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Protein

Nesprin-4

Gene

SYNE4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Biological processi

Names & Taxonomyi

Protein namesi
Recommended name:
Nesprin-4
Alternative name(s):
KASH domain-containing protein 4
Short name:
KASH4
Nuclear envelope spectrin repeat protein 4
Gene namesi
Name:SYNE4
Synonyms:C19orf46
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:26703. SYNE4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 355CytoplasmicPROSITE-ProRule annotationAdd BLAST355
Transmembranei356 – 376Helical; Anchor for type IV membrane proteinPROSITE-ProRule annotationAdd BLAST21
Topological domaini377 – 404Perinuclear spacePROSITE-ProRule annotationAdd BLAST28

GO - Cellular componenti

Keywords - Cellular componenti

Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Deafness, autosomal recessive, 76 (DFNB76)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:615540

Keywords - Diseasei

Deafness, Non-syndromic deafness

Organism-specific databases

DisGeNETi163183.
MalaCardsiSYNE4.
MIMi615540. phenotype.
OpenTargetsiENSG00000181392.
Orphaneti90636. Autosomal recessive non-syndromic sensorineural deafness type DFNB.
PharmGKBiPA145149542.

Polymorphism and mutation databases

BioMutaiSYNE4.
DMDMi158706458.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003062641 – 404Nesprin-4Add BLAST404

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi381Interchain (with C-563 in SUN2); alternateBy similarity
Disulfide bondi381Interchain (with C-657 in SUN1)By similarity

Post-translational modificationi

The disulfid bond with SUN1 or SUN2 is required for stability of the respective LINC complex under tensile forces.By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiQ8N205.
MaxQBiQ8N205.
PaxDbiQ8N205.
PeptideAtlasiQ8N205.
PRIDEiQ8N205.

PTM databases

iPTMnetiQ8N205.
PhosphoSitePlusiQ8N205.

Expressioni

Gene expression databases

BgeeiENSG00000181392.
CleanExiHS_C19orf46.
ExpressionAtlasiQ8N205. baseline and differential.
GenevisibleiQ8N205. HS.

Organism-specific databases

HPAiHPA060253.

Interactioni

Subunit structurei

Core component of LINC complexes which are composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, differentially expression of LINC complex constituents can give rise to specific assemblies (By similarity). Probably part of a SUN1-containing LINC complex. Interacts with kinesins KIF5B and KLC1 (By similarity).By similarity

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi127856. 92 interactors.
IntActiQ8N205. 58 interactors.
MINTiMINT-8247425.
STRINGi9606.ENSP00000316130.

Structurei

3D structure databases

ProteinModelPortaliQ8N205.
SMRiQ8N205.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini347 – 404KASHPROSITE-ProRule annotationAdd BLAST58

Domaini

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

Sequence similaritiesi

Belongs to the nesprin family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IIPP. Eukaryota.
ENOG4111B09. LUCA.
GeneTreeiENSGT00510000049061.
HOGENOMiHOG000111992.
HOVERGENiHBG107763.
InParanoidiQ8N205.
OMAiSHRKHLA.
OrthoDBiEOG091G0CR5.
PhylomeDBiQ8N205.

Family and domain databases

InterProiView protein in InterPro
IPR012315. KASH.
PfamiView protein in Pfam
PF10541. KASH. 1 hit.
SMARTiView protein in SMART
SM01249. KASH. 1 hit.
PROSITEiView protein in PROSITE
PS51049. KASH. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8N205-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MALSLPLGPR LGSEPLNHPP GAPREADIVG CTVCPASGEE STSPEQAQTL
60 70 80 90 100
GQDSLGPPEH FQGGPRGNEP AAHPPRWSTP SSYEDPAGGK HCEHPISGLE
110 120 130 140 150
VLEAEQNSLH LCLLGLGRRL QDLEQGLGHW ALAQSGMVQL QALQVDLRGA
160 170 180 190 200
AERVEALLAF GEGLAQRSEP RAWAALEQIL RALGAYRDSI FRRLWQLQAQ
210 220 230 240 250
LVSYSLVFEE ANTLDQDLEV EGDSDWPGPG GVWGPWAPSS LPTSTELEWD
260 270 280 290 300
PAGDIGGLGP LGQKTARTLG VPCELCGQRG PQGRGQGLEE ADTSHSRQDM
310 320 330 340 350
LESGLGHQKR LARHQRHSLL RKPQDKKRQA SPHLQDVRLE GNPGAPDPAS
360 370 380 390 400
RQPLTFLLIL FLLFLLLVGA MFLLPASGGP CCSHARIPRT PYLVLSYVNG

LPPV
Length:404
Mass (Da):43,512
Last modified:October 2, 2007 - v2
Checksum:iF15E209FB06636D2
GO
Isoform 2 (identifier: Q8N205-2) [UniParc]FASTAAdd to basket

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

Show »
Length:291
Mass (Da):30,975
Checksum:iA8ABE973A89DD240
GO

Sequence cautioni

The sequence BAC04222 differs from that shown. Intron retention.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035284224S → L. Corresponds to variant dbSNP:rs34818970Ensembl.1
Natural variantiVAR_035285278Q → H1 PublicationCorresponds to variant dbSNP:rs2285422Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02844494 – 206Missing in isoform 2. 1 PublicationAdd BLAST113

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK093764 mRNA. Translation: BAC04222.1. Sequence problems.
AC002116 Genomic DNA. No translation available.
AF038458 Genomic DNA. No translation available.
BC052573 mRNA. Translation: AAH52573.1.
CCDSiCCDS42553.1. [Q8N205-1]
CCDS77285.1. [Q8N205-2]
RefSeqiNP_001034965.1. NM_001039876.2. [Q8N205-1]
NP_001284664.1. NM_001297735.2. [Q8N205-2]
UniGeneiHs.436743.

Genome annotation databases

EnsembliENST00000324444; ENSP00000316130; ENSG00000181392. [Q8N205-1]
ENST00000340477; ENSP00000343152; ENSG00000181392. [Q8N205-2]
GeneIDi163183.
KEGGihsa:163183.
UCSCiuc002ocq.2. human. [Q8N205-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiSYNE4_HUMAN
AccessioniPrimary (citable) accession number: Q8N205
Secondary accession number(s): A8MRS0, A8MYE3, Q7Z7L3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: October 2, 2007
Last modified: April 12, 2017
This is version 113 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families