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198  structures 135  species 0  interactions 985  sequences 16  architectures

Family: MHC_I_3 (PF16497)

Summary: MHC-I family domain

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MHC-I family domain Provide feedback

No Pfam abstract.

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR011161

Class I MHC glycoproteins are expressed on the surface of all somatic nucleated cells, with the exception of neurons. MHC class I receptors present peptide antigens that are synthesised in the cytoplasm, which includes self-peptides (presented for self-tolerance) as well as foreign peptides (such as viral proteins). These antigens are generated from degraded protein fragments that are transported to the endoplasmic reticulum by TAP proteins (transporter of antigenic peptides), where they can bind MHC I molecules, before being transported to the cell surface via the Golgi apparatus [ PUBMED:9485452 , PUBMED:15526153 ]. MHC class I receptors display antigens for recognition by cytotoxic T cells, which have the ability to destroy viral-infected or malignant (surfeit of self-peptides) cells.

MHC class I molecules are comprised of two chains: a MHC alpha chain (heavy chain), and a beta2-microglobulin chain (light chain), where only the alpha chain spans the membrane. The alpha chain has three extracellular domains (alpha 1-3, with alpha1 being at the N terminus), a transmembrane region and a C-terminal cytoplasmic tail. The soluble extracellular beta-2 microglobulin chain associates primarily with the alpha-3 domain and is necessary for MHC stability. The alpha1 and alpha2 domains of the alpha chain are referred to as the recognition region, because the peptide antigen binds in a deep groove between these two domains.

This entry represents MHC antigen-recognition-like domains from:

  • MHC class I, alpha-1 and alpha-2 domains [ PUBMED:15454423 ]
  • MHC class I homologue gammadelta T-cell ligand [ PUBMED:17291278 ]
  • MHC class I related Ulbp3 [ PUBMED:12857997 ]
  • MHC class I related Fc (IgG) receptor, alpha-1 and alpha-2 domains [ PUBMED:7969498 ]
  • MHC class I related CD1, alpha-1 and alpha-2 domains [ PUBMED:11677624 ]
  • MHC class I related zinc-alpha-2-glycoprotein ZAG (fat depleting factor) [ PUBMED:16475792 ]
  • Immunomodulatory protein m144, alpha-1 and alpha-2 domains [ PUBMED:16500675 ]
  • Haemochromatosis protein Hfe, alpha-1 and alpha-2 domains [ PUBMED:12667138 ]
  • Endothelial protein C receptor (phospholipid-binding protein) [ PUBMED:17327234 ]
  • NK cell ligand RAE-1 [ PUBMED:12594837 ]. RAE-1 proteins (alpha, beta, delta, and gamma) are distant major histocompatibility complex (MHC) class I homologues, comprising isolated alpha-1 alpha-2 domains, and lack alpha3 domains [ PUBMED:11825567 ].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan MHC (CL0343), which has the following description:

This superfamily includes all the Class I-related antigen-recognition domain families.

The clan contains the following 6 members:

M157 MHC_I MHC_I_2 MHC_I_3 MHC_II_alpha MHC_II_beta


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

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Representative proteomes UniProt

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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: manual
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Coggill P
Number in seed: 15
Number in full: 985
Average length of the domain: 179.70 aa
Average identity of full alignment: 36 %
Average coverage of the sequence by the domain: 58.20 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 35.0 35.0
Trusted cut-off 35.0 35.0
Noise cut-off 34.9 34.9
Model length: 198
Family (HMM) version: 7
Download: download the raw HMM for this family

Species distribution

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Colour assignments

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


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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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 MHC_I_3 domain has been found. There are 198 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 sequence.

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