O94761 (RECQ4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ATP-dependent DNA helicase Q4
EC=3.6.4.12

Alternative name(s):
DNA helicase, RecQ-like type 4
Short name=RecQ4
RTS
RecQ protein-like 4

Gene names

Name:	RECQL4
Synonyms:	RECQ4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1208 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	DNA-dependent ATPase. May modulate chromosome segregation. Ref.7
Catalytic activity	ATP + H2O = ADP + phosphate.
Subunit structure	Interacts with UBR1 and UBR2. Interacts with MCM10; this interaction regulates RECQL4 unwinding activity. Ref.7 Ref.8
Subcellular location	Cytoplasm. Nucleus Ref.2 Ref.7.
Tissue specificity	Ubiquitously expressed, with highest levels in thymus and testis. Ref.1
Induction	Up-regulated in actively dividing cells. Ref.5
Involvement in disease	Rothmund-Thomson syndrome (RTS) [MIM:268400]: Characterized by dermatological features such as atrophy, pigmentation, and telangiectasia and frequently accompanied by juvenile cataract, saddle nose, congenital bone defects, disturbances of hair growth, and hypogonadism. Note: The disease is caused by mutations affecting the gene represented in this entry. RAPADILINO syndrome (RAPADILINOS) [MIM:266280]: Disease characterized by radial and patellar aplasia or hypoplasia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Baller-Gerold syndrome (BGS) [MIM:218600]: An autosomal recessive syndrome characterized by short stature, craniosynostosis, absent or hypoplastic radii, short and curved ulna, fused carpal bones and absent carpals, metacarpals and phalanges. Some patients manifest poikiloderma. Cases reported as Baller-Gerold syndrome have phenotypic overlap with several other disorders, including Saethre-Chotzen syndrome. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11
Sequence similarities	Belongs to the helicase family. RecQ subfamily. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain.
Sequence caution	The sequence AAH13277.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Cataract Craniosynostosis Disease mutation Dwarfism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Helicase Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA recombination Inferred from electronic annotation. Source: InterPro DNA repair Traceable author statement Ref.1. Source: ProtInc DNA replication Inferred from direct assay PubMed 19177149. Source: UniProtKB DNA strand renaturation Inferred from direct assay PubMed 19177149. Source: UniProtKB multicellular organismal development Traceable author statement PubMed 10319867. Source: ProtInc
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from direct assay PubMed 19177149. Source: UniProtKB ATP-dependent 3'-5' DNA helicase activity Inferred from mutant phenotype PubMed 19177149. Source: UniProtKB bubble DNA binding Inferred from direct assay PubMed 19177149. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1208

1208

ATP-dependent DNA helicase Q4

PRO_0000205053

Regions

Domain

489 – 662

174

Helicase ATP-binding

Domain

683 – 850

168

Helicase C-terminal

Nucleotide binding

502 – 509

8

ATP Potential

Motif

605 – 608

4

DEAH box

Natural variations

Natural variant

54

1

Q → R. Ref.3
Corresponds to variant rs35198096 [ dbSNP | Ensembl ].

VAR_025117

Natural variant

71

1

E → G. Ref.3
Corresponds to variant rs34642881 [ dbSNP | Ensembl ].

VAR_025118

Natural variant

92

1

P → S. Ref.3
Corresponds to variant rs2721190 [ dbSNP | Ensembl ].

VAR_025119

Natural variant

189

1

G → S. Ref.3
Corresponds to variant rs34371341 [ dbSNP | Ensembl ].

VAR_025120

Natural variant

267

1

E → D Common polymorphism. Ref.3 Ref.9
Corresponds to variant rs4244612 [ dbSNP | Ensembl ].

VAR_023295

Natural variant

273

1

A → T. Ref.3
Corresponds to variant rs34103564 [ dbSNP | Ensembl ].

VAR_025121

Natural variant

301

1

E → K. Ref.3
Corresponds to variant rs34633809 [ dbSNP | Ensembl ].

VAR_025122

Natural variant

355

1

R → Q. Ref.10

VAR_023296

Natural variant

441

1

P → S. Ref.10

VAR_023297

Natural variant

522

1

R → C. Ref.3
Corresponds to variant rs35407712 [ dbSNP | Ensembl ].

VAR_025123

Natural variant

522

1

R → H. Ref.3
Corresponds to variant rs35842750 [ dbSNP | Ensembl ].

VAR_025124

Natural variant

523

1

S → T. Ref.11

VAR_026590

Natural variant

591

1

P → L. Ref.3
Corresponds to variant rs2721191 [ dbSNP | Ensembl ].

VAR_025125

Natural variant

793

1

P → L.
Corresponds to variant rs35098923 [ dbSNP | Ensembl ].

VAR_057125

Natural variant

793

1

P → S. Ref.3
Corresponds to variant rs35098923 [ dbSNP | Ensembl ].

VAR_025126

Natural variant

799

1

V → M. Ref.3
Corresponds to variant rs34293591 [ dbSNP | Ensembl ].

VAR_025127

Natural variant

857 – 858

2

Missing.

VAR_023298

Natural variant

964

1

P → T. Ref.3
Corresponds to variant rs33972310 [ dbSNP | Ensembl ].

VAR_025128

Natural variant

976

1

E → K. Ref.3
Corresponds to variant rs35070885 [ dbSNP | Ensembl ].

VAR_025129

Natural variant

1004

1

R → W. Ref.3
Corresponds to variant rs36023964 [ dbSNP | Ensembl ].

VAR_025130

Natural variant

1005

1

R → Q. Ref.3 Ref.9
Corresponds to variant rs4251691 [ dbSNP | Ensembl ].

VAR_023299

Natural variant

1021

1

R → Q. Ref.3
Corresponds to variant rs34666647 [ dbSNP | Ensembl ].

VAR_025131

Natural variant

1021

1

R → W in BGS. Ref.11

VAR_026591

Natural variant

1043

1

L → P.
Corresponds to variant rs4925828 [ dbSNP | Ensembl ].

VAR_057126

Natural variant

1045

1

A → T. Ref.3
Corresponds to variant rs35348691 [ dbSNP | Ensembl ].

VAR_025132

Natural variant

1105

1

G → D. Ref.3
Corresponds to variant rs36078464 [ dbSNP | Ensembl ].

VAR_025133

Natural variant

1105

1

G → S. Ref.3
Corresponds to variant rs34915097 [ dbSNP | Ensembl ].

VAR_025134

Natural variant

1106

1

R → H. Ref.3
Corresponds to variant rs34236392 [ dbSNP | Ensembl ].

VAR_025135

Natural variant

1113

1

G → R. Ref.3
Corresponds to variant rs35101495 [ dbSNP | Ensembl ].

VAR_025136

Natural variant

1148

1

S → F. Ref.3
Corresponds to variant rs35346077 [ dbSNP | Ensembl ].

VAR_025137

Secondary structure

1

.

.

.

.

.

.

1208

Helix Strand Turn

Details...

Helix

1 – 21

21

Helix

28 – 31

4

Helix

36 – 52

17

Sequences

	Sequence		Length	Mass (Da)
	O94761 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: CB809A7765AB48A1	FASTA	1,208	133,077
	10 20 30 40 50 60 MERLRDVRER LQAWERAFRR QRGRRPSQDD VEAAPEETRA LYREYRTLKR TTGQAGGGLR 70 80 90 100 110 120 SSESLPAAAE EAPEPRCWGP HLNRAATKSP QPTPGRSRQG SVPDYGQRLK ANLKGTLQAG 130 140 150 160 170 180 PALGRRPWPL GRASSKASTP KPPGTGPVPS FAEKVSDEPP QLPEPQPRPG RLQHLQASLS 190 200 210 220 230 240 QRLGSLDPGW LQRCHSEVPD FLGAPKACRP DLGSEESQLL IPGESAVLGP GAGSQGPEAS 250 260 270 280 290 300 AFQEVSIRVG SPQPSSSGGE KRRWNEEPWE SPAQVQQESS QAGPPSEGAG AVAVEEDPPG 310 320 330 340 350 360 EPVQAQPPQP CSSPSNPRYH GLSPSSQARA GKAEGTAPLH IFPRLARHDR GNYVRLNMKQ 370 380 390 400 410 420 KHYVRGRALR SRLLRKQAWK QKWRKKGECF GGGGATVTTK ESCFLNEQFD HWAAQCPRPA 430 440 450 460 470 480 SEEDTDAVGP EPLVPSPQPV PEVPSLDPTV LPLYSLGPSG QLAETPAEVF QALEQLGHQA 490 500 510 520 530 540 FRPGQERAVM RILSGISTLL VLPTGAGKSL CYQLPALLYS RRSPCLTLVV SPLLSLMDDQ 550 560 570 580 590 600 VSGLPPCLKA ACIHSGMTRK QRESVLQKIR AAQVHVLMLT PEALVGAGGL PPAAQLPPVA 610 620 630 640 650 660 FACIDEAHCL SQWSHNFRPC YLRVCKVLRE RMGVHCFLGL TATATRRTAS DVAQHLAVAE 670 680 690 700 710 720 EPDLHGPAPV PTNLHLSVSM DRDTDQALLT LLQGKRFQNL DSIIIYCNRR EDTERIAALL 730 740 750 760 770 780 RTCLHAAWVP GSGGRAPKTT AEAYHAGMCS RERRRVQRAF MQGQLRVVVA TVAFGMGLDR 790 800 810 820 830 840 PDVRAVLHLG LPPSFESYVQ AVGRAGRDGQ PAHCHLFLQP QGEDLRELRR HVHADSTDFL 850 860 870 880 890 900 AVKRLVQRVF PACTCTCTRP PSEQEGAVGG ERPVPKYPPQ EAEQLSHQAA PGPRRVCMGH 910 920 930 940 950 960 ERALPIQLTV QALDMPEEAI ETLLCYLELH PHHWLELLAT TYTHCRLNCP GGPAQLQALA 970 980 990 1000 1010 1020 HRCPPLAVCL AQQLPEDPGQ GSSSVEFDMV KLVDSMGWEL ASVRRALCQL QWDHEPRTGV 1030 1040 1050 1060 1070 1080 RRGTGVLVEF SELAFHLRSP GDLTAEEKDQ ICDFLYGRVQ ARERQALARL RRTFQAFHSV 1090 1100 1110 1120 1130 1140 AFPSCGPCLE QQDEERSTRL KDLLGRYFEE EEGQEPGGME DAQGPEPGQA RLQDWEDQVR 1150 1160 1170 1180 1190 1200 CDIRQFLSLR PEEKFSSRAV ARIFHGIGSP CYPAQVYGQD RRFWRKYLHL SFHALVGLAT EELLQVAR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of two new human helicase genes of the RecQ family: biological significance of multiple species in higher eukaryotes." Kitao S., Ohsugi I., Ichikawa K., Goto M., Furuichi Y., Shimamoto A. Genomics 54:443-452(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Testis.
[2]	"Rothmund-Thomson syndrome responsible gene, RECQL4: genomic structure and products." Kitao S., Lindor N.M., Shiratori M., Furuichi Y., Shimamoto A. Genomics 61:268-276(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, INVOLVEMENT IN ROTHMUND-THOMSON SYNDROME.
[3]	NIEHS SNPs program Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-54; GLY-71; SER-92; SER-189; ASP-267; THR-273; LYS-301; CYS-522; HIS-522; LEU-591; SER-793; MET-799; THR-964; LYS-976; TRP-1004; GLN-1005; GLN-1021; THR-1045; SER-1105; ASP-1105; HIS-1106; ARG-1113 AND PHE-1148.
[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] OF 468-1208. Tissue: Lymph and Placenta.
[5]	"Differential regulation of human RecQ family helicases in cell transformation and cell cycle." Kawabe T., Tsuyama N., Kitao S., Nishikawa K., Shimamoto A., Shiratori M., Matsumoto T., Anno K., Sato T., Mitsui Y., Seki M., Enomoto T., Goto M., Ellis N.A., Ide T., Furuichi Y., Sugimoto M. Oncogene 19:4764-4772(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[6]	"Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases." Siitonen H.A., Kopra O., Kaeaeriaeinen H., Haravuori H., Winter R.M., Saeaemaenen A.-M., Peltonen L., Kestilae M. Hum. Mol. Genet. 12:2837-2844(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN RAPADILINOS.
[7]	"RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway." Yin J., Kwon Y.T., Varshavsky A., Wang W. Hum. Mol. Genet. 13:2421-2430(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBR1 AND UBR2, SUBCELLULAR LOCATION, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY.
[8]	"MCM10 mediates RECQ4 association with MCM2-7 helicase complex during DNA replication." Xu X., Rochette P.J., Feyissa E.A., Su T.V., Liu Y. EMBO J. 28:3005-3014(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MCM10.
[9]	"Identification of two novel RECQL4exonic SNPs and genomic characterization of the IVS12 minisatellite." Roversi G., Beghini A., Zambruno G., Paradisi M., Larizza L. J. Hum. Genet. 48:107-109(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ASP-267 AND GLN-1005.
[10]	"Mutation analysis of the RECQL4 gene in sporadic osteosarcomas." Nishijo K., Nakayama T., Aoyama T., Okamoto T., Ishibe T., Yasura K., Shima Y., Shibata K.R., Tsuboyama T., Nakamura T., Toguchida J. Int. J. Cancer 111:367-372(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GLN-355; SER-441 AND 857-CYS--THR-858 DEL.
[11]	"Revisiting the craniosynostosis-radial ray hypoplasia association: Baller-Gerold syndrome caused by mutations in the RECQL4 gene." Van Maldergem L., Siitonen H.A., Jalkh N., Chouery E., De Roy M., Delague V., Muenke M., Jabs E.W., Cai J., Wang L.L., Plon S.E., Fourneau C., Kestilae M., Gillerot Y., Megarbane A., Verloes A. J. Med. Genet. 43:148-152(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BGS TRP-1021, VARIANT THR-523.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB006532 mRNA. Translation: BAA74453.1.
AB026546 Genomic DNA. Translation: BAA86899.1.
DQ176868 Genomic DNA. Translation: AAZ85145.1.
BC011602 mRNA. Translation: AAH11602.2.
BC013277 mRNA. Translation: AAH13277.2. Different initiation.

IPI

IPI00014925.

RefSeq

NP_004251.3. NM_004260.3.

UniGene

Hs.31442.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KMU	NMR	-	A	1-54	[»]

ProteinModelPortal

O94761.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48475N.

IntAct

O94761. 3 interactions.

MINT

MINT-1432307.

STRING

9606.ENSP00000410312.

PTM databases

PhosphoSite

O94761.

Proteomic databases

PaxDb

O94761.

PRIDE

O94761.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

9401.

KEGG

hsa:9401.

UCSC

uc003zdj.3. human.

Organism-specific databases

CTD

9401.

GeneCards

GC08M145738.

HGNC

HGNC:9949. RECQL4.

MIM

218600. phenotype.
266280. phenotype.
268400. phenotype.
603780. gene.

neXtProt

NX_O94761.

Orphanet

1225. Baller-Gerold syndrome.
3021. RAPADILINO syndrome.
221016. Rothmund-Thomson syndrome type 2.

PharmGKB

PA34316.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0514.

HOGENOM

HOG000264957.

HOVERGEN

HBG065925.

InParanoid

O94761.

KO

K10730.

Gene expression databases

CleanEx

HS_RECQL4.

Genevestigator

O94761.

GermOnline

ENSG00000160957. Homo sapiens.

Family and domain databases

InterPro

IPR011545. DNA/RNA_helicase_DEAD/DEAH_N.
IPR004589. DNA_helicase_ATP-dep_RecQ.
IPR021110. DNA_rep_checkpnt_protein.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR001878. Znf_CCHC.
[Graphical view]

Pfam

PF00270. DEAD. 1 hit.
PF11719. Drc1-Sld2. 1 hit.
PF00271. Helicase_C. 1 hit.
[Graphical view]

SMART

SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
SM00343. ZnF_C2HC. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00614. recQ_fam. 1 hit.

PROSITE

PS00690. DEAH_ATP_HELICASE. False negative.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O94761.

GenomeRNAi

9401.

NextBio

35219.

SOURCE

Search...

Entry information

Entry name

RECQ4_HUMAN

Accession

Primary (citable) accession number: O94761
Secondary accession number(s): Q3Y424, Q96DW2, Q96F55

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 1, 1999
Last modified:	May 1, 2013
This is version 128 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.