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Q8N205 (SYNE4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 86. 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-4
Alternative name(s):
Nuclear envelope spectrin repeat protein 4
Gene names
Name:SYNE4
Synonyms:C19orf46
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length404 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning By similarity. Behaves as a kinesin cargo, providing a functional binding site for kinesin-1 at the nuclear envelope. Hence may contribute to the establishment of secretory epithelial morphology by promoting kinesin-dependent apical migration of the centrosome and Golgi apparatus and basal localization of the nucleus By similarity.

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 By similarity. Interacts with kinesins KIF5B and KLC1 By similarity.

Subcellular location

Nucleus outer membrane; Single-pass type IV membrane protein. Note: Localization at the nucleus outer membrane requires the presence of SUN1 By similarity. Ref.4

Domain

The KASH domain, which contains a transmembrane domain, mediates the nuclear envelope targeting and is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains By similarity.

Involvement in disease

Deafness, autosomal recessive, 76 (DFNB76) [MIM:615540]: A form of non-syndromic sensorineural deafness, a disorder resulting from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB76 affected individuals have onset of progressive high frequency hearing impairment between birth and 6 years of age. The hearing loss is severe at high frequencies by adulthood.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4

Sequence similarities

Belongs to the nesprin family.

Contains 1 KASH domain.

Sequence caution

The sequence BAC04222.1 differs from that shown. Reason: Intron retention.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8N205-1)

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: Q8N205-2)

The sequence of this isoform differs from the canonical sequence as follows:
     94-206: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 404404Nesprin-4
PRO_0000306264

Regions

Topological domain1 – 355355Cytoplasmic Potential
Transmembrane356 – 37621Helical; Anchor for type IV membrane protein; Potential
Topological domain377 – 40428Perinuclear space Potential
Domain347 – 40458KASH

Natural variations

Alternative sequence94 – 206113Missing in isoform 2.
VSP_028444
Natural variant2241S → L.
Corresponds to variant rs34818970 [ dbSNP | Ensembl ].
VAR_035284
Natural variant2781Q → H. Ref.3
Corresponds to variant rs2285422 [ dbSNP | Ensembl ].
VAR_035285

Sequences

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

Last modified October 2, 2007. Version 2.
Checksum: F15E209FB06636D2

FASTA40443,512
        10         20         30         40         50         60 
MALSLPLGPR LGSEPLNHPP GAPREADIVG CTVCPASGEE STSPEQAQTL GQDSLGPPEH 

        70         80         90        100        110        120 
FQGGPRGNEP AAHPPRWSTP SSYEDPAGGK HCEHPISGLE VLEAEQNSLH LCLLGLGRRL 

       130        140        150        160        170        180 
QDLEQGLGHW ALAQSGMVQL QALQVDLRGA AERVEALLAF GEGLAQRSEP RAWAALEQIL 

       190        200        210        220        230        240 
RALGAYRDSI FRRLWQLQAQ LVSYSLVFEE ANTLDQDLEV EGDSDWPGPG GVWGPWAPSS 

       250        260        270        280        290        300 
LPTSTELEWD PAGDIGGLGP LGQKTARTLG VPCELCGQRG PQGRGQGLEE ADTSHSRQDM 

       310        320        330        340        350        360 
LESGLGHQKR LARHQRHSLL RKPQDKKRQA SPHLQDVRLE GNPGAPDPAS RQPLTFLLIL 

       370        380        390        400 
FLLFLLLVGA MFLLPASGGP CCSHARIPRT PYLVLSYVNG LPPV 

« Hide

Isoform 2 [UniParc].

Checksum: A8ABE973A89DD240
Show »

FASTA29130,975

References

« Hide 'large scale' references
[1]"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] (ISOFORM 1).
Tissue: Thymus.
[2]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [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 2), VARIANT HIS-278.
Tissue: Mammary carcinoma.
[4]"The LINC complex is essential for hearing."
Horn H.F., Brownstein Z., Lenz D.R., Shivatzki S., Dror A.A., Dagan-Rosenfeld O., Friedman L.M., Roux K.J., Kozlov S., Jeang K.T., Frydman M., Burke B., Stewart C.L., Avraham K.B.
J. Clin. Invest. 123:740-750(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN DFNB76, SUBCELLULAR LOCATION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK093764 mRNA. Translation: BAC04222.1. Sequence problems.
AC002116 Genomic DNA. No translation available.
AF038458 Genomic DNA. No translation available.
BC052573 mRNA. Translation: AAH52573.1.
CCDSCCDS42553.1. [Q8N205-1]
RefSeqNP_001034965.1. NM_001039876.1. [Q8N205-1]
UniGeneHs.436743.

3D structure databases

ProteinModelPortalQ8N205.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid127856. 5 interactions.
IntActQ8N205. 6 interactions.
MINTMINT-8247425.

PTM databases

PhosphoSiteQ8N205.

Polymorphism databases

DMDM158706458.

Proteomic databases

MaxQBQ8N205.
PaxDbQ8N205.
PRIDEQ8N205.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000324444; ENSP00000316130; ENSG00000181392. [Q8N205-1]
ENST00000340477; ENSP00000343152; ENSG00000181392. [Q8N205-2]
GeneID163183.
KEGGhsa:163183.
UCSCuc002ocq.1. human. [Q8N205-1]
uc002ocs.1. human. [Q8N205-2]

Organism-specific databases

CTD163183.
GeneCardsGC19M036602.
HGNCHGNC:26703. SYNE4.
HPAHPA060253.
MIM615535. gene.
615540. phenotype.
neXtProtNX_Q8N205.
Orphanet90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
PharmGKBPA145149542.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39456.
HOGENOMHOG000111992.
HOVERGENHBG107763.
InParanoidQ8N205.
OMASHRKHLA.
PhylomeDBQ8N205.

Gene expression databases

ArrayExpressQ8N205.
BgeeQ8N205.
CleanExHS_C19orf46.
GenevestigatorQ8N205.

Family and domain databases

InterProIPR012315. KASH.
[Graphical view]
PfamPF10541. KASH. 1 hit.
[Graphical view]
PROSITEPS51049. KASH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi163183.
NextBio88324.
PROQ8N205.
SOURCESearch...

Entry information

Entry nameSYNE4_HUMAN
AccessionPrimary (citable) accession number: Q8N205
Secondary accession number(s): A8MRS0, A8MYE3, Q7Z7L3
Entry history
Integrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: October 2, 2007
Last modified: July 9, 2014
This is version 86 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 19

Human chromosome 19: entries, gene names and cross-references to MIM