Description:
ATP-dependent DNA helicase 2 subunit 2 (EC 3.6.1.-) (ATP-dependent DNAhelicase II 80 kDa subunit) (Lupus Ku autoantigen protein p86) (Ku86)(Ku80) (86 kDa subunit of Ku antigen) (Thyroid-lupus autoantigen)(TLAA) (CTC box-binding factor 85 kDa subunit) (CTCBF) (CTC85)(Nuclear factor IV) (DNA-repair protein XRCC5).
Molecular weight: 82573
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 ) double-strand break repair( GO:0006302 ) double-strand break repair via nonhomologous end-joining( GO:0006303 )
Important dates:
01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
01-FEB-1995, sequence version 2.
07-MAR-2006, entry version 70.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein KU86_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | J04977 | AAA59475.1 | - |
| EMBL | M30938 | AAA36154.1 | - |
| EMBL | BC019027 | AAH19027.1 | - |
| EMBL | X57500 | CAA40736.1 | - |
| PIR | A35051 | A32626. | |
| PDB | 1JEQ | X-ray | B=1-564. |
| PDB | 1JEY | X-ray | B=1-564. |
| PDB | 1Q2Z | NMR | A=589-708. |
| PDB | 1RW2 | NMR | A=565-709. |
| IntAct | P13010 | -.1 | |
| TRANSFAC | T05111 | -. | |
| SWISS-2DPAGE | P13010 | HUMAN. | |
| Ensembl | ENSG00000079246 | Homo sapiens.1 | |
| HGNC | HGNC:12833 | XRCC5.1 | |
| MIM | 194364 | gene. | |
| Reactome | P13010 | -.1 | |
| GO | GO:0005634 | C:nucleus | TAS. |
| GO | GO:0004003 | F:ATP-dependent DNA helicase activity | TAS. |
| GO | GO:0003690 | F:double-stranded DNA binding | TAS. |
| GO | GO:0005515 | F:protein binding | IPI. |
| GO | GO:0006310 | P:DNA recombination | TAS. |
| GO | GO:0006302 | P:double-strand break repair | TAS. |
| InterPro | IPR006164 | Ku. | |
| InterPro | IPR011210 | Ku80. | |
| InterPro | IPR005160 | Ku_C. | |
| InterPro | IPR005161 | Ku_N. | |
| InterPro | IPR002035 | VWF_A. | |
| Pfam | PF02735 | Ku | 1. |
| Pfam | PF03730 | Ku_C | 1. |
| Pfam | PF03731 | Ku_N | 1. |
| PIRSF | PIRSF016570 | Ku80 | 1. |
| SMART | SM00559 | Ku78 | 1. |
| SMART | SM00327 | VWA | 1. |
Keywords:
3D-structure; ATP-binding; Direct protein sequencing; DNA damage; DNA recombination; DNA repair; DNA-binding; Helicase; Hydrolase; Nuclear protein; Nucleotide-binding; Phosphorylation; Polymorphism; Systemic lupus erythematosus.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 3-21.
RX MEDLINE=89340410; PubMed=2760028;
RA Yaneva M., Wen J., Ayala A., Cook R.;
RT "cDNA-derived amino acid sequence of the 86-kDa subunit of the Ku
RT antigen.";
RL J. Biol. Chem. 264:13407-13411(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX MEDLINE=90175380; PubMed=2308937;
RA Mimori T., Ohosone Y., Hama N., Suwa A., Akizuki M., Homma M.,
RA Griffith A.J., Hardin J.A.;
RT "Isolation and characterization of cDNA encoding the 80-kDa subunit
RT protein of the human autoantigen Ku (p70/p80) recognized by
RT autoantibodies from patients with scleroderma-polymyositis overlap
RT syndrome.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:1777-1781(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 104-731, AND PARTIAL PROTEIN SEQUENCE.
RX MEDLINE=91011245; PubMed=2212941; DOI=10.1084/jem.172.4.1049;
RA Stuiver M.H., Coenjaerts F.E.J., van der Vlied P.C.;
RT "The autoantigen Ku is indistinguishable from NF IV, a protein forming
RT multimeric protein-DNA complexes.";
RL J. Exp. Med. 172:1049-1054(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-21.
RX MEDLINE=91009259; PubMed=2211668;
RA Knuth M.W., Gunderson S.I., Thompson N.E., Strasheim L.A.,
RA Burgess R.R.;
RT "Purification and characterization of proximal sequence element-
RT binding protein 1, a transcription activating protein related to Ku
RT and TREF that binds the proximal sequence element of the human U1
RT promoter.";
RL J. Biol. Chem. 265:17911-17920(1990).
RN [6]
RP PARTIAL PROTEIN SEQUENCE OF 1-19, AND FUNCTION.
RX MEDLINE=95045391; PubMed=7957065;
RA Tuteja N., Tuteja R., Ochem A., Taneja P., Huang N.W., Simoncsits A.,
RA Susic S., Rahman K., Marusic L., Chen J., Zhang J., Wang S.,
RA Pongor S., Falaschi A.;
RT "Human DNA helicase II: a novel DNA unwinding enzyme identified as the
RT Ku autoantigen.";
RL EMBO J. 13:4991-5001(1994).
RN [7]
RP PROTEIN SEQUENCE OF 185-192; 316-325; 544-558 AND 655-660.
RX MEDLINE=94304871; PubMed=8031790;
RA Cao Q.P., Pitt S., Leszyk J., Baril E.F.;
RT "DNA-dependent ATPase from HeLa cells is related to human Ku
RT autoantigen.";
RL Biochemistry 33:8548-8557(1994).
RN [8]
RP PROTEIN SEQUENCE OF 533-541.
RX MEDLINE=95188883; PubMed=7882982;
RA Genersch E., Eckerskorn C., Lottspeich F., Herzog C., Kuehn K.,
RA Poeschl E.;
RT "Purification of the sequence-specific transcription factor CTCBF,
RT involved in the control of human collagen IV genes: subunits with
RT homology to Ku antigen.";
RL EMBO J. 14:791-800(1995).
RN [9]
RP PROTEIN SEQUENCE OF 526-565.
RX MEDLINE=92165807; PubMed=1537839;
RA Wedrychowski A., Henzel W., Huston L., Paslidis N., Ellerson D.,
RA McRae M., Seong D., Howard O.M.Z., Deisseroth A.;
RT "Identification of proteins binding to interferon-inducible
RT transcriptional enhancers in hematopoietic cells.";
RL J. Biol. Chem. 267:4533-4540(1992).
RN [10]
RP PHOSPHORYLATION SITES SER-576; SER-578; SER-579 AND THR-714.
RX PubMed=10026262; DOI=10.1021/bi982584b;
RA Chan D.W., Ye R., Veillette C.J., Lees-Miller S.P.;
RT "DNA-dependent protein kinase phosphorylation sites in Ku 70/80
RT heterodimer.";
RL Biochemistry 38:1819-1828(1999).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTIONS WITH
RP NARG1; MSX2 AND RUNX2.
RC TISSUE=Heart, and Osteoblast;
RX MEDLINE=22241900; PubMed=12145306; DOI=10.1074/jbc.M206482200;
RA Willis D.M., Loewy A.P., Charlton-Kachigian N., Shao J.-S.,
RA Ornitz D.M., Towler D.A.;
RT "Regulation of osteocalcin gene expression by a novel Ku antigen
RT transcription factor complex.";
RL J. Biol. Chem. 277:37280-37291(2002).
RN [12]
RP DOMAIN, AND MUTAGENESIS OF 719-GLU-GLU-720 AND 725-ASP-ASP-726.
RX PubMed=15758953; DOI=10.1038/nature03442;
RA Falck J., Coates J., Jackson S.P.;
RT "Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of
RT DNA damage.";
RL Nature 434:605-611(2005).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 6-564 IN COMPLEX WITH G22P1.
RX MEDLINE=21385640; PubMed=11493912; DOI=10.1038/35088000;
RA Walker J.R., Corpina R.A., Goldberg J.;
RT "Structure of the Ku heterodimer bound to DNA and its implications for
RT double-strand break repair.";
RL Nature 412:607-614(2001).
Feature:
INIT_MET 0 0
CHAIN 1 731 ATP-dependent DNA helicase 2 subunit 2.
/FTId=PRO_0000084340.
DOMAIN 137 164 Leucine-zipper.
MOTIF 719 727 EEXXXDL motif.
COMPBIAS 477 518 Pro-rich.
MOD_RES 576 576 Phosphoserine (by PRKDC).
MOD_RES 578 578 Phosphoserine (by PRKDC) (Probable).
MOD_RES 579 579 Phosphoserine (by PRKDC).
MOD_RES 714 714 Phosphothreonine (by PRKDC) (Probable).
VARIANT 462 462 L -> F (in dbSNP:1805380).
/FTId=VAR_014724.
MUTAGEN 719 720 EE->AA: Abolishes interaction with PRKDC
and its recruitment to sites of DNA
damage.
MUTAGEN 725 726 DD->AA: Abolishes interaction with PRKDC
and its recruitment to sites of DNA
damage.
CONFLICT 314 314 R -> L (in Ref. 4).
STRAND 7 14
HELIX 17 20
STRAND 23 23
TURN 24 25
STRAND 26 26
HELIX 29 46
TURN 47 48
STRAND 52 59
STRAND 61 62
STRAND 64 65
TURN 66 67
TURN 69 71
STRAND 73 73
TURN 74 75
STRAND 76 83
HELIX 87 94
TURN 95 96
STRAND 101 102
HELIX 106 120
STRAND 121 124
STRAND 127 134
STRAND 139 139
TURN 144 145
HELIX 146 155
TURN 156 157
STRAND 158 166
TURN 184 185
STRAND 187 188
TURN 193 195
STRAND 196 196
HELIX 198 215
HELIX 217 222
STRAND 223 225
HELIX 226 229
TURN 230 231
STRAND 232 233
TURN 234 236
HELIX 237 239
STRAND 246 252
TURN 253 255
STRAND 256 266
STRAND 276 279
TURN 280 282
STRAND 285 285
TURN 286 287
STRAND 288 300
STRAND 303 304
HELIX 306 308
STRAND 309 315
TURN 316 317
STRAND 318 321
HELIX 324 330
STRAND 331 331
STRAND 337 346
HELIX 347 349
STRAND 350 350
HELIX 352 354
STRAND 356 365
TURN 367 368
HELIX 370 385
TURN 386 387
STRAND 388 400
STRAND 403 411
STRAND 413 414
STRAND 416 422
HELIX 426 428
STRAND 429 429
STRAND 437 437
TURN 438 439
STRAND 441 443
HELIX 447 459
TURN 460 460
STRAND 461 461
STRAND 463 464
TURN 467 468
STRAND 469 470
STRAND 473 475
HELIX 478 480
STRAND 481 481
HELIX 484 498
TURN 500 501
STRAND 502 502
HELIX 509 515
STRAND 516 516
HELIX 519 535
STRAND 536 536
STRAND 539 540
STRAND 567 567
STRAND 572 572
STRAND 577 577
STRAND 580 585
STRAND 587 591
HELIX 593 600
TURN 601 601
STRAND 602 604
TURN 607 609
HELIX 610 625
HELIX 628 648
STRAND 649 649
HELIX 651 666
TURN 667 668
STRAND 669 669
TURN 670 671
HELIX 672 679
TURN 680 681
STRAND 684 684
STRAND 687 687
TURN 688 689
STRAND 690 692
HELIX 697 700
TURN 701 703
STRAND 704 704
STRAND 706 706
Comments:
-!- FUNCTION: Single stranded DNA-dependent ATP-dependent helicase.
Has a role in chromosome translocation. The DNA helicase II
complex binds preferentially to fork-like ends of double-stranded
DNA in a cell cycle-dependent manner. It works in the 3'-5'
direction. Binding to DNA may be mediated by p70. Involved in DNA
nonhomologous end joining (NHEJ) required for double-strand break
repair and V(D)J recombination. The Ku p70/p86 dimer acts as
regulatory subunit of the DNA-dependent protein kinase complex
DNA-PK by increasing the affinity of the catalytic subunit PRKDC
to DNA by 100-fold. The Ku p70/p86 dimer is probably involved in
stabilizing broken DNA ends and bringing them together. The
assembly of the DNA-PK complex to DNA ends is required for the
NHEJ ligation step. In association with NARG1, the Ku p70/p86
dimer binds to the osteocalcin promoter and activates osteocalcin
expression.
-!- SUBUNIT: Heterodimer of a 70 kDa and a 80 kDa subunit. The dimer
associates in a DNA-dependent manner with PRKDC to form the DNA-
dependent protein kinase complex DNA-PK, and with the LIG4-XRCC4
complex. The dimer also associates with NARG1, and this complex
displays DNA binding activity towards the osteocalcin FGF response
element (OCFRE). In addition, the 80 kDa subunit binds to the
osteoblast-specific transcription factors MSX2 and RUNX2.
-!- INTERACTION:
P12956:G22P1; NbExp=1; IntAct=EBI-357997, EBI-353208;
-!- SUBCELLULAR LOCATION: Nucleus.
-!- INDUCTION: In osteoblasts, by FGF2.
-!- DOMAIN: The EEXXXDDL motif is required for the interaction with
catalytic subunit PRKDC and its recruitment to sites of DNA
damage.
-!- PTM: Phosphorylated on serine residues. Phosphorylation by PRKDC
may enhance helicase activity.
-!- DISEASE: Individuals with systemic lupus erythematosus (SLE) and
related disorders produce extremely large amounts of
autoantibodies to p70 and p86.
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Sequence length: 731
VRSGNKAAVV LCMDVGFTMS NSIPGIESPF EQAKKVITMF VQRQVFAENK DEIALVLFGT
DGTDNPLSGG DQYQNITVHR HLMLPDFDLL EDIESKIQPG SQQADFLDAL IVSMDVIQHE
TIGKKFEKRH IEIFTDLSSR FSKSQLDIII HSLKKCDISL QFFLPFSLGK EDGSGDRGDG
PFRLGGHGPS FPLKGITEQQ KEGLEIVKMV MISLEGEDGL DEIYSFSESL RKLCVFKKIE
RHSIHWPCRL TIGSNLSIRI AAYKSILQER VKKTWTVVDA KTLKKEDIQK ETVYCLNDDD
ETEVLKEDII QGFRYGSDIV PFSKVDEEQM KYKSEGKCFS VLGFCKSSQV QRRFFMGNQV
LKVFAARDDE AAAVALSSLI HALDDLDMVA IVRYAYDKRA NPQVGVAFPH IKHNYECLVY
VQLPFMEDLR QYMFSSLKNS KKYAPTEAQL NAVDALIDSM SLAKKDEKTD TLEDLFPTTK
IPNPRFQRLF QCLLHRALHP REPLPPIQQH IWNMLNPPAE VTTKSQIPLS KIKTLFPLIE
AKKKDQVTAQ EIFQDNHEDG PTAKKLKTEQ GGAHFSVSSL AEGSVTSVGS VNPAENFRVL
VKQKKASFEE ASNQLINHIE QFLDTNETPY FMKSIDCIRA FREEAIKFSE EQRFNNFLKA
LQEKVEIKQL NHFWEIVVQD GITLITKEEA SGSSVTAEEA KKFLAPKDKP SGDTAAVFEE
GGDVDDLLDM I