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.
1678  structures 291  species 11  interactions 2328  sequences 15  architectures

Family: Insulin (PF00049)

Summary: Insulin/IGF/Relaxin family

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

This is the Wikipedia entry entitled "Insulin/IGF/Relaxin family". More...

Insulin/IGF/Relaxin family Edit Wikipedia article

Insulin/IGF/Relaxin family
PBB Protein INS image.jpg
PDB rendering based on 1ai0.
Symbol Insulin
Pfam PF00049
Pfam clan CL0239
InterPro IPR004825
SCOP 1cph

The insulin/IGF/relaxin family is a group of evolutionary related proteins which possess a variety of hormonal activities.[1] Family members in human include two subfamilies:

1) insulin and insulin-like growth factors[2]

2) relaxin family peptides:

  • relaxins 1 and 2
  • relaxin 3
  • Leydig cell-specific insulin-like peptide (gene INSL3)[3]
  • early placenta insulin-like peptide (ELIP) (gene INSL4)[4]
  • insulin-like peptide 5 (gene INSL5)
  • insulin-like peptide 6


These proteins are characterized by having three disulfide bonds in a characteristic motif. Some family members have an additional disulfide bond also in a conserved location. All of these proteins have a helical segment (corresponding to B chain in insulin) followed by a variable-length chain, followed by a domain (A chain in insulin) with two helices pinned against each other via a disulfide bond. These two regions are linked by two or three disulfide bonds.

Amongst the different proteins in the family, very little of the sequence is conserved except for the disulfide bonds. The variable-length chains may exhibit large inter-species variation even when the remainder of the sequence is highly conserved; and as is in the case of insulin, sometimes the variable length chain is cleaved out by secretory endoproteases, leaving a two-chain protein held together by disulfide bonds.

See also


  1. ^ Blundell TL, Humbel RE (October 1980). "Hormone families: pancreatic hormones and homologous growth factors". Nature. 287 (5785): 781–7. doi:10.1038/287781a0. PMID 6107857. 
  2. ^ Humbel RE (July 1990). "Insulin-like growth factors I and II". European Journal of Biochemistry / FEBS. 190 (3): 445–62. doi:10.1111/j.1432-1033.1990.tb15595.x. PMID 2197088. 
  3. ^ Adham IM, Burkhardt E, Benahmed M, Engel W (December 1993). "Cloning of a cDNA for a novel insulin-like peptide of the testicular Leydig cells". The Journal of Biological Chemistry. 268 (35): 26668–72. PMID 8253799. 
  4. ^ Chassin D, Laurent A, Janneau JL, Berger R, Bellet D (September 1995). "Cloning of a new member of the insulin gene superfamily (INSL4) expressed in human placenta". Genomics. 29 (2): 465–70. doi:10.1006/geno.1995.9980. PMID 8666396. 

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

Insulin/IGF/Relaxin family Provide feedback

Superfamily includes insulins; relaxins; insulin-like growth factor; and bombyxin. All are secreted regulatory hormones. Disulfide rich, all-alpha fold. Alignment includes B chain, linker (which is processed out of the final product), and A chain.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR016179

The insulin family of proteins groups together several evolutionarily related active peptides [PUBMED:6107857]: these include insulin [PUBMED:6243748, PUBMED:503234], relaxin [PUBMED:10601981, PUBMED:8735594], insect prothoracicotropic hormone (bombyxin) [PUBMED:8683595], insulin-like growth factors (IGF1 and IGF2) [PUBMED:2036417, PUBMED:1319992], mammalian Leydig cell-specific insulin-like peptide (gene INSL3), early placenta insulin-like peptide (ELIP) (gene INSL4), locust insulin-related peptide (LIRP), molluscan insulin-related peptides (MIP), and Caenorhabditis elegans insulin-like peptides. The 3D structures of a number of family members have been determined [PUBMED:2036417, PUBMED:1319992, PUBMED:9141131]. The fold comprises two polypeptide chains (A and B) linked by two disulphide bonds: all share a conserved arrangement of 4 cysteines in their A chain, the first of which is linked by a disulphide bond to the third, while the second and fourth are linked by interchain disulphide bonds to cysteines in the B chain.

Insulin is found in many animals, and is involved in the regulation of normal glucose homeostasis. It also has other specific physiological effects, such as increasing the permeability of cells to monosaccharides, amino acids and fatty acids, and accelerating glycolysis and glycogen synthesis in the liver [PUBMED:6243748]. Insulin exerts its effects by interaction with a cell-surface receptor, which may also result in the promotion of cell growth [PUBMED:6243748].

Insulin is synthesised as a prepropeptide from which an endoplasmic reticulum-targeting sequence is cleaved to yield proinsulin. The sequence of prosinsulin contains 2 well-conserved regions (designated A and B), separated by an intervening connecting region (C), which is variable between species [PUBMED:503234]. The connecting region is cleaved, liberating the active protein, which contains the A and B chains, held together by 2 disulphide bonds [PUBMED:503234].

This entry represents a disulphide-rich alpha-helical domain found in insulin [PUBMED:12595704], as well as in related proteins, such as insulin-like growth factor [PUBMED:15642270], relaxin [PUBMED:1656049] and bombyxin [PUBMED:7473749].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

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

Loading domain graphics...

Pfam Clan

This family is a member of clan Insulin (CL0239), which has the following description:

This superfamily includes the insulin like hormones.

The clan contains the following 2 members:

Ins_beta Insulin


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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics 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  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   Download    
Gzipped Download   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: Overington enriched
Previous IDs: ins;
Type: Domain
Sequence Ontology: SO:0000417
Author: Eddy SR
Number in seed: 28
Number in full: 2328
Average length of the domain: 71.60 aa
Average identity of full alignment: 30 %
Average coverage of the sequence by the domain: 56.94 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.5 21.5
Trusted cut-off 21.5 21.5
Noise cut-off 21.4 21.4
Model length: 85
Family (HMM) version: 19
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.


There are 11 interactions for this family. More...

IGFBP Insulin CIMR Recep_L_domain IGFBP Thyroglobulin_1 fn2 Recep_L_domain Peptidase_M16 Thyroglobulin_1 Peptidase_M16_C


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 Insulin domain has been found. There are 1678 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.

Loading structure mapping...