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DCLRE1C (Artemis) |
Protein FULL name:
Protein Artemis, DNA cross-link repair 1C protein, SNM1 homolog C, SNM1-like protein, Protein A-SCID.,
Protein SHORT name:
hSNM1C
DCLRE1C (Artemis) (Homo sapiens) is product of expression of DCLRE1C gene.
Human diseases related to this protein:
DCLRE1C (Artemis) is involved in:
NHEJ in Homo sapiens
Keywords:
FUNCTION: Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends. These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively. This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC. The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint. May also be required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ.
SUBUNIT: Interacts with ATM, BRCA1, PRKDC and TP53BP1. Also exhibits ATM- and phosphorylation-dependent interaction with the MRN complex, composed of MRE11A/MRE11, RAD50, and NBN.
SUBCELLULAR LOCATION: Nucleus.
TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in the kidney, lung, pancreas and placenta (at the mRNA level). Expression is not increased in thymus or bone marrow, sites of V(D)J recombination.
PTM: Phosphorylation on undefined residues by PRKDC may stimulate endonucleolytic activity on 5' and 3' hairpins and overhangs. PRKDC must remain present, even after phosphorylation, for efficient hairpin opening. Also phosphorylated by ATM in response to ionizing radiation (IR) and by ATR in response to ultraviolet (UV) radiation.
DISEASE: Defects in DCLRE1C are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell- negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:602450]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T- cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity.
DISEASE: Defects in DCLRE1C are the cause of severe combined immunodeficiency Athabaskan type (SCIDA) [MIM:602450]. SCIDA is a variety of RS-SCID caused by a founder mutation in Athabascan- speaking native Americans, being inherited as an autosomal recessive trait with an estimated gene frequency of 2.1% in the Navajo population. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID.
DISEASE: Defects in DCLRE1C are a cause of Omenn syndrome (OS) [MIM:603554]. OS is characterized by severe combined immunodeficiency associated with erythrodermia, hepatosplenomegaly, lymphadenopathy and alopecia. Affected individuals have elevated T-lymphocyte counts with a restricted T- cell receptor (TCR) repertoire. They also generally lack B- lymphocytes, but have normal natural killer (NK) cell function (T+ B- NK+).
SIMILARITY: Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family.
SEQUENCE CAUTION: Sequence=CAI40018.1; Type=Erroneous gene model prediction; Sequence=CAI40019.1; Type=Erroneous gene model prediction; Sequence=CAI40021.1; Type=Erroneous gene model prediction; Sequence=CAI40023.1; Type=Erroneous gene model prediction;
WEB RESOURCE: Name=DCLRE1Cbase; Note=DCLRE1C mutation db; [LINK]
WEB RESOURCE: Name=GeneReviews; [LINK]
WEB RESOURCE: Name=NIEHS-SNPs; [LINK]
| NCBI GenPept GI number(s): |
71153325 76496495 |
| Species: | Homo sapiens |
Links to other databases:
| Database | ID | Link |
| Uniprot | Q96SD1 |
Q96SD1 |
| PFAM: |
PF07522 |
PF07522 |
| InterPro: |
IPR001279 IPR011084 |
IPR001279 IPR011084 |
| CATH: | - | - |
| SCOP: | - | - |
| PDB: | - | - |
Protein sequence:
|
MSSFEGQMAEYPTISIDRFDRENLRARAYFLSHCHKDHMKGLRAPTLKRR LECSLKVYLYCSPVTKELLLTSPKYRFWKKRIISIEIETPTQISLVDEAS GEKEEIVVTLLPAGHCPGSVMFLFQGNNGTVLYTGDFRLAQGEAARMELL HSGGRVKDIQSVYLDTTFCDPRFYQIPSREECLSGVLELVRSWITRSPYH VVWLNCKAAYGYEYLFTNLSEELGVQVHVNKLDMFRNMPEILHHLTTDRN TQIHACRHPKAEEYFQWSKLPCGITSRNRIPLHIISIKPSTMWFGERSRK TNVIVRTGESSYRACFSFHSSYSEIKDFLSYLCPVNAYPNVIPVGTTMDK VVEILKPLCRSSQSTEPKYKPLGKLKRARTVHRDSEEEDDYLFDDPLPIP LRHKVPYPETFHPEVFSMTAVSEKQPEKLRQTPGCCRAECMQSSRFTNFV DCEESNSESEEEVGIPASLQGDLGSVLHLQKADGDVPQWEVFFKRNDEIT DESLENFPSSTVAGGSQSPKLFSDSDGESTHISSQNSSQSTHITEQGSQG WDSQSDTVLLSSQERNSGDITSLDKADYRPTIKENIPASLMEQNVICPKD TYSDLKSRDKDVTIVPSTGEPTTLSSETHIPEEKSLLNLSTNADSQSSSD FEVPSTPEAELPKREHLQYLYEKLATGESIAVKKRKCSLLDT |
DCLRE1C (Artemis) (Homo sapiens) belongs to following protein families:
References:
| Title | Authors | Journal |
| Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. | Moshous D, Callebaut I, de Chasseval R, Corneo B, Cavazzana-Calvo M, Le Deist F, Tezcan I, Sanal O, Bertrand Y, Philippe N, Fischer A, de Villartay JP | Cell April 20, 2001 |
| Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination. | Ma Y, Pannicke U, Schwarz K, Lieber MR | Cell March 22, 2002 |
| A founder mutation in Artemis, an SNM1-like protein, causes SCID in Athabascan-speaking Native Americans. | Li L, Moshous D, Zhou Y, Wang J, Xie G, Salido E, Hu D, de Villartay JP, Cowan MJ | J Immunol June 15, 2002 |
| Metallo-beta-lactamase fold within nucleic acids processing enzymes: the beta-CASP family. | Callebaut I, Moshous D, Mornon JP, de Villartay JP | Nucleic Acids Res Aug. 15, 2002 |
| Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis. | Moshous D, Pannetier C, Chasseval Rd R, Deist Fl F, Cavazzana-Calvo M, Romana S, Macintyre E, Canioni D, Brousse N, Fischer A, Casanova JL, Villartay JP | J Clin Invest Jan. 1, 2003 |
| Radiosensitive SCID patients with Artemis gene mutations show a complete B-cell differentiation arrest at the pre-B-cell receptor checkpoint in bone marrow. | Noordzij JG, Verkaik NS, van der Burg M, van Veelen LR, de Bruin-Versteeg S, Wiegant W, Vossen JM, Weemaes CM, de Groot R, Zdzienicka MZ, van Gent DC, van Dongen JJ | Blood Jan. 15, 2003 |
| Novel Artemis gene mutations of radiosensitive severe combined immunodeficiency in Japanese families. | Kobayashi N, Agematsu K, Sugita K, Sako M, Nonoyama S, Yachie A, Kumaki S, Tsuchiya S, Ochs HD, Sugita K, Fukushima Y, Komiyama A | Hum Genet April 1, 2003 |
| Expansion of clonotype-restricted HLA-identical maternal CD4+ T cells in a patient with severe combined immunodeficiency and a homozygous mutation in the Artemis gene. | Kobayashi N, Agematsu K, Nagumo H, Yasui K, Katsuyama Y, Yoshizawa K, Ota M, Yachie A, Komiyama A | Clin Immunol Aug. 1, 2003 |
| The metallo-beta-lactamase/beta-CASP domain of Artemis constitutes the catalytic core for V(D)J recombination. | Poinsignon C, Moshous D, Callebaut I, de Chasseval R, Villey I, de Villartay JP | J Exp Med Jan. 2, 2004 |
| 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 TO, 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 Feb. 1, 2004 |
| Functional and biochemical dissection of the structure-specific nuclease ARTEMIS. | Pannicke U, Ma Y, Hopfner KP, Niewolik D, Lieber MR, Schwarz K | EMBO J May 5, 2004 |
| The DNA sequence and comparative analysis of human chromosome 10. | Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J | Nature May 27, 2004 |
| The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). | Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J | Genome Res Oct. 1, 2004 |
| Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response. | Zhang X, Succi J, Feng Z, Prithivirajsingh S, Story MD, Legerski RJ | Mol Cell Biol Oct. 1, 2004 |
| Phosphorylation of Artemis following irradiation-induced DNA damage. | Poinsignon C, de Chasseval R, Soubeyrand S, Moshous D, Fischer A, Hache RJ, de Villartay JP | Eur J Immunol Nov. 1, 2004 |
| A biochemically defined system for mammalian nonhomologous DNA end joining. | Ma Y, Lu H, Tippin B, Goodman MF, Shimazaki N, Koiwai O, Hsieh CL, Schwarz K, Lieber MR | Mol Cell Dec. 3, 2004 |
| A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci. | Riballo E, Kuhne M, Rief N, Doherty A, Smith GC, Recio MJ, Reis C, Dahm K, Fricke A, Krempler A, Parker AR, Jackson SP, Gennery A, Jeggo PA, Lobrich M | Mol Cell Dec. 3, 2004 |
| Ataxia-telangiectasia-mutated dependent phosphorylation of Artemis in response to DNA damage. | Chen L, Morio T, Minegishi Y, Nakada S, Nagasawa M, Komatsu K, Chessa L, Villa A, Lecis D, Delia D, Mizutani S | Cancer Sci Jan. 1, 2005 |
| Artemis deficiency confers a DNA double-strand break repair defect and Artemis phosphorylation status is altered by DNA damage and cell cycle progression. | Wang J, Pluth JM, Cooper PK, Cowan MJ, Chen DJ, Yannone SM | DNA Repair (Amst) May 2, 2005 |
| Omenn syndrome due to ARTEMIS mutations. | Ege M, Ma Y, Manfras B, Kalwak K, Lu H, Lieber MR, Schwarz K, Pannicke U | Blood June 1, 2005 |
| The Artemis:DNA-PKcs endonuclease cleaves DNA loops, flaps, and gaps. | Ma Y, Schwarz K, Lieber MR | DNA Repair (Amst) July 12, 2005 |
Last modification of this entry: Oct. 11, 2010.
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