Powering down the Pfam website
On October 5th, we began redirecting traffic from Pfam (pfam.xfam.org) to InterPro (www.ebi.ac.uk/interpro). The Pfam website will remain available at pfam-legacy.xfam.org until January 2023, when it will be decommissioned. You can read more about the sunset period in our blog post.

Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
2263  structures 9380  species 0  interactions 440379  sequences 2901  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 32 families and the total number of domains in the clan is 440379. 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 32 member families:

Arginosuc_synth Asn_synthase ATP-sulfurylase ATP_bind_3 BshC CDPS Citrate_ly_lig CTP_transf_like Diphthami_syn_2 DNA_photolyase DPRP ETF FAD_syn HIGH_NTase1 HIGH_NTase1_ass NAD_synthase Pantoate_ligase PAPS_reduct QueC QueH 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 UDPG_MGDP_dh_C Usp

External database links

Domain organisation

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

Loading domain graphics...


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

Pfam family Num. domains Alignment
Usp (PF00582) 62462 (14.2%) View
tRNA-synt_1 (PF00133) 46827 (10.6%) View
CTP_transf_like (PF01467) 34489 (7.8%) View
tRNA-synt_1b (PF00579) 26965 (6.1%) View
tRNA-synt_1c (PF00749) 24704 (5.6%) View
tRNA-synt_1g (PF09334) 23206 (5.3%) View
ETF (PF01012) 21131 (4.8%) View
Asn_synthase (PF00733) 20644 (4.7%) View
NAD_synthase (PF02540) 20589 (4.7%) View
UDPG_MGDP_dh_C (PF03720) 17233 (3.9%) View
PAPS_reduct (PF01507) 16149 (3.7%) View
ATP_bind_3 (PF01171) 14925 (3.4%) View
tRNA-synt_1e (PF01406) 13610 (3.1%) View
tRNA-synt_1d (PF00750) 13516 (3.1%) View
DNA_photolyase (PF00875) 12432 (2.8%) View
tRNA_Me_trans (PF03054) 10646 (2.4%) View
Arginosuc_synth (PF00764) 9901 (2.2%) View
Pfam family Num. domains Alignment
tRNA-synt_1_2 (PF13603) 9249 (2.1%) View
FAD_syn (PF06574) 8344 (1.9%) View
Pantoate_ligase (PF02569) 7618 (1.7%) View
QueC (PF06508) 4942 (1.1%) View
ATP-sulfurylase (PF01747) 4764 (1.1%) View
Diphthami_syn_2 (PF01902) 3421 (0.8%) View
ThiI (PF02568) 3098 (0.7%) View
DPRP (PF04244) 2049 (0.5%) View
tRNA-synt_1f (PF01921) 1974 (0.4%) View
HIGH_NTase1 (PF05636) 1723 (0.4%) View
QueH (PF02677) 1624 (0.4%) View
BshC (PF10079) 1301 (0.3%) View
Citrate_ly_lig (PF08218) 575 (0.1%) View
CDPS (PF16715) 235 (0.1%) View
HIGH_NTase1_ass (PF16581) 33 (0.0%) View
Total: 32 Total: 440379 Clan alignment

Please note: Clan alignments can be very large and can cause problems for some browsers. Read the note above before viewing.

Family relationships

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

Species distribution

Tree controls


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.

Loading structure mapping...