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126  structures 479  species 0  interactions 9398  sequences 138  architectures

Family: Integrin_alpha2 (PF08441)

Summary: Integrin alpha

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

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Integrin Edit Wikipedia article

Integrin alphaVbeta3 extracellular domains
PDB 1jv2 EBI.jpg
Structure of the extracellular segment of integrin alpha Vbeta3.[1]
Pfam clanCL0159
OPM superfamily176
OPM protein2knc
Integrin alpha cytoplasmic region
PDB 1dpk EBI.jpg
Structure of chaperone protein PAPD.[2]
Integrin, beta chain (vWA)
Integrin beta 7 cytoplasmic domain: complex with filamin
PDB 2brq EBI.jpg
crystal structure of the filamin a repeat 21 complexed with the integrin beta7 cytoplasmic tail peptide

Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion.[3] Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, and movement of new receptors to the cell membrane.[4] The presence of integrins allows rapid and flexible responses to events at the cell surface (e.g. signal platelets to initiate an interaction with coagulation factors).

Several types of integrins exist, and one cell generally has multiple different types on its surface. Integrins are found in all animals while integrin-like receptors are found in plant cells.[3]

Integrins work alongside other proteins such as cadherins, the immunoglobulin superfamily cell adhesion molecules, selectins and syndecans, to mediate cell–cell and cell–matrix interaction. Ligands for integrins include fibronectin, vitronectin, collagen and laminin.


Integrins are obligate heterodimers composed of α and β subunits. Several genes code for multiple isoforms of these subunits, which gives rise to an array of unique integrins with varied activity. In mammals, integrins are assembled from eighteen α and eight β subunits,[5] in Drosophila five α and two β subunits, and in Caenorhabditis nematodes two α subunits and one β subunit.[6] The α and β subunits are both class I transmembrane proteins, so each penetrates the plasma membrane once, and can possess several cytoplasmic domains.[7]

alpha (mammal)
gene protein synonyms
ITGA11 ITGA11 HsT18964
beta (mammal)
gene protein synonyms

Variants of some subunits are formed by differential RNA splicing; for example, four variants of the beta-1 subunit exist. Through different combinations of the α and β subunits, 24 unique mammalian integrins are generated, excluding splice- and glycosylation variants.[8]

Integrin subunits span the cell membrane and have short cytoplasmic domains of 40–70 amino acids. The exception is the beta-4 subunit, which has a cytoplasmic domain of 1,088 amino acids, one of the largest of any membrane protein. Outside the cell membrane, the α and β chains lie close together along a length of about 23 nm; the final 5 nm N-termini of each chain forms a ligand-binding region for the ECM. They have been compared to lobster claws, although they don't actually "pinch" their ligand, they chemically interact with it at the insides of the "tips" of their "pinchers".

The molecular mass of the integrin subunits can vary from 90 kDa to 160 kDa. Beta subunits have four cysteine-rich repeated sequences. Both α and β subunits bind several divalent cations. The role of divalent cations in the α subunit is unknown, but may stabilize the folds of the protein. The cations in the β subunits are more interesting: they are directly involved in coordinating at least some of the ligands that integrins bind.

Integrins can be categorized in multiple ways. For example, some α chains have an additional structural element (or "domain") inserted toward the N-terminal, the alpha-A domain (so called because it has a similar structure to the A-domains found in the protein von Willebrand factor; it is also termed the α-I domain). Integrins carrying this domain either bind to collagens (e.g. integrins α1 β1, and α2 β1), or act as cell-cell adhesion molecules (integrins of the β2 family). This α-I domain is the binding site for ligands of such integrins. Those integrins that don't carry this inserted domain also have an A-domain in their ligand binding site, but this A-domain is found on the β subunit.

In both cases, the A-domains carry up to three divalent cation binding sites. One is permanently occupied in physiological concentrations of divalent cations, and carries either a calcium or magnesium ion, the principal divalent cations in blood at median concentrations of 1.4 mM (calcium) and 0.8 mM (magnesium). The other two sites become occupied by cations when ligands bind—at least for those ligands involving an acidic amino acid in their interaction sites. An acidic amino acid features in the integrin-interaction site of many ECM proteins, for example as part of the amino acid sequence Arginine-Glycine-Aspartic acid ("RGD" in the one-letter amino acid code).


Despite many years of effort, discovering the high-resolution structure of integrins proved to be challenging, as membrane proteins are classically difficult to purify, and as integrins are large, complex and linked to many sugar trees ("highly glycosylated"). Low-resolution images of detergent extracts of intact integrin GPIIbIIIa, obtained using electron microscopy, and even data from indirect techniques that investigate the solution properties of integrins using ultracentrifugation and light scattering, were combined with fragmentary high-resolution crystallographic or NMR data from single or paired domains of single integrin chains, and molecular models postulated for the rest of the chains.

The X-ray crystal structure obtained for the complete extracellular region of one integrin, αvβ3,[1] shows the molecule to be folded into an inverted V-shape that potentially brings the ligand-binding sites close to the cell membrane. Perhaps more importantly, the crystal structure was also obtained for the same integrin bound to a small ligand containing the RGD-sequence, the drug cilengitide.[9] As detailed above, this finally revealed why divalent cations (in the A-domains) are critical for RGD-ligand binding to integrins. The interaction of such sequences with integrins is believed to be a primary switch by which ECM exerts its effects on cell behaviour.

The structure poses many questions, especially regarding ligand binding and signal transduction. The ligand binding site is directed towards the C-terminal of the integrin, the region where the molecule emerges from the cell membrane. If it emerges orthogonally from the membrane, the ligand binding site would apparently be obstructed, especially as integrin ligands are typically massive and well cross-linked components of the ECM. In fact, little is known about the angle that membrane proteins subtend to the plane of the membrane; this is a problem difficult to address with available technologies. The default assumption is that they emerge rather like little lollipops, but the evidence for this sweet supposition is noticeable by its absence. The integrin structure has drawn attention to this problem, which may have general implications for how membrane proteins work. It appears that the integrin transmembrane helices are tilted (see "Activation" below), which hints that the extracellular chains may also not be orthogonal with respect to the membrane surface.

Although the crystal structure changed surprisingly little after binding to cilengitide, the current hypothesis is that integrin function involves changes in shape to move the ligand-binding site into a more accessible position, away from the cell surface, and this shape change also triggers intracellular signaling. There is a wide body of cell-biological and biochemical literature that supports this view. Perhaps the most convincing evidence involves the use of antibodies that only recognize integrins when they have bound to their ligands, or are activated. As the "footprint" that an antibody makes on its binding target is roughly a circle about 3 nm in diameter, the resolution of this technique is low. Nevertheless, these so-called LIBS (Ligand-Induced-Binding-Sites) antibodies unequivocally show that dramatic changes in integrin shape routinely occur. However, how the changes detected with antibodies look on the structure is still unknown.


When released into the cell membrane, newly synthesized integrin dimers are speculated to be found in the same "bent" conformation revealed by the structural studies described above. One school of thought claims that this bent form prevents them from interacting with their ligands, although bent forms can predominate in high-resolution EM structures of integrin bound to an ECM ligand. Therefore, at least in biochemical experiments, integrin dimers must apparently not be 'unbent' in order to prime them and allow their binding to the ECM. In cells, the priming is accomplished by a protein talin, which binds to the β tail of the integrin dimer and changes its conformation.[10][11] The α and β integrin chains are both class-I transmembrane proteins: they pass the plasma membrane as single transmembrane alpha-helices. Unfortunately, the helices are too long, and recent studies suggest that, for integrin gpIIbIIIa, they are tilted with respect both to one another and to the plane of the membrane. Talin binding alters the angle of tilt of the β3 chain transmembrane helix in model systems and this may reflect a stage in the process of inside-out signalling which primes integrins.[12] Moreover, talin proteins are able to dimerize[13] and thus are thought to intervene in the clustering of integrin dimers which leads to the formation of a focal adhesion. Recently, the Kindlin-1 and Kindlin-2 proteins have also been found to interact with integrin and activate it.[14]


Integrins have two main functions, attachment of the cells to the ECM and signal transduction from the ECM to the cells.[15] They are also involved in a wide range of other biological activities, including extravasation, cell-to-cell adhesion, cell migration, and as receptors for certain viruses, such as adenovirus, echovirus, hantavirus, and foot-and-mouth disease, polio virus and other viruses.

A prominent function of the integrins is seen in the molecule GpIIb/IIIa, an integrin on the surface of blood platelets (thrombocytes) responsible for attachment to fibrin within a developing blood clot. This molecule dramatically increases its binding affinity for fibrin/fibrinogen through association of platelets with exposed collagens in the wound site. Upon association of platelets with collagen, GPIIb/IIIa changes shape, allowing it to bind to fibrin and other blood components to form the clot matrix and stop blood loss.

Attachment of cell to the ECM

Integrins couple the ECM outside a cell to the cytoskeleton (in particular, the microfilaments) inside the cell. Which ligand in the ECM the integrin can bind to is defined by which α and β subunits the integrin is made of. Among the ligands of integrins are fibronectin, vitronectin, collagen, and laminin. The connection between the cell and the ECM may help the cell to endure pulling forces without being ripped out of the ECM. The ability of a cell to create this kind of bond is also of vital importance in ontogeny.

Cell attachment to the ECM is a basic requirement to build a multicellular organism. Integrins are not simply hooks, but give the cell critical signals about the nature of its surroundings. Together with signals arising from receptors for soluble growth factors like VEGF, EGF, and many others, they enforce a cellular decision on what biological action to take, be it attachment, movement, death, or differentiation. Thus integrins lie at the heart of many cellular biological processes. The attachment of the cell takes place through formation of cell adhesion complexes, which consist of integrins and many cytoplasmic proteins, such as talin, vinculin, paxillin, and alpha-actinin. These act by regulating kinases such as FAK (focal adhesion kinase) and Src kinase family members to phosphorylate substrates such as p130CAS thereby recruiting signaling adaptors such as CRK. These adhesion complexes attach to the actin cytoskeleton. The integrins thus serve to link two networks across the plasma membrane: the extracellular ECM and the intracellular actin filamentous system. Integrin α6β4 is an exception: it links to the keratin intermediate filament system in epithelial cells.[16]

Focal adhesions are large molecular complexes, which are generated following interaction of integrins with ECM, then their clustering. The clusters likely provide sufficient intracellular binding sites to permit the formation of stable signaling complexes on the cytoplasmic side of the cell membrane. So the focal adhesions contain integrin ligand, integrin molecule, and associate plaque proteins. Binding is propelled by changes in free energy.[17] As previously stated, these complexes connect the extracellular matrix to actin bundles. Cryo-electron tomography reveals that the adhesion contains particles on the cell membrane with diameter of 25 +/- 5 nm and spaced at approximately 45 nm.[18] Treatment with Rho-kinase inhibitor Y-27632 reduces the size of the particle, and it is extremely mechanosensitive.[19]

One important function of integrins on cells in tissue culture is their role in cell migration. Cells adhere to a substrate through their integrins. During movement, the cell makes new attachments to the substrate at its front and concurrently releases those at its rear. When released from the substrate, integrin molecules are taken back into the cell by endocytosis; they are transported through the cell to its front by the endocytic cycle, where they are added back to the surface. In this way they are cycled for reuse, enabling the cell to make fresh attachments at its leading front.[20] The cycle of integrin endocytosis and recycling back to the cell surface is important also for not migrating cells and during animal development.[21]

Signal transduction

Integrins play an important role in cell signaling by modulating the cell signaling pathways of transmembrane protein kinases such as receptor tyrosine kinases (RTK). While the interaction between integrin and receptor tyrosine kinases originally was thought of as uni-directional and supportive, recent studies indicate that integrins have additional, multi-faceted roles in cell signaling. Integrins can regulate the receptor tyrosine kinase signaling by recruiting specific adaptors to the plasma membrane. For example, β1c integrin recruits Gab1/Shp2 and presents Shp2 to IGF1R, resulting in dephosphorylation of the receptor.[22] In a reverse direction, when a receptor tyrosine kinase is activated, integrins co-localise at focal adhesion with the receptor tyrosine kinases and their associated signaling molecules.

The repertoire of integrins expressed on a particular cell can specify the signaling pathway due to the differential binding affinity of ECM ligands for the integrins. The tissue stiffness and matrix composition can initiate specific signaling pathways regulating cell behavior. Clustering and activation of the integrins/actin complexes strengthen the focal adhesion interaction and initiate the framework for cell signaling through assembly of adhesomes.[23]

Depending on the integrin's regulatory impact on specific receptor tyrosine kinases, the cell can experience:

Knowledge of the relationship between integrins and receptor tyrosine kinase has laid a foundation for new approaches to cancer therapy. Specifically, targeting integrins associated with RTKs is an emerging approach for inhibiting angiogenesis.[25]

Integrins are localised at the growth cone of regenerating neurons.[26]

Integrins and nerve repair

Integrins have an important function in neuroregeneration after injury of the peripheral nervous system (PNS).[26] Integrins are present at the growth cone of damaged PNS neurons and attach to ligands in the ECM to promote axon regeneration. It is unclear whether integrins can promote axon regeneration in the adult central nervous system (CNS). There are two obstacles that prevent integrin-mediated regeneration in the CNS: 1) integrins are not localised in the axon of most adult CNS neurons and 2) integrins become inactivated by molecules in the scar tissue after injury.[26]

Vertebrate integrins

The following are 16 of the ~24 integrins found in vertebrates:

Name Synonyms Distribution Ligands
α1β1 VLA-1 Many Collagens, laminins[27]
α2β1 VLA-2 Many Collagens, laminins[27]
α3β1 VLA-3 Many Laminin-5
α4β1 VLA-4[27] Hematopoietic cells Fibronectin, VCAM-1[27]
α5β1 VLA-5; fibronectin receptor widespread fibronectin[27] and proteinases
α6β1 VLA-6; laminin receptor widespread laminins
α7β1 muscle, glioma laminins
αLβ2 LFA-1[27] T-lymphocytes ICAM-1, ICAM-2[27]
αMβ2 Mac-1, CR3[27] Neutrophils and monocytes Serum proteins, ICAM-1[27]
αIIbβ3 Fibrinogen receptor; gpIIbIIIa[28] Platelets[27] fibrinogen, fibronectin[27]
αVβ1 neurological tumors vitronectin; fibrinogen
αVβ3 vitronectin receptor[29] activated endothelial cells, melanoma, glioblastoma vitronectin,[29] fibronectin, fibrinogen, osteopontin, Cyr61, thyroxine,[30] TETRAC
αVβ5 widespread, esp. fibroblasts, epithelial cells vitronectin and adenovirus
αVβ6 proliferating epithelia, esp. lung and mammary gland fibronectin; TGFβ1+3
αVβ8 neural tissue; peripheral nerve fibronectin; TGFβ1+3
α6β4 Epithelial cells[27] Laminin[27]

Beta-1 integrins interact with many alpha integrin chains. Gene knockouts of integrins in mice are not always lethal, which suggests that during embryonal development, one integrin may substitute its function for another in order to allow survival. Some integrins are on the cell surface in an inactive state, and can be rapidly primed, or put into a state capable of binding their ligands, by cytokines. Integrins can assume several different well-defined shapes or "conformational states". Once primed, the conformational state changes to stimulate ligand binding, which then activates the receptors — also by inducing a shape change — to trigger outside-in signal transduction.


  1. ^ a b Xiong JP, Stehle T, Diefenbach B, Zhang R, Dunker R, Scott DL, Joachimiak A, Goodman SL, Arnaout MA (October 2001). "Crystal structure of the extracellular segment of integrin alpha Vbeta3". Science. 294 (5541): 339–45. Bibcode:2001Sci...294..339X. doi:10.1126/science.1064535. PMC 2885948. PMID 11546839.
  2. ^ Sauer FG, Fütterer K, Pinkner JS, Dodson KW, Hultgren SJ, Waksman G (August 1999). "Structural basis of chaperone function and pilus biogenesis". Science. 285 (5430): 1058–61. doi:10.1126/science.285.5430.1058. PMID 10446050.
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  4. ^ Giancotti FG, Ruoslahti E (August 1999). "Integrin signaling". Science. 285 (5430): 1028–32. doi:10.1126/science.285.5430.1028. PMID 10446041.
  5. ^ Bruce A, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002). "Integrins". Molecular Biology of the Cell (4th ed.). New York: Garland Science.
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  8. ^ Hynes RO (September 2002). "Integrins: bidirectional, allosteric signaling machines". Cell. 110 (6): 673–87. doi:10.1016/S0092-8674(02)00971-6. PMID 12297042. S2CID 30326350.
  9. ^ Smith JW (June 2003). "Cilengitide Merck". Current Opinion in Investigational Drugs. 4 (6): 741–5. PMID 12901235.
  10. ^ Calderwood DA (June 2004). "Talin controls integrin activation". Biochemical Society Transactions. 32 (Pt3): 434–7. doi:10.1042/BST0320434. PMID 15157154.
  11. ^ Calderwood DA, Zent R, Grant R, Rees DJ, Hynes RO, Ginsberg MH (October 1999). "The Talin head domain binds to integrin beta subunit cytoplasmic tails and regulates integrin activation". The Journal of Biological Chemistry. 274 (40): 28071–4. doi:10.1074/jbc.274.40.28071. PMID 10497155.
  12. ^ Shattil SJ, Kim C, Ginsberg MH (April 2010). "The final steps of integrin activation: the end game". Nature Reviews. Molecular Cell Biology. 11 (4): 288–300. doi:10.1038/nrm2871. PMC 3929966. PMID 20308986.
  13. ^ Goldmann WH, Bremer A, Häner M, Aebi U, Isenberg G (1994). "Native talin is a dumbbell-shaped homodimer when it interacts with actin". Journal of Structural Biology. 112 (1): 3–10. doi:10.1006/jsbi.1994.1002. PMID 8031639.
  14. ^ Harburger DS, Bouaouina M, Calderwood DA (April 2009). "Kindlin-1 and -2 directly bind the C-terminal region of beta integrin cytoplasmic tails and exert integrin-specific activation effects". The Journal of Biological Chemistry. 284 (17): 11485–97. doi:10.1074/jbc.M809233200. PMC 2670154. PMID 19240021.
  15. ^ Yamada KM, Miyamoto S (October 1995). "Integrin transmembrane signaling and cytoskeletal control". Current Opinion in Cell Biology. 7 (5): 681–9. doi:10.1016/0955-0674(95)80110-3. PMID 8573343.
  16. ^ Wilhelmsen K, Litjens SH, Sonnenberg A (April 2006). "Multiple functions of the integrin alpha6beta4 in epidermal homeostasis and tumorigenesis". Molecular and Cellular Biology. 26 (8): 2877–86. doi:10.1128/MCB.26.8.2877-2886.2006. PMC 1446957. PMID 16581764.
  17. ^ Olberding JE, Thouless MD, Arruda EM, Garikipati K (August 2010). Buehler MJ (ed.). "The non-equilibrium thermodynamics and kinetics of focal adhesion dynamics". PLOS ONE. 5 (8): e12043. Bibcode:2010PLoSO...512043O. doi:10.1371/journal.pone.0012043. PMC 2923603. PMID 20805876.
  18. ^ Patla I, Volberg T, Elad N, Hirschfeld-Warneken V, Grashoff C, Fässler R, Spatz JP, Geiger B, Medalia O (September 2010). "Dissecting the molecular architecture of integrin adhesion sites by cryo-electron tomography". Nature Cell Biology. 12 (9): 909–15. doi:10.1038/ncb2095. PMID 20694000. S2CID 20775305.
  19. ^ Gullingsrud J, Sotomayor M. "Mechanosensitive channels". Theoretical and Computational Biophysics Group, Beckman Institute for Advanced Science and Technology: University of Illinois at Urbana-Champaign. Archived from the original on 2010-12-02.
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  21. ^ Moreno-Layseca P, Icha J, Hamidi H, Ivaska J (February 2019). "Integrin trafficking in cells and tissues". Nature Cell Biology. 21 (2): 122–132. doi:10.1038/s41556-018-0223-z. PMC 6597357. PMID 30602723.
  22. ^ Goel HL, Breen M, Zhang J, Das I, Aznavoorian-Cheshire S, Greenberg NM, Elgavish A, Languino LR (August 2005). "beta1A integrin expression is required for type 1 insulin-like growth factor receptor mitogenic and transforming activities and localization to focal contacts". Cancer Research. 65 (15): 6692–700. doi:10.1158/0008-5472.CAN-04-4315. PMID 16061650.
  23. ^ Kim SH, Turnbull J, Guimond S (May 2011). "Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor". The Journal of Endocrinology. 209 (2): 139–51. doi:10.1530/JOE-10-0377. PMID 21307119.
  24. ^ a b c Bostwick DG, Cheng L (2020-01-01). "9 - Neoplasms of the Prostate". In Cheng L, MacLennan GT, Bostwick DG (eds.). Urologic Surgical Pathology (Fourth ed.). Philadelphia: Content Repository Only!. pp. 415–525.e42. ISBN 978-0-323-54941-7.
  25. ^ Carbonell WS, DeLay M, Jahangiri A, Park CC, Aghi MK (May 2013). "β1 integrin targeting potentiates antiangiogenic therapy and inhibits the growth of bevacizumab-resistant glioblastoma". Cancer Research. 73 (10): 3145–54. doi:10.1158/0008-5472.CAN-13-0011. PMC 4040366. PMID 23644530.
  26. ^ a b c Nieuwenhuis B, Haenzi B, Andrews MR, Verhaagen J, Fawcett JW (February 2018). "Integrins promote axonal regeneration after injury of the nervous system". Biological Reviews of the Cambridge Philosophical Society. 93 (3): 1339–1362. doi:10.1111/brv.12398. PMC 6055631. PMID 29446228.
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  29. ^ a b Hermann P, Armant M, Brown E, Rubio M, Ishihara H, Ulrich D, Caspary RG, Lindberg FP, Armitage R, Maliszewski C, Delespesse G, Sarfati M (February 1999). "The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23". The Journal of Cell Biology. 144 (4): 767–75. doi:10.1083/jcb.144.4.767. PMC 2132927. PMID 10037797.
  30. ^ Bergh JJ, Lin HY, Lansing L, Mohamed SN, Davis FB, Mousa S, Davis PJ (July 2005). "Integrin alphaVbeta3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis". Endocrinology. 146 (7): 2864–71. doi:10.1210/en.2005-0102. PMID 15802494.

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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.

Integrin alpha Provide feedback

This domain is found in integrin alpha and integrin alpha precursors to the C terminus of a number of PF01839 repeats and to the N-terminus of the PF00357 cytoplasmic region. This region is composed of three immunoglobulin-like domains.

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR013649

This domain is found in integrin alpha and integrin alpha precursors to the C terminus of a number of FG-GAP repeats ( 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 E-set (CL0159), which has the following description:

This clan includes a diverse range of domains that have an Ig-like fold and appear to be distantly related to each other. The clan includes: PKD domains, cadherins and several families of bacterial Ig-like domains as well as viral tail fibre proteins. it also includes several Fibronectin type III domain-containing families.

The clan contains the following 257 members:

A2M A2M_BRD A2M_recep AA9 Adeno_GP19K AlcCBM31 Alpha-amylase_N Alpha_adaptinC2 Alpha_E2_glycop Anth_Ig aRib Arylsulfotran_N ASF1_hist_chap ATG19 BACON BACON_2 BatD BIg21 Big_1 Big_10 Big_11 Big_12 Big_13 Big_14 Big_15 Big_2 Big_3 Big_3_2 Big_3_3 Big_3_4 Big_3_5 Big_4 Big_5 Big_6 Big_7 Big_8 Big_9 Bile_Hydr_Trans BiPBP_C bMG1 bMG10 bMG3 bMG5 bMG6 BslA BsuPI Cadherin Cadherin-like Cadherin_2 Cadherin_3 Cadherin_4 Cadherin_5 Cadherin_pro CagX Calx-beta Candida_ALS_N CARDB CBM39 CBM_X2 CD45 CelD_N Ceramidse_alk_C CHB_HEX_C CHB_HEX_C_1 ChitinaseA_N ChiW_Ig_like Chlam_OMP6 CHU_C Coatamer_beta_C COP-gamma_platf CopC CshA_repeat Cyc-maltodext_N Cytomega_US3 DBB DsbC DUF11 DUF1410 DUF1425 DUF2271 DUF3244 DUF3458 DUF3501 DUF3823_C DUF3859 DUF4165 DUF4179 DUF4426 DUF4469 DUF4625 DUF4784_N DUF4879 DUF4959 DUF4982 DUF4998 DUF5001 DUF5008 DUF5011 DUF5060 DUF5065 DUF5103 DUF5115 DUF525 DUF5643 DUF6383 DUF6595 DUF916 EB_dh ECD Enterochelin_N EpoR_lig-bind ERAP1_C EstA_Ig_like Expansin_C Filamin FixG_C Flavi_glycop_C FlgD_ig fn3 Fn3-like fn3_2 fn3_4 fn3_5 fn3_6 FN3_7 Fn3_assoc fn3_PAP GBS_Bsp-like GlgE_dom_N_S Glucodextran_B Glyco_hydro2_C5 Glyco_hydro_2 Gmad2 GMP_PDE_delta GO-like_E_set GspA_SrpA_N Hanta_G1 He_PIG HECW_N HemeBinding_Shp Hemocyanin_C Herpes_BLLF1 HYR IalB IFNGR1 Ig_GlcNase Ig_mannosidase IL12p40_C Il13Ra_Ig IL17R_fnIII_D1 IL17R_fnIII_D2 IL2RB_N1 IL3Ra_N IL4Ra_N IL6Ra-bind Inhibitor_I42 Inhibitor_I71 InlK_D3 Integrin_alpha2 Interfer-bind Invasin_D3 IRK_C IrmA Iron_transport Kre9_KNH LacZ_4 LEA_2 Lep_receptor_Ig LIFR_D2 LIFR_N Lipase_bact_N LodA_N LPMO_10 LRR_adjacent LTD MALT1_Ig Mannosidase_ig MetallophosC MG1 MG2 MG3 MG4 Mo-co_dimer N_BRCA1_IG Na_K-ATPase NAR2 NDNF NDNF_C NEAT Neocarzinostat Neurexophilin NPCBM_assoc Omp28 PapD_C PBP-Tp47_c Peptidase_C25_C Phlebo_G2_C PhoD_N PKD PKD_2 PKD_3 PKD_4 PKD_5 PKD_6 Por_Secre_tail Pox_vIL-18BP Psg1 PTP_tm Pullulanase_N2 Pur_ac_phosph_N Qn_am_d_aIII Qn_am_d_aIV RabGGT_insert Reeler REJ RET_CLD1 RET_CLD3 RET_CLD4 RGI_lyase RHD_dimer Rho_GDI Rib RibLong SCAB-Ig SKICH SLAM SoxZ SprB SusE SVA SWM_repeat T2SS-T3SS_pil_N Tafi-CsgC TarS_C1 TcA_RBD TcfC TIG TIG_2 TIG_plexin TIG_SUH Tissue_fac Top6b_C TPPII TQ Transglut_C Transglut_N TRAP_beta TraQ_transposon UL16 Velvet WIF Wzt_C Y_Y_Y YBD YscW ZirS_C Zona_pellucida


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.

Representative proteomes UniProt
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PP/heatmap 1            

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: Pfam-B_609 (release 18.0)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Wuster A
Number in seed: 30
Number in full: 9398
Average length of the domain: 363.90 aa
Average identity of full alignment: 20 %
Average coverage of the sequence by the domain: 38.66 %

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 26.0 26.0
Trusted cut-off 26.0 26.0
Noise cut-off 25.9 25.9
Model length: 465
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

Sunburst controls


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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


Align selected sequences to HMM

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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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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.


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 Integrin_alpha2 domain has been found. There are 126 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
A0A0G2JVZ6 View 3D Structure Click here
A0A0G2K1E2 View 3D Structure Click here
A0A0G2K470 View 3D Structure Click here
A0A0R4ICS1 View 3D Structure Click here
A0A0R4IGD8 View 3D Structure Click here
A0A0R4IJT2 View 3D Structure Click here
A0A2R8QKS0 View 3D Structure Click here
A0A2R8RQ80 View 3D Structure Click here
A2ARA8 View 3D Structure Click here
A8WHQ8 View 3D Structure Click here
A8X3A7 View 3D Structure Click here
B3DIZ6 View 3D Structure Click here
B5DEG1 View 3D Structure Click here
B8A5K2 View 3D Structure Click here
B8JK39 View 3D Structure Click here
B8JLK8 View 3D Structure Click here
D3ZAC0 View 3D Structure Click here
D3ZMQ3 View 3D Structure Click here
D3ZN51 View 3D Structure Click here
D3ZQM3 View 3D Structure Click here
D3ZW82 View 3D Structure Click here
D3ZWZ1 View 3D Structure Click here
E7F7L7 View 3D Structure Click here
E9Q6R1 View 3D Structure Click here
E9QDD7 View 3D Structure Click here
E9QHI5 View 3D Structure Click here
F1LP44 View 3D Structure Click here
F1LUU1 View 3D Structure Click here
F1MMS9 View 3D Structure Click here
F1Q8T4 View 3D Structure Click here
F1QC06 View 3D Structure Click here
F1QSJ9 View 3D Structure Click here
F1QWI2 View 3D Structure Click here
F1R108 View 3D Structure Click here
F1R2R3 View 3D Structure Click here
F8W2W0 View 3D Structure Click here
G3V667 View 3D Structure Click here
M0R6T8 View 3D Structure Click here
O44386 View 3D Structure Click here
O75578 View 3D Structure Click here