UniProtKB/SwissProt variant VAR

Variant information

Variant position:

87

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 Phenylalanine (F) to Serine (S) at position 87 (F87S, p.Phe87Ser).

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 large size and aromatic (F) to small size and polar (S)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-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:

In XLP1; reduced protein stability and reduced affinity for SLAMF1 and FYN.

Any additional useful information about the variant.

Sequence information

Variant position:

87

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

128

The length of the canonical sequence.

Location on the sequence:

ETAPGVHKRYFRKIKNLISA F QKPDQGIVIPLQYPVEKKSS

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                         ETAPGVHKRYFRKIKNLISAFQKPDQGIVIPLQYPVEKKSS

Rhesus macaque                ETAPGVHKRYFRKIKNLISAFQKPDQGIVIPLQYPVEKKSS

Mouse                         ETAPGVHKRFFRKVKNLISAFQKPDQGIVTPLQYPVEK-SS

Rat                           ETAPGVHKRFFRKVKNLISAFQKPDQGIVTPLQYPVEK-SS

Pig                           DTAPGVHKRFFRKIKNLISAFQKPDQGIVIPLQYPVEKKSS

Bovine                        ETAPGVHKRFFRKIKNLISAFQKPDQGIVIPLQYPVEKKPS

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 – 128	SH2 domain-containing protein 1A
Domain	6 – 104	SH2
Region	67 – 92	Interaction with FYN SH3 domain
Modified residue	89 – 89	N6-acetyllysine
Alternative sequence	40 – 128	VYCLCVLYHGYIYTYRVSQTETGSWSAETAPGVHKRYFRKIKNLISAFQKPDQGIVIPLQYPVEKKSSARSTQGTTGIREDPDVCLKAP -> ITVTFIHTECPRQKQVLGVLSISEARSRHCNTSAVSS. In isoform E.
Alternative sequence	47 – 128	YHGYIYTYRVSQTETGSWSAETAPGVHKRYFRKIKNLISAFQKPDQGIVIPLQYPVEKKSSARSTQGTTGIREDPDVCLKAP -> QHLGYIKDISGK. In isoform C.
Alternative sequence	47 – 128	YHGYIYTYRVSQTETGSWSAETAPGVHKRYFRKIKNLISAFQKPDQGIVIPLQYPVEKKSSARSTQGTTGIREDPDVCLKAP -> ISEARSRHCNTSAVSS. In isoform F.
Alternative sequence	68 – 128	TAPGVHKRYFRKIKNLISAFQKPDQGIVIPLQYPVEKKSSARSTQGTTGIREDPDVCLKAP -> HFRSQIKA. In isoform B.
Mutagenesis	78 – 78	R -> E. Disrupts interaction with FYN.
Helix	80 – 87

Literature citations

Correlation of mutations of the SH2D1A gene and Epstein-Barr virus infection with clinical phenotype and outcome in X-linked lymphoproliferative disease.
Sumegi J.; Huang D.; Lanyi A.; Davis J.D.; Seemayer T.A.; Maeda A.; Klein G.; Seri M.; Wakiguchi H.; Purtilo D.T.; Gross T.G.;
Blood 96:3118-3125(2000)
Cited for: VARIANTS XLP1 CYS-7; ARG-28; PRO-31; TRP-42; ILE-53; CYS-54; SER-87; PRO-99 AND GLY-102;

Disease-causing SAP mutants are defective in ligand binding and protein folding.
Li C.; Iosef C.; Jia C.Y.H.; Gkourasas T.; Han V.K.M.; Li S.-C.;
Biochemistry 42:14885-14892(2003)
Cited for: CHARACTERIZATION OF VARIANTS XLP1 PRO-31; CYS-54; LEU-55 AND SER-87;

Missense mutations in SH2D1A identified in patients with X-linked lymphoproliferative disease differentially affect the expression and function of SAP.
Hare N.J.; Ma C.S.; Alvaro F.; Nichols K.E.; Tangye S.G.;
Int. Immunol. 18:1055-1065(2006)
Cited for: VARIANTS XLP1 CYS-54; THR-84 AND SER-87; CHARACTERIZATION OF VARIANTS XLP1 CYS-54; THR-84 AND SER-87;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O60880: Variant p.Phe87Ser