Reviewed, UniProtKB/Swiss-Prot Q9UL03 (INT6_HUMAN)

Names and origin

Protein names

Recommended name:
    Integrator complex subunit 6
      Short name=Int6
Alternative name(s):
    Protein deleted in cancer 1
      Short name=DICE1
    Protein DDX26
    DBI-1

Gene names

Name:	INTS6
Synonyms:	DBI1, DDX26, DDX26A

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	887 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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. Ref.7 Ref.10
Subunit structure	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.
Subcellular location	Nucleus. Ref.6
Tissue specificity	Widely expressed. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Ref.1
Induction	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. Ref.8
Sequence similarities	Belongs to the Integrator subunit 6 family. Contains 1 VWFA domain.
Sequence caution	The sequence AAH13358.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	snRNA processing Ref.10 Inferred from direct assay. Source: HGNC
Cellular component	cytoskeleton Inferred from direct assay. Source: HPA integrator complex Ref.10 Inferred from direct assay. Source: HGNC
Molecular function	protein binding Ref.10 Inferred from physical interaction. Source: UniProtKB transmembrane receptor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MCM7	P33993	6	EBI-1381827,EBI-355924

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UL03-1)

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: Q9UL03-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 887	887	Integrator complex subunit 6		PRO_0000259543
Regions
	Domain	3 – 227	225	VWFA
Amino acid modifications
	Modified residue	804	1	Phosphoserine Ref.11
Natural variations
	Alternative sequence	114 – 115	2	GR → VG in isoform 2.		VSP_021457
	Alternative sequence	116 – 887	772	Missing in isoform 2.		VSP_021458
Experimental info
	Sequence conflict	273	1	N → R in AAD39481. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: FCD3FD61B7767E03	FASTA	887	100,390
	10 20 30 40 50 60 MPILLFLIDT SASMNQRSHL GTTYLDTAKG AVETFMKLRA RDPASRGDRY MLVTFEEPPY 70 80 90 100 110 120 AIKAGWKENH ATFMNELKNL QAEGLTTLGQ SLRTAFDLLN LNRLVTGIDN YGQGRNPFFL 130 140 150 160 170 180 EPAIIITITD GSKLTTTSGV QDELHLPLNS PLPGSELTKE PFRWDQRLFA LVLRLPGTMS 190 200 210 220 230 240 VESEQLTGVP LDDSAITPMC EVTGGRSYSV CSPRMLNQCL ESLVQKVQSG VVINFEKAGP 250 260 270 280 290 300 DPSPVEDGQP DISRPFGSQP WHSCHKLIYV RPNPKTGVPI GHWPVPESFW PDQNSPTLPP 310 320 330 340 350 360 RTSHPVVKFS CTDCEPMVID KLPFDKYELE PSPLTQFILE RKSPQTCWQV YVSNSAKYSE 370 380 390 400 410 420 LGHPFGYLKA STALNCVNLF VMPYNYPVLL PLLDDLFKVH KAKPTLKWRQ SFESYLKTMP 430 440 450 460 470 480 PYYLGPLKKA VRMMGAPNLI ADSMEYGLSY SVISYLKKLS QQAKIESDRV IGSVGKKVVQ 490 500 510 520 530 540 ETGIKVRSRS HGLSMAYRKD FQQLLQGISE DVPHRLLDLN MKEYTGFQVA LLNKDLKPQT 550 560 570 580 590 600 FRNAYDIPRR NLLDHLTRMR SNLLKSTRRF LKGQDEDQVH SVPIAQMGNY QEYLKQVPSP 610 620 630 640 650 660 LRELDPDQPR RLHTFGNPFK LDKKGMMIDE ADEFVAGPQN KHKRPGEPNM QGIPKRRRCM 670 680 690 700 710 720 SPLLRGRQQN PVVNNHIGGK GPPAPTTQAQ PDLIKPLPLH KISETTNDSI IHDVVENHVA 730 740 750 760 770 780 DQLSSDITPN AMDTEFSASS PASLLERPTN HMEALGHDHL GTNDLTVGGF LENHEEPRDK 790 800 810 820 830 840 EQCAEENIPA SSLNKGKKLM HCRSHEEVNT ELKAQIMKEI RKPGRKYERI FTLLKHVQGS 850 860 870 880 LQTRLIFLQN VIKEASRFKK RMLIEQLENF LDEIHRRANQ INHINSN
	Isoform 2. Checksum: 89C3CC2495007B4A	FASTA	115	12,854
	10 20 30 40 50 60 MPILLFLIDT SASMNQRSHL GTTYLDTAKG AVETFMKLRA RDPASRGDRY MLVTFEEPPY 70 80 90 100 110 AIKAGWKENH ATFMNELKNL QAEGLTTLGQ SLRTAFDLLN LNRLVTGIDN YGQVG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 10467397] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Brain.
[2]	"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: 15057823] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain, Lung and Placenta.
[4]	"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.
[5]	"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., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 415-887 (ISOFORM 1). Tissue: Testis.
[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: 11939413] [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: 15254679] [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: 16007164] [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: 16271964] [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: 16239144] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, IDENTIFICATION IN THE INTEGRATOR COMPLEX.
[11]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-804, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF097645 mRNA. Translation: AAF03046.1. 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.
IPI	IPI00015922. IPI00738767.
PIR	T17330.
RefSeq	NP_001035026.1. NP_001035027.1. NP_036273.1.
UniGene	Hs.439440
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UL03. 1 interaction.
PTM databases
PhosphoSite	Q9UL03.
Proteomic databases
PRIDE	Q9UL03.
Genome annotation databases
Ensembl	ENSG00000102786. Homo sapiens. [Contig view]
GeneID	26512.
KEGG	hsa:26512.
NMPDR	fig|9606.3.peg.8878.
Organism-specific databases
GeneCards	GC13M050833.
HGNC	HGNC:14879. INTS6.
HPA	HPA001552. HPA001846.
MIM	604331. gene.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9UL03.
OMA	Q9UL03. IDDVVEN.
Gene expression databases
ArrayExpress	Q9UL03.
Bgee	Q9UL03.
CleanEx	HS_INTS6.
GermOnline	ENSG00000102786. Homo sapiens.
Family and domain databases
InterPro	IPR002035. VWF_A. [Graphical view]
SMART	SM00327. VWA. 1 hit. [Graphical view]
PROSITE	PS50234. VWFA. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	48812.
SOURCE	Search...

Entry information

Entry name

INT6_HUMAN

Accession

Primary (citable) accession number: Q9UL03
Secondary accession number(s): Q0P664 , Q6PJP4, Q9UFK0, Q9Y5M9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	May 1, 2000
Last modified:	June 16, 2009
This is version 73 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)