Q2NKX8 (ERC6L_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA excision repair protein ERCC-6-like
EC=3.6.4.12

Alternative name(s):
ATP-dependent helicase ERCC6-like
PLK1-interacting checkpoint helicase
Tumor antigen BJ-HCC-15

Gene names

Name:	ERCC6L
Synonyms:	PICH

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	1250 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	DNA helicase that acts as an essential component of the spindle assembly checkpoint. Contributes to the mitotic checkpoint by recruiting MAD2 to kinetochores and monitoring tension on centromeric chromatin. Acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase. Ref.1
Catalytic activity	ATP + H2O = ADP + phosphate.
Subunit structure	Interacts with PLK1, which phosphorylates it. Both proteins are mutually dependent on each other for correct subcellular localization. Ref.1 Ref.8
Subcellular location	Chromosome › centromere. Chromosome › centromere › kinetochore. Note: Localizes to kinetochores, inner centromeres and thin threads connecting separating chromosomes even during anaphase. In prometaphase cells, it mostly concentrates in between kinetochores. In metaphase, it localizes to numerous thin threads that stretch between sister kinetochores of the aligned chromosomes and are composed of catenated centromeric DNA. Evolution from inner centromeres to thin threads takes place in response to tension. Resolution of thin threads requires topoisomerase 2-alpha (TOP2A) after anaphase onset. Ref.1 Ref.5 Ref.6 Ref.7 Ref.8
Post-translational modification	Phosphorylation by PLK1 prevents the association with chromosome arms and restricts its localization to the kinetochore-centromere region.
Sequence similarities	Belongs to the SNF2/RAD54 helicase family. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain. Contains 2 TPR repeats.
Sequence caution	The sequence AAM82750.1 differs from that shown. Reason: Erroneous termination at position 803. Translated as Lys. The sequence BAA90952.1 differs from that shown. Reason: Erroneous termination at position 803. Translated as Lys.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Centromere Chromosome Kinetochore
Domain	Repeat TPR repeat
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Helicase Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell division Inferred from electronic annotation. Source: UniProtKB-KW mitotic prometaphase Traceable author statement. Source: Reactome
Cellular_component	condensed chromosome kinetochore Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA binding Inferred from electronic annotation. Source: UniProtKB-KW helicase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HTT	P42858	2	EBI-1042535,EBI-466029

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1250	1250	DNA excision repair protein ERCC-6-like		PRO_0000328831
Regions
	Repeat	21 – 54	34	TPR 1
	Domain	109 – 277	169	Helicase ATP-binding
	Domain	464 – 620	157	Helicase C-terminal
	Repeat	1200 – 1233	34	TPR 2
	Nucleotide binding	122 – 129	8	ATP Probable
	Motif	228 – 231	4	DEAH box
Amino acid modifications
	Modified residue	14	1	Phosphoserine Ref.9 Ref.10 Ref.12
	Modified residue	755	1	Phosphoserine Ref.9
	Modified residue	774	1	Phosphoserine Ref.9
	Modified residue	807	1	Phosphoserine Ref.12
	Modified residue	810	1	Phosphoserine Ref.10 Ref.12
	Modified residue	813	1	Phosphothreonine Ref.10
	Modified residue	820	1	Phosphoserine Ref.10 Ref.14
	Modified residue	995	1	Phosphoserine Ref.12
	Modified residue	1021	1	Phosphoserine By similarity
	Modified residue	1028	1	Phosphoserine Ref.10 Ref.11 Ref.12 Ref.14
	Modified residue	1063	1	Phosphothreonine; by PLK1 Ref.1
	Modified residue	1069	1	Phosphoserine Ref.14
	Modified residue	1098	1	Phosphoserine Ref.11
	Modified residue	1181	1	Phosphoserine Ref.9
	Modified residue	1188	1	Phosphoserine Ref.9
Experimental info
	Mutagenesis	127 – 129	3	GKT → AAA: Abolishes chromatin association. Ref.1
	Mutagenesis	1063	1	T → A: Induces a decrease in phosphorylation. Ref.1
	Sequence conflict	145	1	V → M in BAC11160. Ref.3
	Sequence conflict	172	1	R → G in BAC11160. Ref.3
	Sequence conflict	812	1	A → T in BAA90952. Ref.3
	Sequence conflict	812	1	A → T in AAM82750. Ref.4
	Sequence conflict	889	1	I → V in BAC11160. Ref.3
	Sequence conflict	989	1	R → K in BAA90952. Ref.3
	Sequence conflict	989	1	R → K in AAM82750. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q2NKX8 [UniParc]. Last modified February 7, 2006. Version 1. Checksum: C27DB2846F07C45D	FASTA	1,250	141,103
	10 20 30 40 50 60 MEASRRFPEA EALSPEQAAH YLRYVKEAKE ATKNGDLEEA FKLFNLAKDI FPNEKVLSRI 70 80 90 100 110 120 QKIQEALEEL AEQGDDEFTD VCNSGLLLYR ELHNQLFEHQ KEGIAFLYSL YRDGRKGGIL 130 140 150 160 170 180 ADDMGLGKTV QIIAFLSGMF DASLVNHVLL IMPTNLINTW VKEFIKWTPG MRVKTFHGPS 190 200 210 220 230 240 KDERTRNLNR IQQRNGVIIT TYQMLINNWQ QLSSFRGQEF VWDYVILDEA HKIKTSSTKS 250 260 270 280 290 300 AICARAIPAS NRLLLTGTPI QNNLQELWSL FDFACQGSLL GTLKTFKMEY ENPITRAREK 310 320 330 340 350 360 DATPGEKALG FKISENLMAI IKPYFLRRTK EDVQKKKSSN PEARLNEKNP DVDAICEMPS 370 380 390 400 410 420 LSRKNDLIIW IRLVPLQEEI YRKFVSLDHI KELLMETRSP LAELGVLKKL CDHPRLLSAR 430 440 450 460 470 480 ACCLLNLGTF SAQDGNEGED SPDVDHIDQV TDDTLMEESG KMIFLMDLLK RLRDEGHQTL 490 500 510 520 530 540 VFSQSRQILN IIERLLKNRH FKTLRIDGTV THLLEREKRI NLFQQNKDYS VFLLTTQVGG 550 560 570 580 590 600 VGLTLTAATR VVIFDPSWNP ATDAQAVDRV YRIGQKENVV VYRLITCGTV EEKIYRRQVF 610 620 630 640 650 660 KDSLIRQTTG EKKNPFRYFS KQELRELFTI EDLQNSVTQL QLQSLHAAQR KSDIKLDEHI 670 680 690 700 710 720 AYLQSLGIAG ISDHDLMYTC DLSVKEELDV VEESHYIQQR VQKAQFLVEF ESQNKEFLME 730 740 750 760 770 780 QQRTRNEGAW LREPVFPSST KKKCPKLNKP QPQPSPLLST HHTQEEDISS KMASVVIDDL 790 800 810 820 830 840 PKEGEKQDLS SIKVNVTTLQ DGKGTGSADS IATLPKGFGS VEELCTNSSL GMEKSFATKN 850 860 870 880 890 900 EAVQKETLQE GPKQEALQED PLESFNYVLS KSTKADIGPN LDQLKDDEIL RHCNPWPIIS 910 920 930 940 950 960 ITNESQNAES NVSIIEIADD LSASHSALQD AQASEAKLEE EPSASSPQYA CDFNLFLEDS 970 980 990 1000 1010 1020 ADNRQNFSSQ SLEHVEKENS LCGSAPNSRA GFVHSKTCLS WEFSEKDDEP EEVVVKAKIR 1030 1040 1050 1060 1070 1080 SKARRIVSDG EDEDDSFKDT SSINPFNTSL FQFSSVKQFD ASTPKNDISP PGRFFSSQIP 1090 1100 1110 1120 1130 1140 SSVNKSMNSR RSLASRRSLI NMVLDHVEDM EERLDDSSEA KGPEDYPEEG VEESSGEASK 1150 1160 1170 1180 1190 1200 YTEEDPSGET LSSENKSSWL MTSKPSALAQ ETSLGAPEPL SGEQLVGSPQ DKAAEATNDY 1210 1220 1230 1240 1250 ETLVKRGKEL KECGKIQEAL NCLVKALDIK SADPEVMLLT LSLYKQLNNN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PICH, a centromere-associated SNF2 family ATPase, is regulated by Plk1 and required for the spindle checkpoint." Baumann C., Koerner R., Hofmann K., Nigg E.A. Cell 128:101-114(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-1063, INTERACTION WITH PLK1, MUTAGENESIS OF 127-GLY--THR-129 AND THR-1063.
[2]	"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]. Tissue: Ovary and Uterus.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 145-1250. Tissue: Colon and Teratocarcinoma.
[4]	"Cloning and identification of genes which are differentially expressed in carcinoma." Xueyuan D., Weifeng C. Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 603-1250.
[5]	"Persistence of DNA threads in human anaphase cells suggests late completion of sister chromatid decatenation." Wang L.-H., Schwarzbraun T., Speicher M.R., Nigg E.A. Chromosoma 117:123-135(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[6]	"BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges." Chan K.-L., North P.S., Hickson I.D. EMBO J. 26:3397-3409(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[7]	"Depletion of topoisomerase IIalpha leads to shortening of the metaphase interkinetochore distance and abnormal persistence of PICH-coated anaphase threads." Spence J.M., Phua H.-H., Mills W., Carpenter A.J., Porter A.C.G., Farr C.J. J. Cell Sci. 120:3952-3964(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[8]	"Use of the novel Plk1 inhibitor ZK-thiazolidinone to elucidate functions of Plk1 in early and late stages of mitosis." Santamaria A., Neef R., Eberspaecher U., Eis K., Husemann M., Mumberg D., Prechtl S., Schulze V., Siemeister G., Wortmann L., Barr F.A., Nigg E.A. Mol. Biol. Cell 18:4024-4036(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PLK1.
[9]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-755; SER-774; SER-1181 AND SER-1188, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-810; THR-813; SER-820 AND SER-1028, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1028 AND SER-1098, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-807; SER-810; SER-995 AND SER-1028, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-820; SER-1028 AND SER-1069, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	EU069463 mRNA. Translation: ABU25227.1. BC008808 mRNA. Translation: AAH08808.2. BC111486 mRNA. Translation: AAI11487.1. AK000112 mRNA. Translation: BAA90952.1. Sequence problems. AK074719 mRNA. Translation: BAC11160.1. AY121802 mRNA. Translation: AAM82750.1. Sequence problems.
IPI	IPI00552569.
RefSeq	NP_060139.2. NM_017669.2.
UniGene	Hs.47558.
3D structure databases
ProteinModelPortal	Q2NKX8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q2NKX8. 7 interactions.
STRING	9606.ENSP00000334675.
PTM databases
PhosphoSite	Q2NKX8.
Polymorphism databases
DMDM	121948339.
Proteomic databases
PaxDb	Q2NKX8.
PeptideAtlas	Q2NKX8.
PRIDE	Q2NKX8.
Protocols and materials databases
DNASU	54821.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000334463; ENSP00000334675; ENSG00000186871.
GeneID	54821.
KEGG	hsa:54821.
UCSC	uc004eap.1. human.
Organism-specific databases
CTD	54821.
GeneCards	GC0XM071424.
H-InvDB	HIX0016867.
HGNC	HGNC:20794. ERCC6L.
HPA	HPA050492.
MIM	300687. gene.
neXtProt	NX_Q2NKX8.
PharmGKB	PA162385290.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0553.
HOGENOM	HOG000074172.
HOVERGEN	HBG107854.
InParanoid	Q2NKX8.
OMA	TKNGDLE.
Enzyme and pathway databases
Reactome	REACT_115566. Cell Cycle. REACT_21300. Mitotic M-M/G1 phases.
Gene expression databases
ArrayExpress	Q2NKX8.
Bgee	Q2NKX8.
CleanEx	HS_ERCC6L.
Genevestigator	Q2NKX8.
Family and domain databases
Gene3D	1.25.40.10. 2 hits.
InterPro	IPR014001. Helicase_ATP-bd. IPR001650. Helicase_C. IPR000330. SNF2_N. IPR013026. TPR-contain_dom. IPR011990. TPR-like_helical. [Graphical view]
Pfam	PF00271. Helicase_C. 1 hit. PF00176. SNF2_N. 1 hit. [Graphical view]
SMART	SM00487. DEXDc. 1 hit. SM00490. HELICc. 1 hit. [Graphical view]
PROSITE	PS51192. HELICASE_ATP_BIND_1. 1 hit. PS51194. HELICASE_CTER. 1 hit. PS50005. TPR. False negative. PS50293. TPR_REGION. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	54821.
NextBio	57573.
SOURCE	Search...

Entry information

Entry name

ERC6L_HUMAN

Accession

Primary (citable) accession number: Q2NKX8
Secondary accession number(s): Q8NCI1, Q96H93, Q9NXQ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 8, 2008
Last sequence update:	February 7, 2006
Last modified:	May 1, 2013
This is version 78 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.