Reviewed, UniProtKB/Swiss-Prot Q9Y468 (LMBL1_HUMAN)

Names and origin

Protein names

Recommended name:
    Lethal(3)malignant brain tumor-like protein
      Short name=L(3)mbt-like
Alternative name(s):
    L(3)mbt protein homolog
    H-l(3)mbt protein
      Short name=H-L(3)MBT
    L3MBTL1

Gene names

Name:	L3MBTL
Synonyms:	KIAA0681, L3MBT, L3MBTL1

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

General annotation (Comments)

Function	Polycomb group (PcG) protein. PcG proteins maintain the transcriptionally repressive state of genes, probably via a modification of chromatin, rendering it heritably changed in its expressibility. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis.
Subunit structure	Homodimer. Interacts with ETV6. Ref.6
Subcellular location	Nucleus. Note: Excluded from the nucleolus. Does not colocalizes with the PcG protein BMI1, suggesting that these two proteins do not belong to the same complex.
Tissue specificity	Widely expressed. Expression is reduced in colorectal cancer cell line SW480 and promyelocytic leukemia cell line HL-60.
Developmental stage	In interphase cells, it is scattered throughout the nucleoplasm. In mitotic cells, it strongly associates with condensed chromosomes from the prophase to telophase.
Sequence similarities	Contains 1 C2HC-type zinc finger. Contains 3 MBT repeats.
Sequence caution	The sequence CAC18508.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Chromatin regulator Repressor
Technical term	3D-structure
Gene Ontology (GO)
Biological process	chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct transcription factor activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HIST1H1E	P10412	3	EBI-1265089,EBI-358163
HIST1H4A	P62805	2	EBI-1265089,EBI-302023

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y468-1)

Also known as: mbt-I;

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: Q9Y468-2)

Also known as: mbt-II;

The sequence of this isoform differs from the canonical sequence as follows:
     709-772: ARIVRVTHVS...KLSFASDSQY → VRCKCRVGDRAGVTVLKTAGSRCPPQRHFC

Isoform 3 (identifier: Q9Y468-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-348: Missing.
     709-772: ARIVRVTHVS...KLSFASDSQY → VRCKCRVGDRAGVTVLKTAGSRCPPQRHFC

Isoform 4 (identifier: Q9Y468-4)

The sequence of this isoform differs from the canonical sequence as follows:
     709-772: ARIVRVTHVS...KLSFASDSQY → MIDGEAFLLL...MFKNADDTLK

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 772

772

Lethal(3)malignant brain tumor-like protein

PRO_0000084452

Regions

Repeat

206 – 306

101

MBT 1

Repeat

314 – 413

100

MBT 2

Repeat

422 – 517

96

MBT 3

Zinc finger

552 – 578

27

C2HC-type

Natural variations

Alternative sequence

1 – 348

348

Missing in isoform 3.

VSP_003901

Alternative sequence

709 – 772

64

ARIVR…SDSQY → VRCKCRVGDRAGVTVLKTAG SRCPPQRHFC in isoform 2 and isoform 3.

VSP_003902

Alternative sequence

709 – 772

64

ARIVR…SDSQY → MIDGEAFLLLTQADIVKIMS VKLGPALKIYNAILMFKNAD DTLK in isoform 4.

VSP_003903

Natural variant

49

1

S → T: dbSNP rs17857202. Ref.4

VAR_051097

Natural variant

479

1

I → M: dbSNP rs6017104.

VAR_051098

Natural variant

759

1

H → R: dbSNP rs6030948.

VAR_051099

Experimental info

Sequence conflict

305

1

P → L in AAC69438. Ref.1

Sequence conflict

320 – 321

2

LR → MC in AAC69438. Ref.1

Sequence conflict

332

1

L → M in AAC69438. Ref.1

Sequence conflict

595

1

S → P in AAC69438. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

772

Helix Strand Turn

Details...

Helix

208 – 215

8

Helix

222 – 224

3

Helix

227 – 230

4

Beta strand

243 – 248

6

Beta strand

251 – 264

14

Beta strand

267 – 272

6

Helix

277 – 279

3

Beta strand

281 – 284

4

Helix

295 – 299

5

Helix

311 – 313

3

Helix

316 – 323

8

Helix

330 – 332

3

Beta strand

350 – 354

5

Beta strand

362 – 371

10

Beta strand

374 – 379

6

Helix

384 – 386

3

Beta strand

388 – 390

3

Helix

402 – 406

5

Helix

424 – 430

7

Helix

438 – 440

3

Beta strand

454 – 458

5

Beta strand

466 – 474

9

Beta strand

476 – 483

8

Helix

488 – 490

3

Beta strand

492 – 495

4

Helix

506 – 510

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (mbt-I) [UniParc]. Last modified September 19, 2002. Version 2. Checksum: 117B03A628826B29	FASTA	772	85,917
	10 20 30 40 50 60 MRRREGHGTD SEMGQGPVRE SQSSDPPALQ FRISEYKPLN MAGVEQPPSP ELRQEGVTEY 70 80 90 100 110 120 EDGGAPAGDG EAGPQQAEDH PQNPPEDPNQ DPPEDDSTCQ CQACGPHQAA GPDLGSSNDG 130 140 150 160 170 180 CPQLFQERSV IVENSSGSTS ASELLKPMKK RKRREYQSPS EEESEPEAME KQEEGKDPEG 190 200 210 220 230 240 QPTASTPESE EWSSSQPATG EKKECWSWES YLEEQKAITA PVSLFQDSQA VTHNKNGFKL 250 260 270 280 290 300 GMKLEGIDPQ HPSMYFILTV AEVCGYRLRL HFDGYSECHD FWVNANSPDI HPAGWFEKTG 310 320 330 340 350 360 HKLQPPKGYK EEEFSWSQYL RSTRAQAAPK HLFVSQSHSP PPLGFQVGMK LEAVDRMNPS 370 380 390 400 410 420 LVCVASVTDV VDSRFLVHFD NWDDTYDYWC DPSSPYIHPV GWCQKQGKPL TPPQDYPDPD 430 440 450 460 470 480 NFCWEKYLEE TGASAVPTWA FKVRPPHSFL VNMKLEAVDR RNPALIRVAS VEDVEDHRIK 490 500 510 520 530 540 IHFDGWSHGY DFWIDADHPD IHPAGWCSKT GHPLQPPLGP REPSSASPGG CPPLSYRSLP 550 560 570 580 590 600 HTRTSKYSFH HRKCPTPGCD GSGHVTGKFT AHHCLSGCPL AERNQSRLKA ELSDSEASAR 610 620 630 640 650 660 KKNLSGFSPR KKPRHHGRIG RPPKYRKIPQ EDFQTLTPDV VHQSLFMSAL SAHPDRSLSV 670 680 690 700 710 720 CWEQHCKLLP GVAGISASTV AKWTIDEVFG FVQTLTGCED QARLFKDEAR IVRVTHVSGK 730 740 750 760 770 TLVWTVAQLG DLVCSDHLQE GKGILETGVH SLLCSLPTHL LAKLSFASDS QY
	Isoform 2 (mbt-II). Checksum: 091F0E829CE6665D	FASTA	738	82,318
	10 20 30 40 50 60 MRRREGHGTD SEMGQGPVRE SQSSDPPALQ FRISEYKPLN MAGVEQPPSP ELRQEGVTEY 70 80 90 100 110 120 EDGGAPAGDG EAGPQQAEDH PQNPPEDPNQ DPPEDDSTCQ CQACGPHQAA GPDLGSSNDG 130 140 150 160 170 180 CPQLFQERSV IVENSSGSTS ASELLKPMKK RKRREYQSPS EEESEPEAME KQEEGKDPEG 190 200 210 220 230 240 QPTASTPESE EWSSSQPATG EKKECWSWES YLEEQKAITA PVSLFQDSQA VTHNKNGFKL 250 260 270 280 290 300 GMKLEGIDPQ HPSMYFILTV AEVCGYRLRL HFDGYSECHD FWVNANSPDI HPAGWFEKTG 310 320 330 340 350 360 HKLQPPKGYK EEEFSWSQYL RSTRAQAAPK HLFVSQSHSP PPLGFQVGMK LEAVDRMNPS 370 380 390 400 410 420 LVCVASVTDV VDSRFLVHFD NWDDTYDYWC DPSSPYIHPV GWCQKQGKPL TPPQDYPDPD 430 440 450 460 470 480 NFCWEKYLEE TGASAVPTWA FKVRPPHSFL VNMKLEAVDR RNPALIRVAS VEDVEDHRIK 490 500 510 520 530 540 IHFDGWSHGY DFWIDADHPD IHPAGWCSKT GHPLQPPLGP REPSSASPGG CPPLSYRSLP 550 560 570 580 590 600 HTRTSKYSFH HRKCPTPGCD GSGHVTGKFT AHHCLSGCPL AERNQSRLKA ELSDSEASAR 610 620 630 640 650 660 KKNLSGFSPR KKPRHHGRIG RPPKYRKIPQ EDFQTLTPDV VHQSLFMSAL SAHPDRSLSV 670 680 690 700 710 720 CWEQHCKLLP GVAGISASTV AKWTIDEVFG FVQTLTGCED QARLFKDEVR CKCRVGDRAG 730 VTVLKTAGSR CPPQRHFC
	Isoform 3. Checksum: 8C720B89B9DD6388	FASTA	390	43,766
	10 20 30 40 50 60 MKLEAVDRMN PSLVCVASVT DVVDSRFLVH FDNWDDTYDY WCDPSSPYIH PVGWCQKQGK 70 80 90 100 110 120 PLTPPQDYPD PDNFCWEKYL EETGASAVPT WAFKVRPPHS FLVNMKLEAV DRRNPALIRV 130 140 150 160 170 180 ASVEDVEDHR IKIHFDGWSH GYDFWIDADH PDIHPAGWCS KTGHPLQPPL GPREPSSASP 190 200 210 220 230 240 GGCPPLSYRS LPHTRTSKYS FHHRKCPTPG CDGSGHVTGK FTAHHCLSGC PLAERNQSRL 250 260 270 280 290 300 KAELSDSEAS ARKKNLSGFS PRKKPRHHGR IGRPPKYRKI PQEDFQTLTP DVVHQSLFMS 310 320 330 340 350 360 ALSAHPDRSL SVCWEQHCKL LPGVAGISAS TVAKWTIDEV FGFVQTLTGC EDQARLFKDE 370 380 390 VRCKCRVGDR AGVTVLKTAG SRCPPQRHFC
	Isoform 4. Checksum: 6B92FF852FF98CB4	FASTA	752	83,884
	10 20 30 40 50 60 MRRREGHGTD SEMGQGPVRE SQSSDPPALQ FRISEYKPLN MAGVEQPPSP ELRQEGVTEY 70 80 90 100 110 120 EDGGAPAGDG EAGPQQAEDH PQNPPEDPNQ DPPEDDSTCQ CQACGPHQAA GPDLGSSNDG 130 140 150 160 170 180 CPQLFQERSV IVENSSGSTS ASELLKPMKK RKRREYQSPS EEESEPEAME KQEEGKDPEG 190 200 210 220 230 240 QPTASTPESE EWSSSQPATG EKKECWSWES YLEEQKAITA PVSLFQDSQA VTHNKNGFKL 250 260 270 280 290 300 GMKLEGIDPQ HPSMYFILTV AEVCGYRLRL HFDGYSECHD FWVNANSPDI HPAGWFEKTG 310 320 330 340 350 360 HKLQPPKGYK EEEFSWSQYL RSTRAQAAPK HLFVSQSHSP PPLGFQVGMK LEAVDRMNPS 370 380 390 400 410 420 LVCVASVTDV VDSRFLVHFD NWDDTYDYWC DPSSPYIHPV GWCQKQGKPL TPPQDYPDPD 430 440 450 460 470 480 NFCWEKYLEE TGASAVPTWA FKVRPPHSFL VNMKLEAVDR RNPALIRVAS VEDVEDHRIK 490 500 510 520 530 540 IHFDGWSHGY DFWIDADHPD IHPAGWCSKT GHPLQPPLGP REPSSASPGG CPPLSYRSLP 550 560 570 580 590 600 HTRTSKYSFH HRKCPTPGCD GSGHVTGKFT AHHCLSGCPL AERNQSRLKA ELSDSEASAR 610 620 630 640 650 660 KKNLSGFSPR KKPRHHGRIG RPPKYRKIPQ EDFQTLTPDV VHQSLFMSAL SAHPDRSLSV 670 680 690 700 710 720 CWEQHCKLLP GVAGISASTV AKWTIDEVFG FVQTLTGCED QARLFKDEMI DGEAFLLLTQ 730 740 750 ADIVKIMSVK LGPALKIYNA ILMFKNADDT LK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human homolog of Drosophila lethal(3)malignant brain tumor (l(3)mbt) protein associates with condensed mitotic chromosomes." Koga H., Matsui S., Hirota T., Takebayashi S., Okumura K., Saya H. Oncogene 18:3799-3809(1999) [PubMed: 10445843] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Brain.
[2]	"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] (ISOFORM 3). Tissue: Uterus.
[3]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT THR-49. Tissue: Brain.
[5]	"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed: 9734811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 215-772 (ISOFORM 4). Tissue: Brain.
[6]	"The human L(3)MBT Polycomb group protein is a transcriptional repressor and interacts physically and functionally with TEL (ETV6)." Boccuni P., MacGrogan D., Scandura J.M., Nimer S.D. J. Biol. Chem. 278:15412-15420(2003) [PubMed: 12588862] [Abstract] Cited for: INTERACTION WITH ETV6.
[7]	"Malignant brain tumor repeats: a three-leaved propeller architecture with ligand/peptide binding pockets." Wang W.K., Tereshko V., Boccuni P., MacGrogan D., Nimer S.D., Patel D.J. Structure 11:775-789(2003) [PubMed: 12842041] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 197-527.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U89358 mRNA. Translation: AAC69438.1.
AL110279 mRNA. Translation: CAB53714.1.
AL031681, Z98752 Genomic DNA. Translation: CAI23043.1.
Z98752 Genomic DNA. Translation: CAC16800.1.
Z98752 Genomic DNA. Translation: CAC18508.1.
Z98752, AL031681 Genomic DNA. Translation: CAI42318.1.
BC039820 mRNA. Translation: AAH39820.1.
AB014581 mRNA. Translation: BAA31656.1.

IPI

IPI00022956.
IPI00216288.
IPI00216289.
IPI00333371.

PIR

T14794.

RefSeq

NP_056293.4.

UniGene

Hs.709356

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1OYX	X-ray	1.85	A/B/C	197-527	[»]
1OZ2	X-ray	1.55	A	197-527	[»]
1OZ3	X-ray	1.85	A/B/C	197-527	[»]
2PQW	X-ray	2.00	A	200-522	[»]
2RHI	X-ray	1.66	A	197-526	[»]
2RHU	X-ray	1.90	A	206-519	[»]
2RHX	X-ray	2.10	A	197-526	[»]
2RHY	X-ray	1.90	A	206-519	[»]
2RHZ	X-ray	2.20	A	206-519	[»]
2RI2	X-ray	2.20	A	206-519	[»]
2RI3	X-ray	2.00	A	206-519	[»]
2RI5	X-ray	2.00	A	206-519	[»]
2RJC	X-ray	2.00	A/B/C	200-530	[»]
2RJD	X-ray	1.65	A	200-530	[»]
2RJE	X-ray	1.86	A/B/C	200-530	[»]
2RJF	X-ray	2.05	A/C/E	200-530	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y468. 4 interactions.

Proteomic databases

PRIDE

Q9Y468.

Genome annotation databases

Ensembl

ENSG00000185513. Homo sapiens. [Contig view]

GeneID

26013.

KEGG

hsa:26013.

Organism-specific databases

GeneCards

GC20P041576.

H-InvDB

HIX0015827.
HIX0017445.

HGNC

HGNC:15905. L3MBTL.

MIM

608802. gene.

PharmGKB

PA30260.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q9Y468.

OMA

Q9Y468. PPLSYRS.

Gene expression databases

ArrayExpress

Q9Y468.

Bgee

Q9Y468.

CleanEx

HS_L3MBTL.

GermOnline

ENSG00000185513. Homo sapiens.

Family and domain databases

InterPro

IPR004092. Mbt.
IPR013761. SAM_type.
IPR002515. Znf_C2HC.
[Graphical view]

Gene3D

G3DSA:1.10.150.50. SAM_type. 1 hit.

Pfam

PF02820. MBT. 3 hits.
PF01530. zf-C2HC. 1 hit.
[Graphical view]

SMART

SM00561. MBT. 3 hits.
[Graphical view]

PROSITE

PS51079. MBT. 3 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

47770.

SOURCE

Search...

Entry information

Entry name

LMBL1_HUMAN

Accession

Primary (citable) accession number: Q9Y468
Secondary accession number(s): Q5H8Y8 , Q8IUV7, Q9H1E6, Q9H1G5, Q9UG06, Q9UJB9, Q9Y4C9

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	September 19, 2002
Last modified:	June 16, 2009
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)