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3105  structures 3665  species 0  interactions 11967  sequences 140  architectures

Family: Globin (PF00042)

Summary: Globin

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This is the Wikipedia entry entitled "Globin". More...

Globin Edit Wikipedia article

Globin family
PDB 1hba EBI.jpg
the Structure of deoxyhemoglobin Rothschild 37 beta Trp----Arg: a mutation that creates an intersubunit chloride-binding site.[1]
Pfam clanCL0090
Bacterial-like Globin
PDB 1s56 EBI.jpg
crystal structure of "truncated" hemoglobin n (hbn) from mycobacterium tuberculosis, soaked with xe atoms
Pfam clanCL0090

The globins are a superfamily of heme-containing globular proteins, involved in binding and/or transporting oxygen. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members include myoglobin and hemoglobin. Both of these proteins reversibly bind oxygen via a heme prosthetic group. They are widely distributed in many organisms.[2]


Globin superfamily members share a common three-dimensional fold.[3] This 'globin fold' typically consists of eight alpha helices, although some proteins have additional helix extensions at their termini.[4] Since the globin fold contains only helices, it is classified as an all-alpha protein fold.

The globin fold is found in its namesake globin families as well as in phycocyanins. The globin fold was thus the first protein fold discovered (myoglobin was the first protein whose structure was solved).

Helix packing

The eight helices of the globin fold core share significant nonlocal structure, unlike other structural motifs in which amino acids close to each other in primary sequence are also close in space. The helices pack together at an average angle of about 50 degrees, significantly steeper than other helical packings such as the helix bundle. The exact angle of helix packing depends on the sequence of the protein, because packing is mediated by the sterics and hydrophobic interactions of the amino acid side chains near the helix interfaces.


Globins evolved from a common ancestor and can be divided into three groups: single-domain globins, and two types of chimeric globins, flavohaemoglobins and globin-coupled sensors. Bacteria have all three types of globins, while archaea lack flavohaemoglobins, and eukaryotes lack globin-coupled sensors.[5] Several functionally different haemoglobins can coexist in the same species.

Eight globins are known to occur in vertebrates: androglobin, cytoglobin, globin E, globin X, globin Y, hemoglobin, myoglobin and neuroglobin.

Sequence conservation

Although the fold of the globin superfamily is highly evolutionarily conserved, the sequences that form the fold can have as low as 16% sequence identity. While the sequence specificity of the fold is not stringent, the hydrophobic core of the protein must be maintained and hydrophobic patches on the generally hydrophilic solvent-exposed surface must be avoided in order for the structure to remain stable and soluble. The most famous mutation in the globin fold is a change from glutamate to valine in one chain of the hemoglobin molecule. This mutation creates a "hydrophobic patch" on the protein surface that promotes intermolecular aggregation, the molecular event that gives rise to sickle-cell anemia.



Human genes encoding globin proteins include:

The globins include:

See also


  1. ^ Kavanaugh JS, Rogers PH, Case DA, Arnone A (April 1992). "High-resolution X-ray study of deoxyhemoglobin Rothschild 37 beta Trp----Arg: a mutation that creates an intersubunit chloride-binding site". Biochemistry. 31 (16): 4111–21. doi:10.1021/bi00131a030. PMID 1567857.
  2. ^ Vinogradov SN, Hoogewijs D, Bailly X, Mizuguchi K, Dewilde S, Moens L, Vanfleteren JR (August 2007). "A model of globin evolution". Gene. 398 (1–2): 132–42. doi:10.1016/j.gene.2007.02.041. PMID 17540514.
  3. ^ Branden, Carl; Tooze, John (1999). Introduction to protein structure (2nd ed.). New York: Garland Pub. ISBN 978-0815323051.
  4. ^ Bolognesi, M; Onesti, S; Gatti, G; Coda, A; Ascenzi, P; Brunori, M (1989). "Aplysia limacina myoglobin. Crystallographic analysis at 1.6 a resolution". Journal of Molecular Biology. 205 (3): 529–44. doi:10.1016/0022-2836(89)90224-6. PMID 2926816.
  5. ^ Vinogradov SN, Hoogewijs D, Bailly X, Arredondo-Peter R, Gough J, Dewilde S, Moens L, Vanfleteren JR (2006). "A phylogenomic profile of globins". BMC Evol. Biol. 6: 31. doi:10.1186/1471-2148-6-31. PMC 1457004. PMID 16600051.
  6. ^ Pesce A, Dewilde S, Nardini M, Moens L, Ascenzi P, Hankeln T, Burmester T, Bolognesi M (September 2003). "Human brain neuroglobin structure reveals a distinct mode of controlling oxygen affinity". Structure. 11 (9): 1087–95. doi:10.1016/S0969-2126(03)00166-7. PMID 12962627.
  7. ^ Fago A, Hundahl C, Malte H, Weber RE (2004). "Functional properties of neuroglobin and cytoglobin. Insights into the ancestral physiological roles of globins". IUBMB Life. 56 (11–12): 689–96. doi:10.1080/15216540500037299. PMID 15804833.
  8. ^ Royer WE, Omartian MN, Knapp JE (January 2007). "Low resolution crystal structure of Arenicola erythrocruorin: influence of coiled coils on the architecture of a megadalton respiratory protein". J. Mol. Biol. 365 (1): 226–36. doi:10.1016/j.jmb.2006.10.016. PMC 1847385. PMID 17084861.
  9. ^ Mukai M, Mills CE, Poole RK, Yeh SR (March 2001). "Flavohemoglobin, a globin with a peroxidase-like catalytic site". J. Biol. Chem. 276 (10): 7272–7. doi:10.1074/jbc.M009280200. PMID 11092893.
  10. ^ Blank M, Kiger L, Thielebein A, Gerlach F, Hankeln T, Marden MC, Burmeister T (2011). "Oxygen supply from the bird's eye perspective: Globin E is a respiratory protein in the chicken retina". J. Biol. Chem. 286 (30): 26507–15. doi:10.1074/jbc.M111.224634. PMC 3143615. PMID 21622558.
  11. ^ Hou S, Freitas T, Larsen RW, Piatibratov M, Sivozhelezov V, Yamamoto A, Meleshkevitch EA, Zimmer M, Ordal GW, Alam M (July 2001). "Globin-coupled sensors: a class of heme-containing sensors in Archaea and Bacteria". Proc. Natl. Acad. Sci. U.S.A. 98 (16): 9353–8. doi:10.1073/pnas.161185598. PMC 55424. PMID 11481493.
  12. ^ Freitas TA, Saito JA, Hou S, Alam M (January 2005). "Globin-coupled sensors, protoglobins, and the last universal common ancestor". J. Inorg. Biochem. 99 (1): 23–33. doi:10.1016/j.jinorgbio.2004.10.024. PMID 15598488.
  13. ^ Freitas TA, Hou S, Dioum EM, Saito JA, Newhouse J, Gonzalez G, Gilles-Gonzalez MA, Alam M (April 2004). "Ancestral hemoglobins in Archaea". Proc. Natl. Acad. Sci. U.S.A. 101 (17): 6675–80. doi:10.1073/pnas.0308657101. PMC 404104. PMID 15096613.
  14. ^ Lama A, Pawaria S, Dikshit KL (July 2006). "Oxygen binding and NO scavenging properties of truncated hemoglobin, HbN, of Mycobacterium smegmatis". FEBS Lett. 580 (17): 4031–41. doi:10.1016/j.febslet.2006.06.037. PMID 16814781.
  15. ^ Yeh DC, Thorsteinsson MV, Bevan DR, Potts M, La Mar GN (February 2000). "Solution 1H NMR study of the heme cavity and folding topology of the abbreviated chain 118-residue globin from the cyanobacterium Nostoc commune". Biochemistry. 39 (6): 1389–99. doi:10.1021/bi992081l. PMID 10684619.
  16. ^ Pathania R, Navani NK, Rajamohan G, Dikshit KL (May 2002). "Mycobacterium tuberculosis hemoglobin HbO associates with membranes and stimulates cellular respiration of recombinant Escherichia coli". J. Biol. Chem. 277 (18): 15293–302. doi:10.1074/jbc.M111478200. PMID 11796724.
  17. ^ Watts RA, Hunt PW, Hvitved AN, Hargrove MS, Peacock WJ, Dennis ES (August 2001). "A hemoglobin from plants homologous to truncated hemoglobins of microorganisms". Proc. Natl. Acad. Sci. U.S.A. 98 (18): 10119–24. doi:10.1073/pnas.191349198. PMC 56925. PMID 11526234.
This article incorporates text from the public domain Pfam and InterPro: IPR001486

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.

Globin Provide feedback

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Literature references

  1. Bashford D, Chothia C, Lesk AM; , J Mol Biol 1987;196:199-216.: Determinants of a protein fold. Unique features of the globin amino acid sequences. PUBMED:3656444 EPMC:3656444

  2. Neuwald AF, Liu JS, Lipman DJ, Lawrence CE; , Nucleic Acids Res 1997;25:1665-1677.: Extracting protein alignment models from the sequence database. PUBMED:9108146 EPMC:9108146

  3. Bogusz D, Appleby CA, Landsmann J, Dennis ES, Trinick MJ, Peacock WJ; , Nature 1988;331:178-180.: Functioning haemoglobin genes in non-nodulating plants. PUBMED:2448639 EPMC:2448639

  4. Kinniburgh AJ, Maquat LE, Schedl T, Rachmilewitz E, Ross J; , Nucleic Acids Res 1982;10:5421-5427.: mRNA-deficient beta o-thalassemia results from a single nucleotide deletion. PUBMED:6292840 EPMC:6292840

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000971

Globins are haem-containing proteins involved in binding and/or transporting oxygen. They belong to a very large and well studied family that is widely distributed in many organisms [ PUBMED:17540514 ]. Globins have evolved from a common ancestor and can be divided into three groups: single-domain globins, and two types of chimeric globins, flavohaemoglobins and globin-coupled sensors. Bacteria have all three types of globins, while archaea lack flavohaemoglobins, and eukaryotes lack globin-coupled sensors [ PUBMED:16600051 ]. Several functionally different haemoglobins can coexist in the same species. The major types of globins include:

  • Haemoglobin (Hb): tetramer of two alpha and two beta chains, although embryonic and foetal forms can substitute the alpha or beta chain for ones with higher oxygen affinity, such as gamma, delta, epsilon or zeta chains. Hb transports oxygen from lungs to other tissues in vertebrates [ PUBMED:16888280 ]. Hb proteins are also present in unicellular organisms where they act as enzymes or sensors [ PUBMED:15598493 ].
  • Myoglobin (Mb): monomeric protein responsible for oxygen storage in vertebrate muscle [ PUBMED:15339940 ].
  • Neuroglobin: a myoglobin-like haemprotein expressed in vertebrate brain and retina, where it is involved in neuroprotection from damage due to hypoxia or ischemia [ PUBMED:12962627 ]. Neuroglobin belongs to a branch of the globin family that diverged early in evolution.
  • Cytoglobin: an oxygen sensor expressed in multiple tissues. Related to neuroglobin [ PUBMED:15804833 ].
  • Erythrocruorin: highly cooperative extracellular respiratory proteins found in annelids and arthropods that are assembled from as many as 180 subunit into hexagonal bilayers [ PUBMED:17084861 ].
  • Leghaemoglobin (legHb or symbiotic Hb): occurs in the root nodules of leguminous plants, where it facilitates the diffusion of oxygen to symbiotic bacteriods in order to promote nitrogen fixation.
  • Non-symbiotic haemoglobin (NsHb): occurs in non-leguminous plants, and can be over-expressed in stressed plants [ PUBMED:17540516 ].
  • Flavohaemoglobins (FHb): chimeric, with an N-terminal globin domain and a C-terminal ferredoxin reductase-like NAD/FAD-binding domain. FHb provides protection against nitric oxide via its C-terminal domain, which transfers electrons to haem in the globin [ PUBMED:11092893 ].
  • Globin-coupled sensors: chimeric, with an N-terminal myoglobin-like domain and a C-terminal domain that resembles the cytoplasmic signalling domain of bacterial chemoreceptors. They bind oxygen, and act to initiate an aerotactic response or regulate gene expression [ PUBMED:11481493 , PUBMED:15598488 ].
  • Protoglobin: a single domain globin found in archaea that is related to the N-terminal domain of globin-coupled sensors [ PUBMED:15096613 ].
  • Truncated 2/2 globin: lack the first helix, giving them a 2-over-2 instead of the canonical 3-over-3 alpha-helical sandwich fold. Can be divided into three main groups (I, II and II) based on structural features [ PUBMED:17701548 ].

This entry covers most of the globin family of proteins, but it omits some bacterial globins and the protoglobins.

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...

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Pfam Clan

This family is a member of clan Globin (CL0090), which has the following description:

The globin fold is an evolutionary conserved six helical fold that is found in bacteria and eukaryotes.

The clan contains the following 8 members:

Bac_globin Globin HisK-N-like HisK_N Phycobilisome Protoglobin Rsbr_N RsbRD_N


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

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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: Structure_superposition
Previous IDs: globin;
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Chothia C
Number in seed: 73
Number in full: 11967
Average length of the domain: 109.10 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 40.31 %

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 22.0 22.0
Trusted cut-off 22.0 22.0
Noise cut-off 21.9 21.9
Model length: 118
Family (HMM) version: 25
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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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 Globin domain has been found. There are 3105 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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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
A0A0G2JSV6 View 3D Structure Click here
A0A0K3AV45 View 3D Structure Click here
A0A0R0HW51 View 3D Structure Click here
A0A1D6PFS1 View 3D Structure Click here
A0A1D8PD58 View 3D Structure Click here
A0A1D8PU81 View 3D Structure Click here
A0A2R8QE13 View 3D Structure Click here
A0A2R8QFT1 View 3D Structure Click here
A3KNI8 View 3D Structure Click here
A3KP86 View 3D Structure Click here
A4I382 View 3D Structure Click here
A8DUK4 View 3D Structure Click here
A8DZ43 View 3D Structure Click here
B2RVB7 View 3D Structure Click here
B3GWE1 View 3D Structure Click here
B3WFV1 View 3D Structure Click here
B3WFV2 View 3D Structure Click here
C1P638 View 3D Structure Click here
D0VWM4 View 3D Structure Click here
D4A021 View 3D Structure Click here
F6NT71 View 3D Structure Click here
F6P497 View 3D Structure Click here
G3V8R3 View 3D Structure Click here
G5EF00 View 3D Structure Click here
I1LJI1 View 3D Structure Click here
O04985 View 3D Structure Click here
O04986 View 3D Structure Click here
O17824 View 3D Structure Click here
O24520 View 3D Structure Click here
O24521 View 3D Structure Click here
O88752 View 3D Structure Click here
O88753 View 3D Structure Click here
O88754 View 3D Structure Click here
O93548 View 3D Structure Click here
P01942 View 3D Structure Click here
P01946 View 3D Structure Click here
P02008 View 3D Structure Click here
P02042 View 3D Structure Click here
P02088 View 3D Structure Click here
P02089 View 3D Structure Click here