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92  structures 1234  species 1  interaction 5287  sequences 44  architectures

Family: MIP (PF00230)

Summary: Major intrinsic protein

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This is the Wikipedia entry entitled "Major intrinsic proteins". More...

Major intrinsic proteins Edit Wikipedia article

Major intrinsic protein
PDB 1fx8 EBI.jpg
Structure of a glycerol-conducting channel.[1]
Symbol MIP
Pfam PF00230
InterPro IPR000425
SCOP 1fx8
TCDB 1.A.8
OPM superfamily 7
OPM protein 1z98
CDD cd00333

Major intrinsic proteins are a large family of transmembrane protein channels that are grouped together on the basis of sequence similarities.[2][3][4][5] Proteins from this family exhibit essentially two distinct types of channel properties: (1) specific water transport by the aquaporins, and (2) small neutral solutes transport, such as glycerol by the glycerol facilitators.


MIP family includes the following channels:

  • Mammalian major intrinsic protein (MIP). MIP is the major component of lens fibre gap junctions.
  • Mammalian aquaporins.[5] These proteins form water-specific channels that provide the plasma membranes of red cells, as well as kidney proximal and collecting tubules with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient.
  • Soybean nodulin-26, a major component of the peribacteroid membrane induced during nodulation in legume roots after Rhizobium infection.
  • Plants tonoplast intrinsic proteins (TIP). There are various isoforms of TIP : alpha (seed), gamma, Rt (root), and Wsi (water-stress induced). These proteins may allow the diffusion of water, amino acids and/or peptides from the tonoplast interior to the cytoplasm..
  • Bacterial glycerol facilitator protein (gene glpF), which facilitates the movement of glycerol across the cytoplasmic membrane.
  • Salmonella typhimurium propanediol diffusion fac ilitator (gene pduF).
  • Yeast FPS1, a glycerol uptake/efflux facilitator protein.
  • Drosophila neurogenic protein 'big brain' (bib). This protein may mediate in tercellular communication; it may functions by allowing the transport of certain molecules(s) and thereby sending a signal for an exodermal cell to become an ep idermoblast instead of a neuroblast.
  • Yeast hypothetical protein YFL054c.
  • A hypothetical protein from the pepX region of Lactococcus lactis.


MIP family proteins are thought to contain 6 TM domains. Sequence analysis suggests that the proteins may have arisen through tandem, intragenic duplication from an ancestral protein that contained 3 TM domains.[6]

Some of the proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins.[7] Aquaporin-CHIP (Aquaporin 1) belongs to the Colton blood group system and is associated with Co(a/b) antigen.


Human proteins containing this domain


See also


  1. ^ Fu D, Libson A, Miercke LJ; et al. (October 2000). "Structure of a glycerol-conducting channel and the basis for its selectivity". Science 290 (5491): 481–6. doi:10.1126/science.290.5491.481. PMID 11039922. 
  2. ^ Reizer J, Reizer A, Saier Jr MH (1993). "The MIP family of integral membrane channel proteins: sequence comparisons, evolutionary relationships, reconstructed pathway of evolution, and proposed functional differentiation of the two repeated halves of the proteins". Crit. Rev. Biochem. Mol. Biol. 28 (3): 235–257. doi:10.3109/10409239309086796. PMID 8325040. 
  3. ^ Pao GM, Johnson KD, Chrispeels MJ, Sweet G, Sandal NN, Wu LF, Saier Jr MH, Hofte H (1991). "Evolution of the MIP family of integral membrane transport proteins". Mol. Microbiol. 5 (1): 33–37. doi:10.1111/j.1365-2958.1991.tb01823.x. PMID 2014003. 
  4. ^ Wistow GJ, Pisano MM, Chepelinsky AB (1991). "Tandem sequence repeats in transmembrane channel proteins". Trends Biochem. Sci. 16 (5): 170–171. doi:10.1016/0968-0004(91)90065-4. PMID 1715617. 
  5. ^ a b Chrispeels MJ, Agre P (1994). "Aquaporins: water channel proteins of plant and animal cells". Trends Biochem. Sci. 19 (10): 421–425. doi:10.1016/0968-0004(94)90091-4. PMID 7529436. 
  6. ^ . pp. –.  Missing or empty |title= (help)
  7. ^ Reid ME, Lomas-francis C (2002). "Molecular approaches to blood group identification". Current Opinion in Hematology 9 (2): 152–159. doi:10.1097/00062752-200203000-00012. PMID 11845000. 

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Major intrinsic protein Provide feedback

MIP (Major Intrinsic Protein) family proteins exhibit essentially two distinct types of channel properties: (1) specific water transport by the aquaporins, and (2) small neutral solutes transport, such as glycerol by the glycerol facilitators [1].

Literature references

  1. Froger A, Tallur B, Thomas D, Delamarche C; , Protein Sci 1998;7:1458-1468.: Prediction of functional residues in water channels and related proteins. PUBMED:9655351 EPMC:9655351

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000425

The major intrinsic protein (MIP) family is large and diverse, possessing over 100 members that form transmembrane channels. These channel proteins function in water, small carbohydrate (e.g., glycerol), urea, NH3, CO2 and possibly ion transport, by an energy independent mechanism. They are found ubiquitously in bacteria, archaea and eukaryotes.

The MIP family contains two major groups of channels: aquaporins and glycerol facilitators. The known aquaporins cluster loosely together as do the known glycerol facilitators. MIP family proteins are believed to form aqueous pores that selectively allow passive transport of their solute(s) across the membrane with minimal apparent recognition. Aquaporins selectively transport water (but not glycerol) while glycerol facilitators selectively transport glycerol but not water. Some aquaporins can transport NH3 and CO2. Glycerol facilitators function as solute nonspecific channels, and may transport glycerol, dihydroxyacetone, propanediol, urea and other small neutral molecules in physiologically important processes. Some members of the family, including the yeast FPS protein and tobacco NtTIPA may transport both water and small solutes.

The structures of various members of the MIP family have been determined by means of X-ray diffraction [PUBMED:11780053, PUBMED:10957645, PUBMED:11039922], revealing the fold to comprise a right-handed bundle of 6 transmembrane (TM) alpha-helices [PUBMED:11780053, PUBMED:10957645, PUBMED:11039922]. Similarities in the N-and C-terminal halves of the molecule suggest that the proteins may have arisen through tandem, intragenic duplication of an ancestral protein that contained 3 TM domains [PUBMED:1715617].

For more information on the MIP family, see

Gene Ontology

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Domain organisation

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Curation and family details

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Seed source: Prosite
Previous IDs: none
Type: Family
Author: Finn RD, Delamarche C
Number in seed: 12
Number in full: 5287
Average length of the domain: 208.50 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 76.59 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 11927849 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.0 21.0
Trusted cut-off 21.0 21.0
Noise cut-off 20.9 20.9
Model length: 227
Family (HMM) version: 17
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the MIP domain has been found. There are 92 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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