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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49773: Variant p.Arg37Pro

Adenosine 5'-monophosphoramidase HINT1
Gene: HINT1
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Variant information Variant position: help 37 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change: help From Arginine (R) to Proline (P) at position 37 (R37P, p.Arg37Pro). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from large size and basic (R) to medium size and hydrophobic (P) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description: help In NMAN; negligible protein expression due to post-translational degradation; loss of homodimerization; significant decrease in adenosine 5'-monophosphoramidase activity; reduced SUMO-specific isopeptidase activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 37 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 126 The length of the canonical sequence.
Location on the sequence: help TIFGKIIRKEIPAKIIFEDD R CLAFHDISPQAPTHFLVIPK The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         TIFGKIIRKEIPAKIIFEDDRCLAFHDISPQAPTHFLVIPK

Mouse                         TIFGKIIRKEIPAKIIFEDDRCLAFHDISPQAPTHFLVIPK

Rat                           TIFGKIIRKEIPAKIIFEDDRCLAFHDISPQAPTHFLVIPK

Bovine                        TIFGKIIRKEIPAKIIYEDDQCLAFHDISPQAPTHFLVIPK

Rabbit                        TIFGKIIRKEIPAKIIFEDDQCLAFHDISPQAPTHFLVIPK

Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 2 – 126 Adenosine 5'-monophosphoramidase HINT1
Domain 18 – 126 HIT
Modified residue 21 – 21 N6-acetyllysine
Modified residue 30 – 30 N6-acetyllysine
Modified residue 45 – 45 Phosphoserine
Mutagenesis 33 – 33 F -> S. Loss of SUMO-specific isopeptidase activity.
Mutagenesis 34 – 34 E -> K. Reduced SUMO-specific isopeptidase activity.
Mutagenesis 38 – 38 C -> R. No effect on SUMO-specific isopeptidase activity.
Mutagenesis 43 – 43 D -> N. Approximately 50-fold increased affinity for tryptamine adenosine phosphoramidate.
Mutagenesis 44 – 44 I -> F. Approximately 10-fold increased affinity for tryptamine adenosine phosphoramidate.
Mutagenesis 44 – 44 I -> W. Approximately 30-fold increased affinity for tryptamine adenosine phosphoramidate.
Mutagenesis 51 – 51 H -> A. No effect on affinity for 3-indolepropionic acyl-adenylate but a 13.8-fold increased affinity for tryptamine adenosine phosphoramidate monoester.
Mutagenesis 57 – 57 K -> N. Loss of SUMO-specific isopeptidase activity.
Beta strand 36 – 42



Literature citations
Structure and Functional Characterization of Human Histidine Triad Nucleotide-Binding Protein 1 Mutations Associated with Inherited Axonal Neuropathy with Neuromyotonia.
Shah R.M.; Maize K.M.; West H.T.; Strom A.M.; Finzel B.C.; Wagner C.R.;
J. Mol. Biol. 430:2709-2721(2018)
Cited for: FUNCTION; CATALYTIC ACTIVITY; SUBUNIT; BIOPHYSICOCHEMICAL PROPERTIES; MUTAGENESIS OF ASP-43 AND ILE-44; CHARACTERIZATION OF VARIANTS NMAN PRO-37; ARG-84; VAL-89; ASP-93 AND ASN-112; The Axonal Motor Neuropathy-Related HINT1 Protein Is a Zinc- and Calmodulin-Regulated Cysteine SUMO Protease.
Cortes-Montero E.; Rodriguez-Munoz M.; Sanchez-Blazquez P.; Garzon J.;
Antioxid. Redox Signal. 31:503-520(2019)
Cited for: FUNCTION; CATALYTIC ACTIVITY; MUTAGENESIS OF PHE-33; GLU-34; CYS-38; LYS-57; VAL-97 AND HIS-114; CHARACTERIZATION OF VARIANTS NMAN PRO-37; ARG-51; ARG-84; VAL-89; ASP-93 AND ASN-112; Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia.
Zimon M.; Baets J.; Almeida-Souza L.; De Vriendt E.; Nikodinovic J.; Parman Y.; Battaloglu E.; Matur Z.; Guergueltcheva V.; Tournev I.; Auer-Grumbach M.; De Rijk P.; Petersen B.S.; Muller T.; Fransen E.; Van Damme P.; Loscher W.N.; Barisic N.; Mitrovic Z.; Previtali S.C.; Topaloglu H.; Bernert G.; Beleza-Meireles A.; Todorovic S.; Savic-Pavicevic D.; Ishpekova B.; Lechner S.; Peeters K.; Ooms T.; Hahn A.F.; Zuchner S.; Timmerman V.; Van Dijck P.; Rasic V.M.; Janecke A.R.; De Jonghe P.; Jordanova A.;
Nat. Genet. 44:1080-1083(2012)
Cited for: VARIANTS NMAN PRO-37; ARG-51; ARG-84; VAL-89; ASP-93 AND ASN-112; CHARACTERIZATION OF VARIANTS NMAN PRO-37; ARG-51; ARG-84 AND ASN-112;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.