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Protein

SUN domain-containing protein 2

Gene

SUN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Required for nuclear migration in retinal photoreceptor progenitors implicating association with cytoplasmic dynein-dynactin and kinesin motor complexes, and probably B-type lamins; SUN1 and SUN2 seem to act redundantly. The SUN1/2:KASH5 LINC complex couples telomeres to microtubules during meiosis; SUN1 and SUN2 seem to act at least partial redundantly. Anchors chromosome movement in the prophase of meiosis and is involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Required for telomere attachment to nuclear envelope and gametogenesis. May also function on endocytic vesicles as a receptor for RAB5-GDP and participate in the activation of RAB5.By similarityCurated1 Publication

Caution

It is uncertain whether Met-1 or Met-50 is the initiator.Curated

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • lamin binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • protein membrane anchor Source: GO_Central

GO - Biological processi

Keywordsi

Biological processMeiosis

Enzyme and pathway databases

ReactomeiR-HSA-1221632 Meiotic synapsis

Names & Taxonomyi

Protein namesi
Recommended name:
SUN domain-containing protein 2
Alternative name(s):
Protein unc-84 homolog B
Rab5-interacting protein
Short name:
Rab5IP
Sad1/unc-84 protein-like 2
Gene namesi
Name:SUN2
Synonyms:FRIGG, KIAA0668, RAB5IP, UNC84B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100242.15
HGNCiHGNC:14210 SUN2
MIMi613569 gene
neXtProtiNX_Q9UH99

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 212Nuclear1 PublicationAdd BLAST212
Transmembranei213 – 233HelicalAdd BLAST21
Topological domaini234 – 717Perinuclear space1 PublicationAdd BLAST484

Keywords - Cellular componenti

Endosome, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi536L → D: Disrupts interaction with SYNE2. 1 Publication1
Mutagenesisi538Missing : Disrupts interaction with SYNE2. 1 Publication1
Mutagenesisi542D → N: Disrupts interaction with SYNE2. 2 Publications1
Mutagenesisi563C → A: Decreases stability of the SUN2:SYNE2/KASH2 complex under tensile forces and inhibits force transmission through the complex. 1 Publication1
Mutagenesisi603A → E: Decreases interaction with SYNE2. Disrupts interaction with SYNE2; when associated with E-641 and E-703. 1 Publication1
Mutagenesisi609G → D: Decreases interaction with SYNE2. 1 Publication1
Mutagenesisi628H → A: Disrupts interaction with SYNE2. 1 Publication1
Mutagenesisi641S → E: Decreases interaction with SYNE2. Disrupts interaction with SYNE2; when associated with E-603 and E-703. 2 Publications1
Mutagenesisi703Y → E: Decreases interaction with SYNE2. Disrupts interaction with SYNE2; when associated with E-603 and E-641. 1 Publication1
Mutagenesisi707Y → F: Disrupts interaction with SYNE2, impairs localization to the nuclear envelope. 1 Publication1

Organism-specific databases

DisGeNETi25777
OpenTargetsiENSG00000100242
PharmGKBiPA165378369

Polymorphism and mutation databases

BioMutaiSUN2
DMDMi29337242

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002189131 – 717SUN domain-containing protein 2Add BLAST717

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei12Phosphoserine1 Publication1
Modified residuei38PhosphoserineCombined sources1
Modified residuei54PhosphoserineCombined sources1 Publication1
Modified residuei107PhosphothreonineBy similarity1
Modified residuei110PhosphoserineBy similarity1
Modified residuei113PhosphoserineBy similarity1
Modified residuei116Phosphoserine1 Publication1
Modified residuei136PhosphoserineBy similarity1
Disulfide bondi563Interchain (with C-6862 in SYNE2)1 Publication
Disulfide bondi601 ↔ 7052 Publications
Glycosylationi636N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

The disulfid bond with SYNE2 is required for stability of the SUN2:SYNE2/KASH2 LINC complex under tensile forces though not required for the interaction. The disulfid bond is proposed to be conserved in LINC complexes involved in force transmission.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9UH99
PaxDbiQ9UH99
PeptideAtlasiQ9UH99
PRIDEiQ9UH99
ProteomicsDBi84289

PTM databases

GlyConnecti1777
iPTMnetiQ9UH99
PhosphoSitePlusiQ9UH99
SwissPalmiQ9UH99

Expressioni

Tissue specificityi

Widely expressed. Highly expressed in heart, lung and muscle. Weakly expressed in fetal heart. Slightly overexpressed in some heart tissues form patients with congenital heart defects.2 Publications

Gene expression databases

BgeeiENSG00000100242 Expressed in 232 organ(s), highest expression level in popliteal artery
CleanExiHS_UNC84B
ExpressionAtlasiQ9UH99 baseline and differential
GenevisibleiQ9UH99 HS

Organism-specific databases

HPAiHPA001209

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 and KASH domain-containing proteins seem to bind each other promiscuously; however, differentially expression of LINC complex constituents is giving rise to specific assemblies. At least SUN1/2-containing core LINC complexes are proposed to be hexameric composed of three protomers of each KASH and SUN domain-containing protein. Interacts with SYNE2; the SUN2:SYNE2/KASH2 LINC complex is a heterohexamer; the homotrimeric cloverleave-like conformation of the SUN domain is a prerequisite for LINC complex formation in which three separate SYNE2/KASH2 peptides bind at the interface of adjacent SUN domains. Component of a probable SUN2:KASH5 LINC complex. Interacts with SYNE1 and SYNE3; probably forming respective LINC complexes. Interacts with A-type lamin. Interaction with lamins B1 and C is hardly detectable (By similarity). Interacts with EMD and RAB5A. Interacts with TMEM43 and TMEM201.By similarity7 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi117312, 57 interactors
IntActiQ9UH99, 50 interactors
MINTiQ9UH99
STRINGi9606.ENSP00000385616

Structurei

Secondary structure

1717
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UH99
SMRiQ9UH99
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini555 – 716SUNPROSITE-ProRule annotationAdd BLAST162

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 139LMNA-bindingBy similarityAdd BLAST139
Regioni507 – 717Sufficient for interaction with SYNE1 and SYNE21 PublicationAdd BLAST211

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili273 – 296Sequence analysisAdd BLAST24
Coiled coili348 – 440Sequence analysisAdd BLAST93
Coiled coili475 – 506Sequence analysisAdd BLAST32

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi2 – 164Ser-richAdd BLAST163
Compositional biasi100 – 105Poly-Arg6
Compositional biasi316 – 322Poly-Gly7
Compositional biasi468 – 471Poly-Gly4

Domaini

The coiled coil domains differentially mediate trimerization required for binding to nesprins and are proposed to dynamically regulate the oligomeric state by locking the SUN domain in an inactive confirmation (By similarity). The coiled coil domains are proposed to be involved in load-bearing and force transmission from the cytoskeleton.By similarity1 Publication
The SUN domain may play a role in the nuclear anchoring and/or migration.

Keywords - Domaini

Coiled coil, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2687 Eukaryota
ENOG410YM6S LUCA
GeneTreeiENSGT00390000011587
HOGENOMiHOG000253025
HOVERGENiHBG056957
InParanoidiQ9UH99
KOiK19347
OMAiRMTQESF
OrthoDBiEOG091G0AZ8
PhylomeDBiQ9UH99
TreeFamiTF323915

Family and domain databases

Gene3Di2.60.120.260, 1 hit
InterProiView protein in InterPro
IPR008979 Galactose-bd-like_sf
IPR030272 SUN2
IPR012919 SUN_dom
PANTHERiPTHR12911:SF22 PTHR12911:SF22, 1 hit
PfamiView protein in Pfam
PF07738 Sad1_UNC, 1 hit
PROSITEiView protein in PROSITE
PS51469 SUN, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9UH99-1) [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
MSRRSQRLTR YSQGDDDGSS SSGGSSVAGS QSTLFKDSPL RTLKRKSSNM
60 70 80 90 100
KRLSPAPQLG PSSDAHTSYY SESLVHESWF PPRSSLEELH GDANWGEDLR
110 120 130 140 150
VRRRRGTGGS ESSRASGLVG RKATEDFLGS SSGYSSEDDY VGYSDVDQQS
160 170 180 190 200
SSSRLRSAVS RAGSLLWMVA TSPGRLFRLL YWWAGTTWYR LTTAASLLDV
210 220 230 240 250
FVLTRRFSSL KTFLWFLLPL LLLTCLTYGA WYFYPYGLQT FHPALVSWWA
260 270 280 290 300
AKDSRRPDEG WEARDSSPHF QAEQRVMSRV HSLERRLEAL AAEFSSNWQK
310 320 330 340 350
EAMRLERLEL RQGAPGQGGG GGLSHEDTLA LLEGLVSRRE AALKEDFRRE
360 370 380 390 400
TAARIQEELS ALRAEHQQDS EDLFKKIVRA SQESEARIQQ LKSEWQSMTQ
410 420 430 440 450
ESFQESSVKE LRRLEDQLAG LQQELAALAL KQSSVAEEVG LLPQQIQAVR
460 470 480 490 500
DDVESQFPAW ISQFLARGGG GRVGLLQREE MQAQLRELES KILTHVAEMQ
510 520 530 540 550
GKSAREAAAS LSLTLQKEGV IGVTEEQVHH IVKQALQRYS EDRIGLADYA
560 570 580 590 600
LESGGASVIS TRCSETYETK TALLSLFGIP LWYHSQSPRV ILQPDVHPGN
610 620 630 640 650
CWAFQGPQGF AVVRLSARIR PTAVTLEHVP KALSPNSTIS SAPKDFAIFG
660 670 680 690 700
FDEDLQQEGT LLGKFTYDQD GEPIQTFHFQ APTMATYQVV ELRILTNWGH
710
PEYTCIYRFR VHGEPAH
Length:717
Mass (Da):80,311
Last modified:March 25, 2003 - v3
Checksum:iCCF43C118E935E84
GO
Isoform 2 (identifier: Q9UH99-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     141-141: V → VEDSEGRGSKVTETEPVSSFPA

Note: No experimental confirmation available.
Show »
Length:738
Mass (Da):82,502
Checksum:iBD17ECBB9F58069B
GO
Isoform 3 (identifier: Q9UH99-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     683-717: TMATYQVVELRILTNWGHPEYTCIYRFRVHGEPAH → SSFPLCPWRLLPILGVCIYVAYHGGLGSWER

Note: No experimental confirmation available.
Show »
Length:713
Mass (Da):79,612
Checksum:i1D110119E43E562C
GO

Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B0QY63B0QY63_HUMAN
SUN domain-containing protein 2
SUN2
224Annotation score:
H0Y686H0Y686_HUMAN
SUN domain-containing protein 2
SUN2
143Annotation score:
B0QY60B0QY60_HUMAN
SUN domain-containing protein 2
SUN2
198Annotation score:
B0QY69B0QY69_HUMAN
SUN domain-containing protein 2
SUN2
124Annotation score:
B0QY66B0QY66_HUMAN
SUN domain-containing protein 2
SUN2
110Annotation score:
B0QY67B0QY67_HUMAN
SUN domain-containing protein 2
SUN2
144Annotation score:
B0QY65B0QY65_HUMAN
SUN domain-containing protein 2
SUN2
127Annotation score:
B0QY68B0QY68_HUMAN
SUN domain-containing protein 2
SUN2
100Annotation score:
B0QY64B0QY64_HUMAN
SUN domain-containing protein 2
SUN2
228Annotation score:

Sequence cautioni

The sequence BAA31643 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti644K → R in CAD97926 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05228233T → A. Corresponds to variant dbSNP:rs2072799EnsemblClinVar.1
Natural variantiVAR_05228389L → R1 PublicationCorresponds to variant dbSNP:rs35496634Ensembl.1
Natural variantiVAR_052284348R → C. Corresponds to variant dbSNP:rs138708EnsemblClinVar.1
Natural variantiVAR_024624671G → S1 PublicationCorresponds to variant dbSNP:rs2072797Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045882141V → VEDSEGRGSKVTETEPVSSF PA in isoform 2. 1 Publication1
Alternative sequenceiVSP_053702683 – 717TMATY…GEPAH → SSFPLCPWRLLPILGVCIYV AYHGGLGSWER in isoform 3. 1 PublicationAdd BLAST35

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB014568 mRNA Translation: BAA31643.1 Different initiation.
AY682988 mRNA Translation: AAT90500.1
CR456474 mRNA Translation: CAG30360.1
BX537962 mRNA Translation: CAD97926.1
AL008583 Genomic DNA No translation available.
AL021806 Genomic DNA No translation available.
AL021707 Genomic DNA No translation available.
BC030684 mRNA Translation: AAH30684.2
BC094797 mRNA Translation: AAH94797.1
BC111549 mRNA Translation: AAI11550.1
BC111717 mRNA Translation: AAI11718.1
AF202723 mRNA Translation: AAF15887.1
CCDSiCCDS13978.1 [Q9UH99-1]
CCDS56231.1 [Q9UH99-2]
PIRiT00371
RefSeqiNP_001186508.1, NM_001199579.1 [Q9UH99-2]
NP_001186509.1, NM_001199580.1 [Q9UH99-1]
NP_056189.1, NM_015374.2 [Q9UH99-1]
UniGeneiHs.517622
Hs.744734

Genome annotation databases

EnsembliENST00000405018; ENSP00000385616; ENSG00000100242 [Q9UH99-2]
ENST00000405510; ENSP00000385740; ENSG00000100242 [Q9UH99-1]
ENST00000406622; ENSP00000383992; ENSG00000100242 [Q9UH99-1]
GeneIDi25777
KEGGihsa:25777
UCSCiuc003awh.3 human [Q9UH99-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB014568 mRNA Translation: BAA31643.1 Different initiation.
AY682988 mRNA Translation: AAT90500.1
CR456474 mRNA Translation: CAG30360.1
BX537962 mRNA Translation: CAD97926.1
AL008583 Genomic DNA No translation available.
AL021806 Genomic DNA No translation available.
AL021707 Genomic DNA No translation available.
BC030684 mRNA Translation: AAH30684.2
BC094797 mRNA Translation: AAH94797.1
BC111549 mRNA Translation: AAI11550.1
BC111717 mRNA Translation: AAI11718.1
AF202723 mRNA Translation: AAF15887.1
CCDSiCCDS13978.1 [Q9UH99-1]
CCDS56231.1 [Q9UH99-2]
PIRiT00371
RefSeqiNP_001186508.1, NM_001199579.1 [Q9UH99-2]
NP_001186509.1, NM_001199580.1 [Q9UH99-1]
NP_056189.1, NM_015374.2 [Q9UH99-1]
UniGeneiHs.517622
Hs.744734

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3UNPX-ray2.39A520-717[»]
4DXRX-ray2.32A522-717[»]
4DXSX-ray2.71A522-717[»]
4DXTX-ray2.22A522-717[»]
4FI9X-ray3.05A523-717[»]
ProteinModelPortaliQ9UH99
SMRiQ9UH99
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117312, 57 interactors
IntActiQ9UH99, 50 interactors
MINTiQ9UH99
STRINGi9606.ENSP00000385616

PTM databases

GlyConnecti1777
iPTMnetiQ9UH99
PhosphoSitePlusiQ9UH99
SwissPalmiQ9UH99

Polymorphism and mutation databases

BioMutaiSUN2
DMDMi29337242

Proteomic databases

EPDiQ9UH99
PaxDbiQ9UH99
PeptideAtlasiQ9UH99
PRIDEiQ9UH99
ProteomicsDBi84289

Protocols and materials databases

DNASUi25777
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000405018; ENSP00000385616; ENSG00000100242 [Q9UH99-2]
ENST00000405510; ENSP00000385740; ENSG00000100242 [Q9UH99-1]
ENST00000406622; ENSP00000383992; ENSG00000100242 [Q9UH99-1]
GeneIDi25777
KEGGihsa:25777
UCSCiuc003awh.3 human [Q9UH99-1]

Organism-specific databases

CTDi25777
DisGeNETi25777
EuPathDBiHostDB:ENSG00000100242.15
GeneCardsiSUN2
H-InvDBiHIX0159176
HGNCiHGNC:14210 SUN2
HPAiHPA001209
MIMi613569 gene
neXtProtiNX_Q9UH99
OpenTargetsiENSG00000100242
PharmGKBiPA165378369
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2687 Eukaryota
ENOG410YM6S LUCA
GeneTreeiENSGT00390000011587
HOGENOMiHOG000253025
HOVERGENiHBG056957
InParanoidiQ9UH99
KOiK19347
OMAiRMTQESF
OrthoDBiEOG091G0AZ8
PhylomeDBiQ9UH99
TreeFamiTF323915

Enzyme and pathway databases

ReactomeiR-HSA-1221632 Meiotic synapsis

Miscellaneous databases

ChiTaRSiSUN2 human
GeneWikiiUNC84B
GenomeRNAii25777
PROiPR:Q9UH99
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100242 Expressed in 232 organ(s), highest expression level in popliteal artery
CleanExiHS_UNC84B
ExpressionAtlasiQ9UH99 baseline and differential
GenevisibleiQ9UH99 HS

Family and domain databases

Gene3Di2.60.120.260, 1 hit
InterProiView protein in InterPro
IPR008979 Galactose-bd-like_sf
IPR030272 SUN2
IPR012919 SUN_dom
PANTHERiPTHR12911:SF22 PTHR12911:SF22, 1 hit
PfamiView protein in Pfam
PF07738 Sad1_UNC, 1 hit
PROSITEiView protein in PROSITE
PS51469 SUN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSUN2_HUMAN
AccessioniPrimary (citable) accession number: Q9UH99
Secondary accession number(s): B0QY62
, O75156, Q2NKN8, Q2T9F7, Q504T5, Q6B4H1, Q7Z3E3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 2, 2002
Last sequence update: March 25, 2003
Last modified: November 7, 2018
This is version 174 of the entry and version 3 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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