..946
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385"
FT TOPO_DOM 947..975
FT /note="Perinuclear space"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385"
FT REPEAT 220..325
FT /note="Spectrin 1"
FT REPEAT 647..740
FT /note="Spectrin 2"
FT DOMAIN 917..975
FT /note="KASH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00385"
FT REGION 778..798
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 953
FT /note="Interchain (C-577 in SUN2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8WXH0"
FT DISULFID 953
FT /note="Interchain (with C-759 in SUN1)"
FT /evidence="ECO:0000250|UniProtKB:Q8WXH0"
FT VAR_SEQ 1..87
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023979"
FT VAR_SEQ 88..105
FT /note="RDIKSQWEETVTYMTHCH -> MTTRRGPERPWRQGFERQ (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023980"
SQ SEQUENCE 975 AA; 112035 MW; 26D80A295CE0CF8B CRC64;
MTQQPQEDFE RSVEDAQAWM KVIQEQLQVN DNTKGPRAAL EARLRETEKI CQLESEGMVK
VELVLRAAEA LLATCQEGQK PEILARLRDI KSQWEETVTY MTHCHSRIEW VWLHWSEYLL
AQDEFYRWFQ KMVVALEPPV ELQLGLKEKQ WQLSHAQVLL HNVDNQAVLL DRLLEEAGSL
FSRIGDPSVD EDAQKRMKAE YDAVKARAQR RVDLLAQVAQ DHEQYREDVN EFQLWLKAVV
EKVHSCLGRN CKLATELRLS TLQDIAKDFP RGEESLKRLE EQAVGVIQNT SPLGAEKISG
ELEEMRGVLE KLRVLWKEEE GRLRGLLQSR GDCEQQIQQL EAELGDFKKS LQRLAQEGLE
PTVKTATEDE LVAQWRLFSG TRAALASEEP RVDRLQTQLK KLVTFPDLQS LSDSVVATIQ
EYQSMKGKNT RLHNATRAEL WQRFQRPLND LQLWKALAQR LLDITASLPD LASIHTFLPQ
IEAALTESSR LKEQLAMLQL KTDLLGSIFG QERAATLLEQ VTSSVRDRDL LHNSLLQRKS
KLQSLLVQHK DFGVAFDPLN RKLLDLQARI QAEKGLPRDL PGKQVQLLRL QGLQEEGLDL
GTQIEAVRPL AHGNSKHQQK VDQISCDQQA LQRSLEDLVD RCQQNVREHC TFSHRLSELQ
LWITMATQTL ESHQGDVRLW DAESQEAGLE TLLSEIPEKE VQVSLLQALG QLVMKKSSPE
GATMVQEELR KLMESWQALR LLEENMLSLM RNQQLQRTEV DTGKKQVFTN NIPKAGFLIN
PQDPIPRRQH GANPLEGHDL PEDHPQLLRD FEQWLQAENS KLRRIITMRV ATAKDLRTRE
VKLQELEARI PEGQHLFENL LRLRPARDPS NELEDLRYRW MLYKSKLKDS GHLLTESSPG
ELTAFQKSRR QKRWSPCSLL QKACRVALPL QLLLLLFLLL LFLLPAGEEE RSCALANNFA
RSFALMLRYN GPPPT
