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1108  structures 6582  species 40  interactions 177746  sequences 838  architectures

Clan: HUP (CL0039)


HUP - HIGH-signature proteins, UspA, and PP-ATPase. Add an annotation

The HUP class contains the HIGH-signature proteins, UspA superfamily and the PP-ATPase superfamily [1]. The HIGH superfamily has the HIGH Nucleotidyl transferases and the class I tRNA synthetases both of which have the HIGH and the KMSKS motif [1],[2]. The PP-loop ATPase named after the ATP PyroPhosphatase domain, was initially identified as a conserved amino acid sequence motif in four distinct groups of enzymes that catalyse the hydrolysis of the alpha-beta phosphate bond of ATP, namely GMP synthetases, argininosuccinate synthetases, asparagine synthetases, and ATP sulfurylases [3]. The USPA superfamily contains USPA, ETFP and Photolyases [1]

This clan contains 26 families and the total number of domains in the clan is 177746. The clan was built by A Bateman and V Anantharaman.

Literature references

  1. Aravind L, Anantharaman V, Koonin EV; , Proteins 2002;48:1-14.: Monophyly of class I aminoacyl tRNA synthetase, USPA, ETFP, photolyase, and PP-ATPase nucleotide-binding domains: implications for protein evolution in the RNA. PUBMED:12012333 EPMC:12012333
  2. Wolf YI, Aravind L, Grishin NV, Koonin EV; , Genome Res 1999;9:689-710.: Evolution of aminoacyl-tRNA synthetases--analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events. PUBMED:10447505 EPMC:10447505
  3. Bork P, Koonin EV; , Proteins 1994;20:347-355.: A P-loop-like motif in a widespread ATP pyrophosphatase domain: implications for the evolution of sequence motifs and enzyme activity. PUBMED:7731953 EPMC:7731953


This clan contains the following 26 member families:

Arginosuc_synth Asn_synthase ATP-sulfurylase ATP_bind_3 ATP_bind_4 Citrate_ly_lig CTP_transf_2 DNA_photolyase ETF FAD_syn HIGH_NTase1 NAD_synthase Pantoate_ligase PAPS_reduct QueC ThiI tRNA-synt_1 tRNA-synt_1_2 tRNA-synt_1b tRNA-synt_1c tRNA-synt_1d tRNA-synt_1e tRNA-synt_1f tRNA-synt_1g tRNA_Me_trans Usp

External database links

Domain organisation

Below is a listing of the unique domain organisations or architectures from this clan. More...

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The table below shows the number of occurrences of each domain throughout the sequence database. More...

Pfam family Num. domains Alignment
Usp (PF00582) 22843 (12.9%) View
tRNA-synt_1 (PF00133) 21195 (11.9%) View
CTP_transf_2 (PF01467) 14199 (8.0%) View
tRNA-synt_1b (PF00579) 11971 (6.7%) View
tRNA-synt_1c (PF00749) 10836 (6.1%) View
NAD_synthase (PF02540) 9645 (5.4%) View
ETF (PF01012) 9173 (5.2%) View
ATP_bind_3 (PF01171) 7781 (4.4%) View
tRNA-synt_1g (PF09334) 7775 (4.4%) View
PAPS_reduct (PF01507) 7027 (4.0%) View
Asn_synthase (PF00733) 5876 (3.3%) View
tRNA-synt_1e (PF01406) 5726 (3.2%) View
tRNA-synt_1d (PF00750) 5698 (3.2%) View
tRNA_Me_trans (PF03054) 5331 (3.0%) View
Pfam family Num. domains Alignment
tRNA-synt_1_2 (PF13603) 4853 (2.7%) View
FAD_syn (PF06574) 4652 (2.6%) View
Arginosuc_synth (PF00764) 4339 (2.4%) View
DNA_photolyase (PF00875) 3841 (2.2%) View
Pantoate_ligase (PF02569) 3517 (2.0%) View
QueC (PF06508) 3226 (1.8%) View
ThiI (PF02568) 2899 (1.6%) View
HIGH_NTase1 (PF05636) 1483 (0.8%) View
ATP-sulfurylase (PF01747) 1308 (0.7%) View
Citrate_ly_lig (PF08218) 1051 (0.6%) View
ATP_bind_4 (PF01902) 870 (0.5%) View
tRNA-synt_1f (PF01921) 631 (0.4%) View
Total: 26 Total: 177746 Clan alignment

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Family relationships

This diagram shows the relationships between members of this clan. More...

Species distribution

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This tree shows the occurrence of the domains in this clan across different species. More...



For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the MSD group, to allow us to map Pfam domains onto UniProt three-dimensional structures. The table below shows the mapping between the Pfam families in this clan, the corresponding UniProt entries, and the region of the three-dimensional structures that are available for that sequence.

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