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Protein

Tonsoku-like protein

Gene

TONSL

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

Functioni

Component of the MMS22L-TONSL complex, a complex that stimulates the recombination-dependent repair of stalled or collapsed replication forks. The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication by promoting homologous recombination-mediated repair of replication fork-associated double-strand breaks. It may act by mediating the assembly of RAD51 filaments on ssDNA. Within the complex, may act as a scaffold.4 Publications

GO - Molecular functioni

  • histone binding Source: UniProtKB
  • transcription corepressor activity Source: ProtInc

GO - Biological processi

  • cytoplasmic sequestering of transcription factor Source: ProtInc
  • double-strand break repair via homologous recombination Source: UniProtKB
  • replication fork processing Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair

Names & Taxonomyi

Protein namesi
Recommended name:
Tonsoku-like protein
Alternative name(s):
Inhibitor of kappa B-related protein
Short name:
I-kappa-B-related protein
Short name:
IkappaBR
NF-kappa-B inhibitor-like protein 2
Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 2
Gene namesi
Name:TONSL
Synonyms:IKBR, NFKBIL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:7801. TONSL.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Mainly nuclear. Localizes to DNA damage sites, accumulates at stressed replication forks.

GO - Cellular componenti

  • cytoplasm Source: ProtInc
  • nuclear replication fork Source: UniProtKB
  • nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi4796.
OpenTargetsiENSG00000160949.
PharmGKBiPA31605.

Polymorphism and mutation databases

BioMutaiTONSL.
DMDMi182662416.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003266341 – 1378Tonsoku-like proteinAdd BLAST1378

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei719PhosphoserineCombined sources1
Modified residuei797Omega-N-methylarginineBy similarity1

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ96HA7.
MaxQBiQ96HA7.
PaxDbiQ96HA7.
PeptideAtlasiQ96HA7.
PRIDEiQ96HA7.

PTM databases

iPTMnetiQ96HA7.
PhosphoSitePlusiQ96HA7.

Expressioni

Tissue specificityi

Expressed in heart, skeletal muscle and tracheal epithelial cells.1 Publication

Gene expression databases

BgeeiENSG00000160949.
CleanExiHS_NFKBIL2.
ExpressionAtlasiQ96HA7. baseline and differential.
GenevisibleiQ96HA7. HS.

Organism-specific databases

HPAiHPA024679.
HPA046494.

Interactioni

Subunit structurei

Component of the MMS22L-TONSL complex, a complex at least composed of MMS22L and TONSL/NFKBIL2. Interacts with the MCM complex, the FACT complex and the RPA complex. Binds histones.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MMS22LQ6ZRQ55EBI-1052467,EBI-718662

GO - Molecular functioni

  • histone binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110863. 35 interactors.
IntActiQ96HA7. 20 interactors.
MINTiMINT-6780272.
STRINGi9606.ENSP00000386239.

Structurei

Secondary structure

11378
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi532 – 539Combined sources8
Helixi542 – 551Combined sources10
Helixi565 – 572Combined sources8
Helixi575 – 583Combined sources9
Turni594 – 597Combined sources4
Helixi601 – 607Combined sources7
Helixi611 – 616Combined sources6
Helixi634 – 644Combined sources11
Helixi651 – 668Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5JA4X-ray2.42D512-692[»]
ProteinModelPortaliQ96HA7.
SMRiQ96HA7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati27 – 60TPR 1Add BLAST34
Repeati67 – 100TPR 2Add BLAST34
Repeati107 – 147TPR 3Add BLAST41
Repeati162 – 195TPR 4Add BLAST34
Repeati202 – 235TPR 5Add BLAST34
Repeati242 – 275TPR 6Add BLAST34
Repeati311 – 344TPR 7Add BLAST34
Repeati352 – 385TPR 8Add BLAST34
Repeati528 – 557ANK 1Add BLAST30
Repeati561 – 590ANK 2Add BLAST30
Repeati597 – 626ANK 3Add BLAST30
Repeati1069 – 1093LRR 1Add BLAST25
Repeati1097 – 1122LRR 2Add BLAST26
Repeati1128 – 1151LRR 3Add BLAST24
Repeati1188 – 1212LRR 4Add BLAST25
Repeati1247 – 1270LRR 5Add BLAST24
Repeati1275 – 1300LRR 6Add BLAST26
Repeati1331 – 1354LRR 7Add BLAST24

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi448 – 509Glu-richAdd BLAST62

Domaini

The ANK repeats mediate the interaction with the MCM complex and histones, while the LRR repeats mediate the interaction with MMS22L.1 Publication

Sequence similaritiesi

Belongs to the Tonsoku family.Curated
Contains 3 ANK repeats.PROSITE-ProRule annotation
Contains 7 LRR (leucine-rich) repeats.Curated
Contains 8 TPR repeats.Curated

Keywords - Domaini

ANK repeat, Leucine-rich repeat, Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
KOG4308. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00760000119090.
HOGENOMiHOG000113022.
HOVERGENiHBG107999.
InParanoidiQ96HA7.
KOiK09257.
OMAiARCYLNI.
OrthoDBiEOG091G015L.
PhylomeDBiQ96HA7.
TreeFamiTF326440.

Family and domain databases

Gene3Di1.25.40.10. 2 hits.
1.25.40.20. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PfamiPF12796. Ank_2. 1 hit.
PF13516. LRR_6. 2 hits.
PF13176. TPR_7. 1 hit.
PF13181. TPR_8. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 3 hits.
SM00028. TPR. 7 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF48452. SSF48452. 3 hits.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 3 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q96HA7-1) [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
MSLERELRQL SKAKAKAQRA GQRREEAALC HQLGELLAGH GRYAEALEQH
60 70 80 90 100
WQELQLRERA DDPLGCAVAH RKIGERLAEM EDYPAALQHQ HQYLELAHSL
110 120 130 140 150
RNHTELQRAW ATIGRTHLDI YDHCQSRDAL LQAQAAFEKS LAIVDEELEG
160 170 180 190 200
TLAQGELNEM RTRLYLNLGL TFESLQQTAL CNDYFRKSIF LAEQNHLYED
210 220 230 240 250
LFRARYNLGT IHWRAGQHSQ AMRCLEGARE CAHTMRKRFM ESECCVVIAQ
260 270 280 290 300
VLQDLGDFLA AKRALKKAYR LGSQKPVQRA AICQNLQHVL AVVRLQQQLE
310 320 330 340 350
EAEGRDPQGA MVICEQLGDL FSKAGDFPRA AEAYQKQLRF AELLDRPGAE
360 370 380 390 400
RAIIHVSLAT TLGDMKDHHG AVRHYEEELR LRSGNVLEEA KTWLNIALSR
410 420 430 440 450
EEAGDAYELL APCFQKALSC AQQAQRPQLQ RQVLQHLHTV QLRLQPQEAP
460 470 480 490 500
ETETRLRELS VAEDEDEEEE AEEAAATAES EALEAGEVEL SEGEDDTDGL
510 520 530 540 550
TPQLEEDEEL QGHLGRRKGS KWNRRNDMGE TLLHRACIEG QLRRVQDLVR
560 570 580 590 600
QGHPLNPRDY CGWTPLHEAC NYGHLEIVRF LLDHGAAVDD PGGQGCEGIT
610 620 630 640 650
PLHDALNCGH FEVAELLLER GASVTLRTRK GLSPLETLQQ WVKLYRRDLD
660 670 680 690 700
LETRQKARAM EMLLQAAASG QDPHSSQAFH TPSSLLFDPE TSPPLSPCPE
710 720 730 740 750
PPSNSTRLPE ASQAHVRVSP GQAAPAMARP RRSRHGPASS SSSSEGEDSA
760 770 780 790 800
GPARPSQKRP RCSATAQRVA AWTPGPASNR EAATASTSRA AYQAAIRGVG
810 820 830 840 850
SAQSRLGPGP PRGHSKALAP QAALIPEEEC LAGDWLELDM PLTRSRRPRP
860 870 880 890 900
RGTGDNRRPS STSGSDSEES RPRARAKQVR LTCMQSCSAP VNAGPSSLAS
910 920 930 940 950
EPPGSPSTPR VSEPSGDSSA AGQPLGPAPP PPIRVRVQVQ DHLFLIPVPH
960 970 980 990 1000
SSDTHSVAWL AEQAAQRYYQ TCGLLPRLTL RKEGALLAPQ DLIPDVLQSN
1010 1020 1030 1040 1050
DEVLAEVTSW DLPPLTDRYR RACQSLGQGE HQQVLQAVEL QGLGLSFSAC
1060 1070 1080 1090 1100
SLALDQAQLT PLLRALKLHT ALRELRLAGN RLGDKCVAEL VAALGTMPSL
1110 1120 1130 1140 1150
ALLDLSSNHL GPEGLRQLAM GLPGQATLQS LEELDLSMNP LGDGCGQSLA
1160 1170 1180 1190 1200
SLLHACPLLS TLRLQACGFG PSFFLSHQTA LGSAFQDAEH LKTLSLSYNA
1210 1220 1230 1240 1250
LGAPALARTL QSLPAGTLLH LELSSVAAGK GDSDLMEPVF RYLAKEGCAL
1260 1270 1280 1290 1300
AHLTLSANHL GDKAVRDLCR CLSLCPSLIS LDLSANPEIS CASLEELLST
1310 1320 1330 1340 1350
LQKRPQGLSF LGLSGCAVQG PLGLGLWDKI AAQLRELQLC SRRLCAEDRD
1360 1370
ALRQLQPSRP GPGECTLDHG SKLFFRRL
Length:1,378
Mass (Da):150,929
Last modified:April 8, 2008 - v2
Checksum:i8E3013861864DCDE
GO
Isoform 2 (identifier: Q96HA7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     631-641: GLSPLETLQQW → ASARWRRCSSG

Note: No experimental confirmation available.
Show »
Length:1,378
Mass (Da):150,894
Checksum:i22AF7F6F65F703E8
GO

Sequence cautioni

The sequence AAA85819 differs from that shown. Reason: Frameshift at several positions.Curated
The sequence AAH08782 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAB63467 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti193 – 194EQ → DE in AAA85819 (PubMed:7738005).Curated2
Sequence conflicti268A → R in AAA85819 (PubMed:7738005).Curated1
Sequence conflicti427P → A in CAB63467 (PubMed:11246458).Curated1
Sequence conflicti482A → R in AAA85819 (PubMed:7738005).Curated1
Sequence conflicti516R → P in AAA85819 (PubMed:7738005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042411488V → M.Corresponds to variant rs2229314dbSNPEnsembl.1
Natural variantiVAR_042412493G → S.2 PublicationsCorresponds to variant rs2229315dbSNPEnsembl.1
Natural variantiVAR_042413714A → V.1 PublicationCorresponds to variant rs7830832dbSNPEnsembl.1
Natural variantiVAR_0424141276P → L.Corresponds to variant rs4925856dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_032686631 – 641GLSPLETLQQW → ASARWRRCSSG in isoform 2. 1 PublicationAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U16258 mRNA. Translation: AAA85819.1. Frameshift.
AC084125 Genomic DNA. No translation available.
AF205589 Genomic DNA. No translation available.
BC008782 mRNA. Translation: AAH08782.1. Different initiation.
AJ249601 Genomic DNA. Translation: CAB63467.1. Sequence problems.
CCDSiCCDS34968.2. [Q96HA7-1]
PIRiA56429.
RefSeqiNP_038460.4. NM_013432.4. [Q96HA7-1]
UniGeneiHs.675285.

Genome annotation databases

EnsembliENST00000409379; ENSP00000386239; ENSG00000160949. [Q96HA7-1]
GeneIDi4796.
KEGGihsa:4796.
UCSCiuc011llg.3. human. [Q96HA7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U16258 mRNA. Translation: AAA85819.1. Frameshift.
AC084125 Genomic DNA. No translation available.
AF205589 Genomic DNA. No translation available.
BC008782 mRNA. Translation: AAH08782.1. Different initiation.
AJ249601 Genomic DNA. Translation: CAB63467.1. Sequence problems.
CCDSiCCDS34968.2. [Q96HA7-1]
PIRiA56429.
RefSeqiNP_038460.4. NM_013432.4. [Q96HA7-1]
UniGeneiHs.675285.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5JA4X-ray2.42D512-692[»]
ProteinModelPortaliQ96HA7.
SMRiQ96HA7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110863. 35 interactors.
IntActiQ96HA7. 20 interactors.
MINTiMINT-6780272.
STRINGi9606.ENSP00000386239.

PTM databases

iPTMnetiQ96HA7.
PhosphoSitePlusiQ96HA7.

Polymorphism and mutation databases

BioMutaiTONSL.
DMDMi182662416.

Proteomic databases

EPDiQ96HA7.
MaxQBiQ96HA7.
PaxDbiQ96HA7.
PeptideAtlasiQ96HA7.
PRIDEiQ96HA7.

Protocols and materials databases

DNASUi4796.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000409379; ENSP00000386239; ENSG00000160949. [Q96HA7-1]
GeneIDi4796.
KEGGihsa:4796.
UCSCiuc011llg.3. human. [Q96HA7-1]

Organism-specific databases

CTDi4796.
DisGeNETi4796.
GeneCardsiTONSL.
H-InvDBHIX0007858.
HGNCiHGNC:7801. TONSL.
HPAiHPA024679.
HPA046494.
MIMi604546. gene.
neXtProtiNX_Q96HA7.
OpenTargetsiENSG00000160949.
PharmGKBiPA31605.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
KOG4308. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00760000119090.
HOGENOMiHOG000113022.
HOVERGENiHBG107999.
InParanoidiQ96HA7.
KOiK09257.
OMAiARCYLNI.
OrthoDBiEOG091G015L.
PhylomeDBiQ96HA7.
TreeFamiTF326440.

Miscellaneous databases

ChiTaRSiTONSL. human.
GenomeRNAii4796.
PROiQ96HA7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160949.
CleanExiHS_NFKBIL2.
ExpressionAtlasiQ96HA7. baseline and differential.
GenevisibleiQ96HA7. HS.

Family and domain databases

Gene3Di1.25.40.10. 2 hits.
1.25.40.20. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PfamiPF12796. Ank_2. 1 hit.
PF13516. LRR_6. 2 hits.
PF13176. TPR_7. 1 hit.
PF13181. TPR_8. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 3 hits.
SM00028. TPR. 7 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF48452. SSF48452. 3 hits.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 3 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTONSL_HUMAN
AccessioniPrimary (citable) accession number: Q96HA7
Secondary accession number(s): B5MDP0
, C9JKB1, C9JNV8, Q13006, Q9UGJ2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: April 8, 2008
Last modified: November 2, 2016
This is version 138 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

Caution

Was reported to share sequence similarities with IKBKB and therefore named 'NF-kappa-B inhibitor-like protein 2' (PubMed:7738005). However, the sequence similarity is remote and effects as regulator of NF-kappa-B are probably indirect and require additional evidence (PubMed:9242696).2 Publications

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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.