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UniProtKB/Swiss-Prot O60880: Variant p.Pro101Leu

SH2 domain-containing protein 1A
Gene: SH2D1A
Variant information

Variant position:  101
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Proline (P) to Leucine (L) at position 101 (P101L, p.Pro101Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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 XLP1; reduced protein stability and reduced affinity for SLAMF1, decreases interaction with FYN.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  101
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:   KNLISAFQKPDQGIVIPLQY  P VEKKSSARSTQGTTGIREDP
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                         KNLISAFQKPDQGIVIPLQYPVEKKSSARSTQGTTGIREDP

Rhesus macaque                KNLISAFQKPDQGIVIPLQYPVEKKSSARSTQGTTGIREDP

Mouse                         KNLISAFQKPDQGIVTPLQYPVEK-SSGRGPQAPTGRR-DS

Rat                           KNLISAFQKPDQGIVTPLQYPVEK-SSARSPQAPTGRR-DS

Pig                           KNLISAFQKPDQGIVIPLQYPVEKKSSARSTQGATGRREDP

Bovine                        KNLISAFQKPDQGIVIPLQYPVEKKPSARSTQGATGRRDDP

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.

TypePositionsDescription
Chain 1 – 128 SH2 domain-containing protein 1A
Domain 6 – 104 SH2
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.


Literature citations

Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene.
Coffey A.J.; Brooksbank R.A.; Brandau O.; Oohashi T.; Howell G.R.; Bye J.M.; Cahn A.P.; Durham J.; Heath P.; Wray P.; Pavitt R.; Wilkinson J.; Leversha M.; Huckle E.; Shaw-Smith C.J.; Dunham A.; Rhodes S.; Schuster V.; Porta G.; Yin L.; Serafini P.; Sylla B.; Zollo M.; Franco B.; Bentley D.R.;
Nat. Genet. 20:129-135(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS XLP1 THR-32; ILE-68 AND LEU-101;

Dual functional roles for the X-linked lymphoproliferative syndrome gene product SAP/SH2D1A in signaling through the signaling lymphocyte activation molecule (SLAM) family of immune receptors.
Li C.; Iosef C.; Jia C.Y.; Han V.K.; Li S.S.;
J. Biol. Chem. 278:3852-3859(2003)
Cited for: FUNCTION; INTERACTION WITH SLAMF1; CD244; CD84 AND FYN; CHARACTERIZATION OF VARIANTS XLP1 CYS-7; PRO-99; LEU-101 AND GLY-102;

A 'three-pronged' binding mechanism for the SAP/SH2D1A SH2 domain: structural basis and relevance to the XLP syndrome.
Hwang P.M.; Li C.; Morra M.; Lillywhite J.; Muhandiram D.R.; Gertler F.; Terhorst C.; Kay L.E.; Pawson T.; Forman-Kay J.D.; Li S.-C.;
EMBO J. 21:314-323(2002)
Cited for: STRUCTURE BY NMR IN COMPLEX WITH SLAMF1; CHARACTERIZATION OF VARIANTS XLP1 CYS-7; ARG-28; ILE-53; ILE-68; PRO-99; LEU-101 AND GLY-102; MUTAGENESIS OF ARG-32;

Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients.
Morra M.; Simarro-Grande M.; Martin M.; Chen A.S.-I.; Lanyi A.; Silander O.; Calpe S.; Davis J.; Pawson T.; Eck M.J.; Sumegi J.; Engel P.; Li S.-C.; Terhorst C.;
J. Biol. Chem. 276:36809-36816(2001)
Cited for: CHARACTERIZATION OF VARIANTS XLP1 CYS-7; ARG-28; TRP-42; ILE-53; ILE-68; PRO-99; LEU-101 AND GLY-102; INTERACTION WITH CD244; SLAMF1; CD84 AND LY9;

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.