Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
0  structures 240  species 0  interactions 576  sequences 7  architectures

Family: VIT_2 (PF13757)

Summary: Vault protein inter-alpha-trypsin domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

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.

Vault protein inter-alpha-trypsin domain Provide feedback

Inter-alpha-trypsin inhibitors (ITIs) consist of one light chain and a variable set of heavy chains. ITIs play a role in extracellular matrix (ECM) stabilisation and tumour metastasis as well as in plasma protease inhibition [1]. The vault protein inter-alpha-trypsin (VIT) domain described here is found to the N-terminus of a von Willebrand factor type A domain (PF00092) in ITI heavy chains (ITIHs) and their precursors.

Literature references

  1. Himmelfarb M, Klopocki E, Grube S, Staub E, Klaman I, Hinzmann B, Kristiansen G, Rosenthal A, Durst M, Dahl E; , Cancer Lett 2004;204:69-77.: ITIH5, a novel member of the inter-alpha-trypsin inhibitor heavy chain family is downregulated in breast cancer. PUBMED:14744536 EPMC:14744536

  2. Mayne R, Ren ZX, Liu J, Cook T, Carson M, Narayana S;, Biochem Soc Trans. 1999;27:832-835.: VIT-1: the second member of a new branch of the von Willebrand factor A domain superfamily. PUBMED:10830112 EPMC:10830112

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR013694

The inter-alpha-trypsin inhibitor (ITI) family is composed of protease inhibitors that are assembled from two precursor proteins: a light chain and different homologous heavy chains (ITIHs). Originally identified as plasma inhibitors, recent data indicate that ITI plays a role in extracellular matrix stabilisation and in prevention of tumour metastasis [ PUBMED:14744536 ].

Two domains are conserved in all known ITIHs, the vault protein inter-alpha- trypsin (VIT) domain and a von Willebrand type A (vWA) domain. The VIT domain is less widespread than the vWA domain and is not genetically mobile. Therefore, it can be regarded as the characteristic domain of the ITIH family. The VIT domain is approximately 135 amino acids long. Its N-terminal part contains a pattern of hydrophobic residues, interrupted by a conserved arginine. The C terminus is best characterised by its conserved aromatic residues. In the central part, an acidic amino acid resides between two basic residues [ PUBMED:14744536 ].

Domain organisation

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

Loading domain graphics...


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...

View options

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.

Representative proteomes UniProt
Jalview View  View  View  View  View  View  View 
HTML View  View           
PP/heatmap 1 View           

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

Download options

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.

Representative proteomes UniProt
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

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: Jackhmmer:A8MTC4
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Coggill P
Number in seed: 6
Number in full: 576
Average length of the domain: 75.20 aa
Average identity of full alignment: 53 %
Average coverage of the sequence by the domain: 6.90 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.0 23.0
Trusted cut-off 23.0 23.0
Noise cut-off 22.9 22.9
Model length: 78
Family (HMM) version: 9
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

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


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

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...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0R4IHR3 View 3D Structure Click here
A9Z1V5 View 3D Structure Click here
D3ZP60 View 3D Structure Click here
D4A7U5 View 3D Structure Click here
Q3UR50 View 3D Structure Click here
Q5TIE3 View 3D Structure Click here
Q8N398 View 3D Structure Click here

trRosetta Structure

The structural model below was generated by the Baker group with the trRosetta software using the Pfam UniProt multiple sequence alignment.

The InterPro website shows the contact map for the Pfam SEED alignment. Hovering or clicking on a contact position will highlight its connection to other residues in the alignment, as well as on the 3D structure.

Improved protein structure prediction using predicted inter-residue orientations. Jianyi Yang, Ivan Anishchenko, Hahnbeom Park, Zhenling Peng, Sergey Ovchinnikov, David Baker Proceedings of the National Academy of Sciences Jan 2020, 117 (3) 1496-1503; DOI: 10.1073/pnas.1914677117;