Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9P2D0 (IBTK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 105. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inhibitor of Bruton tyrosine kinase

Short name=IBtk
Gene names
Name:IBTK
Synonyms:BTKI, KIAA1417
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1353 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as an inhibitor of BTK tyrosine kinase activity, thereby playing a role in B-cell development. Down-regulates BTK kinase activity, leading to interference with BTK-mediated calcium mobilization and NF-kappa-B-driven transcription. Ref.7

Subunit structure

Interacts with the PH domain of BTK. Isoform 2 does not interact with BTK. Ref.1 Ref.7

Subcellular location

Cytoplasm. Membrane; Peripheral membrane protein. Note: Translocates to the plasma membrane upon IgM stimulation. Ref.1 Ref.7

Isoform 2: Nucleus Ref.1 Ref.7.

Tissue specificity

Expressed in DeFew, HEK293T, HeLa and in Jurkat, MC3 and NB4 lymphoid cells (at protein level). Isoform 1 is the predominant isoform expressedin all examined tissues and cell lines. Highly expressed in hemopoietic tissues (fetal liver, spleen, lymph node, thymus, peripheral blood leukocytes and bone marrow). Weakly or not expressed in other tissues. Ref.1 Ref.7

Sequence similarities

Contains 3 ANK repeats.

Contains 2 BTB (POZ) domains.

Contains 3 RCC1 repeats.

Sequence caution

The sequence AAG27170.1 differs from that shown. Reason: Aberrant splicing.

The sequence BAA92655.2 differs from that shown. Reason: Erroneous initiation.

The sequence CAI23414.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence CAI23416.1 differs from that shown. Reason: Erroneous gene model prediction.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9P2D0-1)

Also known as: IBtk-alpha;

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: Q9P2D0-2)

Also known as: IBtk-beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1145-1196: KTVSHGVKLS...KPVNAWASSL → WVENITKDHF...GQFSLHNIIS
     1197-1353: Missing.
Note: Due to a partial intron retention.
Isoform 3 (identifier: Q9P2D0-3)

Also known as: IBtk-gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1113: Missing.
     1114-1144: PVSPPVVDLRTIMEIEESRQKCGATPKSHLG → MLIDIISSKMISHGIKLCQKKPLKLIGLISS
Note: Due to a partial intron retention.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13531353Inhibitor of Bruton tyrosine kinase
PRO_0000280276

Regions

Repeat51 – 8030ANK 1
Repeat85 – 11430ANK 2
Repeat141 – 19454RCC1 1
Repeat195 – 24652RCC1 2
Repeat248 – 30154RCC1 3
Domain564 – 64481BTB 1
Domain768 – 83669BTB 2
Repeat806 – 83530ANK 3

Amino acid modifications

Modified residue9901Phosphoserine Ref.8
Modified residue10041Phosphoserine Ref.8
Modified residue10451Phosphoserine Ref.8 Ref.10 Ref.11
Modified residue10541Phosphoserine Ref.8
Modified residue11131Phosphoserine Ref.10
Modified residue11161Phosphoserine Ref.10

Natural variations

Alternative sequence1 – 11131113Missing in isoform 3.
VSP_023600
Alternative sequence1114 – 114431PVSPP…KSHLG → MLIDIISSKMISHGIKLCQK KPLKLIGLISS in isoform 3.
VSP_023601
Alternative sequence1145 – 119652KTVSH…WASSL → WVENITKDHFMLYFCPKNWT DLLHLSYYFSAFDVIVNYTS FSGQFSLHNIIS in isoform 2.
VSP_023602
Alternative sequence1197 – 1353157Missing in isoform 2.
VSP_023604
Natural variant10651V → I.
Corresponds to variant rs12662902 [ dbSNP | Ensembl ].
VAR_031106
Natural variant11851A → V. Ref.5 Ref.7
Corresponds to variant rs9449444 [ dbSNP | Ensembl ].
VAR_031107

Experimental info

Sequence conflict9711S → G in CAB43239. Ref.6
Sequence conflict11971H → R in CAB43239. Ref.6
Sequence conflict12181H → L in CAB43239. Ref.6

Sequences

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

Last modified March 20, 2007. Version 3.
Checksum: 67B2D11E276A6AF1

FASTA1,353150,528
        10         20         30         40         50         60 
MSSPMPDCTS KCRSLKHALD VLSVVTKGSE NQIKAFLSSH CYNAATIKDV FGRNALHLVS 

        70         80         90        100        110        120 
SCGKKGVLDW LIQKGVDLLV KDKESGWTAL HRSIFYGHID CVWSLLKHGV SLYIQDKEGL 

       130        140        150        160        170        180 
SALDLVMKDR PTHVVFKNTD PTDVYTWGDN TNFTLGHGSQ NSKHHPELVD LFSRSGIYIK 

       190        200        210        220        230        240 
QVVLCKFHSV FLSQKGQVYT CGHGPGGRLG HGDEQTCLVP RLVEGLNGHN CSQVAAAKDH 

       250        260        270        280        290        300 
TVVLTEDGCV YTFGLNIFHQ LGIIPPPSSC NVPRQIQAKY LKGRTIIGVA AGRFHTVLWT 

       310        320        330        340        350        360 
REAVYTMGLN GGQLGCLLDP NGEKCVTAPR QVSALHHKDI ALSLVAASDG ATVCVTTRGD 

       370        380        390        400        410        420 
IYLLADYQCK KMASKQLNLK KVLVSGGHME YKVDPEHLKE NGGQKICILA MDGAGRVFCW 

       430        440        450        460        470        480 
RSVNSSLKQC RWAYPRQVFI SDIALNRNEI LFVTQDGEGF RGRWFEEKRK SSEKKEILSN 

       490        500        510        520        530        540 
LHNSSSDVSY VSDINSVYER IRLEKLTFAH RAVSVSTDPS GCNFAILQSD PKTSLYEIPA 

       550        560        570        580        590        600 
VSSSSFFEEF GKLLREADEM DSIHDVTFQV GNRLFPAHKY ILAVHSDFFQ KLFLSDGNTS 

       610        620        630        640        650        660 
EFTDIYQKDE DSAGCHLFVV EKVHPDMFEY LLQFIYTDTC DFLTHGFKPR IHLNKNPEEY 

       670        680        690        700        710        720 
QGTLNSHLNK VNFHEDDNQK SAFEVYKSNQ AQTVSERQKS KPKSCKKGKN IREDDPVRML 

       730        740        750        760        770        780 
QTVAKKFDFS NLSSRLDGVR FENEKINVIA KNTGNKLKLS QKKCSFLCDV TMKSVDGKEF 

       790        800        810        820        830        840 
PCHKCVLCAR LEYFHSMLSS SWIEASSCAA LEMPIHSDIL KVILDYLYTD EAVVIKESQN 

       850        860        870        880        890        900 
VDFICSVLVV ADQLLITRLK EICEVALTEK LTLKNAAMLL EFAAMYSAKQ LKLSCLQFIG 

       910        920        930        940        950        960 
LNMAALLEAR SLDVLSDGVL KDLSEFYRKM IPAMDRRVIT PYQDGPDISY LEVEDGDIFL 

       970        980        990       1000       1010       1020 
KEEINMEQNH SETMFKKAKT KAKKKPRKRS DSSGGYNLSD IIQSPSSTGL LKSGKTNSVE 

      1030       1040       1050       1060       1070       1080 
SLPELLTSDS EGSYAGVGSP RDLQSPDFTT GFHSDKIEAK VKPYVNGTSP VYSREDLKPW 

      1090       1100       1110       1120       1130       1140 
EKSPILKISA PQPIPSNRID TTSSASWVAG SFSPVSPPVV DLRTIMEIEE SRQKCGATPK 

      1150       1160       1170       1180       1190       1200 
SHLGKTVSHG VKLSQKQRKM IALTTKENNS GMNSMETVLF TPSKAPKPVN AWASSLHSVS 

      1210       1220       1230       1240       1250       1260 
SKSFRDFLLE EKKSVTSHSS GDHVKKVSFK GIENSQAPKI VRCSTHGTPG PEGNHISDLP 

      1270       1280       1290       1300       1310       1320 
LLDSPNPWLS SSVTAPSMVA PVTFASIVEE ELQQEAALIR SREKPLALIQ IEEHAIQDLL 

      1330       1340       1350 
VFYEAFGNPE EFVIVERTPQ GPLAVPMWNK HGC 

« Hide

Isoform 2 (IBtk-beta) [UniParc].

Checksum: 7AEB0AF9F4B92805
Show »

FASTA1,196133,859
Isoform 3 (IBtk-gamma) [UniParc].

Checksum: 55673D0FC6EE3FEB
Show »

FASTA24026,314

References

« Hide 'large scale' references
[1]"Physical and functional characterization of the genetic locus of IBtk, an inhibitor of Bruton's tyrosine kinase: evidence for three protein isoforms of IBtk."
Spatuzza C., Schiavone M., Di Salle E., Janda E., Sardiello M., Fiume G., Fierro O., Simonetta M., Argiriou N., Faraonio R., Capparelli R., Quinto I., Scala G.
Nucleic Acids Res. 36:4402-4416(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), ALTERNATIVE SPLICING, INTERACTION WITH BTK, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[4]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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 1), VARIANT VAL-1185.
Tissue: Brain and Skin.
[6]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 971-1353 (ISOFORM 1).
Tissue: Brain.
[7]"Direct inhibition of Bruton's tyrosine kinase by IBtk, a Btk-binding protein."
Liu W., Quinto I., Chen X., Palmieri C., Rabin R.L., Schwartz O.M., Nelson D.L., Scala G.
Nat. Immunol. 2:939-946(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1159-1353 (ISOFORMS 1/3), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH BTK, VARIANT VAL-1185.
Tissue: B-cell.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-990; SER-1004; SER-1045 AND SER-1054, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[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-1045; SER-1113 AND SER-1116, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1045, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
DQ005633 mRNA. Translation: AAY55906.1.
DQ005634 mRNA. Translation: AAY55907.1.
DQ005635 mRNA. Translation: AAY55908.1.
AB037838 mRNA. Translation: BAA92655.2. Different initiation.
AL050333 Genomic DNA. Translation: CAI23414.1. Sequence problems.
AL050333 Genomic DNA. Translation: CAI23416.1. Sequence problems.
BC027490 mRNA. Translation: AAH27490.1.
BC038244 mRNA. Translation: AAH38244.2.
BC042171 mRNA. Translation: AAH42171.2.
BC113696 mRNA. Translation: AAI13697.1.
BC113698 mRNA. Translation: AAI13699.1.
AL050018 mRNA. Translation: CAB43239.1.
AF235049 mRNA. Translation: AAG27170.1. Sequence problems.
CCDSCCDS34490.1. [Q9P2D0-1]
PIRT08705.
RefSeqNP_056340.2. NM_015525.2. [Q9P2D0-1]
UniGeneHs.306425.

3D structure databases

ProteinModelPortalQ9P2D0.
SMRQ9P2D0. Positions 21-466, 744-899.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117474. 17 interactions.
IntActQ9P2D0. 4 interactions.
MINTMINT-215747.

PTM databases

PhosphoSiteQ9P2D0.

Polymorphism databases

DMDM134034141.

Proteomic databases

MaxQBQ9P2D0.
PaxDbQ9P2D0.
PRIDEQ9P2D0.

Protocols and materials databases

DNASU25998.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000306270; ENSP00000305721; ENSG00000005700. [Q9P2D0-1]
GeneID25998.
KEGGhsa:25998.
UCSCuc003pjl.1. human. [Q9P2D0-1]
uc003pjm.2. human. [Q9P2D0-2]

Organism-specific databases

CTD25998.
GeneCardsGC06M082879.
HGNCHGNC:17853. IBTK.
HPAHPA023826.
MIM606457. gene.
neXtProtNX_Q9P2D0.
PharmGKBPA134898277.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5184.
HOVERGENHBG081779.
InParanoidQ9P2D0.
OMAVSALHHK.
OrthoDBEOG7K6PT6.
PhylomeDBQ9P2D0.
TreeFamTF323747.

Gene expression databases

ArrayExpressQ9P2D0.
BgeeQ9P2D0.
GenevestigatorQ9P2D0.

Family and domain databases

Gene3D1.25.40.20. 1 hit.
2.130.10.30. 1 hit.
3.30.710.10. 3 hits.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR009091. RCC1/BLIP-II.
IPR000408. Reg_chr_condens.
[Graphical view]
PfamPF12796. Ank_2. 1 hit.
PF00651. BTB. 2 hits.
PF00415. RCC1. 3 hits.
[Graphical view]
SMARTSM00248. ANK. 2 hits.
SM00225. BTB. 2 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
SSF50985. SSF50985. 1 hit.
SSF54695. SSF54695. 2 hits.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
PS50097. BTB. 2 hits.
PS50012. RCC1_3. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSIBTK. human.
GenomeRNAi25998.
NextBio47714.
PROQ9P2D0.
SOURCESearch...

Entry information

Entry nameIBTK_HUMAN
AccessionPrimary (citable) accession number: Q9P2D0
Secondary accession number(s): Q2QKU2 expand/collapse secondary AC list , Q2QKU3, Q2QKU4, Q5TFD7, Q5TFD9, Q8IUQ9, Q8IUY7, Q8TAI4, Q9HBI8, Q9Y3T8
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: March 20, 2007
Last modified: July 9, 2014
This is version 105 of the entry and version 3 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 6

Human chromosome 6: entries, gene names and cross-references to MIM