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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49773: Variant p.His112Asn

Adenosine 5'-monophosphoramidase HINT1
Gene: HINT1
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Variant information Variant position: help 112 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 Histidine (H) to Asparagine (N) at position 112 (H112N, p.His112Asn). 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 Similar physico-chemical property. Both residues are medium size and polar. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 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; the enzyme has no residual activity although the mutant protein is expressed at normal levels; no effect on homodimerization; loss of 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 112 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 KGYRMVVNEGSDGGQSVYHV H LHVLGGRQMHWPPG 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                         KGYRMVVNEGSDGGQSVYHVHLHVLGGRQMHWPPG

Mouse                         RGYRMVVNEGADGGQSVYHIHLHVLGGRQMNWPPG

Rat                           RGYRMVVNEGADGGQSVYHIHLHVLGGRQMNWPPG

Bovine                        KGYRMVVNEGSDGGQSVYHVHLHVLGGRQMNWPPG

Rabbit                        KGYRMVVNEGSDGGQSVYHVHLHVLGGRQMNWPPG

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
Motif 110 – 114 Histidine triad motif
Active site 112 – 112 Tele-AMP-histidine intermediate
Binding site 99 – 99
Binding site 112 – 114
Mutagenesis 97 – 97 V -> D. Loss of dimerization. Strongly reduced adenosine 5'-monophosphoramidase activity. A 110-fold increased affinity for 3-indolepropionic acyl-adenylate and a 100-fold increased affinity for tryptamine adenosine phosphoramidate monoester.
Mutagenesis 97 – 97 V -> E. Loss of dimerization. Strongly reduced adenosine 5'-monophosphoramidase activity. A 128-fold increased affinity for 3-indolepropionic acyl-adenylate and a 1000-fold increased affinity for tryptamine adenosine phosphoramidate monoester.
Mutagenesis 97 – 97 V -> M. Loss of SUMO-specific isopeptidase activity.
Mutagenesis 105 – 105 G -> A. Reduces adenosine 5'-monophosphoramidase activity.
Mutagenesis 107 – 107 S -> A. Reduces adenosine 5'-monophosphoramidase activity.
Mutagenesis 110 – 110 H -> A. No significant effect on affinity for 3-indolepropionic acyl-adenylate and tryptamine adenosine phosphoramidate monoester.
Mutagenesis 114 – 114 H -> A. Nearly abolishes adenosine 5'-monophosphoramidase activity. A 3-fold increased affinity for 3-indolepropionic acyl-adenylate and a 2-fold increased affinity for tryptamine adenosine phosphoramidate monoester.
Mutagenesis 114 – 114 H -> R. Loss of SUMO-specific isopeptidase activity.
Mutagenesis 123 – 123 W -> A. Nearly abolishes adenosine 5'-monophosphoramidase activity.



Literature citations
The histidine triad protein Hint1 triggers apoptosis independent of its enzymatic activity.
Weiske J.; Huber O.;
J. Biol. Chem. 281:27356-27366(2006)
Cited for: FUNCTION; CATALYTIC ACTIVITY; MUTAGENESIS OF GLY-105 AND SER-107; CHARACTERIZATION OF VARIANT NMAN ASN-112; SUBUNIT; IDENTIFICATION IN A COMPLEX WITH KAT5; Caught before Released: Structural Mapping of the Reaction Trajectory for the Sofosbuvir Activating Enzyme, Human Histidine Triad Nucleotide Binding Protein 1 (hHint1).
Shah R.; Maize K.M.; Zhou X.; Finzel B.C.; Wagner C.R.;
Biochemistry 56:3559-3570(2017)
Cited for: FUNCTION; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANT NMAN ASN-112; 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.