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Q13224 (NMDE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glutamate receptor ionotropic, NMDA 2B

Short name=GluN2B
Alternative name(s):
Glutamate [NMDA] receptor subunit epsilon-2
N-methyl D-aspartate receptor subtype 2B
Short name=NMDAR2B
Short name=NR2B
N-methyl-D-aspartate receptor subunit 3
Short name=NR3
Short name=hNR3
Gene names
Name:GRIN2B
Synonyms:NMDAR2B
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1484 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death By similarity.

Subunit structure

Forms heteromeric channel of a zeta subunit (GRIN1), a epsilon subunit (GRIN2A, GRIN2B, GRIN2C or GRIN2D) and a third subunit (GRIN3A or GRIN3B). Found in a complex with GRIN1 and GRIN3B. Found in a complex with GRIN1, GRIN3A and PPP2CB. Interacts with PDZ domains of INADL and DLG4. Interacts with HIP1 and NETO1 By similarity. Interacts with MAGI3. Interacts with DAPK1 By similarity. Ref.7

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctionsynapsepostsynaptic cell membrane; Multi-pass membrane protein.

Tissue specificity

Primarily found in the fronto-parieto-temporal cortex and hippocampus pyramidal cells, lower expression in the basal ganglia. Ref.6

Post-translational modification

Phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity By similarity.

Involvement in disease

Mental retardation, autosomal dominant 6 (MRD6) [MIM:613970]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9

A chromosomal aberrations involving GRIN2B has been found in patients with mental retardation. Translocations t(9;12)(p23;p13.1) and t(10;12)(q21.1;p13.1) with a common breakpoint in 12p13.1.

Sequence similarities

Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2B/GRIN2B subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCell junction
Cell membrane
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityChromosomal rearrangement
Polymorphism
   DiseaseDisease mutation
Mental retardation
   DomainSignal
Transmembrane
Transmembrane helix
   LigandCalcium
Magnesium
Metal-binding
Zinc
   Molecular functionIon channel
Ligand-gated ion channel
Receptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbehavioral fear response

Inferred from electronic annotation. Source: Ensembl

behavioral response to pain

Inferred from electronic annotation. Source: Ensembl

detection of mechanical stimulus involved in sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

glutamate receptor signaling pathway

Traceable author statement Ref.2. Source: ProtInc

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

ion transmembrane transport

Inferred from Biological aspect of Ancestor. Source: RefGenome

ionotropic glutamate receptor signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

learning

Inferred from electronic annotation. Source: Ensembl

learning or memory

Traceable author statement PubMed 10485705. Source: ProtInc

memory

Inferred from electronic annotation. Source: Ensembl

regulation of excitatory postsynaptic membrane potential

Inferred from electronic annotation. Source: Ensembl

regulation of synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from direct assay PubMed 18445116. Source: UniProtKB

sensory organ development

Inferred from electronic annotation. Source: Ensembl

startle response

Inferred from electronic annotation. Source: Ensembl

suckling behavior

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement. Source: Reactome

synaptic transmission, glutamatergic

Inferred from Biological aspect of Ancestor. Source: RefGenome

transport

Traceable author statement Ref.2. Source: ProtInc

   Cellular_componentN-methyl-D-aspartate selective glutamate receptor complex

Inferred from direct assay PubMed 10480938PubMed 17047094. Source: UniProtKB

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cell surface

Inferred from sequence or structural similarity. Source: BHF-UCL

dendrite

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of plasma membrane

Traceable author statement Ref.2. Source: ProtInc

neuron projection

Inferred from sequence or structural similarity. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic density

Inferred from electronic annotation. Source: Ensembl

postsynaptic membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

synaptic vesicle

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionN-methyl-D-aspartate selective glutamate receptor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

calcium channel activity

Inferred from electronic annotation. Source: Ensembl

extracellular-glutamate-gated ion channel activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

glycine binding

Inferred from direct assay PubMed 17047094. Source: UniProtKB

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CAMK2AQ9UQM73EBI-2256942,EBI-1383687
Dlg3Q629364EBI-2256942,EBI-349596From a different organism.
DLG4P783522EBI-2256942,EBI-80389
Dlg4P310162EBI-2256942,EBI-375655From a different organism.
PPP1CAP621392EBI-2256942,EBI-2008988From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 14841458Glutamate receptor ionotropic, NMDA 2B
PRO_0000011577

Regions

Topological domain27 – 557531Extracellular Potential
Transmembrane558 – 57821Helical; Potential
Topological domain579 – 63456Cytoplasmic Potential
Transmembrane635 – 65521Helical; Potential
Topological domain656 – 817162Extracellular Potential
Transmembrane818 – 83821Helical; Potential
Topological domain839 – 1484646Cytoplasmic Potential
Region1292 – 130413Interaction with DAPK1 By similarity
Motif1482 – 14843PDZ-binding By similarity
Compositional bias984 – 9896Poly-His
Compositional bias1361 – 13644Poly-His

Sites

Metal binding1271Zinc By similarity
Metal binding2841Zinc By similarity
Site6151Functional determinant of NMDA receptors By similarity

Amino acid modifications

Modified residue9621Phosphotyrosine By similarity
Modified residue10391Phosphotyrosine By similarity
Modified residue11091Phosphotyrosine By similarity
Modified residue11331Phosphotyrosine By similarity
Modified residue11551Phosphotyrosine By similarity
Modified residue13031Phosphoserine; by DAPK1 By similarity
Modified residue14741Phosphotyrosine By similarity
Glycosylation741N-linked (GlcNAc...) Potential
Glycosylation3411N-linked (GlcNAc...) Potential
Glycosylation3481N-linked (GlcNAc...) Potential
Glycosylation4441N-linked (GlcNAc...) Potential
Glycosylation4911N-linked (GlcNAc...) Potential
Glycosylation5421N-linked (GlcNAc...) Potential
Glycosylation6881N-linked (GlcNAc...) Potential
Disulfide bond86 ↔ 321 By similarity

Natural variations

Natural variant4071S → N. Ref.1
VAR_011317
Natural variant5531P → L in MRD6. Ref.9
VAR_069384
Natural variant6821R → C in MRD6; analysis of agonist dose-response curves reveal no differences in the affinities of wild-type and mutant receptors for glutamate and glycine. Ref.8
VAR_065900

Experimental info

Sequence conflict4341V → A in AAD00659. Ref.3
Sequence conflict7451G → A in AAA69920. Ref.5
Sequence conflict7731K → N in AAA69920. Ref.5
Sequence conflict7731K → N in AAA74930. Ref.5
Sequence conflict7961W → C in AAA69920. Ref.5
Sequence conflict7961W → C in AAA74930. Ref.5
Sequence conflict8881T → P in AAA69920. Ref.5
Sequence conflict8881T → P in AAA74930. Ref.5
Sequence conflict9021L → V in AAA69920. Ref.5
Sequence conflict9021L → V in AAA74930. Ref.5
Sequence conflict920 – 9212SA → RP in AAB60368. Ref.1
Sequence conflict9581L → S in AAA69920. Ref.5
Sequence conflict9581L → S in AAA74930. Ref.5
Sequence conflict980 – 9823VYQ → DHY in AAA69920. Ref.5
Sequence conflict10561I → M in AAA69920. Ref.5
Sequence conflict11671V → I in AAB49993. Ref.2

Secondary structure

.......................................... 1484
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q13224 [UniParc].

Last modified June 20, 2001. Version 3.
Checksum: 40AEB12BE6E50CEF

FASTA1,484166,367
        10         20         30         40         50         60 
MKPRAECCSP KFWLVLAVLA VSGSRARSQK SPPSIGIAVI LVGTSDEVAI KDAHEKDDFH 

        70         80         90        100        110        120 
HLSVVPRVEL VAMNETDPKS IITRICDLMS DRKIQGVVFA DDTDQEAIAQ ILDFISAQTL 

       130        140        150        160        170        180 
TPILGIHGGS SMIMADKDES SMFFQFGPSI EQQASVMLNI MEEYDWYIFS IVTTYFPGYQ 

       190        200        210        220        230        240 
DFVNKIRSTI ENSFVGWELE EVLLLDMSLD DGDSKIQNQL KKLQSPIILL YCTKEEATYI 

       250        260        270        280        290        300 
FEVANSVGLT GYGYTWIVPS LVAGDTDTVP AEFPTGLISV SYDEWDYGLP ARVRDGIAII 

       310        320        330        340        350        360 
TTAASDMLSE HSFIPEPKSS CYNTHEKRIY QSNMLNRYLI NVTFEGRNLS FSEDGYQMHP 

       370        380        390        400        410        420 
KLVIILLNKE RKWERVGKWK DKSLQMKYYV WPRMCPETEE QEDDHLSIVT LEEAPFVIVE 

       430        440        450        460        470        480 
SVDPLSGTCM RNTVPCQKRI VTENKTDEEP GYIKKCCKGF CIDILKKISK SVKFTYDLYL 

       490        500        510        520        530        540 
VTNGKHGKKI NGTWNGMIGE VVMKRAYMAV GSLTINEERS EVVDFSVPFI ETGISVMVSR 

       550        560        570        580        590        600 
SNGTVSPSAF LEPFSADVWV MMFVMLLIVS AVAVFVFEYF SPVGYNRCLA DGREPGGPSF 

       610        620        630        640        650        660 
TIGKAIWLLW GLVFNNSVPV QNPKGTTSKI MVSVWAFFAV IFLASYTANL AAFMIQEEYV 

       670        680        690        700        710        720 
DQVSGLSDKK FQRPNDFSPP FRFGTVPNGS TERNIRNNYA EMHAYMGKFN QRGVDDALLS 

       730        740        750        760        770        780 
LKTGKLDAFI YDAAVLNYMA GRDEGCKLVT IGSGKVFAST GYGIAIQKDS GWKRQVDLAI 

       790        800        810        820        830        840 
LQLFGDGEME ELEALWLTGI CHNEKNEVMS SQLDIDNMAG VFYMLGAAMA LSLITFICEH 

       850        860        870        880        890        900 
LFYWQFRHCF MGVCSGKPGM VFSISRGIYS CIHGVAIEER QSVMNSPTAT MNNTHSNILR 

       910        920        930        940        950        960 
LLRTAKNMAN LSGVNGSPQS ALDFIRRESS VYDISEHRRS FTHSDCKSYN NPPCEENLFS 

       970        980        990       1000       1010       1020 
DYISEVERTF GNLQLKDSNV YQDHYHHHHR PHSIGSASSI DGLYDCDNPP FTTQSRSISK 

      1030       1040       1050       1060       1070       1080 
KPLDIGLPSS KHSQLSDLYG KFSFKSDRYS GHDDLIRSDV SDISTHTVTY GNIEGNAAKR 

      1090       1100       1110       1120       1130       1140 
RKQQYKDSLK KRPASAKSRR EFDEIELAYR RRPPRSPDHK RYFRDKEGLR DFYLDQFRTK 

      1150       1160       1170       1180       1190       1200 
ENSPHWEHVD LTDIYKERSD DFKRDSVSGG GPCTNRSHIK HGTGDKHGVV SGVPAPWEKN 

      1210       1220       1230       1240       1250       1260 
LTNVEWEDRS GGNFCRSCPS KLHNYSTTVT GQNSGRQACI RCEACKKAGN LYDISEDNSL 

      1270       1280       1290       1300       1310       1320 
QELDQPAAPV AVTSNASTTK YPQSPTNSKA QKKNRNKLRR QHSYDTFVDL QKEEAALAPR 

      1330       1340       1350       1360       1370       1380 
SVSLKDKGRF MDGSPYAHMF EMSAGESTFA NNKSSVPTAG HHHHNNPGGG YMLSKSLYPD 

      1390       1400       1410       1420       1430       1440 
RVTQNPFIPT FGDDQCLLHG SKSYFFRQPT VAGASKARPD FRALVTNKPV VSALHGAVPA 

      1450       1460       1470       1480 
RFQKDICIGN QSNPCVPNNK NPRAFNGSSN GHVYEKLSSI ESDV 

« Hide

References

« Hide 'large scale' references
[1]"Human N-methyl-D-aspartate receptor modulatory subunit hNR3: cloning and sequencing of the cDNA and primary structure of the protein."
Adams S.L., Foldes R.L., Kamboj R.K.
Biochim. Biophys. Acta 1260:105-108(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASN-407.
Tissue: Fetal brain.
[2]"Cloning and functional characterization of human heteromeric N-methyl-D-aspartate receptors."
Hess S.D., Daggett L.P., Crona J., Deal C., Lu C.-C., Urrutia A., Chavez-Noriega L., Ellis S.B., Johnson E.C., Velicelebi G.
J. Pharmacol. Exp. Ther. 278:808-816(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal brain.
[3]"Cloning of GRIN2B human subunit."
Mandich P., Schito A.M., Pizzuti A., Ratti A.
Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Cerebellum.
[5]"Mapping of the human NMDAR2B receptor subunit gene (GRIN2B) to chromosome 12p12."
Mandich P., Schito A.M., Bellone E., Antonacci R., Finelli P., Rocchi M., Ajmar F.
Genomics 22:216-218(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-294 AND 661-1089.
[6]"mRNA distribution in adult human brain of GRIN2B, a N-methyl-D-aspartate (NMDA) receptor subunit."
Schito A.M., Pizzuti A., Di Maria E., Schenone A., Ratti A., Defferrari R., Bellone E., Mancardi G.L., Ajmar F., Mandich P.
Neurosci. Lett. 239:49-53(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[7]"Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase."
Wu Y., Dowbenko D., Spencer S., Laura R., Lee J., Gu Q., Lasky L.A.
J. Biol. Chem. 275:21477-21485(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAGI3.
[8]"Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes."
Endele S., Rosenberger G., Geider K., Popp B., Tamer C., Stefanova I., Milh M., Kortum F., Fritsch A., Pientka F.K., Hellenbroich Y., Kalscheuer V.M., Kohlhase J., Moog U., Rappold G., Rauch A., Ropers H.H., von Spiczak S. expand/collapse author list , Tonnies H., Villeneuve N., Villard L., Zabel B., Zenker M., Laube B., Reis A., Wieczorek D., Van Maldergem L., Kutsche K.
Nat. Genet. 42:1021-1026(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATIONS, VARIANT MRD6 CYS-682.
[9]"Diagnostic exome sequencing in persons with severe intellectual disability."
de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G., Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G., Veltman J.A., Vissers L.E.
N. Engl. J. Med. 367:1921-1929(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MRD6 LEU-553.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U90278 mRNA. Translation: AAB49993.1.
U88963 mRNA. Translation: AAD00659.1.
U11287 mRNA. Translation: AAB60368.1.
BC113618 mRNA. Translation: AAI13619.1.
BC113620 mRNA. Translation: AAI13621.1.
U28758 mRNA. Translation: AAA74930.1.
U28861 mRNA. Translation: AAA69919.1.
U28862 mRNA. Translation: AAA69920.1.
PIRI39066.
S52086.
RefSeqNP_000825.2. NM_000834.3.
UniGeneHs.654430.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1S11model-A403-543[»]
B660-801[»]
1S2Smodel-A405-543[»]
B660-801[»]
2IPVmodel-X404-768[»]
ProteinModelPortalQ13224.
SMRQ13224. Positions 32-836.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109161. 25 interactions.
IntActQ13224. 11 interactions.
MINTMINT-127466.
STRING9606.ENSP00000279593.

Chemistry

BindingDBQ13224.
ChEMBLCHEMBL1907603.
DrugBankDB00949. Felbamate.
DB00502. Haloperidol.
DB00142. L-Glutamic Acid.
DB00836. Loperamide.
DB01043. Memantine.
GuidetoPHARMACOLOGY457.

PTM databases

PhosphoSiteQ13224.

Polymorphism databases

DMDM14548162.

Proteomic databases

PaxDbQ13224.
PeptideAtlasQ13224.
PRIDEQ13224.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000609686; ENSP00000477455; ENSG00000273079.
GeneID2904.
KEGGhsa:2904.
UCSCuc001rbt.2. human.

Organism-specific databases

CTD2904.
GeneCardsGC12M013714.
H-InvDBHIX0036873.
HGNCHGNC:4586. GRIN2B.
MIM138252. gene.
613970. phenotype.
neXtProtNX_Q13224.
Orphanet178469. Autosomal dominant nonsyndromic intellectual deficit.
PharmGKBPA28980.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG282132.
HOGENOMHOG000113802.
HOVERGENHBG052635.
InParanoidQ13224.
KOK05210.
OMACTNRSHL.
OrthoDBEOG72ZCD1.
PhylomeDBQ13224.
TreeFamTF314731.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
SignaLinkQ13224.

Gene expression databases

ArrayExpressQ13224.
BgeeQ13224.
CleanExHS_GRIN2B.
GenevestigatorQ13224.

Family and domain databases

InterProIPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu_rcpt_Glu/Gly-bd.
IPR001320. Iontro_glu_rcpt.
IPR001508. NMDA_rcpt.
IPR018884. NMDAR2_C.
IPR028082. Peripla_BP_I.
IPR001638. SBP_bac_3.
[Graphical view]
PfamPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10565. NMDAR2_C. 1 hit.
PF00497. SBP_bac_3. 1 hit.
[Graphical view]
PRINTSPR00177. NMDARECEPTOR.
SMARTSM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
[Graphical view]
SUPFAMSSF53822. SSF53822. 1 hit.
ProtoNetSearch...

Other

GeneWikiGRIN2B.
GenomeRNAi2904.
NextBio11499.
PROQ13224.
SOURCESearch...

Entry information

Entry nameNMDE2_HUMAN
AccessionPrimary (citable) accession number: Q13224
Secondary accession number(s): Q12919 expand/collapse secondary AC list , Q13220, Q13225, Q14CU4, Q9UM56
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: June 20, 2001
Last modified: April 16, 2014
This is version 146 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM