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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

Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Nesprin-4
Alternative name(s):
Nuclear envelope spectrin repeat protein 4
Gene namesi
Name:SYNE4
Synonyms:C19orf46
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:26703. SYNE4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 355355CytoplasmicPROSITE-ProRule annotationAdd
BLAST
Transmembranei356 – 37621Helical; Anchor for type IV membrane proteinPROSITE-ProRule annotationAdd
BLAST
Topological domaini377 – 40428Perinuclear spacePROSITE-ProRule annotationAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

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

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

Polymorphism and mutation databases

BioMutaiSYNE4.
DMDMi158706458.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 404404Nesprin-4PRO_0000306264Add
BLAST

Proteomic databases

MaxQBiQ8N205.
PaxDbiQ8N205.
PRIDEiQ8N205.

PTM databases

PhosphoSiteiQ8N205.

Expressioni

Gene expression databases

BgeeiQ8N205.
CleanExiHS_C19orf46.
ExpressionAtlasiQ8N205. baseline and differential.
GenevisibleiQ8N205. HS.

Organism-specific databases

HPAiHPA060253.

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
ABT1Q9ULW33EBI-7131783,EBI-2602396
ADIPOQA8K6603EBI-7131783,EBI-10174479
BRICD5Q6PL453EBI-7131783,EBI-10254180
C10orf35Q96D053EBI-7131783,EBI-2548784
CD47Q087223EBI-7131783,EBI-1268321
CEP19Q96LK03EBI-7131783,EBI-741885
CLDN7O954713EBI-7131783,EBI-740744
CLDN8P567483EBI-7131783,EBI-10215641
CLEC7AQ9BXN27EBI-7131783,EBI-3939278
CMTM5Q96DZ93EBI-7131783,EBI-2548702
CSGALNACT2Q8N6G53EBI-7131783,EBI-10267100
CXCL9Q073253EBI-7131783,EBI-3911467
DEFB121Q5J5C93EBI-7131783,EBI-10244198
ECE2O603443EBI-7131783,EBI-3906484
EDDM3BP568513EBI-7131783,EBI-10215665
EMP1P548493EBI-7131783,EBI-4319440
ENTPD3O753553EBI-7131783,EBI-10187968
FATE1Q969F05EBI-7131783,EBI-743099
ITM2BQ9Y2873EBI-7131783,EBI-2866431
KLC4Q9NSK03EBI-7131783,EBI-949319
KLHL12Q53G593EBI-7131783,EBI-740929
KLRG1Q96E933EBI-7131783,EBI-750770
KTN1Q86UP23EBI-7131783,EBI-359761
MALLQ130213EBI-7131783,EBI-750078
MARCH2Q9P0N83EBI-7131783,EBI-10317612
OCLNQ166253EBI-7131783,EBI-2903088
OLFM4Q6UX063EBI-7131783,EBI-2804156
OSTCLQ8TBU13EBI-7131783,EBI-10273677
PAQR5Q9NXK63EBI-7131783,EBI-10316423
RIPPLY2Q5TAB73EBI-7131783,EBI-10246897
SEC22AQ96IW73EBI-7131783,EBI-8652744
SEC23BQ154373EBI-7131783,EBI-742673
SENP2Q9HC623EBI-7131783,EBI-714881
SFTPCP116863EBI-7131783,EBI-10197617
SLNO006313EBI-7131783,EBI-10180786
SMCO4Q9NRQ53EBI-7131783,EBI-8640191
TMEM115Q128933EBI-7131783,EBI-8633987
TMEM140Q9NV123EBI-7131783,EBI-2844246
TMEM147Q9BVK83EBI-7131783,EBI-348587
TMEM182Q6ZP803EBI-7131783,EBI-10255122
TMEM248Q9NWD83EBI-7131783,EBI-10314986
TMPRSS4Q9NRS4-33EBI-7131783,EBI-10312990
TRIM69Q86WT63EBI-7131783,EBI-749955
TSPAN15O958583EBI-7131783,EBI-7361096
TTMPQ5BVD13EBI-7131783,EBI-10243654
VTI1BQ9UEU03EBI-7131783,EBI-723716
ZNF250P15622-33EBI-7131783,EBI-10177272

Protein-protein interaction databases

BioGridi127856. 89 interactions.
IntActiQ8N205. 52 interactions.
MINTiMINT-8247425.
STRINGi9606.ENSP00000316130.

Structurei

3D structure databases

ProteinModelPortaliQ8N205.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini347 – 40458KASHPROSITE-ProRule annotationAdd
BLAST

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
Contains 1 KASH domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG39456.
GeneTreeiENSGT00510000049061.
HOGENOMiHOG000111992.
HOVERGENiHBG107763.
InParanoidiQ8N205.
OMAiSHRKHLA.
PhylomeDBiQ8N205.

Family and domain databases

InterProiIPR012315. KASH.
IPR030268. SYNE4.
[Graphical view]
PANTHERiPTHR21640:SF0. PTHR21640:SF0. 1 hit.
PfamiPF10541. KASH. 1 hit.
[Graphical view]
PROSITEiPS51049. KASH. 1 hit.
[Graphical view]

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 BAC04222.1 differs from that shown.Intron retention.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti224 – 2241S → L.
Corresponds to variant rs34818970 [ dbSNP | Ensembl ].
VAR_035284
Natural varianti278 – 2781Q → H.1 Publication
Corresponds to variant rs2285422 [ dbSNP | Ensembl ].
VAR_035285

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei94 – 206113Missing in isoform 2. 1 PublicationVSP_028444Add
BLAST

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]
RefSeqiNP_001034965.1. NM_001039876.1. [Q8N205-1]
NP_001284664.1. NM_001297735.1. [Q8N205-2]
UniGeneiHs.436743.

Genome annotation databases

EnsembliENST00000324444; ENSP00000316130; ENSG00000181392. [Q8N205-1]
ENST00000340477; ENSP00000343152; ENSG00000181392. [Q8N205-2]
GeneIDi163183.
KEGGihsa:163183.
UCSCiuc002ocq.1. human. [Q8N205-1]
uc002ocs.1. human. [Q8N205-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

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]
RefSeqiNP_001034965.1. NM_001039876.1. [Q8N205-1]
NP_001284664.1. NM_001297735.1. [Q8N205-2]
UniGeneiHs.436743.

3D structure databases

ProteinModelPortaliQ8N205.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127856. 89 interactions.
IntActiQ8N205. 52 interactions.
MINTiMINT-8247425.
STRINGi9606.ENSP00000316130.

PTM databases

PhosphoSiteiQ8N205.

Polymorphism and mutation databases

BioMutaiSYNE4.
DMDMi158706458.

Proteomic databases

MaxQBiQ8N205.
PaxDbiQ8N205.
PRIDEiQ8N205.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000324444; ENSP00000316130; ENSG00000181392. [Q8N205-1]
ENST00000340477; ENSP00000343152; ENSG00000181392. [Q8N205-2]
GeneIDi163183.
KEGGihsa:163183.
UCSCiuc002ocq.1. human. [Q8N205-1]
uc002ocs.1. human. [Q8N205-2]

Organism-specific databases

CTDi163183.
GeneCardsiGC19M037065.
HGNCiHGNC:26703. SYNE4.
HPAiHPA060253.
MIMi615535. gene.
615540. phenotype.
neXtProtiNX_Q8N205.
Orphaneti90636. Autosomal recessive non-syndromic sensorineural deafness type DFNB.
PharmGKBiPA145149542.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG39456.
GeneTreeiENSGT00510000049061.
HOGENOMiHOG000111992.
HOVERGENiHBG107763.
InParanoidiQ8N205.
OMAiSHRKHLA.
PhylomeDBiQ8N205.

Miscellaneous databases

GenomeRNAii163183.
NextBioi88324.
PROiQ8N205.
SOURCEiSearch...

Gene expression databases

BgeeiQ8N205.
CleanExiHS_C19orf46.
ExpressionAtlasiQ8N205. baseline and differential.
GenevisibleiQ8N205. HS.

Family and domain databases

InterProiIPR012315. KASH.
IPR030268. SYNE4.
[Graphical view]
PANTHERiPTHR21640:SF0. PTHR21640:SF0. 1 hit.
PfamiPF10541. KASH. 1 hit.
[Graphical view]
PROSITEiPS51049. KASH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
    , 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. Cited for: INVOLVEMENT IN DFNB76, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiSYNE4_HUMAN
AccessioniPrimary (citable) accession number: Q8N205
Secondary accession number(s): A8MRS0, A8MYE3, Q7Z7L3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: October 2, 2007
Last modified: June 24, 2015
This is version 95 of the entry and version 2 of the sequence. [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

External Data

Dasty 3

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 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.