UniProtKB/SwissProt variant VAR

Adenosine 5'-monophosphoramidase HINT1
Gene: HINT1
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Variant information Variant position:

89 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Glycine (G) to Valine (V) at position 89 (G89V, p.Gly89Val). 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:

Change from glycine (G) to medium size and hydrophobic (V) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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:

In NMAN; no effect on homodimerization; no effect on adenosine 5'-monophosphoramidase activity; no effect on affinity for tryptamine adenosine phosphoramidate; loss of SUMO-specific isopeptidase activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs397514490 [ dbSNP | Ensembl ]

Sequence information Variant position:

89 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

126 The length of the canonical sequence.
Location on the sequence:

DDESLLGHLMIVGKKCAADL G LNKGYRMVVNEGSDGGQSVY 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:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         DDESLLGHLMIVGKKCAADLGLNKGYRMVVNEGSDGGQSVY

Mouse                         DDESLLGHLMIVGKKCAADLGLKRGYRMVVNEGADGGQSVY

Rat                           DDESLLGHLMIVGKKCAADLGLKRGYRMVVNEGADGGQSVY

Bovine                        DDESLLGHLMIVGKKCAADLGLKKGYRMVVNEGSDGGQSVY

Rabbit                        ADESLLGHLMIVGKKCAADLGLKKGYRMVVNEGSDGGQSVY

Sequence annotation in neighborhood:

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.

Type	Positions	Description
Chain	2 – 126	Adenosine 5'-monophosphoramidase HINT1
Domain	18 – 126	HIT
Binding site	99 – 99
Modified residue	72 – 72	Phosphoserine
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.

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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49773: Variant p.Gly89Val