UniProtKB/Swiss-Prot P41597: Variant p.Leu133Phe

C-C chemokine receptor type 2
Gene: CCR2
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Variant information Variant position:

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

LB/B 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 Leucine (L) to Phenylalanine (F) at position 133 (L133F, p.Leu133Phe). 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 medium size and hydrophobic (L) to large size and aromatic (F) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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
Polymorphism:

Variations in CCR2 are associated with relative resistance to immunodeficiency virus type 1 (resistance to HIV-1) [MIM:609423]. Additional information on the polymorphism described.
Variant description:

No effect on expression at the cell surface, nor on CCL2 or CCL13 cytokine-mediated signaling pathway; the nucleotide substitution creating this missense variant may lead to abnormally low levels of isoform A at the cell surface, while isoform B levels are similar to the wild-type protein. Any additional useful information about the variant.

Sequence information Variant position:

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

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

CKLFTGLYHIGYFGGIFFII L LTIDRYLAIVHAVFALKART 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                         CKLFTGLYHIGYFGGIFFIILLTIDRYLAIVHAVFALKART

Rhesus macaque                CKLFTGLYHIGYLGGIFFIILLTIDRYLAIVHAVFALKART

Mouse                         CKVFTGLYHIGYFGGIFFIILLTIDRYLAIVHAVFALKART

Rat                           CKLFTGLYHIGYFGGIFFIILLTIDRYLAIVHAVFALKART

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	1 – 374	C-C chemokine receptor type 2
Transmembrane	115 – 136	Helical; Name=3
Modified residue	139 – 139	Phosphotyrosine; by JAK2
Disulfide bond	113 – 190
Helix	110 – 142

Literature citations
Human inherited CCR2 deficiency underlies progressive polycystic lung disease.
Neehus A.L.; Carey B.; Landekic M.; Panikulam P.; Deutsch G.; Ogishi M.; Arango-Franco C.A.; Philippot Q.; Modaresi M.; Mohammadzadeh I.; Corcini Berndt M.; Rinchai D.; Le Voyer T.; Rosain J.; Momenilandi M.; Martin-Fernandez M.; Khan T.; Bohlen J.; Han J.E.; Deslys A.; Bernard M.; Gajardo-Carrasco T.; Soudee C.; Le Floc'h C.; Migaud M.; Seeleuthner Y.; Jang M.S.; Nikolouli E.; Seyedpour S.; Begueret H.; Emile J.F.; Le Guen P.; Tavazzi G.; Colombo C.N.J.; Marzani F.C.; Angelini M.; Trespidi F.; Ghirardello S.; Alipour N.; Molitor A.; Carapito R.; Mazloomrezaei M.; Rokni-Zadeh H.; Changi-Ashtiani M.; Brouzes C.; Vargas P.; Borghesi A.; Lachmann N.; Bahram S.; Crestani B.; Pahari S.; Schlesinger L.S.; Marr N.; Bugonovic D.; Boisson-Dupuis S.; Beziat V.; Abel L.; Borie R.; Young L.R.; Deterding R.; Shahrooei M.; Rezaei N.; Parvaneh N.; Craven D.; Gros P.; Malo D.; Sepulveda F.E.; Nogee L.M.; Aladjidi N.; Trapnell B.C.; Casanova J.L.; Bustamante J.;
Cell 187:390-408(2024)
Cited for: INVOLVEMENT IN PCLUD; VARIANTS PCLUD ARG-61; ARG-119; 214-PRO-LEU-215 DEL AND ASN-296; FUNCTION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; CHARACTERIZATION OF VARIANTS PCLUD ARG-61; ARG-119; 214-PRO-LEU-215 DEL AND ASN-296; VARIANTS ILE-64; PHE-133; LEU-316 AND ASP-355; CHARACTERIZATION OF VARIANTS ILE-64; PHE-133; LEU-316 AND ASP-355;

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.