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Reviewed, UniProtKB/Swiss-Prot Q8NFU7 (TET1_HUMAN)

Last modified June 16, 2009. Version 44. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Methylcytosine dioxygenase TET1
    EC=1.14.11.n2
Alternative name(s):
    Ten-eleven translocation 1 gene protein
    CXXC-type zinc finger protein 6
    Leukemia-associated protein with a CXXC domain
Gene names
Name: TET1
Synonyms: CXXC6, KIAA1676, LCX
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length2136 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Dioxygenase that specifically binds methylcytosine (5mC), a minor base in mammalian DNA found in repetitive DNA elements that is crucial for retrotransposon silencing and mammalian development. Catalyzes the conversion of methylcytosine (5mC) to 5-hydroxymethylcytosine (hmC). The clear function of 5-hydroxymethylcytosine (hmC) is still unclear but it may influence chromatin structure and recruit specific factors or may constitute an intermediate component in cytosine demethylation. 5-hydroxymethylcytosine (hmC) is present in ES cells and is enriched in the brain, especially in Purkinje neurons. May play a role in the fetal development of heart, lung and brain.

Catalytic activity

Methylcytosine + 2-oxoglutarate + O2 = 5-hydroxymethylcytosine + succinate + CO2.

Cofactor

Binds 1 Fe2+ ion per subunit.

Subcellular location

Nucleus Probable.

Tissue specificity

Expressed in fetal heart, lung and brain, and in adult skeletal muscle, thymus and ovary. Not detected in adult heart, lung or brain. Ref.1 Ref.6

Involvement in disease

A chromosomal aberration involving TET1 may be a cause of acute leukemias. Translocation t(10;11)(q22;q23) with MLL. This is a rare chromosomal translocation 5' MLL-TET1 3'.

Sequence similarities

Belongs to the TET family.

Contains 1 CXXC-type zinc finger.

Sequence caution

The sequence CAD28467.3 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
   Cellular componentNucleus
   Coding sequence diversityChromosomal rearrangement
Polymorphism
   DomainZinc-finger
   LigandDNA-binding
Iron
Metal-binding
Zinc
   Molecular functionDioxygenase
Oxidoreductase
Gene Ontology (GO)
   Cellular componentnucleus Ref.7

Inferred by curator. Source: UniProtKB

   Molecular functioniron ion binding Ref.7

Inferred from direct assay. Source: UniProtKB

methylcytosine dioxygenase activity Ref.7

Inferred from direct assay. Source: UniProtKB

structure-specific DNA binding Ref.7

Inferred from direct assay. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 21362136Methylcytosine dioxygenase TET1
PRO_0000251949

Regions

Zinc finger584 – 62542CXXC-type

Sites

Metal binding16721Iron; catalytic
Metal binding16741Iron; catalytic
Metal binding20281Iron; catalytic By similarity
Binding site204312-oxoglutarate By similarity
Site1608 – 16092Breakpoint for translocation to form MLL-TET1 oncogene

Natural variations

Natural variant1621D → G: dbSNP rs10823229.
VAR_027734
Natural variant1931S → T: dbSNP rs12773594.
VAR_027735
Natural variant2561A → V: dbSNP rs12221107.
VAR_027736
Natural variant10181N → S: dbSNP rs16925541.
VAR_027737
Natural variant11231I → M: dbSNP rs3998860. Ref.1
VAR_027738

Experimental info

Mutagenesis16721H → A: Loss of activity.
Mutagenesis16741D → A: Loss of activity.
Sequence conflict20011F → L in CAD28467. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q8NFU7-1 [UniParc].

Last modified October 3, 2006. Version 2.
Checksum: 66E24EF0594A964C

FASTA2,136235,309
        10         20         30         40         50         60 
MSRSRHARPS RLVRKEDVNK KKKNSQLRKT TKGANKNVAS VKTLSPGKLK QLIQERDVKK 

        70         80         90        100        110        120 
KTEPKPPVPV RSLLTRAGAA RMNLDRTEVL FQNPESLTCN GFTMALRSTS LSRRLSQPPL 

       130        140        150        160        170        180 
VVAKSKKVPL SKGLEKQHDC DYKILPALGV KHSENDSVPM QDTQVLPDIE TLIGVQNPSL 

       190        200        210        220        230        240 
LKGKSQETTQ FWSQRVEDSK INIPTHSGPA AEILPGPLEG TRCGEGLFSE ETLNDTSGSP 

       250        260        270        280        290        300 
KMFAQDTVCA PFPQRATPKV TSQGNPSIQL EELGSRVESL KLSDSYLDPI KSEHDCYPTS 

       310        320        330        340        350        360 
SLNKVIPDLN LRNCLALGGS TSPTSVIKFL LAGSKQATLG AKPDHQEAFE ATANQQEVSD 

       370        380        390        400        410        420 
TTSFLGQAFG AIPHQWELPG ADPVHGEALG ETPDLPEIPG AIPVQGEVFG TILDQQETLG 

       430        440        450        460        470        480 
MSGSVVPDLP VFLPVPPNPI ATFNAPSKWP EPQSTVSYGL AVQGAIQILP LGSGHTPQSS 

       490        500        510        520        530        540 
SNSEKNSLPP VMAISNVENE KQVHISFLPA NTQGFPLAPE RGLFHASLGI AQLSQAGPSK 

       550        560        570        580        590        600 
SDRGSSQVSV TSTVHVVNTT VVTMPVPMVS TSSSSYTTLL PTLEKKKRKR CGVCEPCQQK 

       610        620        630        640        650        660 
TNCGECTYCK NRKNSHQICK KRKCEELKKK PSVVVPLEVI KENKRPQREK KPKVLKADFD 

       670        680        690        700        710        720 
NKPVNGPKSE SMDYSRCGHG EEQKLELNPH TVENVTKNED SMTGIEVEKW TQNKKSQLTD 

       730        740        750        760        770        780 
HVKGDFSANV PEAEKSKNSE VDKKRTKSPK LFVQTVRNGI KHVHCLPAET NVSFKKFNIE 

       790        800        810        820        830        840 
EFGKTLENNS YKFLKDTANH KNAMSSVATD MSCDHLKGRS NVLVFQQPGF NCSSIPHSSH 

       850        860        870        880        890        900 
SIINHHASIH NEGDQPKTPE NIPSKEPKDG SPVQPSLLSL MKDRRLTLEQ VVAIEALTQL 

       910        920        930        940        950        960 
SEAPSENSSP SKSEKDEESE QRTASLLNSC KAILYTVRKD LQDPNLQGEP PKLNHCPSLE 

       970        980        990       1000       1010       1020 
KQSSCNTVVF NGQTTTLSNS HINSATNQAS TKSHEYSKVT NSLSLFIPKS NSSKIDTNKS 

      1030       1040       1050       1060       1070       1080 
IAQGIITLDN CSNDLHQLPP RNNEVEYCNQ LLDSSKKLDS DDLSCQDATH TQIEEDVATQ 

      1090       1100       1110       1120       1130       1140 
LTQLASIIKI NYIKPEDKKV ESTPTSLVTC NVQQKYNQEK GTIQQKPPSS VHNNHGSSLT 

      1150       1160       1170       1180       1190       1200 
KQKNPTQKKT KSTPSRDRRK KKPTVVSYQE NDRQKWEKLS YMYGTICDIW IASKFQNFGQ 

      1210       1220       1230       1240       1250       1260 
FCPHDFPTVF GKISSSTKIW KPLAQTRSIM QPKTVFPPLT QIKLQRYPES AEEKVKVEPL 

      1270       1280       1290       1300       1310       1320 
DSLSLFHLKT ESNGKAFTDK AYNSQVQLTV NANQKAHPLT QPSSPPNQCA NVMAGDDQIR 

      1330       1340       1350       1360       1370       1380 
FQQVVKEQLM HQRLPTLPGI SHETPLPESA LTLRNVNVVC SGGITVVSTK SEEEVCSSSF 

      1390       1400       1410       1420       1430       1440 
GTSEFSTVDS AQKNFNDYAM NFFTNPTKNL VSITKDSELP TCSCLDRVIQ KDKGPYYTHL 

      1450       1460       1470       1480       1490       1500 
GAGPSVAAVR EIMENRYGQK GNAIRIEIVV YTGKEGKSSH GCPIAKWVLR RSSDEEKVLC 

      1510       1520       1530       1540       1550       1560 
LVRQRTGHHC PTAVMVVLIM VWDGIPLPMA DRLYTELTEN LKSYNGHPTD RRCTLNENRT 

      1570       1580       1590       1600       1610       1620 
CTCQGIDPET CGASFSFGCS WSMYFNGCKF GRSPSPRRFR IDPSSPLHEK NLEDNLQSLA 

      1630       1640       1650       1660       1670       1680 
TRLAPIYKQY APVAYQNQVE YENVARECRL GSKEGRPFSG VTACLDFCAH PHRDIHNMNN 

      1690       1700       1710       1720       1730       1740 
GSTVVCTLTR EDNRSLGVIP QDEQLHVLPL YKLSDTDEFG SKEGMEAKIK SGAIEVLAPR 

      1750       1760       1770       1780       1790       1800 
RKKRTCFTQP VPRSGKKRAA MMTEVLAHKI RAVEKKPIPR IKRKNNSTTT NNSKPSSLPT 

      1810       1820       1830       1840       1850       1860 
LGSNTETVQP EVKSETEPHF ILKSSDNTKT YSLMPSAPHP VKEASPGFSW SPKTASATPA 

      1870       1880       1890       1900       1910       1920 
PLKNDATASC GFSERSSTPH CTMPSGRLSG ANAAAADGPG ISQLGEVAPL PTLSAPVMEP 

      1930       1940       1950       1960       1970       1980 
LINSEPSTGV TEPLTPHQPN HQPSFLTSPQ DLASSPMEED EQHSEADEPP SDEPLSDDPL 

      1990       2000       2010       2020       2030       2040 
SPAEEKLPHI DEYWSDSEHI FLDANIGGVA IAPAHGSVLI ECARRELHAT TPVEHPNRNH 

      2050       2060       2070       2080       2090       2100 
PTRLSLVFYQ HKNLNKPQHG FELNKIKFEA KEAKNKKMKA SEQKDQAANE GPEQSSEVNE 

      2110       2120       2130 
LNQIPSHKAL TLTHDNVVTV SPYALTHVAG PYNHWV 

« Hide

References

« Hide 'large scale' references
[1]"LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23)."
Ono R., Taki T., Taketani T., Taniwaki M., Kobayashi H., Hayashi Y.
Cancer Res. 62:4075-4080(2002) [PubMed: 12124344] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT MET-1123, FUNCTION, TISSUE SPECIFICITY, CHROMOSOMAL TRANSLOCATION WITH MLL.
Tissue: Leukemia.
[2]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed: 15164054] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.
DNA Res. 7:347-355(2000) [PubMed: 11214970] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1402-2136.
Tissue: Brain.
[4]"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 1665-2074.
Tissue: Brain.
[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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1809-2136.
Tissue: Uterus.
[6]"TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23)."
Lorsbach R.B., Moore J., Mathew S., Raimondi S.C., Mukatira S.T., Downing J.R.
Leukemia 17:637-641(2003) [PubMed: 12646957] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH MLL, TISSUE SPECIFICITY.
[7]"Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by the MLL fusion partner TET1."
Tahiliani M., Koh K.P., Shen Y., Pastor W.A., Bandukwala H., Brudno Y., Agarwal S., Iyer L.M., Liu D.R., Aravind L., Rao A.
Science 0:0-0(2009) [PubMed: 19372391] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, DNA-BINDING, COFACTOR, MUTAGENESIS OF HIS-1672 AND ASP-1674.
[8]"The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain."
Kriaucionis S., Heintz N.
Science 0:0-0(2009) [PubMed: 19372393] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF430147 mRNA. Translation: AAM88301.1.
AL513534, AL713888 Genomic DNA. Translation: CAH70220.1.
AL713888, AL513534 Genomic DNA. Translation: CAI15118.1.
AB051463 mRNA. Translation: BAB21767.1.
AL713658 mRNA. Translation: CAD28467.3. Sequence problems.
BC053905 mRNA. Translation: AAH53905.1.
IPIIPI00303112.
RefSeqNP_085128.2.
UniGeneHs.567594
Hs.708977

3D structure databases

ModBaseSearch...

PTM databases

PhosphoSiteQ8NFU7.

Proteomic databases

PRIDEQ8NFU7.

Genome annotation databases

EnsemblENSG00000138336. Homo sapiens. [Contig view]
GeneID80312.
KEGGhsa:80312.
NMPDRfig|9606.3.peg.4049.

Organism-specific databases

GeneCardsGC10P069991.
HGNCHGNC:29484. TET1.
HPAHPA019032.
MIM607790. gene.
PharmGKBPA134943164.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ8NFU7.
OMAQ8NFU7. PNLQGEP.

Gene expression databases

ArrayExpressQ8NFU7.
BgeeQ8NFU7.
CleanExHS_TET1.
GermOnlineENSG00000138336. Homo sapiens.

Family and domain databases

InterProIPR002857. Znf_CXXC.
[Graphical view]
PfamPF02008. zf-CXXC. 1 hit.
[Graphical view]
PROSITEPS51058. ZF_CXXC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio70802.
SOURCESearch...

Entry information

Entry nameTET1_HUMAN
AccessionPrimary (citable) accession number: Q8NFU7
Secondary accession number(s): Q5VUP7 expand/collapse secondary AC list , Q7Z6B6, Q8TCR1, Q9C0I7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: October 3, 2006
Last modified: June 16, 2009
This is version 44 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents