Homo sapiens L. (human) [HSA]

FULL NAME: DNA polymerase subunit gamma-1


DESCRIPTION:
Involved in the replication of mitochondrial DNA. Associates with mitochondrial DNA.
Human pol γ is isolated from mitochondria as a complex containing two subunits, a catalytic subunit, pol γA,(139 kDa)encoded by POLG at chromosomal locus 15q25 and an accessory subunit, pol γB,(53 kDa)encoded by POLG2 at chromosomal locus 17q24.1.The catalytic subunit is a family A DNA polymerase with separate polymerase and 3′-5′ exonuclease domains. Mutations in the catalytic subunit of human pol γ cause mitochondrial disorders.The accessory subunit is a 55 kDa protein (p55)and is required for tight DNA binding and processive DNA synthesis.
The first POLG disease mutations identified in 2001 were associated with progressive external ophthalmoplegia (PEO). Subsequently, mutations in POLG were identified in patients with Alpers syndrome and other infantile hepatocerebral syndromes, ataxia–neuropathy syndromes, Charcot–Marie–Tooth disease, idiopathic parkinsonism, nucleoside reverse-transcriptase inhibitor (NRTI) toxicity, among others. These diseases are characterized by mtDNA deletions or depletion in symptomatic tissues. Approximately 150 disease mutations in POLG have been identified to date.


MISCELLANEOUS:
The structure of Pol gamma seems to be variable, ranging from a single catalytic subunit in yeast to a heterodimer in Drosophila and a heterotrimer in mammals.


STRUCTURE SIMILARITY:
Belongs to the DNA polymerase type-A family.


CATALYTIC ACTIVITY:
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).


PROTEIN TYPE(S):
A-family DNA polymerase


RELATED PATHWAY(S):
DNA replication


RELATED DISEASE(S):
Leigh syndrome (LS)
progressive external ophthalmoplegia, autosomal dominant 1 (PEOA1)
progressive external ophthalmoplegia, autosomal recessive (PEOB)
mitochondrial recessive ataxia syndrome (includes SANDO and SCAE)
mitochondrial DNA depletion syndrome 4A (Alpers type) MTDPS4A
mitochondrial DNA depletion syndrome 4B (MNGIE type) MTDPS4B


RELATED DAMAGE:
5'-dRP termini


Amino acids sequence

        10         20         30         40         50         60
MSRLLWRKVA GATVGPGPVP APGRWVSSSV PASDPSDGQR RRQQQQQQQQ QQQQQPQQPQ
        70         80         90        100        110        120
VLSSEGGQLR HNPLDIQMLS RGLHEQIFGQ GGEMPGEAAV RRSVEHLQKH GLWGQPAVPL
       130        140        150        160        170        180
PDVELRLPPL YGDNLDQHFR LLAQKQSLPY LEAANLLLQA QLPPKPPAWA WAEGWTRYGP
       190        200        210        220        230        240
EGEAVPVAIP EERALVFDVE VCLAEGTCPT LAVAISPSAW YSWCSQRLVE ERYSWTSQLS
       250        260        270        280        290        300
PADLIPLEVP TGASSPTQRD WQEQLVVGHN VSFDRAHIRE QYLIQGSRMR FLDTMSMHMA
       310        320        330        340        350        360
ISGLSSFQRS LWIAAKQGKH KVQPPTKQGQ KSQRKARRGP AISSWDWLDI SSVNSLAEVH
       370        380        390        400        410        420
RLYVGGPPLE KEPRELFVKG TMKDIRENFQ DLMQYCAQDV WATHEVFQQQ LPLFLERCPH
       430        440        450        460        470        480
PVTLAGMLEM GVSYLPVNQN WERYLAEAQG TYEELQREMK KSLMDLANDA CQLLSGERYK
       490        500        510        520        530        540
EDPWLWDLEW DLQEFKQKKA KKVKKEPATA SKLPIEGAGA PGDPMDQEDL GPCSEEEEFQ
       550        560        570        580        590        600
QDVMARACLQ KLKGTTELLP KRPQHLPGHP GWYRKLCPRL DDPAWTPGPS LLSLQMRVTP
       610        620        630        640        650        660
KLMALTWDGF PLHYSERHGW GYLVPGRRDN LAKLPTGTTL ESAGVVCPYR AIESLYRKHC
       670        680        690        700        710        720
LEQGKQQLMP QEAGLAEEFL LTDNSAIWQT VEELDYLEVE AEAKMENLRA AVPGQPLALT
       730        740        750        760        770        780
ARGGPKDTQP SYHHGNGPYN DVDIPGCWFF KLPHKDGNSC NVGSPFAKDF LPKMEDGTLQ
       790        800        810        820        830        840
AGPGGASGPR ALEINKMISF WRNAHKRISS QMVVWLPRSA LPRAVIRHPD YDEEGLYGAI
       850        860        870        880        890        900
LPQVVTAGTI TRRAVEPTWL TASNARPDRV GSELKAMVQA PPGYTLVGAD VDSQELWIAA
       910        920        930        940        950        960
VLGDAHFAGM HGCTAFGWMT LQGRKSRGTD LHSKTATTVG ISREHAKIFN YGRIYGAGQP
       970        980        990       1000       1010       1020
FAERLLMQFN HRLTQQEAAE KAQQMYAATK GLRWYRLSDE GEWLVRELNL PVDRTEGGWI
      1030       1040       1050       1060       1070       1080
SLQDLRKVQR ETARKSQWKK WEVVAERAWK GGTESEMFNK LESIATSDIP RTPVLGCCIS
      1090       1100       1110       1120       1130       1140
RALEPSAVQE EFMTSRVNWV VQSSAVDYLH LMLVAMKWLF EEFAIDGRFC ISIHDEVRYL
      1150       1160       1170       1180       1190       1200
VREEDRYRAA LALQITNLLT RCMFAYKLGL NDLPQSVAFF SAVDIDRCLR KEVTMDCKTP
      1210       1220       1230
SNPTGMERRY GIPQGEALDI YQIIELTKGS LEKRSQPGP  

Encoded by POLG gene

FULL NAME: polymerase (DNA directed), gamma


OTHER NAME(S):
FLJ27114
MDP1
MIRAS
MTDPS4A
MTDPS4B
PEO
POLG1
POLGA
SANDO
SCAE


DESCRIPTION:
Mitochondrial DNA polymerase is heterotrimeric, consisting of a homodimer of accessory subunits plus a catalytic subunit. The protein encoded by this gene is the catalytic subunit of mitochondrial DNA polymerase. The encoded protein contains a polyglutamine tract near its N-terminus that may be polymorphic. Defects in this gene are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atgagccgcc tgctctggag gaaggtggcc ggcgccaccg tcgggccagg gccggttcca
        70         80         90        100        110        120
gctccggggc gctgggtctc cagctccgtc cccgcgtccg accccagcga cgggcagcgg
       130        140        150        160        170        180
cggcggcagc agcagcagca gcagcagcag cagcagcaac agcagcctca gcagccgcaa
       190        200        210        220        230        240
gtgctatcct cggagggcgg gcagctgcgg cacaacccat tggacatcca gatgctctcg
       250        260        270        280        290        300
agagggctgc acgagcaaat cttcgggcaa ggaggggaga tgcctggcga ggccgcggtg
       310        320        330        340        350        360
cgccgcagcg tcgagcacct gcagaagcac gggctctggg ggcagccagc cgtgcccttg
       370        380        390        400        410        420
cccgacgtgg agctgcgcct gccgcccctc tacggggaca acctggacca gcacttccgc
       430        440        450        460        470        480
ctcctggccc agaagcagag cctgccctac ctggaggcgg ccaacttgct gttgcaggcc
       490        500        510        520        530        540
cagctgcccc cgaagccccc ggcttgggcc tgggcggagg gctggacccg gtacggcccc
       550        560        570        580        590        600
gagggggagg ccgtacccgt ggccatcccc gaggagcggg ccctggtgtt cgacgtggag
       610        620        630        640        650        660
gtctgcttgg cagagggaac ttgccccaca ttggcggtgg ccatatcccc ctcggcctgg
       670        680        690        700        710        720
tattcctggt gcagccagcg gctggtggaa gagcgttact cttggaccag ccagctgtcg
       730        740        750        760        770        780
ccggctgacc tcatccccct ggaggtccct actggtgcca gcagccccac ccagagagac
       790        800        810        820        830        840
tggcaggagc agttagtggt ggggcacaat gtttcctttg accgagctca tatcagggag
       850        860        870        880        890        900
cagtacctga tccagggttc ccgcatgcgt ttcctggaca ccatgagcat gcacatggcc
       910        920        930        940        950        960
atctcagggc taagcagctt ccagcgcagt ctgtggatag cagccaagca gggcaaacac
       970        980        990       1000       1010       1020
aaggtccagc cccccacaaa gcaaggccag aagtcccaga ggaaagccag aagaggccca
      1030       1040       1050       1060       1070       1080
gcgatctcat cctgggactg gctggacatc agcagtgtca acagtctggc agaggtgcac
      1090       1100       1110       1120       1130       1140
agactttatg taggggggcc tcccttagag aaggagcctc gagaactgtt tgtgaagggc
      1150       1160       1170       1180       1190       1200
accatgaagg acattcgtga gaacttccag gacctgatgc agtactgtgc ccaggacgtg
      1210       1220       1230       1240       1250       1260
tgggccaccc atgaggtttt ccagcagcag ctaccgctct tcttggagag gtgtccccac
      1270       1280       1290       1300       1310       1320
ccagtgactc tggccggcat gctggagatg ggtgtctcct acctgcctgt caaccagaac
      1330       1340       1350       1360       1370       1380
tgggagcgtt acctggcaga ggcacagggc acttatgagg agctccagcg ggagatgaag
      1390       1400       1410       1420       1430       1440
aagtcgttga tggatctggc caatgatgcc tgccagctgc tctcaggaga gaggtacaaa
      1450       1460       1470       1480       1490       1500
gaagacccct ggctctggga cctggagtgg gacctgcaag aatttaagca gaagaaagct
      1510       1520       1530       1540       1550       1560
aagaaggtga agaaggaacc agccacagcc agcaagttgc ccatcgaggg ggctggggcc
      1570       1580       1590       1600       1610       1620
cctggtgatc ccatggatca ggaagacctc ggcccctgca gtgaggagga ggagtttcaa
      1630       1640       1650       1660       1670       1680
caagatgtca tggcccgcgc ctgcttgcag aagctgaagg ggaccacaga gctcctgccc
      1690       1700       1710       1720       1730       1740
aagcggcccc agcaccttcc tggacaccct ggatggtacc ggaagctctg cccccggcta
      1750       1760       1770       1780       1790       1800
gacgaccctg catggacccc gggccccagc ctcctcagcc tgcagatgcg ggtcacacct
      1810       1820       1830       1840       1850       1860
aaactcatgg cacttacctg ggatggcttc cctctgcact actcagagcg tcatggctgg
      1870       1880       1890       1900       1910       1920
ggctacttgg tgcctgggcg gcgggacaac ctggccaagc tgccgacagg taccaccctg
      1930       1940       1950       1960       1970       1980
gagtcagctg gggtggtctg cccctacaga gccatcgagt ccctgtacag gaagcactgt
      1990       2000       2010       2020       2030       2040
ctcgaacagg ggaagcagca gctgatgccc caggaggccg gcctggcgga ggagttcctg
      2050       2060       2070       2080       2090       2100
ctcactgaca atagtgccat atggcaaacg gtagaagaac tggattactt agaagtggag
      2110       2120       2130       2140       2150       2160
gctgaggcca agatggagaa cttgcgagct gcagtgccag gtcaacccct agctctgact
      2170       2180       2190       2200       2210       2220
gcccgtggtg gccccaagga cacccagccc agctatcacc atggcaatgg accttacaac
      2230       2240       2250       2260       2270       2280
gacgtggaca tccctggctg ctggtttttc aagctgcctc acaaggatgg taatagctgt
      2290       2300       2310       2320       2330       2340
aatgtgggaa gcccctttgc caaggacttc ctgcccaaga tggaggatgg caccctgcag
      2350       2360       2370       2380       2390       2400
gctggcccag gaggtgccag tgggccccgt gctctggaaa tcaacaaaat gatttctttc
      2410       2420       2430       2440       2450       2460
tggaggaacg cccataaacg tatcagctcc cagatggtgg tgtggctgcc caggtcagct
      2470       2480       2490       2500       2510       2520
ctgccccgtg ctgtgatcag gcaccccgac tatgatgagg aaggcctcta tggggccatc
      2530       2540       2550       2560       2570       2580
ctgccccaag tggtgactgc cggcaccatc actcgccggg ctgtggagcc cacatggctc
      2590       2600       2610       2620       2630       2640
accgccagca atgcccggcc tgaccgagta ggcagtgagt tgaaagccat ggtgcaggcc
      2650       2660       2670       2680       2690       2700
ccacctggct acacccttgt gggtgctgat gtggactccc aagagctgtg gattgcagct
      2710       2720       2730       2740       2750       2760
gtgcttggag acgcccactt tgccggcatg catggctgca cagcctttgg gtggatgaca
      2770       2780       2790       2800       2810       2820
ctgcagggca ggaagagcag gggcactgat ctacacagta agacagccac tactgtgggc
      2830       2840       2850       2860       2870       2880
atcagccgtg agcatgccaa aatcttcaac tacggccgca tctatggtgc tgggcagccc
      2890       2900       2910       2920       2930       2940
tttgctgagc gcttactaat gcagtttaac caccggctca cacagcagga ggcagctgag
      2950       2960       2970       2980       2990       3000
aaggcccagc agatgtacgc tgccaccaag ggcctccgct ggtatcggct gtcggatgag
      3010       3020       3030       3040       3050       3060
ggcgagtggc tggtgaggga gttgaacctc ccagtggaca ggactgaggg tggctggatt
      3070       3080       3090       3100       3110       3120
tccctgcagg atctgcgcaa ggtccagaga gaaactgcaa ggaagtcaca gtggaagaag
      3130       3140       3150       3160       3170       3180
tgggaggtgg ttgctgaacg ggcatggaag gggggcacag agtcagaaat gttcaataag
      3190       3200       3210       3220       3230       3240
cttgagagca ttgctacgtc tgacatacca cgtaccccgg tgctgggctg ctgcatcagc
      3250       3260       3270       3280       3290       3300
cgagccctgg agccctcggc tgtccaggaa gagtttatga ccagccgtgt gaattgggtg
      3310       3320       3330       3340       3350       3360
gtacagagct ctgctgttga ctacttacac ctcatgcttg tggccatgaa gtggctgttt
      3370       3380       3390       3400       3410       3420
gaagagtttg ccatagatgg gcgcttctgc atcagcatcc atgacgaggt tcgctacctg
      3430       3440       3450       3460       3470       3480
gtgcgggagg aggaccgcta ccgcgctgcc ctggccttgc agatcaccaa cctcttgacc
      3490       3500       3510       3520       3530       3540
aggtgcatgt ttgcctacaa gctgggtctg aatgacttgc cccagtcagt cgcctttttc
      3550       3560       3570       3580       3590       3600
agtgcagtcg atattgaccg gtgcctcagg aaggaagtga ccatggattg taaaacccct
      3610       3620       3630       3640       3650       3660
tccaacccaa ctgggatgga aaggagatac gggattcccc agggtgaagc gctggatatt
      3670       3680       3690       3700       3710       3720
taccagataa ttgaactcac caaaggctcc ttggaaaaac gaagccagcc tggaccatag

Last modification date: Oct. 19, 2011