Hmdb loader
Identification
HMDB Protein ID HMDBP00961
Secondary Accession Numbers
  • 6249
Name DNA polymerase epsilon catalytic subunit A
Synonyms
  1. DNA polymerase II subunit A
Gene Name POLE
Protein Type Enzyme
Biological Properties
General Function Involved in nucleotide binding
Specific Function Participates in DNA repair and in chromosomal DNA replication.
Pathways
  • Base excision repair
  • DNA replication
  • Human T-cell leukemia virus 1 infection
  • Nucleotide Excision Repair
  • Nucleotide excision repair
  • Purine metabolism
  • Pyrimidine metabolism
Reactions
Deoxynucleoside triphosphate + DNA(n) → Pyrophosphate + DNA(n+1) details
Deoxyadenosine triphosphate + DNA → Pyrophosphate + DNA details
dGTP + DNA → Pyrophosphate + DNA details
dCTP + DNA → Pyrophosphate + DNA details
Thymidine 5'-triphosphate + DNA → Pyrophosphate + DNA details
GO Classification
Biological Process
telomere maintenance via recombination
telomere maintenance via semi-conservative replication
nucleotide-excision repair, DNA gap filling
transcription-coupled nucleotide-excision repair
S phase of mitotic cell cycle
G1/S transition of mitotic cell cycle
in utero embryonic development
base-excision repair, gap-filling
DNA synthesis involved in DNA repair
DNA replication initiation
M/G1 transition of mitotic cell cycle
Cellular Component
nucleoplasm
epsilon DNA polymerase complex
Component
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
nucleus
Function
ion binding
cation binding
metal ion binding
binding
nucleotide binding
catalytic activity
transition metal ion binding
zinc ion binding
transferase activity
transferase activity, transferring phosphorus-containing groups
nucleotidyltransferase activity
dna polymerase activity
dna-directed dna polymerase activity
nucleic acid binding
dna binding
Molecular Function
metal ion binding
4 iron, 4 sulfur cluster binding
DNA-directed DNA polymerase activity
zinc ion binding
chromatin binding
DNA binding
nucleotide binding
Process
metabolic process
macromolecule metabolic process
cellular macromolecule metabolic process
dna metabolic process
dna replication
Cellular Location
  1. Nucleus
Gene Properties
Chromosome Location 12
Locus 12q24.3
SNPs POLE
Gene Sequence
>6861 bp
ATGTCTCTGAGGAGCGGCGGGCGGCGGCGCGCGGACCCAGGCGCGGATGGCGAGGCCAGC
AGGGATGATGGCGCCACTTCCTCAGTTTCGGCACTCAAGCGCCTGGAACGGAGTCAGTGG
ACGGATAAGATGGATTTGCGGTTTGGTTTTGAGCGGCTGAAGGAGCCTGGTGAGAAGACA
GGCTGGCTCATTAACATGCATCCTACCGAGATTTTAGATGAAGATAAGCGCTTAGGCAGT
GCAGTGGATTACTACTTTATTCAAGATGACGGAAGCAGATTTAAGGTGGCTTTGCCCTAT
AAACCGTATTTCTACATTGCGACCAGAAAGGGTTGTGAGCGAGAAGTTTCATCTTTTCTC
TCCAAGAAGTTTCAGGGCAAAATTGCAAAAGTGGAGACTGTCCCCAAAGAGGATCTGGAC
TTGCCAAATCACTTGGTGGGTTTGAAGCGAAATTACATCAGGCTGTCCTTCCACACTGTG
GAGGATCTTGTCAAAGTGAGGAAGGAGATCTCCCCTGCCGTGAAGAAGAACAGGGAGCAG
GATCACGCCAGCGACGCGTACACAGCTCTGCTTTCCAGTGTTCTGCAGAGGGGCGGTGTC
ATTACTGATGAAGAGGAAACCTCTAAGAAGATAGCTGACCAGTTGGACAACATTGTGGAC
ATGCGCGAGTACGATGTTCCCTACCACATCCGCCTCTCCATTGACCTGAAGATCCACGTG
GCTCATTGGTACAATGTCAGATACCGAGGAAATGCTTTTCCGGTAGAAATCACCCGCCGA
GATGACCTTGTTGAACGACCTGACCCTGTGGTTTTGGCATTTGACATTGAGACGACCAAA
CTGCCCCTCAAGTTTCCTGATGCTGAGACAGACCAGATTATGATGATTTCCTACATGATC
GATGGCCAGGGCTACCTCATCACCAACAGGGAGATTGTTTCAGAAGATATTGAAGATTTT
GAGTTCACCCCCAAGCCAGAATATGAAGGCCCCTTTTGTGTCTTCAATGAACCCGATGAG
GCTCATCTGATCCAAAGGTGGTTTGAACACGTCCAGGAGACCAAACCCACCATCATGGTC
ACCTACAACGGGGACTTTTTTGACTGGCCATTTGTGGAGGCCCGGGCAGCAGTCCACGGT
CTGAGCATGCAGCAGGAGATAGGCTTCCAGAAGGACAGCCAGGGGGAGTACAAGGCGCCC
CAGTGCATCCACATGGACTGCCTCAGGTGGGTGAAGAGGGACAGTTACCTTCCTGTGGGC
AGTCATAATCTCAAGGCGGCCGCCAAGGCCAAGCTAGGCTATGATCCCGTGGAGCTAGAC
CCGGAGGACATGTGCCGGATGGCCACGGAGCAGCCCCAGACTCTGGCCACGTATTCTGTG
TCAGATGCTGTCGCCACTTACTACCTGTACATGAAGTACGTCCACCCATTCATCTTTGCT
CTGTGCACCATTATTCCCATGGAGCCCGACGAGGTGCTGCGGAAGGGCTCTGGCACTCTG
TGTGAGGCCTTGCTGATGGTGCAGGCCTTCCACGCCAACATCATCTTCCCCAACAAGCAA
GAGCAGGAGTTCAATAAGCTGACGGACGACGGACACGTGCTGGACTCTGAGACCTACGTC
GGGGGCCACGTGGAGGCCCTCGAGTCTGGGGTTTTCCGCAGCGATATCCCTTGCCGGTTT
AGGATGAATCCTGCCGCCTTTGACTTCCTGCTGCAGCGGGTTGAGAAGACCTTGCGCCAC
GCCCTTGAGGAAGAGGAGAAAGTGCCTGTGGAGCAAGTCACCAACTTTGAAGAGGTGTGT
GATGAGATTAAGAGCAAGCTTGCCTCCCTGAAGGACGTTCCCAGCCGCATCGAGTGTCCA
CTCATCTACCACCTGGACGTGGGGGCCATGTACCCCAACATCATCCTGACCAACCGCCTG
CAGCCCTCTGCCATGGTGGACGAAGCCACCTGTGCTGCCTGTGACTTCAATAAGCCTGGA
GCAAACTGCCAGCGGAAGATGGCCTGGCAGTGGAGGGGCGAGTTCATGCCAGCCAGTCGC
AGCGAATACCATCGGATCCAGCACCAGCTGGAGTCAGAGAAGTTCCCCCCCTTGTTCCCA
GAGGGGCCAGCTCGGGCCTTTCATGAACTGTCCCGCGAGGAACAGGCGAAATACGAGAAG
AGAAGGCTGGCGGATTACTGCCGGAAAGCCTACAAGAAGATCCACATCACCAAGGTGGAA
GAGCGTCTCACCACCATCTGCCAGCGGGAAAACTCCTTCTACGTGGACACCGTGCGTGCC
TTCCGGGACAGGCGTTACGAGTTCAAAGGGCTCCACAAGGTGTGGAAAAAGAAGCTCTCG
GCGGCCGTGGAGGTGGGCGACGCGGCTGAGGTGAAGCGCTGCAAGAACATGGAGGTGCTG
TATGACTCGCTGCAGCTGGCCCACAAGTGCATCCTGAACTCCTTCTATGGCTATGTCATG
CGCAAGGGGGCTCGCTGGTACTCCATGGAGATGGCTGGCATCGTCTGCTTCACAGGGGCC
AACATCATCACCCAGGCACGGGAGCTGATCGAGCAGATTGGGAGGCCCTTAGAGCTGGAC
ACAGATGGTATATGGTGCGTCCTGCCCAACAGCTTCCCAGAAAATTTTGTCTTCAAGACG
ACCAATGTGAAGAAGCCCAAAGTGACCATCTCCTACCCAGGCGCCATGTTGAACATCATG
GTCAAGGAAGGCTTCACCAATGACCAGTACCAGGAGCTGGCTGAGCCGTCCTCACTCACC
TACGTCACCCGCTCAGAGAACAGCATCTTTTTTGAGGTTGATGGGCCCTACCTTGCCATG
ATTCTTCCAGCCTCCAAGGAAGAAGGCAAGAAATTGAAGAAGAGGTATGCTGTGTTCAAT
GAAGACGGTTCTCTGGCTGAGCTCAAGGGCTTTGAGGTCAAACGCCGCGGGGAACTGCAG
CTGATTAAGATCTTCCAATCCTCGGTGTTTGAGGCCTTCCTCAAGGGCAGCACGCTGGAA
GAGGTGTATGGCTCTGTAGCCAAGGTGGCTGACTACTGGCTGGACGTGCTGTACAGCAAG
GCAGCCAACATGCCTGACTCTGAGCTATTCGAGCTCATCTCTGAGAACCGTTCCATGTCT
CGGAAGCTGGAAGATTACGGGGAGCAGAAGTCTACGTCCATCAGCACAGCAAAGCGCCTG
GCCGAGTTCCTGGGAGACCAGATGGTCAAGGATGCAGGGCTGAGTTGCCGCTACATCATC
TCCCGCAAGCCCGAGGGCTCCCCTGTCACGGAGAGGGCCATCCCACTTGCCATTTTCCAA
GCAGAGCCCACGGTGAGGAAGCACTTTCTCCGGAAATGGCTCAAGAGCTCTTCCCTTCAA
GACTTTGATATTCGAGCAATTCTGGATTGGGACTACTACATTGAGCGGCTGGGAAGCGCC
ATCCAGAAGATCATCACCATCCCTGCGGCCCTGCAGCAGGTAAAGAACCCAGTGCCACGT
GTCAAACACCCCGACTGGCTGCACAAAAAACTGCTGGAGAAGAATGATGTCTACAAGCAG
AAGAAGATCAGTGAGCTCTTCACCCTGGAGGGCAGGAGACAGGTCACGATGGCCGAGGCC
TCAGAAGACAGTCCGAGGCCAAGTGCTCCTGACATGGAGGACTTCGGCCTCGTAAAGCTG
CCTCACCCAGCAGCCCCTGTCACTGTGAAGAGGAAGCGAGTTCTTTGGGAGAGCCAGGAG
GAGTCCCAGGACCTCACGCCGACTGTGCCCTGGCAGGAAATCTTGGGGCAGCCTCCCGCC
CTGGGAACCAGCCAGGAGGAATGGCTTGTCTGGCTCCGGTTCCACAAGAAGAAGTGGCAG
CTGCAGGCCCGGCAGCGCCTCGCCCGCAGGAAGAGGCAGCGTCTGGAGTCGGCAGAGGGT
GTGCTCAGGCCCGGGGCCATCCGGGATGGTCCTGCCACGGGGCTGGGGAGCTTCTTGCGA
AGAACTGCCCGCAGCATCCTGGACCTTCCGTGGCAGATTGTGCAGATCAGCGAGACCAGC
CAGGCCGGCCTGTTCAGGCTGTGGGCGCTCGTTGGCAGTGACTTGCACTGCATCAGGCTG
AGCATCCCCCGTGTGTTCTACGTGAACCAGCGAGTCGCTAAAGCGGAGGAGGGTGCTTCG
TATCGCAAGGTAAATCGGGTCCTTCCTCGCTCCAACATGGTCTACAATCTCTATGAGTAT
TCAGTGCCAGAGGACATGTACCAGGAACACATCAACGAGATCAACGCTGAGCTGTCAGCG
CCAGACATCGAGGGCGTATATGAGACTCAGGTTCCGTTACTGTTCCGGGCCCTGGTGCAC
CTGGGCTGTGTGTGTGTGGTCAATAAACAGCTGGTGAGGCACCTTTCAGGCTGGGAAGCA
GAGACCTTTGCTCTTGAGCACCTGGAGATGCGCTCTCTGGCCCAGTTCAGCTACCTGGAA
CCAGGGAGTATCCGCCATATCTACCTGTACCACCACGCACAGGCCCACAAAGCGCTCTTC
GGGATCTTCATCCCCTCACAGCGCAGGGCATCCGTCTTTGTGCTGGACACTGTGCGCAGC
AACCAGATGCCCAGCCTTGGCGCCCTGTACTCAGCAGAGCACGGCCTCCTCCTGGAGAAG
GTGGGCCCTGAGCTCCTGCCACCCCCCAAACACACCTTCGAAGTTCGGGCAGAAACTGAC
CTGAAGACCATCTGCAGAGCCATCCAGCGATTCCTGCTCGCCTACAAGGAGGAGCGCCGG
GGGCCCACACTCATCGCTGTTCAGTCCAGCTGGGAGCTGAAGAGGCTGGCCAGTGAAATT
CCTGTCTTGGAGGAATTCCCACTGGTGCCTATCTGTGTGGCTGACAAGATCAACTATGGG
GTCCTGGACTGGCAGCGCCATGGAGCCCGGCGCATGATCCGTCACTACCTCAACCTGGAC
ACCTGCCTGTCGCAGGCCTTCGAGATGAGCAGGTACTTTCACATTCCCATTGGGAACCTA
CCAGAGGACATCTCCACATTCGGCTCCGACCTCTTCTTTGCCCGCCACCTCCAGCGCCAC
AACCACCTGCTCTGGCTGTCCCCTACAGCCCGCCCTGACCTGGGTGGAAAGGAGGCTGAT
GACAACTGTCTTGTCATGGAGTTCGATGACCAAGCCACTGTTGAGATCAACAGTTCAGGC
TGTTACTCCACAGTGTGTGTGGAGCTGGACCTTCAGAACCTGGCCGTCAACACCATTCTC
CAGTCTCACCATGTCAACGACATGGAGGGGGCCGACAGCATGGGGATCAGCTTCGACGTG
ATCCAGCAGGCCTCCCTGGAGGACATGATCACGGGTGGTCAGGCTGCCAGTGCCCCGGCC
AGCTACGATGAGACAGCCCTGTGCTCTAACACCTTCAGGATCCTGAAGAGCATGGTCGTG
GGCTGGGTGAAGGAGATCACCCAGTACCACAACATCTATGCAGACAACCAGGTGATGCAC
TTCTACCGCTGGCTTCGGTCGCCATCCTCTCTGCTTCATGACCCTGCCCTGCACCGCACA
CTCCACAACATGATGAAGAAGCTCTTCCTGCAGCTCATCGCTGAGTTCAAGCGCCTGGGG
TCATCAGTCATCTACGCCAACTTCAACCGCATCATCCTCTGTACAAAGAAGCGCCGTGTG
GAAGATGCCATCGCTTACGTGGAGTACATCACCAGCAGCATCCATTCAAAGGAGACCTTC
CATTCTCTGACAATTTCTTTCTCTCGATGCTGGGAATTTCTTCTCTGGATGGATCCATCT
AACTATGGCGGAATCAAAGGAAAAGTTTCATCTCGTATTCACTGTGGACTGCAAGACTCC
CAGAAAGCAGGGGGAGCAGAGGATGAGCAGGAAAATGAGGACGATGAGGAGGAAAGAGAT
GGGGAGGAGGAGGAAGAGGCGGAGGAATCCAACGTGGAGGATTTACTGGAAAACAACTGG
AACATTTTGCAGTTTTTGCCACAGGCAGCCTCCTGCCAGAACTACTTCCTCATGATTGTT
TCAGCGTACATCGTGGCCGTGTACCACTGCATGAAGGACGGGCTGAGGCGCAGTGCTCCA
GGGAGCACCCCCGTGAGGAGGAGGGGGGCCAGCCAGCTCTCCCAGGAGGCCGAGGGGGCG
GTCGGAGCCCTTCCCGGAATGATCACCTTCTCTCAGGATTATGTCGCAAATGAGCTCACT
CAGAGCTTCTTCACCATCACTCAGAAGATTCAGAAGAAAGTCACAGGCTCTCGGAACTCC
ACTGAGCTCTCAGAGATGTTTCCTGTCCTCCCCGGTTCCCACTTGCTGCTCAATAACCCT
GCCCTGGAGTTCATCAAATACGTGTGCAAGGTGCTGTCCCTGGACACCAACATCACAAAC
CAGGTGAATAAGCTGAACCGAGACCTGCTTCGCCTGGTGGATGTCGGCGAGTTCTCCGAG
GAGGCCCAGTTCCGAGACCCCTGCCGCTCCTACGTGCTTCCTGAGGTCATCTGCCGCAGC
TGTAACTTCTGCCGCGACCTGGACCTGTGTAAAGACTCTTCCTTCTCAGAGGATGGGGCG
GTCCTGCCTCAGTGGCTCTGCTCCAACTGTCAGGCGCCCTACGACTCCTCTGCCATCGAG
ATGACGCTGGTGGAAGTTCTACAGAAGAAGCTGATGGCCTTCACCCTGCAGGACCTGGTC
TGCCTGAAGTGCCGCGGGGTGAAGGAGACCAGCATGCCTGTGTACTGCAGCTGCGCGGGA
GACTTCGCCCTCACCATCCACACCCAGGTCTTCATGGAACAGATCGGAATATTCCGGAAC
ATTGCCCAGCACTACGGCATGTCGTACCTCCTGGAGACCCTGGAGTGGCTGCTGCAGAAG
AACCCACAGCTGGGCCATTAG
Protein Properties
Number of Residues 2286
Molecular Weight 261515.525
Theoretical pI 6.392
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>DNA polymerase epsilon catalytic subunit A
MSLRSGGRRRADPGADGEASRDDGATSSVSALKRLERSQWTDKMDLRFGFERLKEPGEKT
GWLINMHPTEILDEDKRLGSAVDYYFIQDDGSRFKVALPYKPYFYIATRKGCEREVSSFL
SKKFQGKIAKVETVPKEDLDLPNHLVGLKRNYIRLSFHTVEDLVKVRKEISPAVKKNREQ
DHASDAYTALLSSVLQRGGVITDEEETSKKIADQLDNIVDMREYDVPYHIRLSIDLKIHV
AHWYNVRYRGNAFPVEITRRDDLVERPDPVVLAFDIETTKLPLKFPDAETDQIMMISYMI
DGQGYLITNREIVSEDIEDFEFTPKPEYEGPFCVFNEPDEAHLIQRWFEHVQETKPTIMV
TYNGDFFDWPFVEARAAVHGLSMQQEIGFQKDSQGEYKAPQCIHMDCLRWVKRDSYLPVG
SHNLKAAAKAKLGYDPVELDPEDMCRMATEQPQTLATYSVSDAVATYYLYMKYVHPFIFA
LCTIIPMEPDEVLRKGSGTLCEALLMVQAFHANIIFPNKQEQEFNKLTDDGHVLDSETYV
GGHVEALESGVFRSDIPCRFRMNPAAFDFLLQRVEKTLRHALEEEEKVPVEQVTNFEEVC
DEIKSKLASLKDVPSRIECPLIYHLDVGAMYPNIILTNRLQPSAMVDEATCAACDFNKPG
ANCQRKMAWQWRGEFMPASRSEYHRIQHQLESEKFPPLFPEGPARAFHELSREEQAKYEK
RRLADYCRKAYKKIHITKVEERLTTICQRENSFYVDTVRAFRDRRYEFKGLHKVWKKKLS
AAVEVGDAAEVKRCKNMEVLYDSLQLAHKCILNSFYGYVMRKGARWYSMEMAGIVCFTGA
NIITQARELIEQIGRPLELDTDGIWCVLPNSFPENFVFKTTNVKKPKVTISYPGAMLNIM
VKEGFTNDQYQELAEPSSLTYVTRSENSIFFEVDGPYLAMILPASKEEGKKLKKRYAVFN
EDGSLAELKGFEVKRRGELQLIKIFQSSVFEAFLKGSTLEEVYGSVAKVADYWLDVLYSK
AANMPDSELFELISENRSMSRKLEDYGEQKSTSISTAKRLAEFLGDQMVKDAGLSCRYII
SRKPEGSPVTERAIPLAIFQAEPTVRKHFLRKWLKSSSLQDFDIRAILDWDYYIERLGSA
IQKIITIPAALQQVKNPVPRVKHPDWLHKKLLEKNDVYKQKKISELFTLEGRRQVTMAEA
SEDSPRPSAPDMEDFGLVKLPHPAAPVTVKRKRVLWESQEESQDLTPTVPWQEILGQPPA
LGTSQEEWLVWLRFHKKKWQLQARQRLARRKRQRLESAEGVLRPGAIRDGPATGLGSFLR
RTARSILDLPWQIVQISETSQAGLFRLWALVGSDLHCIRLSIPRVFYVNQRVAKAEEGAS
YRKVNRVLPRSNMVYNLYEYSVPEDMYQEHINEINAELSAPDIEGVYETQVPLLFRALVH
LGCVCVVNKQLVRHLSGWEAETFALEHLEMRSLAQFSYLEPGSIRHIYLYHHAQAHKALF
GIFIPSQRRASVFVLDTVRSNQMPSLGALYSAEHGLLLEKVGPELLPPPKHTFEVRAETD
LKTICRAIQRFLLAYKEERRGPTLIAVQSSWELKRLASEIPVLEEFPLVPICVADKINYG
VLDWQRHGARRMIRHYLNLDTCLSQAFEMSRYFHIPIGNLPEDISTFGSDLFFARHLQRH
NHLLWLSPTARPDLGGKEADDNCLVMEFDDQATVEINSSGCYSTVCVELDLQNLAVNTIL
QSHHVNDMEGADSMGISFDVIQQASLEDMITGGQAASAPASYDETALCSNTFRILKSMVV
GWVKEITQYHNIYADNQVMHFYRWLRSPSSLLHDPALHRTLHNMMKKLFLQLIAEFKRLG
SSVIYANFNRIILCTKKRRVEDAIAYVEYITSSIHSKETFHSLTISFSRCWEFLLWMDPS
NYGGIKGKVSSRIHCGLQDSQKAGGAEDEQENEDDEEERDGEEEEEAEESNVEDLLENNW
NILQFLPQAASCQNYFLMIVSAYIVAVYHCMKDGLRRSAPGSTPVRRRGASQLSQEAEGA
VGALPGMITFSQDYVANELTQSFFTITQKIQKKVTGSRNSTELSEMFPVLPGSHLLLNNP
ALEFIKYVCKVLSLDTNITNQVNKLNRDLLRLVDVGEFSEEAQFRDPCRSYVLPEVICRS
CNFCRDLDLCKDSSFSEDGAVLPQWLCSNCQAPYDSSAIEMTLVEVLQKKLMAFTLQDLV
CLKCRGVKETSMPVYCSCAGDFALTIHTQVFMEQIGIFRNIAQHYGMSYLLETLEWLLQK
NPQLGH
GenBank ID Protein 62198237
UniProtKB/Swiss-Prot ID Q07864
UniProtKB/Swiss-Prot Entry Name DPOE1_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_006231.2
GeneCard ID POLE
GenAtlas ID POLE
HGNC ID HGNC:9177
References
General References
  1. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007 May 25;316(5828):1160-6. [PubMed:17525332 ]
  2. Kesti T, Frantti H, Syvaoja JE: Molecular cloning of the cDNA for the catalytic subunit of human DNA polymerase epsilon. J Biol Chem. 1993 May 15;268(14):10238-45. [PubMed:8486689 ]
  3. Makiniemi M, Hillukkala T, Tuusa J, Reini K, Vaara M, Huang D, Pospiech H, Majuri I, Westerling T, Makela TP, Syvaoja JE: BRCT domain-containing protein TopBP1 functions in DNA replication and damage response. J Biol Chem. 2001 Aug 10;276(32):30399-406. Epub 2001 Jun 6. [PubMed:11395493 ]
  4. Post SM, Tomkinson AE, Lee EY: The human checkpoint Rad protein Rad17 is chromatin-associated throughout the cell cycle, localizes to DNA replication sites, and interacts with DNA polymerase epsilon. Nucleic Acids Res. 2003 Oct 1;31(19):5568-75. [PubMed:14500819 ]