Homo sapiens L. (human) [HSA]

FULL NAME: protein artemis


DESCRIPTION:
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.
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.


STRUCTURE SIMILARITY:
Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family.


SUBUNIT STRUCTURE:
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.


CATALYTIC ACTIVITY:
5'-3' exonuclease activity single-stranded DNA specific endodeoxyribonuclease activity


POST-TRANSLATIONAL MODIFICATION:
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.


PROTEIN TYPE(S):
DNase
5'-3' exonuclease


RELATED PATHWAY(S):
non-homologous end-joining (NHEJ)


RELATED DISEASE(S):
Omenn syndrome
severe combined immunodeficiency, Athabaskan type (SCIDA)
severe combined immunodeficiency with radiation sensitivity (RS-SCID)


Amino acids sequence

        10         20         30         40         50         60
MSSFEGQMAE YPTISIDRFD RENLRARAYF LSHCHKDHMK GLRAPTLKRR LECSLKVYLY
        70         80         90        100        110        120
CSPVTKELLL TSPKYRFWKK RIISIEIETP TQISLVDEAS GEKEEIVVTL LPAGHCPGSV
       130        140        150        160        170        180
MFLFQGNNGT VLYTGDFRLA QGEAARMELL HSGGRVKDIQ SVYLDTTFCD PRFYQIPSRE
       190        200        210        220        230        240
ECLSGVLELV RSWITRSPYH VVWLNCKAAY GYEYLFTNLS EELGVQVHVN KLDMFRNMPE
       250        260        270        280        290        300
ILHHLTTDRN TQIHACRHPK AEEYFQWSKL PCGITSRNRI PLHIISIKPS TMWFGERSRK
       310        320        330        340        350        360
TNVIVRTGES SYRACFSFHS SYSEIKDFLS YLCPVNAYPN VIPVGTTMDK VVEILKPLCR
       370        380        390        400        410        420
SSQSTEPKYK PLGKLKRART VHRDSEEEDD YLFDDPLPIP LRHKVPYPET FHPEVFSMTA
       430        440        450        460        470        480
VSEKQPEKLR QTPGCCRAEC MQSSRFTNFV DCEESNSESE EEVGIPASLQ GDLGSVLHLQ
       490        500        510        520        530        540
KADGDVPQWE VFFKRNDEIT DESLENFPSS TVAGGSQSPK LFSDSDGEST HISSQNSSQS
       550        560        570        580        590        600
THITEQGSQG WDSQSDTVLL SSQERNSGDI TSLDKADYRP TIKENIPASL MEQNVICPKD
       610        620        630        640        650        660
TYSDLKSRDK DVTIVPSTGE PTTLSSETHI PEEKSLLNLS TNADSQSSSD FEVPSTPEAE
       670        680        690
LPKREHLQYL YEKLATGESI AVKKRKCSLL DT  

Encoded by DCLRE1C gene

FULL NAME: DNA cross-link repair 1C


OTHER NAME(S):
A-SCID
DCLREC1C
FLJ11360
FLJ36438
RS-SCID
SCIDA
SNM1C
hSNM1C


DESCRIPTION:
This gene encodes a nuclear protein that is involved in V(D)J recombination and DNA repair. The protein has single-strand-specific 5'-3' exonuclease activity; it also exhibits endonuclease activity on 5' and 3' overhangs and hairpins when complexed with protein kinase, DNA-activated, catalytic polypeptide. Mutations in this gene cause Athabascan-type severe combined immunodeficiency (SCIDA). [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atgagttctt tcgaggggca gatggccgag tatccaacta tctccataga ccgcttcgat
        70         80         90        100        110        120
agggagaacc tgagggcccg cgcctacttc ctgtcccact gccacaaaga tcacatgaaa
       130        140        150        160        170        180
ggattaagag cccctacctt gaaaagaagg ttggagtgca gcttgaaggt ttatctatac
       190        200        210        220        230        240
tgttcacctg tgactaagga gttgttgtta acgagcccga aatacagatt ttggaagaaa
       250        260        270        280        290        300
cgaattatat ctattgaaat cgagactcct acccagatat ctttagtgga tgaagcatca
       310        320        330        340        350        360
ggagagaagg aagagattgt tgtgactctc ttaccagctg gtcactgtcc gggatcagtt
       370        380        390        400        410        420
atgtttttat ttcagggcaa taatggaact gtcctgtaca caggagactt cagattggcg
       430        440        450        460        470        480
caaggagaag ctgctagaat ggagcttctg cactccgggg gcagagtcaa agacatccaa
       490        500        510        520        530        540
agtgtatatt tggatactac gttctgtgat ccaagatttt accaaattcc aagtcgggag
       550        560        570        580        590        600
gagtgtttaa gtggagtctt agagctggtc cgaagctgga tcactcggag cccgtaccat
       610        620        630        640        650        660
gttgtgtggc tgaactgcaa agcggcttat ggctatgaat atctgttcac caaccttagt
       670        680        690        700        710        720
gaagaattag gagtccaggt tcatgtgaat aagctagaca tgtttaggaa catgcctgag
       730        740        750        760        770        780
atccttcatc atctcacaac agaccgcaac actcagatcc atgcatgccg gcatcccaag
       790        800        810        820        830        840
gcagaggaat attttcagtg gagcaaatta ccctgtggaa ttacttccag aaatagaatt
       850        860        870        880        890        900
ccactccaca taatcagcat taagccatcc accatgtggt ttggagaaag gagcagaaaa
       910        920        930        940        950        960
acaaatgtaa ttgtgaggac tggagagagt tcatacagag cttgtttttc ttttcactcc
       970        980        990       1000       1010       1020
tcctacagtg agattaaaga tttcttgagc tacctctgtc ctgtgaacgc atatccaaat
      1030       1040       1050       1060       1070       1080
gtcattccag ttggcacaac tatggataaa gttgtcgaaa tcttaaagcc tttatgccgg
      1090       1100       1110       1120       1130       1140
tcttcccaaa gtacggagcc aaagtataaa ccactgggaa aactgaagag agctagaaca
      1150       1160       1170       1180       1190       1200
gttcaccgag actcagagga ggaagatgac tatctctttg atgatcctct gccaatacct
      1210       1220       1230       1240       1250       1260
ttaaggcaca aagttccata cccggaaact tttcaccctg aggtattttc aatgactgca
      1270       1280       1290       1300       1310       1320
gtatcagaaa agcagcctga aaaactgaga caaaccccag gatgctgcag agcagagtgt
      1330       1340       1350       1360       1370       1380
atgcagagct ctcgtttcac aaactttgta gattgtgaag aatccaacag tgaaagtgaa
      1390       1400       1410       1420       1430       1440
gaagaagtag gaatcccagc ttcactgcaa ggagatctgg gctctgtact tcacctgcaa
      1450       1460       1470       1480       1490       1500
aaggctgatg gggatgtacc ccagtgggaa gtattcttta aaagaaatga tgaaatcaca
      1510       1520       1530       1540       1550       1560
gatgagagtt tggaaaactt cccttcctcc acagtggcag ggggatctca gtcaccaaag
      1570       1580       1590       1600       1610       1620
cttttcagtg actctgatgg agaatcaact cacatctcct cccagaattc ttcccagtca
      1630       1640       1650       1660       1670       1680
acacacataa cagaacaagg aagtcaaggc tgggacagcc aatctgatac tgttttgtta
      1690       1700       1710       1720       1730       1740
tcttcccaag agagaaacag tggggatatt acttccttgg acaaagctga ctacagacca
      1750       1760       1770       1780       1790       1800
acaatcaaag agaatattcc tgcctctctc atggaacaaa atgtaatttg cccaaaggat
      1810       1820       1830       1840       1850       1860
acttactctg atttgaaaag cagagataaa gatgtgacaa tagttcctag tactggagaa
      1870       1880       1890       1900       1910       1920
ccaactactc taagcagtga gacacatata cccgaggaaa aaagtttgct aaatcttagc
      1930       1940       1950       1960       1970       1980
acaaatgcag attcccagag ctcttctgat tttgaagttc cctcaactcc agaagctgag
      1990       2000       2010       2020       2030       2040
ttacctaaac gagagcattt acaatattta tatgagaagc tggcaactgg tgagagtata
      2050       2060       2070
gcagtcaaaa aaagaaaatg ctcactctta gatacctaa  

Last modification date: Feb. 4, 2012