FANCM

Protein identityUniProt · HPA

UniProt accession

Q8IYD8

Gene

FANCM

Ensembl

ENSG00000187790

Chromosome

14

Canonical length

2048 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group M. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

Canonical amino-acid sequenceUniProt

2048 residues, UniProt reviewed canonical sequence.

>Q8IYD8|FANCM
     1  MSGRQRTLFQ TWGSSISRSS GTPGCSSGTE RPQSPGSSKA PLPAAAEAQL ESDDDVLLVA
    61  AYEAERQLCL ENGGFCTSAG ALWIYPTNCP VRDYQLHISR AALFCNTLVC LPTGLGKTFI
   121  AAVVMYNFYR WFPSGKVVFM APTKPLVTQQ IEACYQVMGI PQSHMAEMTG STQASTRKEI
   181  WCSKRVLFLT PQVMVNDLSR GACPAAEIKC LVIDEAHKAL GNYAYCQVVR ELVKYTNHFR
   241  ILALSATPGS DIKAVQQVIT NLLIGQIELR SEDSPDILTY SHERKVEKLI VPLGEELAAI
   301  QKTYIQILES FARSLIQRNV LMRRDIPNLT KYQIILARDQ FRKNPSPNIV GIQQGIIEGE
   361  FAICISLYHG YELLQQMGMR SLYFFLCGIM DGTKGMTRSK NELGRNEDFM KLYNHLECMF
   421  ARTRSTSANG ISAIQQGDKN KKFVYSHPKL KKLEEVVIEH FKSWNAENTT EKKRDETRVM
   481  IFSSFRDSVQ EIAEMLSQHQ PIIRVMTFVG HASGKSTKGF TQKEQLEVVK QFRDGGYNTL
   541  VSTCVGEEGL DIGEVDLIIC FDSQKSPIRL VQRMGRTGRK RQGRIVIILS EGREERIYNQ
   601  SQSNKRSIYK AISSNRQVLH FYQRSPRMVP DGINPKLHKM FITHGVYEPE KPSRNLQRKS
   661  SIFSYRDGMR QSSLKKDWFL SEEEFKLWNR LYRLRDSDEI KEITLPQVQF SSLQNEENKP
   721  AQESTTGIHQ LSLSEWRLWQ DHPLPTHQVD HSDRCRHFIG LMQMIEGMRH EEGECSYELE
   781  VESYLQMEDV TSTFIAPRNE SNNLASDTFI THKKSSFIKN INQGSSSSVI ESDEECAEIV
   841  KQTHIKPTKI VSLKKKVSKE IKKDQLKKEN NHGIIDSVDN DRNSTVENIF QEDLPNDKRT
   901  SDTDEIAATC TINENVIKEP CVLLTECQFT NKSTSSLAGN VLDSGYNSFN DEKSVSSNLF
   961  LPFEEELYIV RTDDQFYNCH SLTKEVLANV ERFLSYSPPP LSGLSDLEYE IAKGTALENL
  1021  LFLPCAEHLR SDKCTCLLSH SAVNSQQNLE LNSLKCINYP SEKSCLYDIP NDNISDEPSL
  1081  CDCDVHKHNQ NENLVPNNRV QIHRSPAQNL VGENNHDVDN SDLPVLSTDQ DESLLLFEDV
  1141  NTEFDDVSLS PLNSKSESLP VSDKTAISET PLVSQFLISD ELLLDNNSEL QDQITRDANS
  1201  FKSRDQRGVQ EEKVKNHEDI FDCSRDLFSV TFDLGFCSPD SDDEILEHTS DSNRPLDDLY
  1261  GRYLEIKEIS DANYVSNQAL IPRDHSKNFT SGTVIIPSNE DMQNPNYVHL PLSAAKNEEL
  1321  LSPGYSQFSL PVQKKVMSTP LSKSNTLNSF SKIRKEILKT PDSSKEKVNL QRFKEALNST
  1381  FDYSEFSLEK SKSSGPMYLH KSCHSVEDGQ LLTSNESEDD EIFRRKVKRA KGNVLNSPED
  1441  QKNSEVDSPL HAVKKRRFPI NRSELSSSDE SENFPKPCSQ LEDFKVCNGN ARRGIKVPKR
  1501  QSHLKHVARK FLDDEAELSE EDAEYVSSDE NDESENEQDS SLLDFLNDET QLSQAINDSE
  1561  MRAIYMKSLR SPMMNNKYKM IHKTHKNINI FSQIPEQDET YLEDSFCVDE EESCKGQSSE
  1621  EEVCVDFNLI TDDCFANSKK YKTRRAVMLK EMMEQNCAHS KKKLSRIILP DDSSEEENNV
  1681  NDKRESNIAV NPSTVKKNKQ QDHCLNSVPS GSSAQSKVRS TPRVNPLAKQ SKQTSLNLKD
  1741  TISEVSDFKP QNHNEVQSTT PPFTTVDSQK DCRKFPVPQK DGSALEDSST SGASCSKSRP
  1801  HLAGTHTSLR LPQEGKGTCI LVGGHEITSG LEVISSLRAI HGLQVEVCPL NGCDYIVSNR
  1861  MVVERRSQSE MLNSVNKNKF IEQIQHLQSM FERICVIVEK DREKTGDTSR MFRRTKSYDS
  1921  LLTTLIGAGI RILFSSCQEE TADLLKELSL VEQRKNVGIH VPTVVNSNKS EALQFYLSIP
  1981  NISYITALNM CHQFSSVKRM ANSSLQEISM YAQVTHQKAE EIYRYIHYVF DIQMLPNDLN
  2041  QDRLKSDI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FANCM 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)

0.5

Highest tissue expression

6.5 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FANCM.

Disease | AllUniProt

Conditions FANCM is implicated in, by any mechanism.

• Spermatogenic failure 28 (SPGF28) MIM:618086
• Premature ovarian failure 15 (POF15) MIM:618096

Disease | GeneticClinVar

206 pathogenic / likely-pathogenic of 4,028 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Fanconi anemia
• Spermatogenic failure 28
• Premature ovarian failure 15
• FANCM-related disorder
• Hereditary cancer-predisposing syndrome

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)

0.59

gnomAD pLI

0

gnomAD missense Z

-0.13

DepMap mean gene effect

-0.45

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• double-strand break repair via synthesis-dependent strand annealing
• interstrand cross-link repair
• positive regulation of protein monoubiquitination
• replication fork processing
• resolution of meiotic recombination intermediates

Molecular functions

• 3'-5' DNA helicase activity
• ATP binding
• ATP hydrolysis activity
• chromatin binding
• four-way junction DNA binding
• four-way junction helicase activity
• nuclease activity
• RNA helicase activity

Cellular components

• chromatin
• cytosol
• FANCM-MHF complex
• Fanconi anaemia nuclear complex
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• Helicase, C-terminal domain-like
• ERCC4 domain
• RuvA domain 2-like
• Restriction endonuclease type II-like
• DEAD/DEAH-box helicase domain
• Helicase superfamily 1/2, ATP-binding domain
• P-loop containing nucleoside triphosphate hydrolase
• DEAD/DEAH box helicase
• Helicase conserved C-terminal domain
• ERCC4 domain
• Fanconi anemia group M protein, MHF binding domain
• FANCM/Mph1-like, insert domain
• FANCM, DEAH-box helicase domain
• Fanconi anemia group M protein, XPF-like nuclease domain
• FANCM to MHF binding domain

KeywordsUniProt

• ATP-binding
• DNA damage
• DNA repair
• DNA-binding
• Helicase
• Hydrolase
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Premature ovarian failure

InteractionsUniProt · HPA

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

• FAAP24
• CENPS
• MCM2