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92  structures 2259  species 0  interactions 26184  sequences 1116  architectures

Family: NHL (PF01436)

Summary: NHL repeat

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 "NHL repeat". More...

NHL repeat Edit Wikipedia article

NHL repeat
PDB 1q7f EBI.jpg
Structure of the brain tumor-Pumilio translation repressor complex.[1]
Identifiers
SymbolNHL
PfamPF01436
Pfam clanCL0186
InterProIPR001258
SCOPe1q7f / SUPFAM
CDDcd05819

The NHL repeat, named after ncl-1, HT2A and lin-41, is an amino acid sequence found largely in a large number of eukaryotic and prokaryotic proteins. For example, the repeat is found in a variety of enzymes of the copper type II, ascorbate-dependent monooxygenase family which catalyse the C-terminus alpha-amidation of biological peptides.[2] In many it occurs in tandem arrays, for example in the RING finger beta-box, coiled-coil (RBCC) eukaryotic growth regulators.[3] The arthropod 'Brain Tumor' protein (Brat; Q8MQJ9) is one such growth regulator that contains a 6-bladed NHL-repeat beta-propeller.[1][4]

The NHL repeats are also found in serine/threonine protein kinase (STPK) in diverse range of pathogenic bacteria. These STPK are transmembrane receptors with an intracellular N-terminal kinase domain and extracellular C-terminal sensor domain. In the STPK, PknD, from Mycobacterium tuberculosis, the sensor domain forms a rigid, six-bladed b-propeller composed of NHL repeats with a flexible tether to the transmembrane domain.

The NHL repeat has also been used to design a family of fully symmetrical 6-blade beta-propeller proteins called "Pizza".[5] These proteins can also be engineered to bind mineral nanocrystals.[6]

References

  1. ^ a b Edwards TA, Wilkinson BD, Wharton RP, Aggarwal AK (October 2003). "Model of the brain tumor-Pumilio translation repressor complex". Genes Dev. 17 (20): 2508–2513. doi:10.1101/gad.1119403. PMC 218144. PMID 14561773.
  2. ^ Kano S, Miyajima N, Fukuda S, Hatakeyama S (July 2008). "Tripartite motif protein 32 facilitates cell growth and migration via degradation of Abl-interactor 2". Cancer Res. 68 (14): 5572–5580. doi:10.1158/0008-5472.CAN-07-6231. PMID 18632609.
  3. ^ Slack FJ, Ruvkun G (December 1998). "A novel repeat domain that is often associated with RING finger and B-box motifs". Trends Biochem. Sci. 23 (12): 474–5. doi:10.1016/S0968-0004(98)01299-7. PMID 9868369.
  4. ^ Edwards TA, Pyle SE, Wharton RP, Aggarwal AK (April 2001). "Structure of Pumilio reveals similarity between RNA and peptide binding motifs". Cell. 105 (2): 281–9. doi:10.1016/S0092-8674(01)00318-X. PMID 11336677.
  5. ^ Tame, Jeremy R. H.; Zhang, Kam Y. J.; Park, Sam-Yong; Unzai, Satoru; Terada, Daiki; Simoncini, David; Addy, Christine; Noguchi, Hiroki; Voet, Arnout R. D. (21 October 2014). "Computational design of a self-assembling symmetrical β-propeller protein". Proceedings of the National Academy of Sciences. 111 (42): 15102–15107. Bibcode:2014PNAS..11115102V. doi:10.1073/pnas.1412768111. ISSN 0027-8424. PMC 4210308.
  6. ^ Voet, AR; Noguchi, H; Addy, C; Zhang, KY; Tame, JR (17 August 2015). "Biomineralization of a Cadmium Chloride Nanocrystal by a Designed Symmetrical Protein". Angewandte Chemie International Edition. 54 (34): 9857–60. doi:10.1002/anie.201503575. PMID 26136355.
This article incorporates text from the public domain Pfam and InterPro: IPR001258

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.

NHL repeat Provide feedback

The NHL (NCL-1, HT2A and LIN-41) repeat is found in multiple tandem copies. It is about 40 residues long and resembles the WD repeat PF00400. The repeats have a catalytic activity in P10731 proteolysis has shown that the Peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) activity is localised to the repeats [2]. Q13049 interacts with the activation domain of Tat. This interaction is me diated by the NHL repeats [3].

Literature references

  1. Slack FJ, Ruvkun G; , Trends Biochem Sci 1998;23:474-475.: A novel repeat domain that is often associated with RING finger and B-box motifs. PUBMED:9868369 EPMC:9868369

  2. Husten EJ, Eipper BA; , J Biol Chem 1991;266:17004-17010.: The membrane-bound bifunctional peptidylglycine alpha-amidating monooxygenase protein. Exploration of its domain structure through limited proteolysis. PUBMED:1894599 EPMC:1894599

  3. Fridell RA, Harding LS, Bogerd HP, Cullen BR; , Virology 1995;209:347-357.: Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins. PUBMED:7778269 EPMC:7778269


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001258

The NHL repeat, named after NCL-1, HT2A and Lin-41, is found largely in a large number of eukaryotic and prokaryotic proteins. For example, the repeat is found in a variety of enzymes of the copper type II, ascorbate-dependent monooxygenase family which catalyse the C terminus alpha-amidation of biological peptides [ PUBMED:1894599 ]. In many it occurs in tandem arrays, for example in the ringfinger beta-box, coiled-coil (RBCC) eukaryotic growth regulators [ PUBMED:9868369 ]. The 'Brain Tumor' protein (Brat) is one such growth regulator that contains a 6-bladed NHL-repeat beta-propeller [ PUBMED:14561773 , PUBMED:11336677 ].

The NHL repeats are also found in serine/threonine protein kinase (STPK) in diverse range of pathogenic bacteria. These STPK are transmembrane receptors with a intracellular N-terminal kinase domain and extracellular C-terminal sensor domain. In the STPK, PknD, from Mycobacterium tuberculosis, the sensor domain forms a rigid, six-bladed b-propeller composed of NHL repeats with a flexible tether to the transmembrane domain.

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 Beta_propeller (CL0186), which has the following description:

This large clan contains proteins that contain beta propellers. These are composed of between 6 and 8 repeats. The individual repeats are composed of a four stranded sheet. The clan includes families such as WD40 Pfam:PF00400 where the individual repeats are modeled. The clan also includes families where the entire propeller is modeled such as Pfam:PF02239 usually because the individual repeats are not discernible. These proteins carry out a very wide diversity of functions including catalysis.

The clan contains the following 88 members:

ANAPC4_WD40 APMAP_N Arylesterase Arylsulfotran_2 Arylsulfotrans B_lectin BBS2_Mid Beta_propel Coatomer_WDAD CPSF_A CyRPA Cytochrom_D1 Dpp_8_9_N DPPIV_N DPPIV_rep DUF1513 DUF1668 DUF2415 DUF3748 DUF4221 DUF4933 DUF4934 DUF5046 DUF5050 DUF5122 DUF5128 DUF5711 DUF839 eIF2A FG-GAP FG-GAP_2 FG-GAP_3 Frtz Ge1_WD40 Glu_cyclase_2 Gmad1 GSDH Hyd_WA IKI3 Itfg2 Kelch_1 Kelch_2 Kelch_3 Kelch_4 Kelch_5 Kelch_6 Lactonase Ldl_recept_b LGFP Lgl_C LVIVD Me-amine-dh_H MgpC MRJP Nbas_N Neisseria_PilC NHL nos_propeller nos_propeller_2 Nucleoporin_N Nup160 PALB2_WD40 PD40 Pectate_lyase22 Peptidase_S9_N PHTB1_N Phytase-like PQQ PQQ_2 PQQ_3 RAG2 RCC1 RCC1_2 Reg_prop SBBP SBP56 SdiA-regulated SGL Str_synth TcdB_toxin_midN Tectonin TolB_like VID27 WD40 WD40_2 WD40_3 WD40_4 WD40_like

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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

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
(76)
Full
(26184)
Representative proteomes UniProt
(77143)
RP15
(6190)
RP35
(12750)
RP55
(24362)
RP75
(33144)
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HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

Format an alignment

  Seed
(76)
Full
(26184)
Representative proteomes UniProt
(77143)
RP15
(6190)
RP35
(12750)
RP55
(24362)
RP75
(33144)
Alignment:
Format:
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Sequence:
Gaps:
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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.

  Seed
(76)
Full
(26184)
Representative proteomes UniProt
(77143)
RP15
(6190)
RP35
(12750)
RP55
(24362)
RP75
(33144)
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...

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: [1]
Previous IDs: none
Type: Repeat
Sequence Ontology: SO:0001068
Author: Bateman A
Number in seed: 76
Number in full: 26184
Average length of the domain: 28.00 aa
Average identity of full alignment: 34 %
Average coverage of the sequence by the domain: 10.52 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.0 20.0
Trusted cut-off 20.0 20.0
Noise cut-off 19.9 19.9
Model length: 28
Family (HMM) version: 23
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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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 NHL domain has been found. There are 92 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
A0A0R4IIV2 View 3D Structure Click here
A0A0R4IIV2 View 3D Structure Click here
A0A0R4IL45 View 3D Structure Click here
A0A0R4IL45 View 3D Structure Click here
A0A0R4IL45 View 3D Structure Click here
A0A1D6EEA7 View 3D Structure Click here
A0A1D6EXF8 View 3D Structure Click here
A0A1D6H6B9 View 3D Structure Click here
A0A1D6K0T3 View 3D Structure Click here
A0A1D6K0T3 View 3D Structure Click here
A0A1D6MZQ1 View 3D Structure Click here
A0A1D6PWI7 View 3D Structure Click here
A0A286YB14 View 3D Structure Click here
A0A286YB14 View 3D Structure Click here
A0A286YB14 View 3D Structure Click here
A0A286YB14 View 3D Structure Click here
A0A286YB14 View 3D Structure Click here
A0A286YB14 View 3D Structure Click here
B7YZK8 View 3D Structure Click here
B7YZK8 View 3D Structure Click here
B7YZK8 View 3D Structure Click here
B7YZK8 View 3D Structure Click here
B7YZK8 View 3D Structure Click here
B7YZK8 View 3D Structure Click here
B8A5M1 View 3D Structure Click here
B8A5M1 View 3D Structure Click here
B8A5M1 View 3D Structure Click here
B8A5M1 View 3D Structure Click here
B8A5M1 View 3D Structure Click here
B8A5M1 View 3D Structure Click here
D3ZLM5 View 3D Structure Click here
D3ZLM5 View 3D Structure Click here
D3ZLM5 View 3D Structure Click here
D3ZQG6 View 3D Structure Click here
D3ZQG6 View 3D Structure Click here
D3ZQG6 View 3D Structure Click here
D3ZQG6 View 3D Structure Click here
D3ZQG6 View 3D Structure Click here
D3ZQG6 View 3D Structure Click here
D3ZVM4 View 3D Structure Click here
D3ZVM4 View 3D Structure Click here
D3ZVM4 View 3D Structure Click here
D3ZVM4 View 3D Structure Click here
D3ZVM4 View 3D Structure Click here
D3ZVM4 View 3D Structure Click here
D4A2F6 View 3D Structure Click here
E7F1U3 View 3D Structure Click here
E7F1U3 View 3D Structure Click here
E7F1U3 View 3D Structure Click here
E7F1U3 View 3D Structure Click here
E7F1U3 View 3D Structure Click here
E7F1U3 View 3D Structure Click here
E7FAM5 View 3D Structure Click here
E7FAM5 View 3D Structure Click here
E7FAM5 View 3D Structure Click here
E7FAM5 View 3D Structure Click here
E7FAM5 View 3D Structure Click here
E7FAM5 View 3D Structure Click here
F1QFW2 View 3D Structure Click here
F1QFW2 View 3D Structure Click here
F1QFW2 View 3D Structure Click here
F1QFW2 View 3D Structure Click here
F1QFW2 View 3D Structure Click here
F1QFW2 View 3D Structure Click here
F4I5D7 View 3D Structure Click here
F4I7N5 View 3D Structure Click here
F4IXC9 View 3D Structure Click here
F4K891 View 3D Structure Click here
I1M2Z0 View 3D Structure Click here
I1N1F2 View 3D Structure Click here
I1NBR0 View 3D Structure Click here
I1NBR0 View 3D Structure Click here
I6X7J6 View 3D Structure Click here
I6X7J6 View 3D Structure Click here
I6X7J6 View 3D Structure Click here
K7L9K2 View 3D Structure Click here
K7LWI0 View 3D Structure Click here
O70277 View 3D Structure Click here
O70277 View 3D Structure Click here
O70277 View 3D Structure Click here
O70277 View 3D Structure Click here
O70277 View 3D Structure Click here
O70277 View 3D Structure Click here
O75382 View 3D Structure Click here
O75382 View 3D Structure Click here
O75382 View 3D Structure Click here
O75382 View 3D Structure Click here
O75382 View 3D Structure Click here
O75382 View 3D Structure Click here
P0CG21 View 3D Structure Click here
P14925 View 3D Structure Click here
P14925 View 3D Structure Click here
P14925 View 3D Structure Click here
P19021 View 3D Structure Click here
P19021 View 3D Structure Click here
P19021 View 3D Structure Click here
P34611 View 3D Structure Click here
P34611 View 3D Structure Click here
P34611 View 3D Structure Click here
P34611 View 3D Structure Click here
P34611 View 3D Structure Click here
P83388 View 3D Structure Click here
P83388 View 3D Structure Click here
P83388 View 3D Structure Click here
P91268 View 3D Structure Click here
P91268 View 3D Structure Click here
P91268 View 3D Structure Click here
P97467 View 3D Structure Click here
P97467 View 3D Structure Click here
P97467 View 3D Structure Click here
P9WI79 View 3D Structure Click here
P9WI79 View 3D Structure Click here
P9WI79 View 3D Structure Click here
P9WI79 View 3D Structure Click here
P9WI79 View 3D Structure Click here
Q03601 View 3D Structure Click here
Q03601 View 3D Structure Click here
Q03601 View 3D Structure Click here
Q03601 View 3D Structure Click here
Q03601 View 3D Structure Click here
Q13049 View 3D Structure Click here
Q13049 View 3D Structure Click here
Q13049 View 3D Structure Click here
Q19818 View 3D Structure Click here
Q19818 View 3D Structure Click here
Q19818 View 3D Structure Click here
Q1PSW8 View 3D Structure Click here
Q1PSW8 View 3D Structure Click here
Q1PSW8 View 3D Structure Click here
Q1PSW8 View 3D Structure Click here
Q1PSW8 View 3D Structure Click here
Q1PSW8 View 3D Structure Click here
Q2Q1W2 View 3D Structure Click here
Q2Q1W2 View 3D Structure Click here
Q2Q1W2 View 3D Structure Click here
Q2Q1W2 View 3D Structure Click here
Q2Q1W2 View 3D Structure Click here
Q2Q1W2 View 3D Structure Click here
Q3UP44 View 3D Structure Click here
Q5JS37 View 3D Structure Click here
Q66H79 View 3D Structure Click here
Q66H79 View 3D Structure Click here
Q66H79 View 3D Structure Click here
Q6EUK9 View 3D Structure Click here
Q79FU0 View 3D Structure Click here
Q79FU2 View 3D Structure Click here
Q8BZW8 View 3D Structure Click here
Q8BZW8 View 3D Structure Click here
Q8BZW8 View 3D Structure Click here
Q8CCH2 View 3D Structure Click here
Q8CH72 View 3D Structure Click here
Q8CH72 View 3D Structure Click here
Q8CH72 View 3D Structure Click here
Q8MQJ9 View 3D Structure Click here
Q8MQJ9 View 3D Structure Click here
Q8MQJ9 View 3D Structure Click here
Q8MQJ9 View 3D Structure Click here
Q8NBF2 View 3D Structure Click here
Q8NBF2 View 3D Structure Click here
Q8NBF2 View 3D Structure Click here
Q8S9K1 View 3D Structure Click here
Q8VZ10 View 3D Structure Click here
Q8VZ10 View 3D Structure Click here
Q9C040 View 3D Structure Click here
Q9C040 View 3D Structure Click here
Q9C040 View 3D Structure Click here
Q9C040 View 3D Structure Click here
Q9C040 View 3D Structure Click here
Q9C040 View 3D Structure Click here
Q9ESN6 View 3D Structure Click here
Q9ESN6 View 3D Structure Click here
Q9ESN6 View 3D Structure Click here
Q9ESN6 View 3D Structure Click here
Q9ESN6 View 3D Structure Click here
Q9ESN6 View 3D Structure Click here
Q9R1R2 View 3D Structure Click here
Q9R1R2 View 3D Structure Click here
Q9R1R2 View 3D Structure Click here
Q9R1R2 View 3D Structure Click here
Q9R1R2 View 3D Structure Click here
Q9R1R2 View 3D Structure Click here
Q9U489 View 3D Structure Click here
Q9U489 View 3D Structure Click here
Q9U489 View 3D Structure Click here
Q9U489 View 3D Structure Click here
Q9U489 View 3D Structure Click here
Q9U489 View 3D Structure Click here
Q9V4M2 View 3D Structure Click here
Q9V4M2 View 3D Structure Click here
Q9V4M2 View 3D Structure Click here
Q9V4M2 View 3D Structure Click here
Q9V4M2 View 3D Structure Click here
Q9V5E1 View 3D Structure Click here
Q9V5E1 View 3D Structure Click here
Q9V5E1 View 3D Structure Click here
Q9W1L5 View 3D Structure Click here
Q9W5T4 View 3D Structure Click here
Q9W5T4 View 3D Structure Click here
Q9W5T4 View 3D Structure Click here
U3JAV2 View 3D Structure Click here