SUN2_HUMAN
ID SUN2_HUMAN Reviewed; 717 AA.
AC Q9UH99; B0QY62; O75156; Q2NKN8; Q2T9F7; Q504T5; Q6B4H1; Q7Z3E3;
DT 02-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 25-MAR-2003, sequence version 3.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=SUN domain-containing protein 2;
DE AltName: Full=Protein unc-84 homolog B;
DE AltName: Full=Rab5-interacting protein;
DE Short=Rab5IP;
DE AltName: Full=Sad1/unc-84 protein-like 2;
GN Name=SUN2 {ECO:0000312|HGNC:HGNC:14210};
GN Synonyms=FRIGG, KIAA0668, RAB5IP, UNC84B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND INTERACTION WITH RAB5A.
RC TISSUE=B-cell;
RX PubMed=10818110; DOI=10.1074/jbc.m909600199;
RA Hoffenberg S., Liu X., Nikolova L., Hall H.S., Dai W., Baughn R.E.,
RA Dickey B.F., Barbieri M.A., Aballay A., Stahl P.D., Knoll B.J.;
RT "A novel membrane-anchored Rab5 interacting protein required for homotypic
RT endosome fusion.";
RL J. Biol. Chem. 275:24661-24669(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, SUBUNIT, AND
RP ASSOCIATION WITH THE CENTROSOME.
RX PubMed=17132086; DOI=10.1089/dna.2006.25.554;
RA Wang Q., Du X., Cai Z., Greene M.I.;
RT "Characterization of the structures involved in localization of the SUN
RT proteins to the nuclear envelope and the centrosome.";
RL DNA Cell Biol. 25:554-562(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal kidney;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANTS
RP ARG-89 AND SER-671.
RC TISSUE=Brain, and Pancreas;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 278-717 (ISOFORM 1).
RX PubMed=10375507; DOI=10.1242/dev.126.14.3171;
RA Malone C.J., Fixsen W.D., Horvitz H.R., Han M.;
RT "UNC-84 localizes to the nuclear envelope and is required for nuclear
RT migration and anchoring during C. elegans development.";
RL Development 126:3171-3181(1999).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=12393179; DOI=10.1016/s0925-4439(02)00171-0;
RA Sun G., Yuen Chan S., Yuan Y., Wang Chan K., Qiu G., Sun K., Ping Leung M.;
RT "Isolation of differentially expressed genes in human heart tissues.";
RL Biochim. Biophys. Acta 1588:241-246(2002).
RN [10]
RP PHOSPHORYLATION AT SER-12; SER-54 AND SER-116.
RX PubMed=12239280; DOI=10.1074/mcp.m200010-mcp200;
RA Gronborg M., Kristiansen T.Z., Stensballe A., Andersen J.S., Ohara O.,
RA Mann M., Jensen O.N., Pandey A.;
RT "A mass spectrometry-based proteomic approach for identification of
RT serine/threonine-phosphorylated proteins by enrichment with phospho-
RT specific antibodies: identification of a novel protein, Frigg, as a protein
RT kinase A substrate.";
RL Mol. Cell. Proteomics 1:517-527(2002).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=12958361; DOI=10.1126/science.1088176;
RA Schirmer E.C., Florens L., Guan T., Yates J.R. III, Gerace L.;
RT "Nuclear membrane proteins with potential disease links found by
RT subtractive proteomics.";
RL Science 301:1380-1382(2003).
RN [12]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=15082709; DOI=10.1074/jbc.m313157200;
RA Hodzic D.M., Yeater D.B., Bengtsson L., Otto H., Stahl P.D.;
RT "Sun2 is a novel mammalian inner nuclear membrane protein.";
RL J. Biol. Chem. 279:25805-25812(2004).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=17724119; DOI=10.1083/jcb.200704108;
RA Liu Q., Pante N., Misteli T., Elsagga M., Crisp M., Hodzic D., Burke B.,
RA Roux K.J.;
RT "Functional association of Sun1 with nuclear pore complexes.";
RL J. Cell Biol. 178:785-798(2007).
RN [15]
RP INTERACTION WITH SUN1.
RX PubMed=18845190; DOI=10.1016/j.bbamcr.2008.09.001;
RA Lu W., Gotzmann J., Sironi L., Jaeger V.M., Schneider M., Luke Y.,
RA Uhlen M., Szigyarto C.A., Brachner A., Ellenberg J., Foisner R.,
RA Noegel A.A., Karakesisoglou I.;
RT "Sun1 forms immobile macromolecular assemblies at the nuclear envelope.";
RL Biochim. Biophys. Acta 1783:2415-2426(2008).
RN [16]
RP INTERACTION WITH SYNE1; SYNE2 AND SYNE3, AND FUNCTION OF THE LINC
RP COMPLEXES.
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 [17]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-636.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-38, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP INTERACTION WITH TMEM43.
RX PubMed=21391237; DOI=10.1002/ana.22338;
RA Liang W.C., Mitsuhashi H., Keduka E., Nonaka I., Noguchi S., Nishino I.,
RA Hayashi Y.K.;
RT "TMEM43 mutations in Emery-Dreifuss muscular dystrophy-related myopathy.";
RL Ann. Neurol. 69:1005-1013(2011).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-38, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [23]
RP SUBUNIT, DISULFIDE BOND, AND MUTAGENESIS OF CYS-563.
RX PubMed=26244732; DOI=10.1016/j.bpj.2015.06.057;
RA Jahed Z., Shams H., Mofrad M.R.;
RT "A disulfide bond is required for the transmission of forces through SUN-
RT KASH complexes.";
RL Biophys. J. 109:501-509(2015).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS) OF 522-717, X-RAY CRYSTALLOGRAPHY
RP (2.71 ANGSTROMS) OF 522-717 IN COMPLEX WITH SYNE2, X-RAY CRYSTALLOGRAPHY
RP (2.32 ANGSTROMS) OF 522-717 IN COMPLEX WITH SYNE1, SUBUNIT, AND MUTAGENESIS
RP OF LEU-536; ARG-538; ASP-542; GLY-609; HIS-628; SER-641 AND TYR-707.
RX PubMed=22632968; DOI=10.1016/j.cell.2012.03.046;
RA Sosa B.A., Rothballer A., Kutay U., Schwartz T.U.;
RT "LINC complexes form by binding of three KASH peptides to domain interfaces
RT of trimeric SUN proteins.";
RL Cell 149:1035-1047(2012).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 523-717 IN COMPLEX WITH SYNE2,
RP FUNCTION, AND MUTAGENESIS OF ALA-603; SER-641 AND TYR-703.
RX PubMed=22945352; DOI=10.1038/cr.2012.126;
RA Wang W., Shi Z., Jiao S., Chen C., Wang H., Liu G., Wang Q., Zhao Y.,
RA Greene M.I., Zhou Z.;
RT "Structural insights into SUN-KASH complexes across the nuclear envelope.";
RL Cell Res. 22:1440-1452(2012).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS) OF 520-717, AND SUBUNIT.
RX PubMed=22170055; DOI=10.1074/jbc.m111.304543;
RA Zhou Z., Du X., Cai Z., Song X., Zhang H., Mizuno T., Suzuki E., Yee M.R.,
RA Berezov A., Murali R., Wu S.L., Karger B.L., Greene M.I., Wang Q.;
RT "Structure of Sad1-UNC84 homology (SUN) domain defines features of
RT molecular bridge in nuclear envelope.";
RL J. Biol. Chem. 287:5317-5326(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. Specifically, SYNE2 and SUN2 assemble
CC in arrays of transmembrane actin-associated nuclear (TAN) lines which
CC are bound to F-actin cables and couple the nucleus to retrograde actin
CC flow during actin-dependent nuclear movement. Required for interkinetic
CC nuclear migration (INM) and essential for nucleokinesis and centrosome-
CC nucleus coupling during radial neuronal migration in the cerebral
CC cortex and during glial migration. Required for nuclear migration in
CC retinal photoreceptor progenitors implicating association with
CC cytoplasmic dynein-dynactin and kinesin motor complexes, and probably
CC B-type lamins; SUN1 and SUN2 seem to act redundantly. The SUN1/2:KASH5
CC LINC complex couples telomeres to microtubules during meiosis; SUN1 and
CC SUN2 seem to act at least partial redundantly. Anchors chromosome
CC movement in the prophase of meiosis and is involved in selective gene
CC expression of coding and non-coding RNAs needed for gametogenesis.
CC Required for telomere attachment to nuclear envelope and gametogenesis.
CC May also function on endocytic vesicles as a receptor for RAB5-GDP and
CC participate in the activation of RAB5. {ECO:0000250|UniProtKB:Q8BJS4,
CC ECO:0000269|PubMed:18396275, ECO:0000305}.
CC -!- SUBUNIT: Core component of the LINC complex which is 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 is giving rise
CC to specific assemblies. At least SUN1/2-containing core LINC complexes
CC are proposed to be hexameric composed of three protomers of each KASH
CC and SUN domain-containing protein. Interacts with SYNE2; the
CC SUN2:SYNE2/KASH2 LINC complex is a heterohexamer; the homotrimeric
CC cloverleave-like conformation of the SUN domain is a prerequisite for
CC LINC complex formation in which three separate SYNE2/KASH2 peptides
CC bind at the interface of adjacent SUN domains. Component of a probable
CC SUN2:KASH5 LINC complex. Interacts with SYNE1 and SYNE3; probably
CC forming respective LINC complexes. Interacts with A-type lamin.
CC Interaction with lamins B1 and C is hardly detectable (By similarity).
CC Interacts with EMD and RAB5A. Interacts with TMEM43 and TMEM201.
CC {ECO:0000250|UniProtKB:Q8BJS4, ECO:0000269|PubMed:10818110,
CC ECO:0000269|PubMed:17132086, ECO:0000269|PubMed:18396275,
CC ECO:0000269|PubMed:18845190, ECO:0000269|PubMed:21391237,
CC ECO:0000269|PubMed:22632968, ECO:0000269|PubMed:22945352}.
CC -!- INTERACTION:
CC Q9UH99; P53618: COPB1; NbExp=3; IntAct=EBI-1044964, EBI-359063;
CC Q9UH99; P50402: EMD; NbExp=4; IntAct=EBI-1044964, EBI-489887;
CC Q9UH99; P52292: KPNA2; NbExp=3; IntAct=EBI-1044964, EBI-349938;
CC Q9UH99; P02545: LMNA; NbExp=4; IntAct=EBI-1044964, EBI-351935;
CC Q9UH99; Q8IXM6: NRM; NbExp=3; IntAct=EBI-1044964, EBI-10262547;
CC Q9UH99; P20339: RAB5A; NbExp=5; IntAct=EBI-1044964, EBI-399437;
CC Q9UH99; Q9UH99: SUN2; NbExp=2; IntAct=EBI-1044964, EBI-1044964;
CC Q9UH99; Q8NF91: SYNE1; NbExp=3; IntAct=EBI-1044964, EBI-928867;
CC Q9UH99; Q8NF91-1: SYNE1; NbExp=2; IntAct=EBI-1044964, EBI-6170938;
CC Q9UH99; Q8WXH0: SYNE2; NbExp=8; IntAct=EBI-1044964, EBI-2372294;
CC Q9UH99; Q8WXH0-1: SYNE2; NbExp=2; IntAct=EBI-1044964, EBI-6170976;
CC -!- SUBCELLULAR LOCATION: Nucleus inner membrane
CC {ECO:0000269|PubMed:15082709}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:15082709}. Nucleus envelope
CC {ECO:0000269|PubMed:15082709, ECO:0000269|PubMed:17132086,
CC ECO:0000269|PubMed:17724119}. Endosome membrane
CC {ECO:0000269|PubMed:10818110}; Single-pass type II membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UH99-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UH99-2; Sequence=VSP_045882;
CC Name=3;
CC IsoId=Q9UH99-3; Sequence=VSP_053702;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in heart, lung
CC and muscle. Weakly expressed in fetal heart. Slightly overexpressed in
CC some heart tissues form patients with congenital heart defects.
CC {ECO:0000269|PubMed:10818110, ECO:0000269|PubMed:12393179}.
CC -!- DOMAIN: The coiled coil domains differentially mediate trimerization
CC required for binding to nesprins and are proposed to dynamically
CC regulate the oligomeric state by locking the SUN domain in an inactive
CC confirmation (By similarity). The coiled coil domains are proposed to
CC be involved in load-bearing and force transmission from the
CC cytoskeleton. {ECO:0000250|UniProtKB:Q8BJS4,
CC ECO:0000305|PubMed:26244732}.
CC -!- DOMAIN: The SUN domain may play a role in nuclear anchoring and/or
CC migration. {ECO:0000250|UniProtKB:Q8BJS4}.
CC -!- PTM: The disulfide bond with SYNE2 is required for stability of the
CC SUN2:SYNE2/KASH2 LINC complex under tensile forces though not required
CC for the interaction. The disulfide bond is proposed to be conserved in
CC LINC complexes involved in force transmission.
CC {ECO:0000269|PubMed:26244732}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-50 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA31643.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB014568; BAA31643.1; ALT_INIT; mRNA.
DR EMBL; AY682988; AAT90500.1; -; mRNA.
DR EMBL; CR456474; CAG30360.1; -; mRNA.
DR EMBL; BX537962; CAD97926.1; -; mRNA.
DR EMBL; AL008583; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL021806; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL021707; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC030684; AAH30684.2; -; mRNA.
DR EMBL; BC094797; AAH94797.1; -; mRNA.
DR EMBL; BC111549; AAI11550.1; -; mRNA.
DR EMBL; BC111717; AAI11718.1; -; mRNA.
DR EMBL; AF202723; AAF15887.1; -; mRNA.
DR CCDS; CCDS13978.1; -. [Q9UH99-1]
DR CCDS; CCDS56231.1; -. [Q9UH99-2]
DR PIR; T00371; T00371.
DR RefSeq; NP_001186508.1; NM_001199579.1. [Q9UH99-2]
DR RefSeq; NP_001186509.1; NM_001199580.1. [Q9UH99-1]
DR RefSeq; NP_056189.1; NM_015374.2. [Q9UH99-1]
DR PDB; 3UNP; X-ray; 2.39 A; A=520-717.
DR PDB; 4DXR; X-ray; 2.32 A; A=522-717.
DR PDB; 4DXS; X-ray; 2.71 A; A=522-717.
DR PDB; 4DXT; X-ray; 2.22 A; A=522-717.
DR PDB; 4FI9; X-ray; 3.05 A; A=523-717.
DR PDB; 6WMD; X-ray; 1.50 A; A=522-717.
DR PDB; 6WME; X-ray; 1.53 A; A=522-717.
DR PDB; 6WMF; X-ray; 2.60 A; A=522-717.
DR PDB; 6WMG; X-ray; 1.90 A; A=500-717.
DR PDBsum; 3UNP; -.
DR PDBsum; 4DXR; -.
DR PDBsum; 4DXS; -.
DR PDBsum; 4DXT; -.
DR PDBsum; 4FI9; -.
DR PDBsum; 6WMD; -.
DR PDBsum; 6WME; -.
DR PDBsum; 6WMF; -.
DR PDBsum; 6WMG; -.
DR AlphaFoldDB; Q9UH99; -.
DR SMR; Q9UH99; -.
DR BioGRID; 117312; 231.
DR IntAct; Q9UH99; 100.
DR MINT; Q9UH99; -.
DR STRING; 9606.ENSP00000385616; -.
DR TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family.
DR GlyConnect; 1777; 6 N-Linked glycans (1 site).
DR GlyGen; Q9UH99; 3 sites, 5 N-linked glycans (1 site), 1 O-linked glycan (2 sites).
DR iPTMnet; Q9UH99; -.
DR PhosphoSitePlus; Q9UH99; -.
DR SwissPalm; Q9UH99; -.
DR BioMuta; SUN2; -.
DR DMDM; 29337242; -.
DR EPD; Q9UH99; -.
DR jPOST; Q9UH99; -.
DR MassIVE; Q9UH99; -.
DR MaxQB; Q9UH99; -.
DR PaxDb; Q9UH99; -.
DR PeptideAtlas; Q9UH99; -.
DR PRIDE; Q9UH99; -.
DR ProteomicsDB; 2587; -.
DR ProteomicsDB; 84289; -. [Q9UH99-1]
DR Antibodypedia; 228; 194 antibodies from 26 providers.
DR DNASU; 25777; -.
DR Ensembl; ENST00000405018.5; ENSP00000385616.1; ENSG00000100242.16. [Q9UH99-2]
DR Ensembl; ENST00000405510.5; ENSP00000385740.1; ENSG00000100242.16. [Q9UH99-1]
DR Ensembl; ENST00000406622.5; ENSP00000383992.1; ENSG00000100242.16. [Q9UH99-1]
DR Ensembl; ENST00000689035.1; ENSP00000508608.1; ENSG00000100242.16. [Q9UH99-1]
DR GeneID; 25777; -.
DR KEGG; hsa:25777; -.
DR MANE-Select; ENST00000689035.1; ENSP00000508608.1; NM_015374.3; NP_056189.1.
DR UCSC; uc003awh.3; human. [Q9UH99-1]
DR CTD; 25777; -.
DR DisGeNET; 25777; -.
DR GeneCards; SUN2; -.
DR HGNC; HGNC:14210; SUN2.
DR HPA; ENSG00000100242; Low tissue specificity.
DR MIM; 613569; gene.
DR neXtProt; NX_Q9UH99; -.
DR OpenTargets; ENSG00000100242; -.
DR PharmGKB; PA165378369; -.
DR VEuPathDB; HostDB:ENSG00000100242; -.
DR eggNOG; KOG2687; Eukaryota.
DR GeneTree; ENSGT00940000160024; -.
DR HOGENOM; CLU_012938_1_0_1; -.
DR InParanoid; Q9UH99; -.
DR OMA; SWAASCF; -.
DR OrthoDB; 1000585at2759; -.
DR PhylomeDB; Q9UH99; -.
DR TreeFam; TF323915; -.
DR PathwayCommons; Q9UH99; -.
DR Reactome; R-HSA-1221632; Meiotic synapsis.
DR SignaLink; Q9UH99; -.
DR SIGNOR; Q9UH99; -.
DR BioGRID-ORCS; 25777; 18 hits in 1094 CRISPR screens.
DR ChiTaRS; SUN2; human.
DR GeneWiki; UNC84B; -.
DR GenomeRNAi; 25777; -.
DR Pharos; Q9UH99; Tbio.
DR PRO; PR:Q9UH99; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q9UH99; protein.
DR Bgee; ENSG00000100242; Expressed in granulocyte and 200 other tissues.
DR ExpressionAtlas; Q9UH99; baseline and differential.
DR Genevisible; Q9UH99; HS.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005639; C:integral component of nuclear inner membrane; IEA:InterPro.
DR GO; GO:0034993; C:meiotic nuclear membrane microtubule tethering complex; IDA:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0140444; F:cytoskeleton-nuclear membrane anchor activity; IDA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005521; F:lamin binding; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; TAS:UniProtKB.
DR GO; GO:0043495; F:protein-membrane adaptor activity; IBA:GO_Central.
DR GO; GO:0051642; P:centrosome localization; ISS:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0007052; P:mitotic spindle organization; TAS:UniProtKB.
DR GO; GO:0006998; P:nuclear envelope organization; IGI:MGI.
DR GO; GO:0090292; P:nuclear matrix anchoring at nuclear membrane; IDA:UniProtKB.
DR GO; GO:0007097; P:nuclear migration; TAS:UniProtKB.
DR GO; GO:0031022; P:nuclear migration along microfilament; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR InterPro; IPR045119; SUN1-5.
DR InterPro; IPR030272; SUN2.
DR InterPro; IPR040994; Sun_CC2.
DR InterPro; IPR012919; SUN_dom.
DR PANTHER; PTHR12911; PTHR12911; 1.
DR PANTHER; PTHR12911:SF22; PTHR12911:SF22; 1.
DR Pfam; PF18580; HTH_SUN2; 1.
DR Pfam; PF07738; Sad1_UNC; 1.
DR PROSITE; PS51469; SUN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Disulfide bond; Endosome;
KW Glycoprotein; Meiosis; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..717
FT /note="SUN domain-containing protein 2"
FT /id="PRO_0000218913"
FT TOPO_DOM 1..212
FT /note="Nuclear"
FT /evidence="ECO:0000269|PubMed:15082709"
FT TRANSMEM 213..233
FT /note="Helical"
FT TOPO_DOM 234..717
FT /note="Perinuclear space"
FT /evidence="ECO:0000269|PubMed:15082709"
FT DOMAIN 555..716
FT /note="SUN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00802"
FT REGION 1..139
FT /note="LMNA-binding"
FT /evidence="ECO:0000250"
FT REGION 1..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 507..717
FT /note="Sufficient for interaction with SYNE1 and SYNE2"
FT /evidence="ECO:0000269|PubMed:22632968"
FT COILED 273..296
FT /evidence="ECO:0000255"
FT COILED 348..440
FT /evidence="ECO:0000255"
FT COILED 475..506
FT /evidence="ECO:0000255"
FT COMPBIAS 1..38
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..66
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12239280"
FT MOD_RES 38
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12239280,
FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:24275569"
FT MOD_RES 107
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8BJS4"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BJS4"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BJS4"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12239280"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BJS4"
FT CARBOHYD 636
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT DISULFID 563
FT /note="Interchain (with C-6862 in SYNE2)"
FT /evidence="ECO:0000269|PubMed:22632968"
FT DISULFID 601..705
FT /evidence="ECO:0000269|PubMed:22632968,
FT ECO:0000269|PubMed:22945352"
FT VAR_SEQ 141
FT /note="V -> VEDSEGRGSKVTETEPVSSFPA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045882"
FT VAR_SEQ 683..717
FT /note="TMATYQVVELRILTNWGHPEYTCIYRFRVHGEPAH -> SSFPLCPWRLLPI
FT LGVCIYVAYHGGLGSWER (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_053702"
FT VARIANT 33
FT /note="T -> A (in dbSNP:rs2072799)"
FT /id="VAR_052282"
FT VARIANT 89
FT /note="L -> R (in dbSNP:rs35496634)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_052283"
FT VARIANT 348
FT /note="R -> C (in dbSNP:rs138708)"
FT /id="VAR_052284"
FT VARIANT 671
FT /note="G -> S (in dbSNP:rs2072797)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_024624"
FT MUTAGEN 536
FT /note="L->D: Disrupts interaction with SYNE2."
FT /evidence="ECO:0000269|PubMed:22632968"
FT MUTAGEN 538
FT /note="Missing: Disrupts interaction with SYNE2."
FT /evidence="ECO:0000269|PubMed:22632968"
FT MUTAGEN 542
FT /note="D->N: Disrupts interaction with SYNE2."
FT /evidence="ECO:0000269|PubMed:22170055,
FT ECO:0000269|PubMed:22632968"
FT MUTAGEN 563
FT /note="C->A: Decreases stability of the SUN2:SYNE2/KASH2
FT complex under tensile forces and inhibits force
FT transmission through the complex."
FT /evidence="ECO:0000269|PubMed:26244732"
FT MUTAGEN 603
FT /note="A->E: Decreases interaction with SYNE2. Disrupts
FT interaction with SYNE2; when associated with E-641 and E-
FT 703."
FT /evidence="ECO:0000269|PubMed:22945352"
FT MUTAGEN 609
FT /note="G->D: Decreases interaction with SYNE2."
FT /evidence="ECO:0000269|PubMed:22170055"
FT MUTAGEN 628
FT /note="H->A: Disrupts interaction with SYNE2."
FT /evidence="ECO:0000269|PubMed:22632968"
FT MUTAGEN 641
FT /note="S->E: Decreases interaction with SYNE2. Disrupts
FT interaction with SYNE2; when associated with E-603 and E-
FT 703."
FT /evidence="ECO:0000269|PubMed:22632968,
FT ECO:0000269|PubMed:22945352"
FT MUTAGEN 703
FT /note="Y->E: Decreases interaction with SYNE2. Disrupts
FT interaction with SYNE2; when associated with E-603 and E-
FT 641."
FT /evidence="ECO:0000269|PubMed:22945352"
FT MUTAGEN 707
FT /note="Y->F: Disrupts interaction with SYNE2, impairs
FT localization to the nuclear envelope."
FT /evidence="ECO:0000269|PubMed:22632968"
FT CONFLICT 644
FT /note="K -> R (in Ref. 5; CAD97926)"
FT /evidence="ECO:0000305"
FT HELIX 525..540
FT /evidence="ECO:0007829|PDB:6WMD"
FT TURN 541..544
FT /evidence="ECO:0007829|PDB:6WMD"
FT HELIX 552..554
FT /evidence="ECO:0007829|PDB:6WMD"
FT HELIX 560..562
FT /evidence="ECO:0007829|PDB:6WMD"
FT STRAND 572..576
FT /evidence="ECO:0007829|PDB:6WMD"
FT STRAND 579..583
FT /evidence="ECO:0007829|PDB:6WMD"
FT HELIX 588..592
FT /evidence="ECO:0007829|PDB:6WMD"
FT STRAND 601..607
FT /evidence="ECO:0007829|PDB:6WMD"
FT STRAND 609..627
FT /evidence="ECO:0007829|PDB:6WMD"
FT HELIX 631..633
FT /evidence="ECO:0007829|PDB:6WMD"
FT HELIX 635..637
FT /evidence="ECO:0007829|PDB:6WMD"
FT STRAND 645..655
FT /evidence="ECO:0007829|PDB:6WMD"
FT STRAND 660..666
FT /evidence="ECO:0007829|PDB:6WMD"
FT STRAND 669..671
FT /evidence="ECO:0007829|PDB:3UNP"
FT STRAND 673..678
FT /evidence="ECO:0007829|PDB:6WMD"
FT STRAND 687..694
FT /evidence="ECO:0007829|PDB:6WMD"
FT STRAND 697..699
FT /evidence="ECO:0007829|PDB:6WMD"
FT STRAND 701..706
FT /evidence="ECO:0007829|PDB:6WMD"
FT STRAND 708..715
FT /evidence="ECO:0007829|PDB:6WMD"
SQ SEQUENCE 717 AA; 80311 MW; CCF43C118E935E84 CRC64;
MSRRSQRLTR YSQGDDDGSS SSGGSSVAGS QSTLFKDSPL RTLKRKSSNM KRLSPAPQLG
PSSDAHTSYY SESLVHESWF PPRSSLEELH GDANWGEDLR VRRRRGTGGS ESSRASGLVG
RKATEDFLGS SSGYSSEDDY VGYSDVDQQS SSSRLRSAVS RAGSLLWMVA TSPGRLFRLL
YWWAGTTWYR LTTAASLLDV FVLTRRFSSL KTFLWFLLPL LLLTCLTYGA WYFYPYGLQT
FHPALVSWWA AKDSRRPDEG WEARDSSPHF QAEQRVMSRV HSLERRLEAL AAEFSSNWQK
EAMRLERLEL RQGAPGQGGG GGLSHEDTLA LLEGLVSRRE AALKEDFRRE TAARIQEELS
ALRAEHQQDS EDLFKKIVRA SQESEARIQQ LKSEWQSMTQ ESFQESSVKE LRRLEDQLAG
LQQELAALAL KQSSVAEEVG LLPQQIQAVR DDVESQFPAW ISQFLARGGG GRVGLLQREE
MQAQLRELES KILTHVAEMQ GKSAREAAAS LSLTLQKEGV IGVTEEQVHH IVKQALQRYS
EDRIGLADYA LESGGASVIS TRCSETYETK TALLSLFGIP LWYHSQSPRV ILQPDVHPGN
CWAFQGPQGF AVVRLSARIR PTAVTLEHVP KALSPNSTIS SAPKDFAIFG FDEDLQQEGT
LLGKFTYDQD GEPIQTFHFQ APTMATYQVV ELRILTNWGH PEYTCIYRFR VHGEPAH
