REV3L

Protein identityUniProt · HPA

UniProt accession

O60673

Gene

REV3L

Ensembl

ENSG00000009413

Chromosome

6

Canonical length

3130 aa

Protein class

Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

The protein encoded by this gene represents the catalytic subunit of DNA polymerase zeta, which functions in translesion DNA synthesis. The encoded protein can be found in mitochondria, where it protects DNA from damage. Defects in this gene are a cause of Mobius syndrome. [provided by RefSeq, Jan 2017]

Canonical amino-acid sequenceUniProt

3130 residues, UniProt reviewed canonical sequence.

>O60673|REV3L
     1  MFSVRIVTAD YYMASPLQGL DTCQSPLTQA PVKKVPVVRV FGATPAGQKT CLHLHGIFPY
    61  LYVPYDGYGQ QPESYLSQMA FSIDRALNVA LGNPSSTAQH VFKVSLVSGM PFYGYHEKER
   121  HFMKIYLYNP TMVKRICELL QSGAIMNKFY QPHEAHIPYL LQLFIDYNLY GMNLINLAAV
   181  KFRKARRKSN TLHATGSCKN HLSGNSLADT LFRWEQDEIP SSLILEGVEP QSTCELEVDA
   241  VAADILNRLD IEAQIGGNPG LQAIWEDEKQ RRRNRNETSQ MSQPESQDHR FVPATESEKK
   301  FQKRLQEILK QNDFSVTLSG SVDYSDGSQE FSAELTLHSE VLSPEMLQCT PANMVEVHKD
   361  KESSKGHTRH KVEEALINEE AILNLMENSQ TFQPLTQRLS ESPVFMDSSP DEALVHLLAG
   421  LESDGYRGER NRMPSPCRSF GNNKYPQNSD DEENEPQIEK EEMELSLVMS QRWDSNIEEH
   481  CAKKRSLCRN THRSSTEDDD SSSGEEMEWS DNSLLLASLS IPQLDGTADE NSDNPLNNEN
   541  SRTHSSVIAT SKLSVKPSIF HKDAATLEPS SSAKITFQCK HTSALSSHVL NKEDLIEDLS
   601  QTNKNTEKGL DNSVTSFTNE STYSMKYPGS LSSTVHSENS HKENSKKEIL PVSSCESSIF
   661  DYEEDIPSVT RQVPSRKYTN IRKIEKDSPF IHMHRHPNEN TLGKNSFNFS DLNHSKNKVS
   721  SEGNEKGNST ALSSLFPSSF TENCELLSCS GENRTMVHSL NSTADESGLN KLKIRYEEFQ
   781  EHKTEKPSLS QQAAHYMFFP SVVLSNCLTR PQKLSPVTYK LQPGNKPSRL KLNKRKLAGH
   841  QETSTKSSET GSTKDNFIQN NPCNSNPEKD NALASDLTKT TRGAFENKTP TDGFIDCHFG
   901  DGTLETEQSF GLYGNKYTLR AKRKVNYETE DSESSFVTHN SKISLPHPME IGESLDGTLK
   961  SRKRRKMSKK LPPVIIKYII INRFRGRKNM LVKLGKIDSK EKQVILTEEK MELYKKLAPL
  1021  KDFWPKVPDS PATKYPIYPL TPKKSHRRKS KHKSAKKKTG KQQRTNNENI KRTLSFRKKR
  1081  SHAILSPPSP SYNAETEDCD LNYSDVMSKL GFLSERSTSP INSSPPRCWS PTDPRAEEIM
  1141  AAAEKEAMLF KGPNVYKKTV NSRIGKTSRA RAQIKKSKAK LANPSIVTKK RNKRNQTNKL
  1201  VDDGKKKPRA KQKTNEKGTS RKHTTLKDEK IKSQSGAEVK FVLKHQNVSE FASSSGGSQL
  1261  LFKQKDMPLM GSAVDHPLSA SLPTGINAQQ KLSGCFSSFL ESKKSVDLQT FPSSRDDLHP
  1321  SVVCNSIGPG VSKINVQRPH NQSAMFTLKE STLIQKNIFD LSNHLSQVAQ NTQISSGMSS
  1381  KIEDNANNIQ RNYLSSIGKL SEYRNSLESK LDQAYTPNFL HCKDSQQQIV CIAEQSKHSE
  1441  TCSPGNTASE ESQMPNNCFV TSLRSPIKQI AWEQKQRGFI LDMSNFKPER VKPRSLSEAI
  1501  SQTKALSQCK NRNVSTPSAF GEGQSGLAVL KELLQKRQQK AQNANTTQDP LSNKHQPNKN
  1561  ISGSLEHNKA NKRTRSVTSP RKPRTPRSTK QKEKIPKLLK VDSLNLQNSS QLDNSVSDDS
  1621  PIFFSDPGFE SCYSLEDSLS PEHNYNFDIN TIGQTGFCSF YSGSQFVPAD QNLPQKFLSD
  1681  AVQDLFPGQA IEKNEFLSHD NQKCDEDKHH TTDSASWIRS GTLSPEIFEK STIDSNENRR
  1741  HNQWKNSFHP LTTRSNSIMD SFCVQQAEDC LSEKSRLNRS SVSKEVFLSL PQPNNSDWIQ
  1801  GHTRKEMGQS LDSANTSFTA ILSSPDGELV DVACEDLELY VSRNNDMLTP TPDSSPRSTS
  1861  SPSQSKNGSF TPRTANILKP LMSPPSREEI MATLLDHDLS ETIYQEPFCS NPSDVPEKPR
  1921  EIGGRLLMVE TRLANDLAEF EGDFSLEGLR LWKTAFSAMT QNPRPGSPLR SGQGVVNKGS
  1981  SNSPKMVEDK KIVIMPCKCA PSRQLVQVWL QAKEEYERSK KLPKTKPTGV VKSAENFSSS
  2041  VNPDDKPVVP PKMDVSPCIL PTTAHTKEDV DNSQIALQAP TTGCSQTASE SQMLPPVASA
  2101  SDPEKDEDDD DNYYISYSSP DSPVIPPWQQ PISPDSKALN GDDRPSSPVE ELPSLAFENF
  2161  LKPIKDGIQK SPCSEPQEPL VISPINTRAR TGKCESLCFH STPIIQRKLL ERLPEAPGLS
  2221  PLSTEPKTQK LSNKKGSNTD TLRRVLLTQA KNQFAAVNTP QKETSQIDGP SLNNTYGFKV
  2281  SIQNLQEAKA LHEIQNLTLI SVELHARTRR DLEPDPEFDP ICALFYCISS DTPLPDTEKT
  2341  ELTGVIVIDK DKTVFSQDIR YQTPLLIRSG ITGLEVTYAA DEKALFHEIA NIIKRYDPDI
  2401  LLGYEIQMHS WGYLLQRAAA LSIDLCRMIS RVPDDKIENR FAAERDEYGS YTMSEINIVG
  2461  RITLNLWRIM RNEVALTNYT FENVSFHVLH QRFPLFTFRV LSDWFDNKTD LYRWKMVDHY
  2521  VSRVRGNLQM LEQLDLIGKT SEMARLFGIQ FLHVLTRGSQ YRVESMMLRI AKPMNYIPVT
  2581  PSVQQRSQMR APQCVPLIME PESRFYSNSV LVLDFQSLYP SIVIAYNYCF STCLGHVENL
  2641  GKYDEFKFGC TSLRVPPDLL YQVRHDITVS PNGVAFVKPS VRKGVLPRML EEILKTRFMV
  2701  KQSMKAYKQD RALSRMLDAR QLGLKLIANV TFGYTSANFS GRMPCIEVGD SIVHKARETL
  2761  ERAIKLVNDT KKWGARVVYG DTDSMFVLLK GATKEQSFKI GQEIAEAVTA TNPKPVKLKF
  2821  EKVYLPCVLQ TKKRYVGYMY ETLDQKDPVF DAKGIETVRR DSCPAVSKIL ERSLKLLFET
  2881  RDISLIKQYV QRQCMKLLEG KASIQDFIFA KEYRGSFSYK PGACVPALEL TRKMLTYDRR
  2941  SEPQVGERVP YVIIYGTPGV PLIQLVRRPV EVLQDPTLRL NATYYITKQI LPPLARIFSL
  3001  IGIDVFSWYH ELPRIHKATS SSRSEPEGRK GTISQYFTTL HCPVCDDLTQ HGICSKCRSQ
  3061  PQHVAVILNQ EIRELERQQE QLVKICKNCT GCFDRHIPCV SLNCPVLFKL SRVNRELSKA
  3121  PYLRQLLDQF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against REV3L can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0

Highest tissue expression

24 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about REV3L.

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 473 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Carcinoma of colon

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.12

gnomAD pLI

1

gnomAD missense Z

2.47

DepMap mean gene effect

-0.51

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA biosynthetic process
• DNA synthesis involved in DNA repair
• DNA-templated DNA replication
• double-strand break repair via homologous recombination
• error-prone translesion synthesis
• translesion synthesis

Molecular functions

• 4 iron, 4 sulfur cluster binding
• DNA binding
• DNA-directed DNA polymerase activity
• nucleotide binding
• zinc ion binding

Cellular components

• nucleolus
• nucleoplasm
• nucleus
• site of DNA damage
• zeta DNA polymerase complex

Protein domainsUniProt · Pfam · InterPro

• DNA-directed DNA polymerase, family B, exonuclease domain
• DNA-directed DNA polymerase, family B, multifunctional domain
• DNA-directed DNA polymerase, family B
• Ribonuclease H-like superfamily
• DNA-directed DNA polymerase, family B, conserved site
• DNA polymerase, palm domain superfamily
• C4-type zinc-finger of DNA polymerase delta
• Domain of unknown function DUF4683
• Ribonuclease H superfamily
• DNA polymerase family B, thumb domain
• DNA/RNA polymerase superfamily
• DNA polymerase delta/zeta catalytic subunit, N-terminal domain
• DNA polymerase family B
• DNA polymerase family B, exonuclease domain
• C4-type zinc-finger of DNA polymerase delta
• Domain of unknown function (DUF4683)
• DNA polymerase delta catalytic subunit-like, N-terminal domain
• DNA polymerase zeta catalytic subunit
• DNA polymerase zeta catalytic subunit, N-terminal
• DNA polymerase zeta catalytic subunit, N-terminal

KeywordsUniProt

• 4Fe-4S
• DNA damage
• DNA repair
• DNA replication
• DNA-binding
• DNA-directed DNA polymerase
• Iron
• Iron-sulfur
• Metal-binding
• Nucleotidyltransferase
• Nucleus
• Phosphoprotein
• Transferase
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of REV3L in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MAD2L2