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115  structures 556  species 6  interactions 5460  sequences 68  architectures

Family: Arf (PF00025)

Summary: ADP-ribosylation factor 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 "ADP ribosylation factor". More...

ADP ribosylation factor Edit Wikipedia article

This article is about a small GTP-binding protein. For p14ARF tumor suppressor gene, see p14arf.
1ksg opm.png
Membrane-bound ADP ribosylation factor-like protein 2 (ARL2 mouse, red), complex with phosphodiesterase delta (yellow) (1ksg) Blue dots show hydrocarbon boundary of the lipid bilayer
Identifiers
Symbol Arf
Pfam PF00025
InterPro IPR006689
SMART ARF
PROSITE PDOC01020
SCOP 1hur
SUPERFAMILY 1hur
OPM superfamily 99
OPM protein 1ksg
CDD cd00878
Distribution of ARF in a living macrophage, highlighting the Golgi apparatus.

ADP Ribosylation Factors (ARFs) are members of the ARF family of GTP-binding proteins of the Ras superfamily. ARF family proteins are ubiquitous in eukaryotic cells, and six highly conserved members of the family have been identified in mammalian cells. Although ARFs are soluble, they generally associate with membranes because of N-terminus myristoylation. They function as regulators of vesicular traffic and actin remodelling.

The small ADP ribosylation factor (Arf) GTP-binding proteins are major regulators of vesicle biogenesis in intracellular traffic.[1] They are the founding members of a growing family that includes Arl (Arf-like), Arp (Arf-related proteins) and the remotely related Sar (Secretion-associated and Ras-related) proteins. Arf proteins cycle between inactive GDP-bound and active GTP-bound forms that bind selectively to effectors. The classical structural GDP/GTP switch is characterised by conformational changes at the so-called switch 1 and switch 2 regions, which bind tightly to the gamma-phosphate of GTP but poorly or not at all to the GDP nucleotide. Structural studies of Arf1 and Arf6 have revealed that although these proteins feature the switch 1 and 2 conformational changes, they depart from other small GTP-binding proteins in that they use an additional, unique switch to propagate structural information from one side of the protein to the other.

The GDP/GTP structural cycles of human Arf1 and Arf6 feature a unique conformational change that affects the beta2beta3 strands connecting switch 1 and switch 2 (interswitch) and also the amphipathic helical N-terminus. In GDP-bound Arf1 and Arf6, the interswitch is retracted and forms a pocket to which the N-terminal helix binds, the latter serving as a molecular hasp to maintain the inactive conformation. In the GTP-bound form of these proteins, the interswitch undergoes a two-residue register shift that pulls switch 1 and switch 2 up, restoring an active conformation that can bind GTP. In this conformation, the interswitch projects out of the protein and extrudes the N-terminal hasp by occluding its binding pocket.

Regulatory proteins

ARFs regularly associate with two types of protein, those involved in catalyzing GTP/GDP exchange, and those that serve other functions.

GTP/GDP exchange proteins

ARF binds to two forms of the guanosine nucleotide, guanosine triphosphate (GTP) and guanosine diphosphate (GDP). The shape of the ARF molecule is dependent upon which form it is bound to, allowing it to serve in a regulatory capacity. ARF requires assistance from other proteins in order to switch between binding to GTP and GDP. GTPase activating proteins (GAPs) force ARF to hydrolyze bound GTP to GDP, and Guanine nucleotide exchange factors force ARF to adopt a new GTP molecule in place of a bound GDP.

Other proteins

Other proteins interact with ARF, depending upon whether it is bound to GTP or GDP. The active form, ARF*GTP, binds to vesicle coat proteins and adaptors, including coat protein I (COPI) and various phospholipids. The inactive form is only known to bind to a class of transmembrane proteins. Different types of ARF bind specifically different kinds of effector proteins.

Phylogeny

There are currently 6 known mammalian ARF proteins, which are divided into three classes of ARFs:

Structure

ARFs are small proteins of approximately 20 kD in size. They contain two switch regions, which change relative positions between cycles of GDP/GTP-binding. ARFs are frequently myristoylated in their N-terminal region, which contributes to their membrane association.

Examples

Human genes encoding proteins containing this domain include:

References

Further reading

  • Donaldson JG, Honda A (2005). "Localization and function of Arf family GTPases". Biochemical Society Transactions 33 (4): 639–642. doi:10.1042/BST0330639. PMID 16042562.  edit
  • "Arf and its many interactors". Current opinion in cell biology 15 (4): 396–404. 2003. doi:10.1016/S0955-0674(03)00071-1. PMID 12892779.  edit
  • Amor JC, Harrison DH, Kahn RA, Ringe D (1994). "Structure of the human ADP-ribosylation factor 1 complexed with GDP". Nature 372 (6507): 704–708. doi:10.1038/372704a0. PMID 7990966.  edit
  • Moss J, Vaughan M; Vaughan (1995). "Structure and function of ARF proteins: Activators of cholera toxin and critical components of intracellular vesicular transport processes". The Journal of biological chemistry 270 (21): 12327–12330. doi:10.1074/jbc.270.21.12327. PMID 7759471.  edit
  • Boman AL, Kahn RA; Kahn (1995). "Arf proteins: The membrane traffic police?". Trends in biochemical sciences 20 (4): 147–150. doi:10.1016/s0968-0004(00)88991-4. PMID 7770914.  edit
  • Kahn RA, Kern FG, Clark J, Gelmann EP, Rulka C (1991). "Human ADP-ribosylation factors. A functionally conserved family of GTP-binding proteins". The Journal of biological chemistry 266 (4): 2606–2614. PMID 1899243.  edit

See also


External links

This article incorporates text from the public domain Pfam and InterPro IPR006689

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.

ADP-ribosylation factor family Provide feedback

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Literature references

  1. Amor JC, Harrison DH, Kahn RA, Ringe D; , Nature 1994;372:704-708.: Structure of the human ADP-ribosylation factor 1 complexed with GDP. PUBMED:7990966 EPMC:7990966

  2. Moss J, Vaughan M; , J. Biol. Chem. 1995;270:12327-12330.: Structure and function of ARF proteins: Activators of cholera toxin and critical components of intracellular vesicular transport processes. PUBMED:7759471 EPMC:7759471

  3. Boman AL, Kahn RA; , Trends Biochem Sci 1995;20:147-150.: Arf proteins: the membrane traffic police? PUBMED:7770914 EPMC:7770914

  4. Kahn RA, Kern FG, Clark J, Gelmann EP, Rulka C; , J Biol Chem 1991;266:2606-2614.: Human ADP-ribosylation factors. A functionally conserved family of GTP-binding proteins. PUBMED:1899243 EPMC:1899243


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR006689

Small GTPases form an independent superfamily within the larger class of regulatory GTP hydrolases. This superfamily contains proteins that control a vast number of important processes and possess a common, structurally preserved GTP-binding domain [PUBMED:2122258, PUBMED:1898771]. Sequence comparisons of small G proteins from various species have revealed that they are conserved in primary structures at the level of 30-55% similarity [PUBMED:2029511].

Crystallographic analysis of various small G proteins revealed the presence of a 20 kDa catalytic domain that is unique for the whole superfamily [PUBMED:1898771, PUBMED:2196171]. The domain is built of five alpha helices (A1-A5), six beta-strands (B1-B6) and five polypeptide loops (G1-G5). A structural comparison of the GTP- and GDP-bound form, allows one to distinguish two functional loop regions: switch I and switch II that surround the gamma-phosphate group of the nucleotide. The G1 loop (also called the P-loop) that connects the B1 strand and the A1 helix is responsible for the binding of the phosphate groups. The G3 loop provides residues for Mg(2+) and phosphate binding and is located at the N terminus of the A2 helix. The G1 and G3 loops are sequentially similar to Walker A and Walker B boxes that are found in other nucleotide binding motifs. The G2 loop connects the A1 helix and the B2 strand and contains a conserved Thr residue responsible for Mg(2+) binding. The guanine base is recognised by the G4 and G5 loops. The consensus sequence NKXD of the G4 loop contains Lys and Asp residues directly interacting with the nucleotide. Part of the G5 loop located between B6 and A5 acts as a recognition site for the guanine base [PUBMED:11995995].

The small GTPase superfamily can be divided into at least 8 different families, including:

  • Arf small GTPases. GTP-binding proteins involved in protein trafficking by modulating vesicle budding and uncoating within the Golgi apparatus.
  • Ran small GTPases. GTP-binding proteins involved in nucleocytoplasmic transport. Required for the import of proteins into the nucleus and also for RNA export.
  • Rab small GTPases. GTP-binding proteins involved in vesicular traffic.
  • Rho small GTPases. GTP-binding proteins that control cytoskeleton reorganisation.
  • Ras small GTPases. GTP-binding proteins involved in signalling pathways.
  • Sar1 small GTPases. Small GTPase component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER).
  • Mitochondrial Rho (Miro). Small GTPase domain found in mitochondrial proteins involved in mitochondrial trafficking.
  • Roc small GTPases domain. Small GTPase domain always found associated with the COR domain.

This entry represents a branch of the small GTPase superfamily that includes the ADP ribosylation factor Arf, Arl (Arf-like), Arp (Arf-related proteins) and the remotely related Sar (Secretion-associated and Ras-related) proteins. Arf proteins are major regulators of vesicle biogenesis in intracellular traffic [PUBMED:12429613]. They cycle between inactive GDP-bound and active GTP-bound forms that bind selectively to effectors. The classical structural GDP/GTP switch is characterised by conformational changes at the so-called switch 1 and switch 2 regions, which bind tightly to the gamma-phosphate of GTP but poorly or not at all to the GDP nucleotide. Structural studies of Arf1 and Arf6 have revealed that although these proteins feature the switch 1 and 2 conformational changes, they depart from other small GTP-binding proteins in that they use an additional, unique switch to propagate structural information from one side of the protein to the other.

The GDP/GTP structural cycles of human Arf1 and Arf6 feature a unique conformational change that affects the beta2-beta3 strands connecting switch 1 and switch 2 (interswitch) and also the amphipathic helical N terminus. In GDP-bound Arf1 and Arf6, the interswitch is retracted and forms a pocket to which the N-terminal helix binds, the latter serving as a molecular hasp to maintain the inactive conformation. In the GTP-bound form of these proteins, the interswitch undergoes a two-residue register shift that pulls switch 1 and switch 2 up, restoring an active conformation that can bind GTP. In this conformation, the interswitch projects out of the protein and extrudes the N-terminal hasp by occluding its binding pocket.

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 P-loop_NTPase (CL0023), which has the following description:

AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes [2].

The clan contains the following 198 members:

6PF2K AAA AAA-ATPase_like AAA_10 AAA_11 AAA_12 AAA_13 AAA_14 AAA_15 AAA_16 AAA_17 AAA_18 AAA_19 AAA_2 AAA_21 AAA_22 AAA_23 AAA_24 AAA_25 AAA_26 AAA_27 AAA_28 AAA_29 AAA_3 AAA_30 AAA_31 AAA_32 AAA_33 AAA_34 AAA_35 AAA_4 AAA_5 AAA_6 AAA_7 AAA_8 AAA_9 AAA_PrkA ABC_ATPase ABC_tran ABC_tran_2 Adeno_IVa2 Adenylsucc_synt ADK AFG1_ATPase AIG1 APS_kinase Arch_ATPase Arf ArgK ArsA_ATPase ATP-synt_ab ATP_bind_1 ATP_bind_2 Bac_DnaA CbiA CMS1 CoaE CobA_CobO_BtuR CobU cobW CPT CTP_synth_N Cytidylate_kin Cytidylate_kin2 DAP3 DEAD DEAD_2 DLIC DNA_pack_C DNA_pack_N DNA_pol3_delta DNA_pol3_delta2 DnaB_C dNK DUF1253 DUF1611 DUF2075 DUF2478 DUF258 DUF2791 DUF2813 DUF3584 DUF463 DUF815 DUF853 DUF87 DUF927 Dynamin_N Exonuc_V_gamma FeoB_N Fer4_NifH Flavi_DEAD FTHFS FtsK_SpoIIIE G-alpha Gal-3-0_sulfotr GBP GTP_EFTU GTP_EFTU_D2 GTP_EFTU_D4 Gtr1_RagA Guanylate_kin GvpD HDA2-3 Helicase_C Helicase_C_2 Helicase_C_4 Helicase_RecD Herpes_Helicase Herpes_ori_bp Herpes_TK IIGP IPPT IPT IstB_IS21 KaiC KAP_NTPase Kinesin Kinesin-relat_1 Kinesin-related KTI12 LpxK MCM MEDS Mg_chelatase Mg_chelatase_2 MipZ Miro MMR_HSR1 MobB MukB MutS_V Myosin_head NACHT NB-ARC NOG1 NTPase_1 ParA Parvo_NS1 PAXNEB PduV-EutP PhoH PIF1 Podovirus_Gp16 Polyoma_lg_T_C Pox_A32 PPK2 PPV_E1_C PRK Rad17 Rad51 Ras RecA ResIII RHD3 RHSP RNA12 RNA_helicase RuvB_N SbcCD_C SecA_DEAD Septin Sigma54_activ_2 Sigma54_activat SKI SMC_N SNF2_N Spore_IV_A SRP54 SRPRB Sulfotransfer_1 Sulfotransfer_2 Sulfotransfer_3 Sulphotransf T2SE T4SS-DNA_transf Terminase_1 Terminase_3 Terminase_6 Terminase_GpA Thymidylate_kin TIP49 TK TniB Torsin TraG-D_C tRNA_lig_kinase TrwB_AAD_bind UPF0079 UvrD-helicase UvrD_C UvrD_C_2 Viral_helicase1 VirC1 VirE YhjQ Zeta_toxin Zot

Alignments

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics 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.

  Seed
(20)
Full
(5460)
Representative proteomes NCBI
(26010)
Meta
(2506)
RP15
(1187)
RP35
(1801)
RP55
(2657)
RP75
(3415)
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  Seed
(20)
Full
(5460)
Representative proteomes NCBI
(26010)
Meta
(2506)
RP15
(1187)
RP35
(1801)
RP55
(2657)
RP75
(3415)
Alignment:
Format:
Order:
Sequence:
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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.

  Seed
(20)
Full
(5460)
Representative proteomes NCBI
(26010)
Meta
(2506)
RP15
(1187)
RP35
(1801)
RP55
(2657)
RP75
(3415)
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.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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...

Trees

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: Swissprot
Previous IDs: arf;
Type: Domain
Author: Sonnhammer ELL
Number in seed: 20
Number in full: 5460
Average length of the domain: 161.80 aa
Average identity of full alignment: 36 %
Average coverage of the sequence by the domain: 79.30 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.3 20.3
Trusted cut-off 20.3 20.3
Noise cut-off 20.2 20.2
Model length: 175
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 6 interactions for this family. More...

Sec23_trunk Sec7 Sec23_helical Arf Gelsolin GMP_PDE_delta

Structures

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 Arf domain has been found. There are 115 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.

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