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Protein

SH2 domain-containing protein 1A

Gene

Sh2d1a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as SLAMF1, CD244, LY9, CD84, SLAMF6 and SLAMF7. In SLAM signaling seems to cooperate with SH2D1B/EAT-2. Initially it has been proposed that association with SLAMF1 prevents SLAMF1 binding to inhibitory effectors including INPP5D/SHIP1 and PTPN11/SHP-2. However, by simultaneous interactions, recruits FYN which subsequently phosphorylates and activates SLAMF1 (By similarity). Positively regulates CD244/2B4- and CD84-mediated natural killer (NK) cell functions (PubMed:22683124). Can also promote CD48-, SLAMF6 -, LY9-, and SLAMF7-mediated NK cell activation (PubMed:19648922). In the context of NK cell-mediated cytotoxicity enhances conjugate formation with target cells (PubMed:22683124). May also regulate the activity of the neurotrophin receptors NTRK1, NTRK2 and NTRK3.By similarity1 Publication4 Publications

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • cell-cell signaling Source: MGI
  • cellular defense response Source: InterPro
  • humoral immune response Source: MGI
  • innate immune response Source: UniProtKB-KW
  • positive regulation of natural killer cell mediated cytotoxicity Source: MGI
  • positive regulation of signal transduction Source: GOC
Complete GO annotation...

Keywords - Biological processi

Adaptive immunity, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.

Names & Taxonomyi

Protein namesi
Recommended name:
SH2 domain-containing protein 1A
Alternative name(s):
Signaling lymphocytic activation molecule-associated protein
Short name:
SLAM-associated protein
T-cell signal transduction molecule SAP
Gene namesi
Name:Sh2d1a
Synonyms:Xlp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:1328352. Sh2d1a.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi32 – 321R → K: No effect on interaction with FYN SH3 domain. 1 Publication
Mutagenesisi68 – 681T → I: No effect on interaction with FYN SH3 domain. 1 Publication
Mutagenesisi70 – 701P → A: No effect on interaction with FYN SH3 domain. 1 Publication
Mutagenesisi74 – 752KR → AA: Disrupts interaction with FYN SH3 domain. 1 Publication
Mutagenesisi78 – 792RK → AA: Disrupts interaction with FYN SH3 domain. 1 Publication
Mutagenesisi78 – 781R → A: No effect on NK cell development, impairs promotion of NK cell cytotoxicity and IFN-gamma production in response to hematopoietic cells. 1 Publication
Mutagenesisi90 – 901P → K: No effect on interaction with FYN SH3 domain. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 126126SH2 domain-containing protein 1APRO_0000097723Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei89 – 891N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

EPDiO88890.
MaxQBiO88890.
PaxDbiO88890.
PRIDEiO88890.

PTM databases

iPTMnetiO88890.
PhosphoSiteiO88890.

Expressioni

Tissue specificityi

T-cells.

Gene expression databases

BgeeiO88890.
CleanExiMM_SH2D1A.
ExpressionAtlasiO88890. baseline and differential.
GenevisibleiO88890. MM.

Interactioni

Subunit structurei

Interacts with CD84, CD244, LY9, SLAMF1 and FYN (By similarity). Interacts with NTRK1, NTRK2 and NTRK3.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Slamf1Q9QUM43EBI-7910438,EBI-7910086

Protein-protein interaction databases

IntActiO88890. 2 interactions.
MINTiMINT-205896.
STRINGi10090.ENSMUSP00000005839.

Structurei

3D structure databases

ProteinModelPortaliO88890.
SMRiO88890. Positions 1-104.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini6 – 10499SH2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni67 – 9226Interaction with FYN SH3 domain1 PublicationAdd
BLAST

Sequence similaritiesi

Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiKOG0565. Eukaryota.
COG5411. LUCA.
GeneTreeiENSGT00510000046904.
HOGENOMiHOG000231700.
HOVERGENiHBG003702.
InParanoidiO88890.
KOiK07990.
OMAiCLCVLCK.
OrthoDBiEOG72VH86.
PhylomeDBiO88890.
TreeFamiTF343096.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR017289. SH2_prot_1A.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
[Graphical view]
PIRSFiPIRSF037828. SH2_p1A. 1 hit.
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: O88890-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDAVTVYHGK ISRETGEKLL LATGLDGSYL LRDSESVPGV YCLCVLYQGY
60 70 80 90 100
IYTYRVSQTE TGSWSAETAP GVHKRFFRKV KNLISAFQKP DQGIVTPLQY
110 120
PVEKSSGRGP QAPTGRRDSD ICLNAP
Length:126
Mass (Da):13,904
Last modified:November 1, 1998 - v1
Checksum:iD78FA7CE425AA680
GO
Isoform Short (identifier: O88890-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     44-46: Missing.

Show »
Length:123
Mass (Da):13,588
Checksum:iD44BC29EA4A82439
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei44 – 463Missing in isoform Short. CuratedVSP_004391

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF072903 mRNA. Translation: AAC62629.1.
AF097633 mRNA. Translation: AAC95999.1.
AF097632 mRNA. Translation: AAC95998.1.
AF154505, AF154503, AF154504 Genomic DNA. Translation: AAF14526.1.
AL831716 Genomic DNA. Translation: CAM19525.1.
CCDSiCCDS30099.1. [O88890-1]
RefSeqiNP_001300617.1. NM_001313688.1.
NP_001300618.1. NM_001313689.1. [O88890-2]
NP_001300620.1. NM_001313691.1.
NP_035494.1. NM_011364.4. [O88890-1]
UniGeneiMm.441197.

Genome annotation databases

EnsembliENSMUST00000005839; ENSMUSP00000005839; ENSMUSG00000005696. [O88890-1]
ENSMUST00000115070; ENSMUSP00000110722; ENSMUSG00000005696. [O88890-2]
ENSMUST00000189753; ENSMUSP00000141070; ENSMUSG00000005696. [O88890-1]
GeneIDi20400.
KEGGimmu:20400.
UCSCiuc009tbb.1. mouse. [O88890-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF072903 mRNA. Translation: AAC62629.1.
AF097633 mRNA. Translation: AAC95999.1.
AF097632 mRNA. Translation: AAC95998.1.
AF154505, AF154503, AF154504 Genomic DNA. Translation: AAF14526.1.
AL831716 Genomic DNA. Translation: CAM19525.1.
CCDSiCCDS30099.1. [O88890-1]
RefSeqiNP_001300617.1. NM_001313688.1.
NP_001300618.1. NM_001313689.1. [O88890-2]
NP_001300620.1. NM_001313691.1.
NP_035494.1. NM_011364.4. [O88890-1]
UniGeneiMm.441197.

3D structure databases

ProteinModelPortaliO88890.
SMRiO88890. Positions 1-104.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO88890. 2 interactions.
MINTiMINT-205896.
STRINGi10090.ENSMUSP00000005839.

PTM databases

iPTMnetiO88890.
PhosphoSiteiO88890.

Proteomic databases

EPDiO88890.
MaxQBiO88890.
PaxDbiO88890.
PRIDEiO88890.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000005839; ENSMUSP00000005839; ENSMUSG00000005696. [O88890-1]
ENSMUST00000115070; ENSMUSP00000110722; ENSMUSG00000005696. [O88890-2]
ENSMUST00000189753; ENSMUSP00000141070; ENSMUSG00000005696. [O88890-1]
GeneIDi20400.
KEGGimmu:20400.
UCSCiuc009tbb.1. mouse. [O88890-1]

Organism-specific databases

CTDi4068.
MGIiMGI:1328352. Sh2d1a.

Phylogenomic databases

eggNOGiKOG0565. Eukaryota.
COG5411. LUCA.
GeneTreeiENSGT00510000046904.
HOGENOMiHOG000231700.
HOVERGENiHBG003702.
InParanoidiO88890.
KOiK07990.
OMAiCLCVLCK.
OrthoDBiEOG72VH86.
PhylomeDBiO88890.
TreeFamiTF343096.

Enzyme and pathway databases

ReactomeiR-MMU-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.

Miscellaneous databases

PROiO88890.
SOURCEiSearch...

Gene expression databases

BgeeiO88890.
CleanExiMM_SH2D1A.
ExpressionAtlasiO88890. baseline and differential.
GenevisibleiO88890. MM.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR017289. SH2_prot_1A.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
[Graphical view]
PIRSFiPIRSF037828. SH2_p1A. 1 hit.
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM."
    Sayos J., Wu C., Morra M., Wang N., Zhang X., Allen D., van Schaik S., Notarangelo L., Geha R., Roncarolo M.G., Oettgen H., de Vries J.E., Aversa G., Terhorst C.
    Nature 395:462-469(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
    Strain: BALB/cJ.
  2. "cDNA sequence of the mouse homolog of the human X-linked lymphoproliferative-disease gene."
    Garrity D.B., Amemiya C.T.
    Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS LONG AND SHORT).
    Strain: C57BL/6J.
  3. "Genomic organization and characterization of mouse SAP, the gene that is altered in X-linked lymphoproliferative disease."
    Wu C., Sayos J., Wang N., Howie D., Coyle A., Terhorst C.
    Immunogenetics 51:805-815(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM LONG).
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  5. "Binding of SAP SH2 domain to FynT SH3 domain reveals a novel mechanism of receptor signalling in immune regulation."
    Latour S., Roncagalli R., Chen R., Bakinowski M., Shi X., Schwartzberg P.L., Davidson D., Veillette A.
    Nat. Cell Biol. 5:149-154(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FYN, MUTAGENESIS OF ARG-32; PRO-70; 74-LYS-ARG-75; 78-ARG-LYS-79 AND PRO-90.
  6. "SLAM-associated protein as a potential negative regulator in Trk signaling."
    Lo K.Y., Chin W.H., Ng Y.P., Cheng A.W., Cheung Z.H., Ip N.Y.
    J. Biol. Chem. 280:41744-41752(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN NTRK2 SIGNALING, INTERACTION WITH NTRK1; NTRK2 AND NTRK3.
  7. "Essential function for SAP family adaptors in the surveillance of hematopoietic cells by natural killer cells."
    Dong Z., Cruz-Munoz M.E., Zhong M.C., Chen R., Latour S., Veillette A.
    Nat. Immunol. 10:973-980(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "The adapters EAT-2A and -2B are positive regulators of CD244- and CD84-dependent NK cell functions in the C57BL/6 mouse."
    Wang N., Calpe S., Westcott J., Castro W., Ma C., Engel P., Schatzle J.D., Terhorst C.
    J. Immunol. 185:5683-5687(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. Cited for: REVIEW.
  10. "The adaptor SAP controls NK cell activation by regulating the enzymes Vav-1 and SHIP-1 and by enhancing conjugates with target cells."
    Dong Z., Davidson D., Perez-Quintero L.A., Kurosaki T., Swat W., Veillette A.
    Immunity 36:974-985(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF ARG-78.

Entry informationi

Entry nameiSH21A_MOUSE
AccessioniPrimary (citable) accession number: O88890
Secondary accession number(s): A2ANL8, Q9QWV6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1998
Last modified: June 8, 2016
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.