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Q96HA7 (TONSL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 112. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:TONSL
Synonyms:IKBR, NFKBIL2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1378 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.7 Ref.8 Ref.9

Subunit structure

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. Ref.7 Ref.8 Ref.9

Subcellular location

Cytoplasm. Nucleus. Note: Mainly nuclear. Localizes to DNA damage sites, accumulates at stressed replication forks. Ref.5 Ref.7 Ref.8

Tissue specificity

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

Domain

The ANK repeats mediate the interaction with the MCM complex and histones, while the LRR repeats mediate the interaction with MMS22L. Ref.8

Sequence similarities

Belongs to the Tonsoku family.

Contains 3 ANK repeats.

Contains 7 LRR (leucine-rich) repeats.

Contains 8 TPR repeats.

Caution

Was reported to share sequence similarities with IKBKB and therefore named 'NF-kappa-B inhibitor-like protein 2' (Ref.1). However, the sequence similarity is remote and effects as regulator of NF-kappa-B are probably indirect and require additional evidence (Ref.5).

Sequence caution

The sequence AAA85819.1 differs from that shown. Reason: Frameshift at several positions.

The sequence AAH08782.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence CAB63467.1 differs from that shown. Reason: Erroneous gene model prediction.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MMS22LQ6ZRQ55EBI-1052467,EBI-718662

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96HA7-1)

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: Q96HA7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     631-641: GLSPLETLQQW → ASARWRRCSSG
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13781378Tonsoku-like protein
PRO_0000326634

Regions

Repeat27 – 6034TPR 1
Repeat67 – 10034TPR 2
Repeat107 – 14741TPR 3
Repeat162 – 19534TPR 4
Repeat202 – 23534TPR 5
Repeat242 – 27534TPR 6
Repeat311 – 34434TPR 7
Repeat352 – 38534TPR 8
Repeat528 – 55730ANK 1
Repeat561 – 59030ANK 2
Repeat597 – 62630ANK 3
Repeat1069 – 109325LRR 1
Repeat1097 – 112226LRR 2
Repeat1128 – 115124LRR 3
Repeat1188 – 121225LRR 4
Repeat1247 – 127024LRR 5
Repeat1275 – 130026LRR 6
Repeat1331 – 135424LRR 7
Compositional bias448 – 50962Glu-rich

Amino acid modifications

Modified residue7191Phosphoserine Ref.6 Ref.10

Natural variations

Alternative sequence631 – 64111GLSPLETLQQW → ASARWRRCSSG in isoform 2.
VSP_032686
Natural variant4881V → M.
Corresponds to variant rs2229314 [ dbSNP | Ensembl ].
VAR_042411
Natural variant4931G → S. Ref.1 Ref.4
Corresponds to variant rs2229315 [ dbSNP | Ensembl ].
VAR_042412
Natural variant7141A → V. Ref.3
Corresponds to variant rs7830832 [ dbSNP | Ensembl ].
VAR_042413
Natural variant12761P → L.
Corresponds to variant rs4925856 [ dbSNP | Ensembl ].
VAR_042414

Experimental info

Sequence conflict193 – 1942EQ → DE in AAA85819. Ref.1
Sequence conflict2681A → R in AAA85819. Ref.1
Sequence conflict4271P → A in CAB63467. Ref.4
Sequence conflict4821A → R in AAA85819. Ref.1
Sequence conflict5161R → P in AAA85819. Ref.1

Sequences

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

Last modified April 8, 2008. Version 2.
Checksum: 8E3013861864DCDE

FASTA1,378150,929
        10         20         30         40         50         60 
MSLERELRQL SKAKAKAQRA GQRREEAALC HQLGELLAGH GRYAEALEQH WQELQLRERA 

        70         80         90        100        110        120 
DDPLGCAVAH RKIGERLAEM EDYPAALQHQ HQYLELAHSL RNHTELQRAW ATIGRTHLDI 

       130        140        150        160        170        180 
YDHCQSRDAL LQAQAAFEKS LAIVDEELEG TLAQGELNEM RTRLYLNLGL TFESLQQTAL 

       190        200        210        220        230        240 
CNDYFRKSIF LAEQNHLYED LFRARYNLGT IHWRAGQHSQ AMRCLEGARE CAHTMRKRFM 

       250        260        270        280        290        300 
ESECCVVIAQ VLQDLGDFLA AKRALKKAYR LGSQKPVQRA AICQNLQHVL AVVRLQQQLE 

       310        320        330        340        350        360 
EAEGRDPQGA MVICEQLGDL FSKAGDFPRA AEAYQKQLRF AELLDRPGAE RAIIHVSLAT 

       370        380        390        400        410        420 
TLGDMKDHHG AVRHYEEELR LRSGNVLEEA KTWLNIALSR EEAGDAYELL APCFQKALSC 

       430        440        450        460        470        480 
AQQAQRPQLQ RQVLQHLHTV QLRLQPQEAP ETETRLRELS VAEDEDEEEE AEEAAATAES 

       490        500        510        520        530        540 
EALEAGEVEL SEGEDDTDGL TPQLEEDEEL QGHLGRRKGS KWNRRNDMGE TLLHRACIEG 

       550        560        570        580        590        600 
QLRRVQDLVR QGHPLNPRDY CGWTPLHEAC NYGHLEIVRF LLDHGAAVDD PGGQGCEGIT 

       610        620        630        640        650        660 
PLHDALNCGH FEVAELLLER GASVTLRTRK GLSPLETLQQ WVKLYRRDLD LETRQKARAM 

       670        680        690        700        710        720 
EMLLQAAASG QDPHSSQAFH TPSSLLFDPE TSPPLSPCPE PPSNSTRLPE ASQAHVRVSP 

       730        740        750        760        770        780 
GQAAPAMARP RRSRHGPASS SSSSEGEDSA GPARPSQKRP RCSATAQRVA AWTPGPASNR 

       790        800        810        820        830        840 
EAATASTSRA AYQAAIRGVG SAQSRLGPGP PRGHSKALAP QAALIPEEEC LAGDWLELDM 

       850        860        870        880        890        900 
PLTRSRRPRP RGTGDNRRPS STSGSDSEES RPRARAKQVR LTCMQSCSAP VNAGPSSLAS 

       910        920        930        940        950        960 
EPPGSPSTPR VSEPSGDSSA AGQPLGPAPP PPIRVRVQVQ DHLFLIPVPH SSDTHSVAWL 

       970        980        990       1000       1010       1020 
AEQAAQRYYQ TCGLLPRLTL RKEGALLAPQ DLIPDVLQSN DEVLAEVTSW DLPPLTDRYR 

      1030       1040       1050       1060       1070       1080 
RACQSLGQGE HQQVLQAVEL QGLGLSFSAC SLALDQAQLT PLLRALKLHT ALRELRLAGN 

      1090       1100       1110       1120       1130       1140 
RLGDKCVAEL VAALGTMPSL ALLDLSSNHL GPEGLRQLAM GLPGQATLQS LEELDLSMNP 

      1150       1160       1170       1180       1190       1200 
LGDGCGQSLA SLLHACPLLS TLRLQACGFG PSFFLSHQTA LGSAFQDAEH LKTLSLSYNA 

      1210       1220       1230       1240       1250       1260 
LGAPALARTL QSLPAGTLLH LELSSVAAGK GDSDLMEPVF RYLAKEGCAL AHLTLSANHL 

      1270       1280       1290       1300       1310       1320 
GDKAVRDLCR CLSLCPSLIS LDLSANPEIS CASLEELLST LQKRPQGLSF LGLSGCAVQG 

      1330       1340       1350       1360       1370 
PLGLGLWDKI AAQLRELQLC SRRLCAEDRD ALRQLQPSRP GPGECTLDHG SKLFFRRL 

« Hide

Isoform 2 [UniParc].

Checksum: 22AF7F6F65F703E8
Show »

FASTA1,378150,894

References

« Hide 'large scale' references
[1]"Cloning of a differentially expressed I kappa B-related protein."
Ray P., Zhang D.H., Elias J.A., Ray A.
J. Biol. Chem. 270:10680-10685(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, VARIANT SER-493.
Tissue: Cervix carcinoma.
[2]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [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] OF 6-1378 (ISOFORM 1), VARIANT VAL-714.
Tissue: Brain.
[4]"Isolation, sequence, and chromosomal localisation of the human IkappaBR gene (NFKBIL2)."
Norman D.A., Barton P.J.
Ann. Hum. Genet. 64:15-23(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 64-671, VARIANT SER-493.
[5]"Selective up-regulation of cytokine-induced RANTES gene expression in lung epithelial cells by overexpression of IkappaBR."
Ray P., Yang L., Zhang D.H., Ghosh S.K., Ray A.
J. Biol. Chem. 272:20191-20197(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[6]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-719, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"The MMS22L-TONSL complex mediates recovery from replication stress and homologous recombination."
O'Donnell L., Panier S., Wildenhain J., Tkach J.M., Al-Hakim A., Landry M.C., Escribano-Diaz C., Szilard R.K., Young J.T., Munro M., Canny M.D., Kolas N.K., Zhang W., Harding S.M., Ylanko J., Mendez M., Mullin M., Sun T. expand/collapse author list , Habermann B., Datti A., Bristow R.G., Gingras A.C., Tyers M.D., Brown G.W., Durocher D.
Mol. Cell 40:619-631(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE MMS22L-TONSL COMPLEX.
[8]"Identification of the MMS22L-TONSL complex that promotes homologous recombination."
Duro E., Lundin C., Ask K., Sanchez-Pulido L., MacArtney T.J., Toth R., Ponting C.P., Groth A., Helleday T., Rouse J.
Mol. Cell 40:632-644(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE MMS22L-TONSL COMPLEX, DOMAIN.
[9]"A genome-wide camptothecin sensitivity screen identifies a mammalian MMS22L-NFKBIL2 complex required for genomic stability."
O'Connell B.C., Adamson B., Lydeard J.R., Sowa M.E., Ciccia A., Bredemeyer A.L., Schlabach M., Gygi S.P., Elledge S.J., Harper J.W.
Mol. Cell 40:645-657(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN THE MMS22L-TONSL COMPLEX.
[10]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-719, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA56429.
RefSeqNP_038460.4. NM_013432.4.
UniGeneHs.675285.

3D structure databases

ProteinModelPortalQ96HA7.
SMRQ96HA7. Positions 27-363, 470-679, 975-1362.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110863. 28 interactions.
IntActQ96HA7. 20 interactions.
MINTMINT-6780272.
STRING9606.ENSP00000386239.

PTM databases

PhosphoSiteQ96HA7.

Polymorphism databases

DMDM182662416.

Proteomic databases

PaxDbQ96HA7.
PRIDEQ96HA7.

Protocols and materials databases

DNASU4796.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000409379; ENSP00000386239; ENSG00000160949. [Q96HA7-1]
GeneID4796.
KEGGhsa:4796.
UCSCuc011llg.2. human. [Q96HA7-1]

Organism-specific databases

CTD4796.
GeneCardsGC08M145659.
H-InvDBHIX0007858.
HGNCHGNC:7801. TONSL.
HPAHPA024679.
HPA046494.
MIM604546. gene.
neXtProtNX_Q96HA7.
PharmGKBPA31605.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0666.
HOGENOMHOG000113022.
HOVERGENHBG107999.
InParanoidQ96HA7.
KOK09257.
OMALAPCFQK.
OrthoDBEOG7VQJC6.
PhylomeDBQ96HA7.
TreeFamTF326440.

Gene expression databases

BgeeQ96HA7.
CleanExHS_NFKBIL2.
GenevestigatorQ96HA7.

Family and domain databases

Gene3D1.25.40.10. 2 hits.
1.25.40.20. 1 hit.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR019734. TPR_repeat.
[Graphical view]
PfamPF00023. Ank. 3 hits.
[Graphical view]
PRINTSPR01415. ANKYRIN.
SMARTSM00248. ANK. 3 hits.
SM00028. TPR. 6 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 3 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi4796.
NextBio18484.
PROQ96HA7.
SOURCESearch...

Entry information

Entry nameTONSL_HUMAN
AccessionPrimary (citable) accession number: Q96HA7
Secondary accession number(s): B5MDP0 expand/collapse secondary AC list , C9JKB1, C9JNV8, Q13006, Q9UGJ2
Entry history
Integrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: April 8, 2008
Last modified: April 16, 2014
This is version 112 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 8

Human chromosome 8: entries, gene names and cross-references to MIM