Reviewed, UniProtKB/Swiss-Prot P54132 (BLM_HUMAN)

Names and origin

Protein names

Recommended name:
    Bloom syndrome protein
    EC=3.6.1.-
Alternative name(s):
    RecQ protein-like 3
    DNA helicase, RecQ-like type 2

Gene names

Name:	BLM
Synonyms:	RECQ2, RECQL3

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	1417 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Participates in DNA replication and repair. Exhibits a magnesium-dependent ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction. Ref.2 Ref.8
Subunit structure	Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with ubiquitinated FANCD2. Interacts with RMI complex. Interacts directly with RMI1 component of RMI complex. Ref.7 Ref.11 Ref.15 Ref.16
Subcellular location	Nucleus.
Post-translational modification	Phosphorylated in response to DNA damage. Phosphorylation requires the FANCA-FANCC-FANCE-FANCF-FANCG protein complex, as well as the presence of RMI1. Ref.7 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.17
Involvement in disease	Defects in BLM are the cause of Bloom syndrome (BLM) [MIM:210900]. BLM is an autosomal recessive disorder characterized by proportionate pre- and postnatal growth deficiency, sun-sensitive telangiectatic hypo- and hyperpigmented skin, predisposition to malignancy, and chromosomal instability. Ref.1 Ref.6 Ref.19 Ref.20
Sequence similarities	Belongs to the helicase family. RecQ subfamily. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain. Contains 1 HRDC domain.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Helicase Hydrolase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	DNA replication Inferred from electronic annotation. Source: UniProtKB-KW G2 phase of mitotic cell cycle Non-traceable author statement. Source: UniProtKB G2/M transition DNA damage checkpoint Non-traceable author statement. Source: UniProtKB double-strand break repair via homologous recombination Non-traceable author statement. Source: UniProtKB negative regulation of cell division Inferred from mutant phenotype. Source: UniProtKB positive regulation of transcription Inferred from direct assay. Source: UniProtKB protein oligomerization Inferred from direct assay. Source: UniProtKB regulation of cyclin-dependent protein kinase activity Inferred from mutant phenotype. Source: UniProtKB replication fork processing Inferred from direct assay. Source: UniProtKB replication fork protection Non-traceable author statement. Source: UniProtKB response to X-ray Inferred from direct assay. Source: UniProtKB
Cellular component	PML body Inferred from direct assay. Source: UniProtKB cytoplasm Inferred from direct assay. Source: HPA lateral element Inferred from direct assay. Source: UniProtKB nuclear matrix Inferred from direct assay. Source: UniProtKB nucleolus Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from direct assay. Source: UniProtKB DNA strand annealing activity Inferred from direct assay. Source: UniProtKB G-quadruplex DNA binding Inferred from direct assay. Source: UniProtKB bubble DNA binding Inferred from direct assay. Source: UniProtKB four-way junction helicase activity Inferred from direct assay. Source: UniProtKB p53 binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FEN1	P39748	3	EBI-621372,EBI-707816
RPA1	P27694	1	EBI-621372,EBI-621389
TERF1	P54274	2	EBI-621372,EBI-710997
TERF2	Q15554	5	EBI-621372,EBI-706637
WRN	Q14191	4	EBI-621372,EBI-368417

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1417	1417	Bloom syndrome protein		PRO_0000205039
Regions
	Domain	676 – 851	176	Helicase ATP-binding
	Domain	877 – 1024	148	Helicase C-terminal
	Domain	1212 – 1292	81	HRDC
	Nucleotide binding	689 – 696	8	ATP By similarity
	Motif	795 – 798	4	DEAH box
	Motif	1334 – 1349	16	Nuclear localization signal Potential
	Compositional bias	292 – 299	8	Poly-Asp
	Compositional bias	310 – 316	7	Poly-Ser
	Compositional bias	557 – 566	10	Poly-Asp
Amino acid modifications
	Modified residue	48	1	Phosphoserine Ref.17
	Modified residue	53	1	Phosphoserine Ref.17
	Modified residue	57	1	Phosphothreonine Ref.17
	Modified residue	114	1	Phosphothreonine Ref.17
	Modified residue	358	1	Phosphoserine Ref.17
	Modified residue	419	1	Phosphoserine Ref.13 Ref.17
	Modified residue	422	1	Phosphoserine Ref.13 Ref.17
	Modified residue	480	1	Phosphoserine Ref.14
	Modified residue	499	1	Phosphoserine Ref.12
	Modified residue	508	1	Phosphothreonine Ref.12
	Modified residue	1295	1	Phosphoserine Ref.17
	Modified residue	1296	1	Phosphoserine Ref.9 Ref.17
	Modified residue	1303	1	Phosphoserine Ref.17
	Modified residue	1310	1	Phosphoserine Ref.17
Natural variations
	Natural variant	137	1	K → R: dbSNP rs28384988. Ref.3		VAR_022295
	Natural variant	298	1	T → M: dbSNP rs28384991. Ref.3		VAR_022296
	Natural variant	591	1	R → Q: dbSNP rs28385012. Ref.3		VAR_022297
	Natural variant	672	1	Q → R in BLM. Ref.1		VAR_006901
	Natural variant	841	1	I → T in BLM.		VAR_016032
	Natural variant	843	1	T → I in BLM. Ref.1		VAR_006902
	Natural variant	868	1	P → L: dbSNP rs11852361. Ref.3		VAR_022298
	Natural variant	878	1	C → R in BLM. Ref.20		VAR_016033
	Natural variant	891	1	G → E in BLM.		VAR_009138
	Natural variant	901	1	C → Y in BLM.		VAR_009139
	Natural variant	1036	1	C → F in BLM. Ref.19		VAR_009140
	Natural variant	1043	1	A → D: dbSNP rs2229035.		VAR_051731
	Natural variant	1055	1	C → S in BLM. Ref.1		VAR_006903
	Natural variant	1205	1	V → I: dbSNP rs28385141. Ref.3		VAR_022299
	Natural variant	1209	1	S → T: dbSNP rs1801256.		VAR_014912
	Natural variant	1213	1	E → K: dbSNP rs28385142. Ref.3		VAR_022300
	Natural variant	1321	1	V → I: dbSNP rs7167216. Ref.3		VAR_022301

Sequences

	Sequence		Length	Mass (Da)
	P54132-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 423DF5F381194E11	FASTA	1,417	159,000
	10 20 30 40 50 60 MAAVPQNNLQ EQLERHSART LNNKLSLSKP KFSGFTFKKK TSSDNNVSVT NVSVAKTPVL 70 80 90 100 110 120 RNKDVNVTED FSFSEPLPNT TNQQRVKDFF KNAPAGQETQ RGGSKSLLPD FLQTPKEVVC 130 140 150 160 170 180 TTQNTPTVKK SRDTALKKLE FSSSPDSLST INDWDDMDDF DTSETSKSFV TPPQSHFVRV 190 200 210 220 230 240 STAQKSKKGK RNFFKAQLYT TNTVKTDLPP PSSESEQIDL TEEQKDDSEW LSSDVICIDD 250 260 270 280 290 300 GPIAEVHINE DAQESDSLKT HLEDERDNSE KKKNLEEAEL HSTEKVPCIE FDDDDYDTDF 310 320 330 340 350 360 VPPSPEEIIS ASSSSSKCLS TLKDLDTSDR KEDVLSTSKD LLSKPEKMSM QELNPETSTD 370 380 390 400 410 420 CDARQISLQQ QLIHVMEHIC KLIDTIPDDK LKLLDCGNEL LQQRNIRRKL LTEVDFNKSD 430 440 450 460 470 480 ASLLGSLWRY RPDSLDGPME GDSCPTGNSM KELNFSHLPS NSVSPGDCLL TTTLGKTGFS 490 500 510 520 530 540 ATRKNLFERP LFNTHLQKSF VSSNWAETPR LGKKNESSYF PGNVLTSTAV KDQNKHTASI 550 560 570 580 590 600 NDLERETQPS YDIDNFDIDD FDDDDDWEDI MHNLAASKSS TAAYQPIKEG RPIKSVSERL 610 620 630 640 650 660 SSAKTDCLPV SSTAQNINFS ESIQNYTDKS AQNLASRNLK HERFQSLSFP HTKEMMKIFH 670 680 690 700 710 720 KKFGLHNFRT NQLEAINAAL LGEDCFILMP TGGGKSLCYQ LPACVSPGVT VVISPLRSLI 730 740 750 760 770 780 VDQVQKLTSL DIPATYLTGD KTDSEATNIY LQLSKKDPII KLLYVTPEKI CASNRLISTL 790 800 810 820 830 840 ENLYERKLLA RFVIDEAHCV SQWGHDFRQD YKRMNMLRQK FPSVPVMALT ATANPRVQKD 850 860 870 880 890 900 ILTQLKILRP QVFSMSFNRH NLKYYVLPKK PKKVAFDCLE WIRKHHPYDS GIIYCLSRRE 910 920 930 940 950 960 CDTMADTLQR DGLAALAYHA GLSDSARDEV QQKWINQDGC QVICATIAFG MGIDKPDVRF 970 980 990 1000 1010 1020 VIHASLPKSV EGYYQESGRA GRDGEISHCL LFYTYHDVTR LKRLIMMEKD GNHHTRETHF 1030 1040 1050 1060 1070 1080 NNLYSMVHYC ENITECRRIQ LLAYFGENGF NPDFCKKHPD VSCDNCCKTK DYKTRDVTDD 1090 1100 1110 1120 1130 1140 VKSIVRFVQE HSSSQGMRNI KHVGPSGRFT MNMLVDIFLG SKSAKIQSGI FGKGSAYSRH 1150 1160 1170 1180 1190 1200 NAERLFKKLI LDKILDEDLY INANDQAIAY VMLGNKAQTV LNGNLKVDFM ETENSSSVKK 1210 1220 1230 1240 1250 1260 QKALVAKVSQ REEMVKKCLG ELTEVCKSLG KVFGVHYFNI FNTVTLKKLA ESLSSDPEVL 1270 1280 1290 1300 1310 1320 LQIDGVTEDK LEKYGAEVIS VLQKYSEWTS PAEDSSPGIS LSSSRGPGRS AAEELDEEIP 1330 1340 1350 1360 1370 1380 VSSHYFASKT RNERKRKKMP ASQRSKRRKT ASSGSKAKGG SATCRKISSK TKSSSIIGSS 1390 1400 1410 SASHTSQATS GANSKLGIMA PPKPINRPFL KPSYAFS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The Bloom's syndrome gene product is homologous to RecQ helicases." Ellis N.A., Groden J., Ye T.-Z., Straughen J., Lennon D.J., Ciocci S., Proytcheva M., German J. Cell 83:655-666(1995) [PubMed: 7585968] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS BLM ARG-672; ILE-843 AND SER-1055.
[2]	"The Bloom's syndrome gene product is a 3'-5' DNA helicase." Karow J.K., Chakraverty R.K., Hickson I.D. J. Biol. Chem. 272:30611-30614(1997) [PubMed: 9388193] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: B-cell.
[3]	NIEHS SNPs program Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-137; MET-298; GLN-591; LEU-868; ILE-1205 LYS-1213 AND ILE-1321.
[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].
[5]	"BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal." Kaneko H., Orii K.O., Matsui E., Shimozawa N., Fukao T., Matsumoto T., Shimamoto A., Furuichi Y., Hayakawa S., Kasahara K., Kondo N. Biochem. Biophys. Res. Commun. 240:348-353(1997) [PubMed: 9388480] [Abstract] Cited for: NUCLEAR LOCALIZATION SIGNAL.
[6]	"BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures." Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J. Genes Dev. 14:927-939(2000) [PubMed: 10783165] [Abstract] Cited for: IDENTIFICATION OF BLM AS MEMBER OF BASC.
[7]	"BLM and the FANC proteins collaborate in a common pathway in response to stalled replication forks." Pichierri P., Franchitto A., Rosselli F. EMBO J. 23:3154-3163(2004) [PubMed: 15257300] [Abstract] Cited for: INTERACTION WITH FANCD2, PHOSPHORYLATION.
[8]	"The BLM helicase is necessary for normal DNA double-strand break repair." Langland G., Elliott J., Li Y., Creaney J., Dixon K., Groden J. Cancer Res. 62:2766-2770(2002) [PubMed: 12019152] [Abstract] Cited for: FUNCTION IN DNA REPAIR.
[9]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1296, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity." Yin J., Sobeck A., Xu C., Meetei A.R., Hoatlin M., Li L., Wang W. EMBO J. 24:1465-1476(2005) [PubMed: 15775963] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH RMI1, PHOSPHORYLATION.
[11]	"A double Holliday junction dissolvasome comprising BLM, topoisomerase III alpha, and BLAP75." Raynard S., Bussen W., Sung P. J. Biol. Chem. 281:13861-13864(2006) [PubMed: 16595695] [Abstract] Cited for: INTERACTION WITH RMI1.
[12]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-499 AND THR-508, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419 AND SER-422, MASS SPECTROMETRY. Tissue: Epithelium.
[14]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-480, MASS SPECTROMETRY. Tissue: Epithelium.
[15]	"RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability." Xu D., Guo R., Sobeck A., Bachrati C.Z., Yang J., Enomoto T., Brown G.W., Hoatlin M.E., Hickson I.D., Wang W. Genes Dev. 22:2843-2855(2008) [PubMed: 18923082] [Abstract] Cited for: INTERACTION WITH RMI1.
[16]	"BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome." Singh T.R., Ali A.M., Busygina V., Raynard S., Fan Q., Du C.-H., Andreassen P.R., Sung P., Meetei A.R. Genes Dev. 22:2856-2868(2008) [PubMed: 18923083] [Abstract] Cited for: INTERACTION WITH RMI1.
[17]	"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-48; SER-53; THR-57; THR-114; SER-358; SER-419; SER-422; SER-1295; SER-1296; SER-1303 AND SER-1310, MASS SPECTROMETRY.
[18]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[19]	"Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom's syndrome." Foucault F., Vaury C., Barakat A., Thibout D., Planchon P., Jaulin C., Praz F., Amor-Gueret M. Hum. Mol. Genet. 6:1427-1434(1997) [PubMed: 9285778] [Abstract] Cited for: VARIANT BLM PHE-1036.
[20]	"Identification of a novel BLM missense mutation (2706T>C) in a Moroccan patient with Bloom's syndrome." Barakat A., Ababou M., Onclercq R., Dutertre S., Chadli E., Hda N., Benslimane A., Amor-Gueret M. Hum. Mutat. 15:584-585(2000) [PubMed: 10862105] [Abstract] Cited for: VARIANT BLM ARG-878.
+	Additional computationally mapped references.

Web resources

BLMbase

BLM mutation db

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	U39817 mRNA. Translation: AAA87850.1. AY886902 Genomic DNA. Translation: AAW62255.1. BC093622 mRNA. Translation: AAH93622.1. BC101567 mRNA. Translation: AAI01568.1. BC115030 mRNA. Translation: AAI15031.1. BC115032 mRNA. Translation: AAI15033.1.
IPI	IPI00004859.
PIR	A57570.
RefSeq	NP_000048.1.
UniGene	Hs.169348
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P54132. 9 interactions.
PTM databases
PhosphoSite	P54132.
Proteomic databases
PRIDE	P54132.
Genome annotation databases
Ensembl	ENSG00000197299. Homo sapiens. [Contig view]
GeneID	641.
KEGG	hsa:641.
Organism-specific databases
GeneCards	GC15P089061.
H-InvDB	HIX0038129.
HGNC	HGNC:1058. BLM.
HPA	HPA005689.
MIM	210900. phenotype. 604610. gene.
Orphanet	125. Bloom syndrome.
PharmGKB	PA25369.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P54132.
HOVERGEN	P54132.
OMA	P54132. PHTKEMM.
Enzyme and pathway databases
Pathway_Interaction_DB	telomerasepathway. Regulation of Telomerase.
Gene expression databases
ArrayExpress	P54132.
Bgee	P54132.
CleanEx	HS_BLM.
GermOnline	ENSG00000197299. Homo sapiens.
Family and domain databases
InterPro	IPR012532. BDHCT. IPR014001. DEAD-like_N. IPR001650. DNA/RNA_helicase_C. IPR011545. DNA/RNA_helicase_DEAD/DEAH_N. IPR002464. DNA/RNA_helicase_DEAH_CS. IPR004589. DNA_helicase_ATP-dep_RecQ. IPR018329. DNA_helicase_ATP-dep_RecQ_N. IPR014021. Helicase_SF1/SF2_ATP-bd. IPR002121. HRDC. IPR018982. RQC_domain. [Graphical view]
PANTHER	PTHR13710. RecQ. 1 hit.
Pfam	PF08072. BDHCT. 1 hit. PF00270. DEAD. 1 hit. PF00271. Helicase_C. 1 hit. PF00570. HRDC. 1 hit. PF09382. RQC. 1 hit. [Graphical view]
SMART	SM00487. DEXDc. 1 hit. SM00490. HELICc. 1 hit. SM00341. HRDC. 1 hit. [Graphical view]
TIGRFAMs	TIGR00614. recQ_fam. 1 hit.
PROSITE	PS00690. DEAH_ATP_HELICASE. 1 hit. PS51192. HELICASE_ATP_BIND_1. 1 hit. PS51194. HELICASE_CTER. 1 hit. PS50967. HRDC. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	2600.
PMAP-CutDB	P54132.
SOURCE	Search...

Entry information

Entry name

BLM_HUMAN

Accession

Primary (citable) accession number: P54132
Secondary accession number(s): Q52M96

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	June 16, 2009
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)