UniProtKB - P39748 (FEN1_HUMAN)
Flap endonuclease 1
FEN1
Functioni
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 34 | Magnesium 1Combined sources1 Publication | 1 | |
Binding sitei | 47 | DNA substrate | 1 | |
Binding sitei | 70 | DNA substrate | 1 | |
Metal bindingi | 86 | Magnesium 1Combined sources1 Publication | 1 | |
Metal bindingi | 158 | Magnesium 1Combined sources1 Publication | 1 | |
Binding sitei | 158 | DNA substrate | 1 | |
Metal bindingi | 160 | Magnesium 1Combined sources1 Publication | 1 | |
Metal bindingi | 179 | Magnesium 2Combined sources | 1 | |
Metal bindingi | 181 | Magnesium 2Combined sources1 Publication | 1 | |
Binding sitei | 231 | DNA substrate | 1 | |
Metal bindingi | 233 | Magnesium 2Combined sources | 1 | |
Binding sitei | 233 | DNA substrate | 1 |
GO - Molecular functioni
- 5'-3' exonuclease activity Source: UniProtKB
- 5'-flap endonuclease activity Source: UniProtKB
- damaged DNA binding Source: ProtInc
- DNA binding Source: UniProtKB
- double-stranded DNA binding Source: ProtInc
- double-stranded DNA exodeoxyribonuclease activity Source: ProtInc
- endonuclease activity Source: ProtInc
- exonuclease activity Source: ProtInc
- flap endonuclease activity Source: UniProtKB
- magnesium ion binding Source: GO_Central
- manganese ion binding Source: GO_Central
- RNA-DNA hybrid ribonuclease activity Source: UniProtKB
GO - Biological processi
- base-excision repair Source: UniProtKB-UniRule
- DNA repair Source: ProtInc
- DNA replication Source: ProtInc
- DNA replication, removal of RNA primer Source: UniProtKB
- double-strand break repair Source: ProtInc
- double-strand break repair via homologous recombination Source: Reactome
- memory Source: Ensembl
- nucleic acid phosphodiester bond hydrolysis Source: UniProtKB
- positive regulation of sister chromatid cohesion Source: UniProtKB
- telomere maintenance via semi-conservative replication Source: Reactome
- UV protection Source: ProtInc
Keywordsi
Molecular function | Endonuclease, Exonuclease, Hydrolase, Nuclease |
Biological process | DNA damage, DNA repair, DNA replication |
Ligand | Magnesium, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | P39748 |
Reactomei | R-HSA-110362, POLB-Dependent Long Patch Base Excision Repair R-HSA-162594, Early Phase of HIV Life Cycle R-HSA-174437, Removal of the Flap Intermediate from the C-strand R-HSA-5651801, PCNA-Dependent Long Patch Base Excision Repair R-HSA-5685939, HDR through MMEJ (alt-NHEJ) R-HSA-69166, Removal of the Flap Intermediate |
SignaLinki | P39748 |
SIGNORi | P39748 |
Names & Taxonomyi
Protein namesi | Recommended name: Flap endonuclease 1UniRule annotation (EC:3.1.-.-UniRule annotation)Short name: FEN-1UniRule annotation Alternative name(s): DNase IV Flap structure-specific endonuclease 1UniRule annotation Maturation factor 1 Short name: MF1 Short name: hFEN-1 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000168496.3 |
HGNCi | HGNC:3650, FEN1 |
MIMi | 600393, gene |
neXtProti | NX_P39748 |
Subcellular locationi
Nucleus
Note: Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage.
Mitochondrion
- Mitochondrion UniRule annotation1 Publication
Mitochondrion
- mitochondrion Source: UniProtKB
Nucleus
- nuclear chromosome, telomeric region Source: BHF-UCL
- nucleolus Source: HPA
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- membrane Source: UniProtKB
- protein-containing complex Source: MGI
Keywords - Cellular componenti
Mitochondrion, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 29 | R → A: No significant effect on exonuclease activity or flap endonuclease activity. 1 Publication | 1 | |
Mutagenesisi | 34 | D → A: Loss of flap endonuclease activity but substrate binding activity is retained. 1 Publication | 1 | |
Mutagenesisi | 47 | R → A: Significantly reduced exonuclease activity and reduced substrate binding. The positions of the cleavage sites are also shifted. 1 Publication | 1 | |
Mutagenesisi | 70 | R → A: Loss of exonuclease activity and reduced endonuclease activity. Reduced substrate binding. 1 Publication | 1 | |
Mutagenesisi | 73 | R → A: No significant effect on exonuclease activity or flap endonuclease activity. 1 Publication | 1 | |
Mutagenesisi | 80 | K → A: No significant effect on exonuclease activity or flap endonuclease activity. 1 Publication | 1 | |
Mutagenesisi | 86 | D → A: Loss of flap endonuclease activity but substrate binding activity is retained. 1 Publication | 1 | |
Mutagenesisi | 103 | R → A: No effect on flap endonuclease activity or substrate binding. 1 Publication | 1 | |
Mutagenesisi | 158 | E → A: Loss of flap endonuclease activity and substrate binding. 1 Publication | 1 | |
Mutagenesisi | 179 | D → A: No effect on flap endonuclease activity or substrate binding. 1 Publication | 1 | |
Mutagenesisi | 181 | D → A: Loss of flap endonuclease activity but substrate binding activity is retained. 1 Publication | 1 | |
Mutagenesisi | 187 | S → A: Fails to translocate from nucleoli to the nuclear plasma. 1 Publication | 1 | |
Mutagenesisi | 187 | S → D: Diminishes nucleolar localization. 1 Publication | 1 | |
Mutagenesisi | 192 | R → K: Impairs ability to localize to sites of DNA replication or repair. 1 Publication | 1 | |
Mutagenesisi | 231 | G → A: Loss of flap endonuclease activity and substrate binding. 1 Publication | 1 | |
Mutagenesisi | 233 | D → A: Loss of flap endonuclease activity and substrate binding. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 2237 |
OpenTargetsi | ENSG00000168496 |
PharmGKBi | PA28090 |
Miscellaneous databases
Pharosi | P39748, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5027 |
DrugBanki | DB14490, Ferrous ascorbate DB14491, Ferrous fumarate DB14488, Ferrous gluconate DB14501, Ferrous glycine sulfate DB14489, Ferrous succinate DB01592, Iron |
Polymorphism and mutation databases
BioMutai | FEN1 |
DMDMi | 729475 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000154069 | 1 – 380 | Flap endonuclease 1Add BLAST | 380 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 19 | Symmetric dimethylarginine; by PRMT5UniRule annotation1 Publication | 1 | |
Modified residuei | 80 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 100 | Symmetric dimethylarginine; by PRMT5UniRule annotation1 Publication | 1 | |
Modified residuei | 104 | Symmetric dimethylarginine; by PRMT5UniRule annotation1 Publication | 1 | |
Modified residuei | 187 | Phosphoserine; by CDK2UniRule annotation1 Publication | 1 | |
Modified residuei | 192 | Symmetric dimethylarginine; by PRMT5UniRule annotation1 Publication | 1 | |
Modified residuei | 197 | PhosphoserineCombined sources | 1 | |
Modified residuei | 255 | PhosphoserineCombined sources | 1 | |
Modified residuei | 293 | PhosphoserineCombined sources | 1 | |
Modified residuei | 335 | PhosphoserineCombined sources | 1 | |
Modified residuei | 336 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 354 | N6-acetyllysineUniRule annotation1 Publication | 1 | |
Modified residuei | 364 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 375 | N6-acetyllysineUniRule annotationCombined sources1 Publication | 1 | |
Modified residuei | 377 | N6-acetyllysineUniRule annotation1 Publication | 1 | |
Modified residuei | 380 | N6-acetyllysineUniRule annotation1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Methylation, PhosphoproteinProteomic databases
CPTACi | CPTAC-1409 CPTAC-1410 CPTAC-1411 CPTAC-3230 CPTAC-700 |
EPDi | P39748 |
jPOSTi | P39748 |
MassIVEi | P39748 |
PaxDbi | P39748 |
PeptideAtlasi | P39748 |
PRIDEi | P39748 |
ProteomicsDBi | 55319 [P39748-1] |
TopDownProteomicsi | P39748-1 [P39748-1] |
PTM databases
iPTMneti | P39748 |
MetOSitei | P39748 |
PhosphoSitePlusi | P39748 |
SwissPalmi | P39748 |
Expressioni
Gene expression databases
Bgeei | ENSG00000168496, Expressed in amniotic fluid and 231 other tissues |
ExpressionAtlasi | P39748, baseline and differential |
Genevisiblei | P39748, HS |
Organism-specific databases
HPAi | ENSG00000168496, Tissue enhanced (lymphoid) |
Interactioni
Subunit structurei
Three molecules of FEN1 bind to one PCNA trimer with each molecule binding to one PCNA monomer (PubMed:15616578). PCNA stimulates the nuclease activity without altering cleavage specificity (PubMed:15616578). The C-terminal domain binds EP300; can bind simultaneously to both PCNA and EP300 (PubMed:11430825).
Interacts with PCNA; can bind simultaneously to both PCNA and EP300 (PubMed:9305916, PubMed:11430825).
Interacts with DDX11; this interaction is direct and increases flap endonuclease activity of FEN1 (PubMed:18499658).
Interacts with WDR4; regulating its endonuclease activity (PubMed:26751069).
UniRule annotation5 PublicationsBinary interactionsi
Hide detailsP39748
With | #Exp. | IntAct |
---|---|---|
BLM [P54132] | 4 | EBI-707816,EBI-621372 |
MUS81 [Q96NY9] | 5 | EBI-707816,EBI-2370806 |
PCNA [P12004] | 19 | EBI-707816,EBI-358311 |
WDR4 [P57081] | 8 | EBI-707816,EBI-750427 |
WRN [Q14191] | 9 | EBI-707816,EBI-368417 |
Protein-protein interaction databases
BioGRIDi | 108528, 111 interactors |
CORUMi | P39748 |
DIPi | DIP-24216N |
ELMi | P39748 |
IntActi | P39748, 47 interactors |
MINTi | P39748 |
STRINGi | 9606.ENSP00000305480 |
Chemistry databases
BindingDBi | P39748 |
Miscellaneous databases
RNActi | P39748, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P39748 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P39748 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 104 | N-domainAdd BLAST | 104 | |
Regioni | 122 – 253 | I-domainAdd BLAST | 132 | |
Regioni | 336 – 344 | Interaction with PCNA1 Publication | 9 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2519, Eukaryota |
GeneTreei | ENSGT00940000155807 |
HOGENOMi | CLU_032444_2_0_1 |
InParanoidi | P39748 |
OMAi | CDYLDPI |
PhylomeDBi | P39748 |
TreeFami | TF105701 |
Family and domain databases
DisProti | DP01974 |
HAMAPi | MF_00614, Fen, 1 hit |
IDEALi | IID00044 |
InterProi | View protein in InterPro IPR036279, 5-3_exonuclease_C_sf IPR023426, Flap_endonuc IPR008918, HhH2 IPR029060, PIN-like_dom_sf IPR006086, XPG-I_dom IPR006084, XPG/Rad2 IPR019974, XPG_CS IPR006085, XPG_DNA_repair_N |
PANTHERi | PTHR11081, PTHR11081, 1 hit |
Pfami | View protein in Pfam PF00867, XPG_I, 1 hit PF00752, XPG_N, 1 hit |
PRINTSi | PR00853, XPGRADSUPER |
SMARTi | View protein in SMART SM00279, HhH2, 1 hit SM00484, XPGI, 1 hit SM00485, XPGN, 1 hit |
SUPFAMi | SSF47807, SSF47807, 1 hit SSF88723, SSF88723, 1 hit |
PROSITEi | View protein in PROSITE PS00841, XPG_1, 1 hit PS00842, XPG_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative initiation. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGIQGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG
60 70 80 90 100
DVLQNEEGET TSHLMGMFYR TIRMMENGIK PVYVFDGKPP QLKSGELAKR
110 120 130 140 150
SERRAEAEKQ LQQAQAAGAE QEVEKFTKRL VKVTKQHNDE CKHLLSLMGI
160 170 180 190 200
PYLDAPSEAE ASCAALVKAG KVYAAATEDM DCLTFGSPVL MRHLTASEAK
210 220 230 240 250
KLPIQEFHLS RILQELGLNQ EQFVDLCILL GSDYCESIRG IGPKRAVDLI
260 270 280 290 300
QKHKSIEEIV RRLDPNKYPV PENWLHKEAH QLFLEPEVLD PESVELKWSE
310 320 330 340 350
PNEEELIKFM CGEKQFSEER IRSGVKRLSK SRQGSTQGRL DDFFKVTGSL
360 370 380
SSAKRKEPEP KGSTKKKAKT GAAGKFKRGK
The sequence of this isoform differs from the canonical sequence as follows:
1-64: Missing.
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF5H1Y3 | F5H1Y3_HUMAN | Flap endonuclease 1 | FEN1 | 165 | Annotation score: | ||
I3L3E9 | I3L3E9_HUMAN | Flap endonuclease 1 | FEN1 | 154 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_047520 | 1 – 64 | Missing in isoform FENMIT. CuratedAdd BLAST | 64 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X76771 mRNA Translation: CAA54166.1 L37374 mRNA Translation: AAA91331.1 AF523117 Genomic DNA Translation: AAM74238.1 AC004770 Genomic DNA Translation: AAC23394.1 BC000323 mRNA Translation: AAH00323.1 |
CCDSi | CCDS8010.1 [P39748-1] |
PIRi | A56531 |
RefSeqi | NP_004102.1, NM_004111.5 [P39748-1] |
Genome annotation databases
Ensembli | ENST00000305885; ENSP00000305480; ENSG00000168496 [P39748-1] |
GeneIDi | 2237 |
KEGGi | hsa:2237 |
Keywords - Coding sequence diversityi
Alternative initiationSimilar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X76771 mRNA Translation: CAA54166.1 L37374 mRNA Translation: AAA91331.1 AF523117 Genomic DNA Translation: AAM74238.1 AC004770 Genomic DNA Translation: AAC23394.1 BC000323 mRNA Translation: AAH00323.1 |
CCDSi | CCDS8010.1 [P39748-1] |
PIRi | A56531 |
RefSeqi | NP_004102.1, NM_004111.5 [P39748-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1U7B | X-ray | 1.88 | B | 331-350 | [»] | |
1UL1 | X-ray | 2.90 | X/Y/Z | 2-380 | [»] | |
3Q8K | X-ray | 2.20 | A | 2-336 | [»] | |
3Q8L | X-ray | 2.32 | A | 2-336 | [»] | |
3Q8M | X-ray | 2.60 | A/B | 2-336 | [»] | |
3UVU | X-ray | 2.38 | B | 352-370 | [»] | |
5E0V | X-ray | 2.07 | C/D | 335-350 | [»] | |
5FV7 | X-ray | 2.84 | A/B | 1-336 | [»] | |
5K97 | X-ray | 2.10 | A | 2-336 | [»] | |
5KSE | X-ray | 2.10 | A | 2-336 | [»] | |
5UM9 | X-ray | 2.81 | A | 2-336 | [»] | |
5ZOD | X-ray | 1.90 | A | 1-333 | [»] | |
5ZOE | X-ray | 1.95 | A | 1-333 | [»] | |
5ZOF | X-ray | 2.25 | A | 1-333 | [»] | |
5ZOG | X-ray | 2.30 | A | 1-333 | [»] | |
6TNZ | electron microscopy | 4.05 | H | 1-380 | [»] | |
SMRi | P39748 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108528, 111 interactors |
CORUMi | P39748 |
DIPi | DIP-24216N |
ELMi | P39748 |
IntActi | P39748, 47 interactors |
MINTi | P39748 |
STRINGi | 9606.ENSP00000305480 |
Chemistry databases
BindingDBi | P39748 |
ChEMBLi | CHEMBL5027 |
DrugBanki | DB14490, Ferrous ascorbate DB14491, Ferrous fumarate DB14488, Ferrous gluconate DB14501, Ferrous glycine sulfate DB14489, Ferrous succinate DB01592, Iron |
PTM databases
iPTMneti | P39748 |
MetOSitei | P39748 |
PhosphoSitePlusi | P39748 |
SwissPalmi | P39748 |
Polymorphism and mutation databases
BioMutai | FEN1 |
DMDMi | 729475 |
Proteomic databases
CPTACi | CPTAC-1409 CPTAC-1410 CPTAC-1411 CPTAC-3230 CPTAC-700 |
EPDi | P39748 |
jPOSTi | P39748 |
MassIVEi | P39748 |
PaxDbi | P39748 |
PeptideAtlasi | P39748 |
PRIDEi | P39748 |
ProteomicsDBi | 55319 [P39748-1] |
TopDownProteomicsi | P39748-1 [P39748-1] |
Protocols and materials databases
ABCDi | P39748, 1 sequenced antibody |
Antibodypediai | 1878, 553 antibodies |
CPTCi | P39748, 1 antibody |
DNASUi | 2237 |
Genome annotation databases
Ensembli | ENST00000305885; ENSP00000305480; ENSG00000168496 [P39748-1] |
GeneIDi | 2237 |
KEGGi | hsa:2237 |
Organism-specific databases
CTDi | 2237 |
DisGeNETi | 2237 |
EuPathDBi | HostDB:ENSG00000168496.3 |
GeneCardsi | FEN1 |
HGNCi | HGNC:3650, FEN1 |
HPAi | ENSG00000168496, Tissue enhanced (lymphoid) |
MIMi | 600393, gene |
neXtProti | NX_P39748 |
OpenTargetsi | ENSG00000168496 |
PharmGKBi | PA28090 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2519, Eukaryota |
GeneTreei | ENSGT00940000155807 |
HOGENOMi | CLU_032444_2_0_1 |
InParanoidi | P39748 |
OMAi | CDYLDPI |
PhylomeDBi | P39748 |
TreeFami | TF105701 |
Enzyme and pathway databases
PathwayCommonsi | P39748 |
Reactomei | R-HSA-110362, POLB-Dependent Long Patch Base Excision Repair R-HSA-162594, Early Phase of HIV Life Cycle R-HSA-174437, Removal of the Flap Intermediate from the C-strand R-HSA-5651801, PCNA-Dependent Long Patch Base Excision Repair R-HSA-5685939, HDR through MMEJ (alt-NHEJ) R-HSA-69166, Removal of the Flap Intermediate |
SignaLinki | P39748 |
SIGNORi | P39748 |
Miscellaneous databases
BioGRID-ORCSi | 2237, 482 hits in 852 CRISPR screens |
ChiTaRSi | FEN1, human |
EvolutionaryTracei | P39748 |
GeneWikii | Flap_structure-specific_endonuclease_1 |
GenomeRNAii | 2237 |
Pharosi | P39748, Tchem |
PROi | PR:P39748 |
RNActi | P39748, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000168496, Expressed in amniotic fluid and 231 other tissues |
ExpressionAtlasi | P39748, baseline and differential |
Genevisiblei | P39748, HS |
Family and domain databases
DisProti | DP01974 |
HAMAPi | MF_00614, Fen, 1 hit |
IDEALi | IID00044 |
InterProi | View protein in InterPro IPR036279, 5-3_exonuclease_C_sf IPR023426, Flap_endonuc IPR008918, HhH2 IPR029060, PIN-like_dom_sf IPR006086, XPG-I_dom IPR006084, XPG/Rad2 IPR019974, XPG_CS IPR006085, XPG_DNA_repair_N |
PANTHERi | PTHR11081, PTHR11081, 1 hit |
Pfami | View protein in Pfam PF00867, XPG_I, 1 hit PF00752, XPG_N, 1 hit |
PRINTSi | PR00853, XPGRADSUPER |
SMARTi | View protein in SMART SM00279, HhH2, 1 hit SM00484, XPGI, 1 hit SM00485, XPGN, 1 hit |
SUPFAMi | SSF47807, SSF47807, 1 hit SSF88723, SSF88723, 1 hit |
PROSITEi | View protein in PROSITE PS00841, XPG_1, 1 hit PS00842, XPG_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | FEN1_HUMAN | |
Accessioni | P39748Primary (citable) accession number: P39748 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | February 1, 1995 | |
Last modified: | December 2, 2020 | |
This is version 205 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM