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Q6ZMZ3 (SYNE3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nesprin-3
Alternative name(s):
Nuclear envelope spectrin repeat protein 3
Gene names
Name:SYNE3
Synonyms:C14orf49
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length975 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Component of SUN-protein-containing multivariate complexes also called LINC complexes which link the nucleoskeleton and cytoskeleton by providing versatile outer nuclear membrane attachment sites for cytoskeletal filaments. Involved in the maintenance of nuclear organization and structural integrity. Probable anchoring protein which tethers the nucleus to the cytoskeleton by binding PLEC which can associate with the intermediate filament system. Plays a role in the regulation of aortic epithelial cell morphology, and is required for flow-induced centrosome polarization and directional migration in aortic endothelial cells. Ref.5 Ref.6 Ref.9

Subunit structure

Core component of the LINC complex which is composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN domain-containing proteins interact with A-type lamins of the nuclear lamina, while at the other end of the complex, nesprins interact with unique cytoskeletal components. Interacts with PLEC (via actin-binding domain). Interacts with DST. Interacts with SYNE1 via spectrin repeats. Interacts (via KASH domain) with TOR1A (ATP-bound); the interaction is required for SYNE3 nuclear envelope localization. Ref.6 Ref.7 Ref.10

Subcellular location

Nucleus outer membrane; Single-pass type IV membrane protein. Nucleus envelope. Rough endoplasmic reticulum By similarity Ref.9.

Tissue specificity

Expressed in aortic endothelial cells (at protein level). Ref.9

Domain

The KASH domain is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains. Ref.6

Sequence similarities

Belongs to the nesprin family.

Contains 1 KASH domain.

Contains 2 spectrin repeats.

Sequence caution

The sequence BAC05312.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAD18582.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence CAD62365.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6ZMZ3-1)

Also known as: Alpha;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q6ZMZ3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     793-797: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q6ZMZ3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     593-596: GLQE → VRGL
     597-975: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 975975Nesprin-3
PRO_0000281120

Regions

Topological domain1 – 925925Cytoplasmic Potential
Transmembrane926 – 94621Helical; Anchor for type IV membrane protein; Potential
Topological domain947 – 97529Perinuclear space Potential
Repeat220 – 325106Spectrin 1
Repeat647 – 74094Spectrin 2
Domain917 – 97559KASH
Coiled coil617 – 64529 Potential

Natural variations

Alternative sequence593 – 5964GLQE → VRGL in isoform 3.
VSP_023976
Alternative sequence597 – 975379Missing in isoform 3.
VSP_023977
Alternative sequence793 – 7975Missing in isoform 2.
VSP_023978
Natural variant6681T → M. Ref.3 Ref.4
Corresponds to variant rs9671369 [ dbSNP | Ensembl ].
VAR_031231
Natural variant7951Missing. Ref.3
Corresponds to variant rs76499929 [ dbSNP | Ensembl ].
VAR_068433
Natural variant8641R → H.
Corresponds to variant rs17092216 [ dbSNP | Ensembl ].
VAR_031232
Natural variant9231A → V. Ref.4
Corresponds to variant rs12434757 [ dbSNP | Ensembl ].
VAR_031233
Natural variant9461I → V.
Corresponds to variant rs10130647 [ dbSNP | Ensembl ].
VAR_031234

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha) [UniParc].

Last modified March 20, 2007. Version 2.
Checksum: A409AF86E1E781F4

FASTA975112,216
        10         20         30         40         50         60 
MTQQPQDDFD RSVEDAQAWM KAVQDQLQVN DNTQGPRAAL EARLWETEKI CQLEPEGRVR 

        70         80         90        100        110        120 
VDLVLRMAEA LLACCPGDQK PGILARLKDI KAQWEETVTY MTHCHSRIEW VWLHWSEYLL 

       130        140        150        160        170        180 
ARDEFYRWFQ KMMVTLEPHI ELQLGLKEKQ WQLSHAQVLL HNVDNQAVLL DRLLEEAASL 

       190        200        210        220        230        240 
FNRIGDPSVD EDAQKRMKAE YDAVKAKAQK RVDLLEQVAR EHEEYQAGVD EFQLWLKAVV 

       250        260        270        280        290        300 
EKVNGCLGRN CKLPITQRLS TLQDIAKDFP RGEESLETLE EQSAGVIRNT SPLGAEKITG 

       310        320        330        340        350        360 
ELEEMRKVLE KLRALWEEEE ERLRGLLRSR GAWEQQIKQL EAELSEFRMV LQRLAQEGLQ 

       370        380        390        400        410        420 
PAAKAGTEDE LVAHWRRYSA TRAALASEEP RVDRLQAQLK ELIVFPHNLK PLSDSVIATI 

       430        440        450        460        470        480 
QEYQSLKVKS ARLRNAAAVE LWQHFQRPLQ DLQLWKALAQ RLLEVTASLP DLPSLHTFLP 

       490        500        510        520        530        540 
QIEAALMESS RLKELLTMLQ LKKDLLIGIF GQERATALLE QVAGSMRDRD LLHNSLLQRK 

       550        560        570        580        590        600 
SKLQSLLAQH KDFGAAFEPL QRKLLDLQVR VQAEKGLQRD LPGKQAQLSR LQGLQEEGLD 

       610        620        630        640        650        660 
LGAQMEAARP LVQENPNHQH KMDQLSSDFQ ALQRSLEDLV DRCRQSVQEH CTFSHQLLEL 

       670        680        690        700        710        720 
RQWIVVTTQK LEAHRGEAGP GDAESQEAEF ERLVAEFPEK EAQLSLVEAQ GWLVMEKSSP 

       730        740        750        760        770        780 
EGAAVVQEEL RELAESWRAL RLLEESLLSL IRNWHLQRME VDSGKKMVFT NNIPKSGFLI 

       790        800        810        820        830        840 
NPMDPIPRHR RRANLLQEEE GSHEDFSQLL RNFGQWLQVE NSKLVRIIAM RTSTAEDLRT 

       850        860        870        880        890        900 
RKSKLQELEA RVPEGQHLFE NLLRLGPARG TSDELEDLRY QWMLYKSKLK DSGHLLTQSS 

       910        920        930        940        950        960 
PGEPTGFQKT RRWRGLGSLF RRACCVALPL QLLLLLFLLL LFLLPIREED RSCTLANNFA 

       970 
RSFTLMLRYN GPPPT 

« Hide

Isoform 2 [UniParc].

Checksum: 1A0FB44FD60A578D
Show »

FASTA970111,677
Isoform 3 [UniParc].

Checksum: 093499D5CF2671F4
Show »

FASTA59668,582

References

« Hide 'large scale' references
[1]"Full-length cDNA libraries and normalization."
Li W.B., Gruber C., Jessee J., Polayes D.
Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: B-cell.
[2]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS MET-668 AND LEU-795 DEL.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 41-975 (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 411-975 (ISOFORM 1), VARIANTS MET-668 AND VAL-923.
Tissue: Synovial cell and Thyroid.
[5]"Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin."
Wilhelmsen K., Litjens S.H.M., Kuikman I., Tshimbalanga N., Janssen H., van den Bout I., Raymond K., Sonnenberg A.
J. Cell Biol. 171:799-810(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness."
Stewart-Hutchinson P.J., Hale C.M., Wirtz D., Hodzic D.
Exp. Cell Res. 314:1892-1905(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DOMAIN, INTERACTION WITH SUN1 AND SUN2.
[7]"TorsinA binds the KASH domain of nesprins and participates in linkage between nuclear envelope and cytoskeleton."
Nery F.C., Zeng J., Niland B.P., Hewett J., Farley J., Irimia D., Li Y., Wiche G., Sonnenberg A., Breakefield X.O.
J. Cell Sci. 121:3476-3486(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TOR1A.
[8]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Nesprin-3 regulates endothelial cell morphology, perinuclear cytoskeletal architecture, and flow-induced polarization."
Morgan J.T., Pfeiffer E.R., Thirkill T.L., Kumar P., Peng G., Fridolfsson H.N., Douglas G.C., Starr D.A., Barakat A.I.
Mol. Biol. Cell 22:4324-4334(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[10]"Cytoskeletal interactions at the nuclear envelope mediated by nesprins."
Taranum S., Sur I., Muller R., Lu W., Rashmi R.N., Munck M., Neumann S., Karakesisoglou I., Noegel A.A.
Int. J. Cell Biol. 2012:736524-736524(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SYNE1.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BX248076 mRNA. Translation: CAD62365.1. Different initiation.
AL138539 Genomic DNA. No translation available.
BC146604 mRNA. Translation: AAI46605.1.
AK098471 mRNA. Translation: BAC05312.1. Different initiation.
AK131436 mRNA. Translation: BAD18582.1. Different initiation.
CCDSCCDS9935.1. [Q6ZMZ3-1]
RefSeqNP_689805.3. NM_152592.3. [Q6ZMZ3-1]
XP_005267433.1. XM_005267376.2. [Q6ZMZ3-1]
XP_005267434.1. XM_005267377.1. [Q6ZMZ3-1]
XP_006720126.1. XM_006720063.1. [Q6ZMZ3-1]
XP_006720127.1. XM_006720064.1. [Q6ZMZ3-2]
UniGeneHs.354645.

3D structure databases

ProteinModelPortalQ6ZMZ3.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000334308.

PTM databases

PhosphoSiteQ6ZMZ3.

Polymorphism databases

DMDM134035037.

Proteomic databases

MaxQBQ6ZMZ3.
PaxDbQ6ZMZ3.
PRIDEQ6ZMZ3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000334258; ENSP00000334308; ENSG00000176438. [Q6ZMZ3-1]
ENST00000553340; ENSP00000450774; ENSG00000176438. [Q6ZMZ3-3]
ENST00000557275; ENSP00000450562; ENSG00000176438. [Q6ZMZ3-2]
GeneID161176.
KEGGhsa:161176.
UCSCuc001yei.4. human. [Q6ZMZ3-1]
uc001yej.1. human. [Q6ZMZ3-3]
uc010avi.3. human. [Q6ZMZ3-2]

Organism-specific databases

CTD161176.
GeneCardsGC14M095884.
H-InvDBHIX0011939.
HGNCHGNC:19861. SYNE3.
HPAHPA055227.
MIM610861. gene.
neXtProtNX_Q6ZMZ3.
PharmGKBPA134931380.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG145316.
HOGENOMHOG000154475.
HOVERGENHBG094014.
InParanoidQ6ZMZ3.
OMAIKAQWEE.
OrthoDBEOG7XM2X7.
PhylomeDBQ6ZMZ3.
TreeFamTF331132.

Gene expression databases

ArrayExpressQ6ZMZ3.
BgeeQ6ZMZ3.
CleanExHS_C14orf49.
GenevestigatorQ6ZMZ3.

Family and domain databases

InterProIPR012315. KASH.
IPR018159. Spectrin/alpha-actinin.
IPR002017. Spectrin_repeat.
[Graphical view]
PfamPF10541. KASH. 1 hit.
PF00435. Spectrin. 1 hit.
[Graphical view]
SMARTSM00150. SPEC. 3 hits.
[Graphical view]
PROSITEPS51049. KASH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi161176.
NextBio88029.
PROQ6ZMZ3.
SOURCESearch...

Entry information

Entry nameSYNE3_HUMAN
AccessionPrimary (citable) accession number: Q6ZMZ3
Secondary accession number(s): A6H8H3, Q86SX5, Q8N7G8
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: March 20, 2007
Last modified: July 9, 2014
This is version 93 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM