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162  structures 1567  species 0  interactions 19712  sequences 360  architectures

Family: IBN_N (PF03810)

Summary: Importin-beta N-terminal domain

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

Importin Edit Wikipedia article

Karyopherin subunit alpha 1
NCBI gene3836
Other data
LocusChr. 3 q21.1
Karyopherin subunit beta 1
NCBI gene3837
Other data
LocusChr. 17 q21.32

Importin is a type of karyopherin[1] that transports protein molecules into the nucleus by binding to specific recognition sequences, called nuclear localization sequences (NLS).

Importin has two subunits, importin α and importin β. Members of the importin-β family can bind and transport cargo by themselves, or can form heterodimers with importin-α. As part of a heterodimer, importin-β mediates interactions with the pore complex, while importin-α acts as an adaptor protein to bind the nuclear localisation signal (NLS) on the cargo. The NLS-Importin α-Importin β trimer dissociates after binding to Ran GTP inside the nucleus,[2] with the two importin proteins being recycled to the cytoplasm for further use.


Importin can exist as either a heterodimer of importin-α/β or as a monomer of Importin-β. Importin-α was first isolated in 1994 by a group including Enno Hartmann, based at the Max Delbrück Center for Molecular Medicine.[1] The process of nuclear protein import had already been characterised in previous reviews,[3] but the key proteins involved had not been elucidated up until that point. A 60kDa cytosolic protein, essential for protein import into the nucleus, and with a 44% sequence identity to SRP1p, was purified from Xenopus eggs. It was cloned, sequenced and expressed in E.coli and in order to completely reconstitute signal dependent transport, had to be combined with Ran(TC4). Other key stimulatory factors were also found in the study.[1]

Importin-β, unlike importin-α, has no direct homologues in yeast, but was purified as a 90-95kDa protein and found to form a heterodimer with importin-α in a number of different cases. These included a study led by Michael Rexach[4] </ref> and further studies by Dirk Görlich.[5] These groups found that importin-α requires another protein, importin-β to function, and that together they form a receptor for nuclear localization signals (NLS), thus allowing transport into the nucleus. Since these initial discoveries in 1994 and 1995, a host of Importin genes, such as IPO4 and IPO7, have been found that facilitate the import of slightly different cargo proteins, due to their differing structure and locality.



A large proportion of the importin-α adaptor protein is made up of several armadillo repeats (ARM) arranged in tandem. These repeats can stack together to form a curved shaped structure, which facilitates binding to the NLS of specific cargo proteins. The major NLS binding site is found towards the N-terminus, with a minor site being found at the C-terminus. As well as the ARM structures, Importin-α also contains a 90 amino acid N-terminal region, responsible for binding to Importin-β, known as IBB (Importin-β binding domain). This is also a site of autoinhibition, and is implicated in the release of cargo once importin-α reaches the nucleus.[6]


Importin-β is the typical structure of a larger superfamily of karyopherins. The basis of their structure is 18-20 tandem repeats of the HEAT motif. Each one of these repeats contains two antiparallel alpha helices linked by a turn, which stack together to form the overall structure of the protein.[7]

In order to transport cargo into the nucleus, importin-β must associate with the nuclear pore complexes. It does this by forming weak, transient bonds with nucleoporins at their various FG (Phe-Gly) motifs. Crystallographic analysis has shown that these motifs bind to importin-β at shallow hydrophobic pockets found on its surface.[8]

Nuclear protein import cycle

The primary function of importin is to mediate the translocation of proteins with nuclear localization signals into the nucleus, through nuclear pore complexes (NPC), in a process known as the nuclear protein import cycle.

Cargo binding

The first step of this cycle is the binding of cargo. Importin can perform this function as a monomeric importin-β protein, but usually requires the presence of importin-α, which acts as an adaptor to cargo proteins (via interactions with the NLS). The NLS is a sequence of basic amino acids that tags the protein as cargo destined for the nucleus. A cargo protein can contain either one or two of these motifs, which will bind to the major and/or minor binding sites on importin-α.[9]

Overview of the nuclear protein import cycle.

Cargo transport

Once the cargo protein is bound, importin-β interacts with the NPC, and the complex diffuses into the nucleus from the cytoplasm. The rate of diffusion depends on both the concentration of importin-α present in the cytoplasm and also the binding affinity of importin-α to the cargo. Once inside the nucleus, the complex interacts with the Ras-family GTPase, Ran-GTP. This leads to the dissociation of the complex by altering the conformation of Importin-β. Importin-β is left bound to Ran-GTP, ready to be recycled.[9]

Cargo release

Now that the importin-α/cargo complex is free of importin-β, the cargo protein can be released into the nucleus. The N-terminal importin-β-binding (IBB) domain of importin-α contains an auto-regulatory region that mimics the NLS motif. The release of importin-β frees this region and allows it to loop back and compete for binding with the cargo protein at the major NLS-binding site. This competition leads to the release of the protein. In some cases, specific release factors such as Nup2 and Nup50 can be employed to help release the cargo as well.[9]


Finally, in order to return to the cytoplasm, importin-α must associate with a Ran-GTP/CAS (nuclear export factor) complex which facilitates its exit from the nucleus. CAS (cellular apoptosis susceptibility protein) is part of the importin-β superfamily of karyopherins and is defined as a nuclear export factor. Importin-β returns to the cytoplasm, still bound to Ran-GTP. Once in the cytoplasm, Ran-GTP is hydrolysed by RanGAP, forming Ran-GDP, and releasing the two importins for further activity. It is this hydrolysis of GTP that provides the energy for the cycle as a whole. In the nucleus, a GEF will charge Ran with a GTP molecule, which is then hydrolysed by a GAP in the cytoplasm, as stated above. It is this activity of Ran that allows for the unidirectional transport of proteins.[9]


There are several disease states and pathologies that are associated with mutations or changes in expression of importin-α and importin-β.

Importins are vital regulatory proteins during the processes of gametogenesis and embryogenesis. As a result, a disruption in the expression patterns of importin-α has been shown to cause fertility defects in Drosophila melanogaster.[10]

There have also been studies that link altered importin-α to some cases of cancer. Breast cancer studies have implicated a truncated form of importin-α in which the NLS binding domain is missing.[11] In addition, importin-α has been shown to transport the tumour suppressor gene, BRCA1 (breast cancer type 1 susceptibility protein), into the nucleus. The overexpression of importin-α has also been linked with poor survival rates seen in certain melanoma patients.[12]

Importin activity is also associated with some viral pathologies. For instance, in the infection pathway of the Ebola virus, a key step is the inhibition of the nuclear import of PY-STAT1. This is achieved by the virus sequestering importin-α in the cytoplasm, meaning it can no longer bind its cargo at the NLS.[13] As a result, importin cannot function and the cargo protein stays in the cytoplasm.

Types of cargo

Many different cargo proteins can be transported into the nucleus by importin. Often, different proteins will require different combinations of α and β in order to translocate. Some examples of different cargo are listed below.

Cargo Import Receptor
SV40 Importin-β and importin-α
Nucleoplasmin Importin-β and importin-α
STAT1 Importin-β and NPI-1 (type of importin-α)
TFIIA Importin-α not required
U1A Importin-α not required

Human importin genes

Although importin-α and importin-β are used to describe importin as a whole, they actually represent larger families of proteins that share a similar structure and function. Various different genes have been identified for both α and β, with some of them listed below. Note that often karyopherin and importin are used interchangeably.

See also


  1. ^ a b c Görlich D, Prehn S, Laskey RA, Hartmann E (December 1994). "Isolation of a protein that is essential for the first step of nuclear protein import". Cell. 79 (5): 767–78. doi:10.1016/0092-8674(94)90067-1. PMID 8001116.
  2. ^ Mattaj IW, Englmeier L (1998). "Nucleocytoplasmic transport: the soluble phase". Annual Review of Biochemistry. 67: 265–306. doi:10.1146/annurev.biochem.67.1.265. PMID 9759490.
  3. ^ Garcia-Bustos J, Heitman J, Hall MN (March 1991). "Nuclear protein localization". Biochim. Biophys. Acta. 1071 (1): 83–101. doi:10.1016/0304-4157(91)90013-m. PMID 2004116.
  4. ^ Enenkel C, Blobel G, Rexach M (July 1995). "Identification of a yeast karyopherin heterodimer that targets import substrate to mammalian nuclear pore complexes". J. Biol. Chem. 270 (28): 16499–502. doi:10.1074/jbc.270.28.16499. PMID 7622450.
  5. ^ Görlich D, Kostka S, Kraft R, Dingwall C, Laskey RA, Hartmann E, Prehn S (April 1995). "Two different subunits of importin cooperate to recognize nuclear localization signals and bind them to the nuclear envelope". Current Biology. 5 (4): 383–92. doi:10.1016/s0960-9822(95)00079-0. PMID 7627554.
  6. ^ Conti E, Uy M, Leighton L, Blobel G, Kuriyan J (July 1998). "Crystallographic analysis of the recognition of a nuclear localization signal by the nuclear import factor karyopherin alpha". Cell. 94 (2): 193–204. doi:10.1016/s0092-8674(00)81419-1. PMID 9695948.
  7. ^ Lee SJ, Matsuura Y, Liu SM, Stewart M (June 2005). "Structural basis for nuclear import complex dissociation by RanGTP". Nature. 435 (7042): 693–6. doi:10.1038/nature03578. PMID 15864302.
  8. ^ Bayliss R, Littlewood T, Stewart M (July 2000). "Structural basis for the interaction between FxFG nucleoporin repeats and importin-beta in nuclear trafficking". Cell. 102 (1): 99–108. doi:10.1016/s0092-8674(00)00014-3. PMID 10929717.
  9. ^ a b c d Weis K (February 2003). "Regulating access to the genome: nucleocytoplasmic transport throughout the cell cycle". Cell. 112 (4): 441–51. doi:10.1016/s0092-8674(03)00082-5. PMID 12600309.
  10. ^ Terry LJ, Shows EB, Wente SR (November 2007). "Crossing the nuclear envelope: hierarchical regulation of nucleocytoplasmic transport". Science. 318 (5855): 1412–6. doi:10.1126/science.1142204. PMID 18048681.
  11. ^ Kim IS, Kim DH, Han SM, Chin MU, Nam HJ, Cho HP, Choi SY, Song BJ, Kim ER, Bae YS, Moon YH (July 2000). "Truncated form of importin alpha identified in breast cancer cell inhibits nuclear import of p53". The Journal of Biological Chemistry. 275 (30): 23139–45. doi:10.1074/jbc.M909256199. PMID 10930427.
  12. ^ Winnepenninckx V, Lazar V, Michiels S, Dessen P, Stas M, Alonso SR, Avril MF, Ortiz Romero PL, Robert T, Balacescu O, Eggermont AM, Lenoir G, Sarasin A, Tursz T, van den Oord JJ, Spatz A (April 2006). "Gene expression profiling of primary cutaneous melanoma and clinical outcome". Journal of the National Cancer Institute. 98 (7): 472–82. doi:10.1093/jnci/djj103. PMID 16595783.
  13. ^ Sekimoto T, Imamoto N, Nakajima K, Hirano T, Yoneda Y (December 1997). "Extracellular signal-dependent nuclear import of Stat1 is mediated by nuclear pore-targeting complex formation with NPI-1, but not Rch1". The EMBO Journal. 16 (23): 7067–77. doi:10.1093/emboj/16.23.7067. PMC 1170309. PMID 9384585.

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This article incorporates text from the public domain Pfam and InterPro: IPR002652
This article incorporates text from the public domain Pfam and InterPro: IPR001494

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Importin-beta N-terminal domain Provide feedback

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This tab holds annotation information from the InterPro database.

InterPro entry IPR001494

Members of the importin-beta (karyopherin-beta) family can bind and transport cargo by themselves, or can form heterodimers with importin-alpha. As part of a heterodimer, importin-beta mediates interactions with the pore complex, while importin-alpha acts as an adaptor protein to bind the nuclear localisation signal (NLS) on the cargo through the classical NLS import of proteins. Importin-beta is a helicoidal molecule constructed from 19 HEAT repeats. Many nuclear pore proteins contain FG sequence repeats that can bind to HEAT repeats within importins [ PUBMED:12372823 , PUBMED:17161424 ], which is important for importin-beta mediated transport.

Ran GTPase helps to control the unidirectional transfer of cargo. The cytoplasm contains primarily RanGDP and the nucleus RanGTP through the actions of RanGAP and RanGEF, respectively. In the nucleus, RanGTP binds to importin-beta within the importin/cargo complex, causing a conformational change in importin-beta that releases it from importin-alpha-bound cargo. As a result, the N-terminal auto-inhibitory region on importin-alpha is free to loop back and bind to the major NLS-binding site, causing the cargo to be released [ PUBMED:17170104 ]. There are additional release factors as well.

This entry represents the N-terminal domain of importin-beta (also known as karyopherins-beta) that is important for the binding of the Ran GTPase protein [ PUBMED:10367892 ].

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan TPR (CL0020), which has the following description:

Tetratricopeptide-like repeats are found in a numerous and diverse proteins involved in such functions as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neurogenesis and protein folding.

The clan contains the following 252 members:

14-3-3 AAR2 Aconitase_B_N Adaptin_N Alkyl_sulf_dimr ANAPC3 ANAPC5 ANAPC8 Apc1_MidN APC_rep API5 Aquarius_N Arm Arm_2 Arm_3 Arm_vescicular Atx10homo_assoc B56 BAF250_C BRO1 BTAD CAS_CSE1 ChAPs CHIP_TPR_N CID CLASP_N Clathrin Clathrin-link Clathrin_H_link Clathrin_propel Cnd1 Cnd1_N Cnd3 CNOT1_CAF1_bind CNOT1_HEAT_N CNOT1_TTP_bind Coatomer_E Cohesin_HEAT Cohesin_load ComR_TPR COPI_C CPL CRM1_C CRM1_repeat CRM1_repeat_3 Cse1 CTK3 CTNNBL Cullin DHR-2_Lobe_A DHR-2_Lobe_C DIL DNA-PKcs_N DNA_alkylation DNAPKcs_CC1-2 DNAPKcs_CC3 DNAPKcs_CC5 Dopey_N Drf_FH3 Drf_GBD DUF1822 DUF2019 DUF2225 DUF3385 DUF3458_C DUF3730 DUF3856 DUF4042 DUF4704 DUF5071 DUF5106 DUF5588 DUF5691 DUF6340 DUF6377 DUF6584 DUF924 E_motif EAD11 eIF-3c_N ELMO_ARM EST1 EST1_DNA_bind FA_FANCE FANCF FANCI_HD1 FANCI_HD2 FANCI_S1 FANCI_S1-cap FANCI_S2 FANCI_S3 FANCI_S4 FAT Fes1 Fis1_TPR_C Fis1_TPR_N Focadhesin Foie-gras_1 GET4 GLE1 GUN4_N HAT HEAT HEAT_2 HEAT_EZ HEAT_PBS HEAT_UF HemY_N HMW1C_N HPS6_C HrpB1_HrpK HSM3_C HSM3_N Hyccin IBB IBN_N IFRD Iml2-TPR_39 Importin_rep Importin_rep_2 Importin_rep_3 Importin_rep_4 Importin_rep_5 Importin_rep_6 Insc_C Ints3_N KAP Kinetochor_Ybp2 Laa1_Sip1_HTR5 Leuk-A4-hydro_C LRV LRV_FeS MA3 Mad3_BUB1_I MAP3K_TRAF_bd MIF4G MIF4G_like MIF4G_like_2 MIX MMS19_C Mo25 MRP-S27 Mtf2 MUN NatA_aux_su Neurobeachin Neurochondrin Nic96 Nipped-B_C Not1 Nro1 NSF Paf67 ParcG PAT1 PC_rep PDS5 Peptidase_M9_N PHAT PI3Ka PknG_TPR PPP5 PPR PPR_1 PPR_2 PPR_3 PPR_long PPTA Proteasom_PSMB PUF PUL RAI16-like Rapsyn_N Rcd1 RIH_assoc RINT1_TIP1 RIX1 RNPP_C RPM2 RPN6_N RPN7 RYDR_ITPR Sel1 SHNi-TPR SIL1 SLT_L SNAP SPO22 SRP_TPR_like ST7 STAG Suf SusD-like SusD-like_2 SusD-like_3 SusD_RagB SYCP2_ARLD SYMPK_PTA1_N TAF1_subA TAF6_C TAL_effector TAP42 TAtT Tcf25 TIP120 TOM20_plant TPR-S TPR_1 TPR_10 TPR_11 TPR_12 TPR_14 TPR_15 TPR_16 TPR_17 TPR_18 TPR_19 TPR_2 TPR_20 TPR_21 TPR_22 TPR_3 TPR_4 TPR_5 TPR_6 TPR_7 TPR_8 TPR_9 TPR_MalT Tra1_ring TRF TTC7_N Type_III_YscG UNC45-central Upf2 Uso1_p115_head V-ATPase_H_C V-ATPase_H_N Vac14_Fab1_bd Vitellogenin_N Vps16_C Vps35 Vps39_1 VPS53_C W2 Wap1 WSLR Wzy_C_2 Xpo1 YcaO_C YfiO Zmiz1_N


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Curation and family details

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Seed source: PROSITE
Previous IDs: IBN_NT;
Type: Repeat
Sequence Ontology: SO:0001068
Author: Griffiths-Jones SR
Number in seed: 52
Number in full: 19712
Average length of the domain: 71.90 aa
Average identity of full alignment: 20 %
Average coverage of the sequence by the domain: 7.44 %

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 21.0 21.0
Trusted cut-off 21.0 21.0
Noise cut-off 20.9 20.9
Model length: 74
Family (HMM) version: 22
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Species distribution

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Archea Archea Eukaryota Eukaryota
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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 IBN_N domain has been found. There are 162 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
A0A096UGL9 View 3D Structure Click here
A0A0G2K6J6 View 3D Structure Click here
A0A0G2KAF6 View 3D Structure Click here
A0A0P0V093 View 3D Structure Click here
A0A0P0VVN2 View 3D Structure Click here
A0A0P0VWC2 View 3D Structure Click here
A0A0P0W8L8 View 3D Structure Click here
A0A0R0FZ83 View 3D Structure Click here
A0A0R0KIF2 View 3D Structure Click here
A0A0R0L5C7 View 3D Structure Click here
A0A0R4IK82 View 3D Structure Click here
A0A0R4IMZ8 View 3D Structure Click here
A0A0R4IWU7 View 3D Structure Click here
A0A131MBF9 View 3D Structure Click here
A0A1D6F4Y6 View 3D Structure Click here
A0A1D6FRJ2 View 3D Structure Click here
A0A1D6GCV9 View 3D Structure Click here
A0A1D6GJ40 View 3D Structure Click here
A0A1D6H818 View 3D Structure Click here
A0A1D6JIW5 View 3D Structure Click here
A0A1D6JWX6 View 3D Structure Click here
A0A1D6KE00 View 3D Structure Click here
A0A1D6KT45 View 3D Structure Click here
A0A1D6LCD9 View 3D Structure Click here
A0A1D6LU85 View 3D Structure Click here
A0A1D6M2S2 View 3D Structure Click here
A0A1D6MWV6 View 3D Structure Click here
A0A1D6NYH3 View 3D Structure Click here
A0A1D6Q212 View 3D Structure Click here
A0A1D8PE78 View 3D Structure Click here
A0A1D8PGN9 View 3D Structure Click here
A0A1D8PNS3 View 3D Structure Click here
A0A1D8PQJ7 View 3D Structure Click here
A0A1D8PRI4 View 3D Structure Click here
A0A1D8PRR9 View 3D Structure Click here
A0A286Y8U4 View 3D Structure Click here
A0A2R8PW20 View 3D Structure Click here
A0A2R8PZ81 View 3D Structure Click here
A0A2R8Q4D0 View 3D Structure Click here
A0A2R8RNP8 View 3D Structure Click here