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Protein

Integrator complex subunit 6

Gene

INTS6

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

Functioni

Component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. May have a tumor suppressor role; an ectopic expression suppressing tumor cell growth.2 Publications

GO - Molecular functioni

  • transmembrane signaling receptor activity Source: ProtInc

GO - Biological processi

  • snRNA processing Source: HGNC
  • snRNA transcription from RNA polymerase II promoter Source: Reactome
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-6807505. RNA polymerase II transcribes snRNA genes.

Names & Taxonomyi

Protein namesi
Recommended name:
Integrator complex subunit 6
Short name:
Int6
Alternative name(s):
DBI-1
Protein DDX26
Protein deleted in cancer 1
Short name:
DICE1
Gene namesi
Name:INTS6
Synonyms:DBI1, DDX26, DDX26A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:14879. INTS6.

Subcellular locationi

  • Nucleus 1 Publication

GO - Cellular componenti

  • actin cytoskeleton Source: HPA
  • integrator complex Source: HGNC
  • nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27212.

Polymorphism and mutation databases

BioMutaiINTS6.
DMDMi74753376.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 887887Integrator complex subunit 6PRO_0000259543Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei804 – 8041PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UL03.
MaxQBiQ9UL03.
PaxDbiQ9UL03.
PeptideAtlasiQ9UL03.
PRIDEiQ9UL03.
TopDownProteomicsiQ9UL03-2. [Q9UL03-2]

PTM databases

iPTMnetiQ9UL03.
PhosphoSiteiQ9UL03.

Expressioni

Tissue specificityi

Widely expressed. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.1 Publication

Inductioni

Frequently down-regulated in nonsmall cell lung carcinomas and prostate cancers. Down-regulation in prostate cancer is due to CpG hypermethylation of its promoter. However, some involvement in cancer is unclear.1 Publication

Gene expression databases

BgeeiQ9UL03.
CleanExiHS_INTS6.
ExpressionAtlasiQ9UL03. baseline and differential.
GenevisibleiQ9UL03. HS.

Organism-specific databases

HPAiHPA001552.
HPA001846.

Interactioni

Subunit structurei

Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, CPSF3L/INTS11 and INTS12.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
MCM7P3399310EBI-1381827,EBI-355924

Protein-protein interaction databases

BioGridi117717. 59 interactions.
DIPiDIP-38627N.
IntActiQ9UL03. 19 interactions.
MINTiMINT-4541530.
STRINGi9606.ENSP00000310260.

Structurei

3D structure databases

ProteinModelPortaliQ9UL03.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini3 – 227225VWFAPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the Integrator subunit 6 family.Curated
Contains 1 VWFA domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3768. Eukaryota.
ENOG410XRER. LUCA.
GeneTreeiENSGT00390000016655.
HOGENOMiHOG000015308.
HOVERGENiHBG081468.
InParanoidiQ9UL03.
KOiK13143.
OMAiKEQCPEE.
OrthoDBiEOG7ZGX2C.
PhylomeDBiQ9UL03.
TreeFamiTF323386.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR029307. INT_SG_DDX_CT_C.
IPR002035. VWF_A.
[Graphical view]
PfamiPF15300. INT_SG_DDX_CT_C. 1 hit.
PF13519. VWA_2. 1 hit.
[Graphical view]
SUPFAMiSSF53300. SSF53300. 1 hit.
PROSITEiPS50234. VWFA. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9UL03-1) [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
MPILLFLIDT SASMNQRSHL GTTYLDTAKG AVETFMKLRA RDPASRGDRY
60 70 80 90 100
MLVTFEEPPY AIKAGWKENH ATFMNELKNL QAEGLTTLGQ SLRTAFDLLN
110 120 130 140 150
LNRLVTGIDN YGQGRNPFFL EPAIIITITD GSKLTTTSGV QDELHLPLNS
160 170 180 190 200
PLPGSELTKE PFRWDQRLFA LVLRLPGTMS VESEQLTGVP LDDSAITPMC
210 220 230 240 250
EVTGGRSYSV CSPRMLNQCL ESLVQKVQSG VVINFEKAGP DPSPVEDGQP
260 270 280 290 300
DISRPFGSQP WHSCHKLIYV RPNPKTGVPI GHWPVPESFW PDQNSPTLPP
310 320 330 340 350
RTSHPVVKFS CTDCEPMVID KLPFDKYELE PSPLTQFILE RKSPQTCWQV
360 370 380 390 400
YVSNSAKYSE LGHPFGYLKA STALNCVNLF VMPYNYPVLL PLLDDLFKVH
410 420 430 440 450
KAKPTLKWRQ SFESYLKTMP PYYLGPLKKA VRMMGAPNLI ADSMEYGLSY
460 470 480 490 500
SVISYLKKLS QQAKIESDRV IGSVGKKVVQ ETGIKVRSRS HGLSMAYRKD
510 520 530 540 550
FQQLLQGISE DVPHRLLDLN MKEYTGFQVA LLNKDLKPQT FRNAYDIPRR
560 570 580 590 600
NLLDHLTRMR SNLLKSTRRF LKGQDEDQVH SVPIAQMGNY QEYLKQVPSP
610 620 630 640 650
LRELDPDQPR RLHTFGNPFK LDKKGMMIDE ADEFVAGPQN KHKRPGEPNM
660 670 680 690 700
QGIPKRRRCM SPLLRGRQQN PVVNNHIGGK GPPAPTTQAQ PDLIKPLPLH
710 720 730 740 750
KISETTNDSI IHDVVENHVA DQLSSDITPN AMDTEFSASS PASLLERPTN
760 770 780 790 800
HMEALGHDHL GTNDLTVGGF LENHEEPRDK EQCAEENIPA SSLNKGKKLM
810 820 830 840 850
HCRSHEEVNT ELKAQIMKEI RKPGRKYERI FTLLKHVQGS LQTRLIFLQN
860 870 880
VIKEASRFKK RMLIEQLENF LDEIHRRANQ INHINSN
Length:887
Mass (Da):100,390
Last modified:May 1, 2000 - v1
Checksum:iFCD3FD61B7767E03
GO
Isoform 2 (identifier: Q9UL03-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     114-115: GR → VG
     116-887: Missing.

Note: No experimental confirmation available.
Show »
Length:115
Mass (Da):12,854
Checksum:i89C3CC2495007B4A
GO
Isoform 3 (identifier: Q9UL03-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: Missing.

Show »
Length:874
Mass (Da):98,987
Checksum:iC1F5FA55ADA2C443
GO

Sequence cautioni

The sequence AAH13358.1 differs from that shown.Contaminating sequence. Potential poly-A sequence.Curated
The sequence AL833524 differs from that shown. Reason: Erroneous termination at position 796. Translated as Gly.Curated
The sequence CAB56020.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti273 – 2731N → R in AAD39481 (Ref. 5) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1313Missing in isoform 3. 1 PublicationVSP_041356Add
BLAST
Alternative sequencei114 – 1152GR → VG in isoform 2. 1 PublicationVSP_021457
Alternative sequencei116 – 887772Missing in isoform 2. 1 PublicationVSP_021458Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF097645 mRNA. Translation: AAF03046.1.
AL833524 mRNA. No translation available.
AL354820, AL137780 Genomic DNA. Translation: CAI15586.1.
AL137780, AL354820 Genomic DNA. Translation: CAI12905.1.
BC013358 mRNA. Translation: AAH13358.1. Sequence problems.
BC018725 mRNA. Translation: AAH18725.1.
BC032386 mRNA. Translation: AAH32386.1.
BC039829 mRNA. Translation: AAH39829.1.
AF141326 mRNA. Translation: AAD39481.1.
AL117626 mRNA. Translation: CAB56020.1. Different initiation.
BK005730 mRNA. Translation: DAA05730.1.
CCDSiCCDS41890.1. [Q9UL03-3]
CCDS45048.1. [Q9UL03-2]
CCDS9428.1. [Q9UL03-1]
PIRiT17330.
RefSeqiNP_001035026.1. NM_001039937.1. [Q9UL03-3]
NP_001035027.1. NM_001039938.1. [Q9UL03-2]
NP_001293020.1. NM_001306091.1.
NP_036273.1. NM_012141.2. [Q9UL03-1]
XP_011533342.1. XM_011535040.1. [Q9UL03-1]
UniGeneiHs.439440.

Genome annotation databases

EnsembliENST00000311234; ENSP00000310260; ENSG00000102786. [Q9UL03-1]
ENST00000398119; ENSP00000381187; ENSG00000102786. [Q9UL03-3]
ENST00000442263; ENSP00000411245; ENSG00000102786. [Q9UL03-2]
GeneIDi26512.
KEGGihsa:26512.
UCSCiuc001vfj.4. human. [Q9UL03-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF097645 mRNA. Translation: AAF03046.1.
AL833524 mRNA. No translation available.
AL354820, AL137780 Genomic DNA. Translation: CAI15586.1.
AL137780, AL354820 Genomic DNA. Translation: CAI12905.1.
BC013358 mRNA. Translation: AAH13358.1. Sequence problems.
BC018725 mRNA. Translation: AAH18725.1.
BC032386 mRNA. Translation: AAH32386.1.
BC039829 mRNA. Translation: AAH39829.1.
AF141326 mRNA. Translation: AAD39481.1.
AL117626 mRNA. Translation: CAB56020.1. Different initiation.
BK005730 mRNA. Translation: DAA05730.1.
CCDSiCCDS41890.1. [Q9UL03-3]
CCDS45048.1. [Q9UL03-2]
CCDS9428.1. [Q9UL03-1]
PIRiT17330.
RefSeqiNP_001035026.1. NM_001039937.1. [Q9UL03-3]
NP_001035027.1. NM_001039938.1. [Q9UL03-2]
NP_001293020.1. NM_001306091.1.
NP_036273.1. NM_012141.2. [Q9UL03-1]
XP_011533342.1. XM_011535040.1. [Q9UL03-1]
UniGeneiHs.439440.

3D structure databases

ProteinModelPortaliQ9UL03.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117717. 59 interactions.
DIPiDIP-38627N.
IntActiQ9UL03. 19 interactions.
MINTiMINT-4541530.
STRINGi9606.ENSP00000310260.

PTM databases

iPTMnetiQ9UL03.
PhosphoSiteiQ9UL03.

Polymorphism and mutation databases

BioMutaiINTS6.
DMDMi74753376.

Proteomic databases

EPDiQ9UL03.
MaxQBiQ9UL03.
PaxDbiQ9UL03.
PeptideAtlasiQ9UL03.
PRIDEiQ9UL03.
TopDownProteomicsiQ9UL03-2. [Q9UL03-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000311234; ENSP00000310260; ENSG00000102786. [Q9UL03-1]
ENST00000398119; ENSP00000381187; ENSG00000102786. [Q9UL03-3]
ENST00000442263; ENSP00000411245; ENSG00000102786. [Q9UL03-2]
GeneIDi26512.
KEGGihsa:26512.
UCSCiuc001vfj.4. human. [Q9UL03-1]

Organism-specific databases

CTDi26512.
GeneCardsiINTS6.
HGNCiHGNC:14879. INTS6.
HPAiHPA001552.
HPA001846.
MIMi604331. gene.
neXtProtiNX_Q9UL03.
PharmGKBiPA27212.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3768. Eukaryota.
ENOG410XRER. LUCA.
GeneTreeiENSGT00390000016655.
HOGENOMiHOG000015308.
HOVERGENiHBG081468.
InParanoidiQ9UL03.
KOiK13143.
OMAiKEQCPEE.
OrthoDBiEOG7ZGX2C.
PhylomeDBiQ9UL03.
TreeFamiTF323386.

Enzyme and pathway databases

ReactomeiR-HSA-6807505. RNA polymerase II transcribes snRNA genes.

Miscellaneous databases

ChiTaRSiINTS6. human.
GeneWikiiINTS6.
GenomeRNAii26512.
PROiQ9UL03.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UL03.
CleanExiHS_INTS6.
ExpressionAtlasiQ9UL03. baseline and differential.
GenevisibleiQ9UL03. HS.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR029307. INT_SG_DDX_CT_C.
IPR002035. VWF_A.
[Graphical view]
PfamiPF15300. INT_SG_DDX_CT_C. 1 hit.
PF13519. VWA_2. 1 hit.
[Graphical view]
SUPFAMiSSF53300. SSF53300. 1 hit.
PROSITEiPS50234. VWFA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation of DICE1: a gene frequently affected by LOH and downregulated in lung carcinomas."
    Wieland I., Arden K.C., Michels D., Klein-Hitpass L., Boehm M., Viars C.S., Weidle U.H.
    Oncogene 18:4530-4537(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Tissue: Brain.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 415-887 (ISOFORM 1).
    Tissue: Testis.
  3. "The DNA sequence and analysis of human chromosome 13."
    Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
    Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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] (ISOFORMS 1 AND 2).
    Tissue: Brain, Lung and Placenta.
  5. "Human DBI-1 homolog."
    Hoff H.B. III, Oh C., Sell C.
    Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 273-887 (ISOFORM 1).
    Tissue: Lung.
  6. "Molecular characterization of the DICE1 (DDX26) tumor suppressor gene in lung carcinoma cells."
    Wieland I., Roepke A., Stumm M., Sell C., Weidle U.H., Wieacker P.F.
    Oncol. Res. 12:491-500(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  7. "Ectopic expression of DICE1 suppresses tumor cell growth."
    Wieland I., Sell C., Weidle U.H., Wieacker P.
    Oncol. Rep. 12:207-211(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Promoter CpG hypermethylation and downregulation of DICE1 expression in prostate cancer."
    Roepke A., Buhtz P., Boehm M., Seger J., Wieland I., Allhoff E.P., Wieacker P.F.
    Oncogene 24:6667-6675(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  9. "Absence of mutations in DICE1/DDX26 gene in human cancer cell lines with frequent 13q14 deletions."
    Hernandez M., Papadopoulos N., Almeida T.A.
    Cancer Genet. Cytogenet. 163:91-92(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: LACK OF INVOLVEMENT IN CANCER.
  10. "Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II."
    Baillat D., Hakimi M.-A., Naeaer A.M., Shilatifard A., Cooch N., Shiekhattar R.
    Cell 123:265-276(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, IDENTIFICATION IN THE INTEGRATOR COMPLEX.
  11. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-804, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.

Entry informationi

Entry nameiINT6_HUMAN
AccessioniPrimary (citable) accession number: Q9UL03
Secondary accession number(s): Q0P664
, Q6PJP4, Q9UFK0, Q9Y5M9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: May 1, 2000
Last modified: July 6, 2016
This is version 139 of the entry and version 1 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 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. 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.