
2467  structures 1088  species 12  interactions 3049  sequences 48  architectures

Family: Globin (PF00042)

Summary: Globin


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

Globin Edit Wikipedia article

Not to be confused with globulin or globular protein.
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]
Symbol Globin
Pfam PF00042
Pfam clan CL0090
InterPro IPR000971
SCOP 1hba
CDD cd01067
Bacterial-like Globin
PDB 1s56 EBI.jpg
crystal structure of "truncated" hemoglobin n (hbn) from mycobacterium tuberculosis, soaked with xe atoms
Symbol Bac_globin
Pfam PF01152
Pfam clan CL0090
InterPro IPR001486
SCOP 1dlw

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, haemoglobin, 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. 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 1457004Freely accessible. 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 1847385Freely accessible. 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 3143615Freely accessible. 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 55424Freely accessible. 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 404104Freely accessible. 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 56925Freely accessible. PMID 11526234. 

This article incorporates text from the public domain Pfam and InterPro IPR001486



Globin Provide feedback

No Pfam abstract.

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


Domain organisation


Loading domain graphics...

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 4 members:

Bac_globin Globin Phycobilisome Protoglobin



View options


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


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

Format an alignment

Representative proteomes UniProt

Download options


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


HMM logo





Curation and family details


Curation View help on the curation process

Seed source: Structure_superposition
Previous IDs: globin;
Type: Domain
Author: Bateman A, Chothia C
Number in seed: 73
Number in full: 3049
Average length of the domain: 100.70 aa
Average identity of full alignment: 20 %
Average coverage of the sequence by the domain: 37.46 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
Model details:
Parameter Sequence Domain
Gathering cut-off 20.8 20.8
Trusted cut-off 20.8 20.8
Noise cut-off 20.6 20.7
Model length: 110
Family (HMM) version: 20
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


Loading sunburst data...

Tree controls






There are 12 interactions for this family. More...

MHC_I Globin Trypsin AHSP NAD_binding_1 FAD_binding_6 AHSP NEAT FAD_binding_6 NAD_binding_1 NEAT Ldl_recept_a


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 2467 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.

Loading structure mapping...