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Protein

SH2 domain-containing protein 1B

Gene

Sh2d1b

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 CD84, SLAMF1, LY9 and CD244. In SLAM signaling seems to cooperate with SH2D1A/SAP. Plays a role in regulation of effector functions of natural killer (NK) cells by controlling signal transduction through CD244/2B4. However, conflicting results are reported which may reflect the use of different strain backgrounds. Proposed to act as an inhibitor of CD244-mediated NK cell function including cytotoxicity and IFN-gamma production, the latter found also by triggering KLRA4 and KLRK1 next to CD244 (PubMed:16127454). Seems to positively regulate CD244- and CD84-dependent NK cell functions implicating CD244-mediated phosphorylation of VAV1. Activation of SLAMF7-mediated NK cell function does not effect receptor tyrosine phosphorylation but distal signaling (PubMed:19151721, PubMed:20962259, PubMed:24687958). In the context of NK cell-mediated cytotoxicity does not enhance conjugate formation with target cells but stimulates polarization of the microtubule-organizing center and cytotoxic granules toward the NK cell synapse (PubMed:24687958). Negatively regulates CD40-induced cytokine production in dendritic cells downstream of SLAM family receptors probably by inducing activation of the PI3K pathway to inhibit p38 MAPK and JNK activation (PubMed:26432891).By similarity5 Publications

GO - Molecular functioni

  • phosphotyrosine residue binding Source: MGI
  • signaling adaptor activity Source: UniProtKB

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • leukocyte activation involved in immune response Source: UniProtKB
  • natural killer cell inhibitory signaling pathway Source: MGI
  • negative regulation of interferon-gamma production Source: MGI
  • negative regulation of natural killer cell mediated cytotoxicity Source: MGI
  • negative regulation of peptidyl-tyrosine phosphorylation Source: MGI
  • peptidyl-tyrosine phosphorylation Source: MGI
  • positive regulation of innate immune response Source: UniProtKB
  • positive regulation of natural killer cell mediated cytotoxicity Source: MGI
  • positive regulation of natural killer cell mediated immunity Source: UniProtKB
  • positive regulation of peptidyl-tyrosine phosphorylation Source: MGI
  • positive regulation of signal transduction Source: UniProtKB

Keywordsi

Biological processAdaptive immunity, Immunity, Innate immunity

Names & Taxonomyi

Protein namesi
Recommended name:
SH2 domain-containing protein 1B
Alternative name(s):
EWS/FLI1-activated transcript 2
Short name:
EAT-2
Gene namesi
Name:Sh2d1b
Synonyms:Eat2, Eat2a, Sh2d1b1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1349420. Sh2d1b1.

Subcellular locationi

GO - Cellular componenti

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi120Y → F: Abolishes tyrosine phosphorylation, no effect on interaction with SLAMF7 and CD244, abolishes SLAMF7-, CD244-, LY9- and CD8 mediated NK cell activation, fails to inhibit natural cytotoxicity and to suppress IFN-gamma secretion in response to ligation with CD244, FCGR3 or KLRB1C; when associated with F-127. 3 Publications1
Mutagenesisi127Y → F: Abolishes tyrosine phosphorylation, no effect on interaction with SLAMF7 and CD244, abolishes SLAMF7-, CD244-, LY9- and CD84-mediated NK cell activation, fails to inhibit natural cytotoxicity and to suppress IFN-gamma secretion in response to ligation with CD244, FCGR3 or KLRB1C; when associated with F-120. 3 Publications1
Mutagenesisi127Y → F: No stimulation of granule polarization during NK-mediated cytoxicity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000977251 – 132SH2 domain-containing protein 1BAdd BLAST132

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei127Phosphotyrosine1 Publication1

Post-translational modificationi

Phosphorylated on tyrosine residues; probably at Tyr-120 and/or Tyr-127.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO35324.
PaxDbiO35324.
PRIDEiO35324.

PTM databases

iPTMnetiO35324.
PhosphoSitePlusiO35324.

Expressioni

Tissue specificityi

Expressed in spleen, thymus, lung, kidney, heart, colon and small bowel. Expressed in NK cells (all stages of cell maturation), macrophages and dendritic cells.3 Publications

Gene expression databases

CleanExiMM_SH2D1B1.

Interactioni

Subunit structurei

Binds to the phosphorylated receptors CD84, SLAMF1, LY9 and CD244. Does not bind to non-phosphorylated SLAMF1 (By similarity). Interacts with SLAMF7 (via ITSM phosphorylated on 'Tyr-302'). Interacts with Src kinases HCK, LYN, FYN, FGR and LCK (via kinase domains). Interacts (phosphorylated at Tyr-127) with PLCG2.By similarity1 Publication4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Slamf7Q8BHK63EBI-8022357,EBI-11463802

GO - Molecular functioni

  • phosphotyrosine residue binding Source: MGI

Protein-protein interaction databases

IntActiO35324. 2 interactors.
MINTiMINT-5312801.
STRINGi10090.ENSMUSP00000137069.

Structurei

Secondary structure

1132
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 9Combined sources4
Helixi12 – 20Combined sources9
Beta strandi27 – 32Combined sources6
Beta strandi34 – 36Combined sources3
Beta strandi40 – 45Combined sources6
Beta strandi47 – 57Combined sources11
Beta strandi63 – 65Combined sources3
Beta strandi75 – 79Combined sources5
Helixi80 – 85Combined sources6
Beta strandi88 – 95Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1I3ZX-ray2.15A1-103[»]
ProteinModelPortaliO35324.
SMRiO35324.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO35324.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini5 – 101SH2PROSITE-ProRule annotationAdd BLAST97

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiKOG0565. Eukaryota.
COG5411. LUCA.
HOGENOMiHOG000231700.
HOVERGENiHBG003702.
InParanoidiO35324.
PhylomeDBiO35324.

Family and domain databases

CDDicd10342. SH2_SAP1. 1 hit.
Gene3Di3.30.505.10. 1 hit.
InterProiView protein in InterPro
IPR035049. EAT2_SH2.
IPR000980. SH2.
PfamiView protein in Pfam
PF00017. SH2. 1 hit.
PRINTSiPR00401. SH2DOMAIN.
SMARTiView protein in SMART
SM00252. SH2. 1 hit.
SUPFAMiSSF55550. SSF55550. 1 hit.
PROSITEiView protein in PROSITE
PS50001. SH2. 1 hit.

Sequencei

Sequence statusi: Complete.

O35324-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLPYYHGCL TKRECEALLL KGGVDGNFLI RDSESVPGAL CLCVSFKKLV
60 70 80 90 100
YSYRIFREKH GYYRIETDAH TPRTIFPNLQ ELVSKYGKPG QGLVVHLSNP
110 120 130
IMRNNLCQRG RRMELELNVY ENTDEEYVDV LP
Length:132
Mass (Da):15,259
Last modified:January 1, 1998 - v1
Checksum:i7B8201836026C02D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti71T → S in BAC40784 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020263 mRNA. Translation: AAB70923.1.
AK089191 mRNA. Translation: BAC40784.1.
CCDSiCCDS35767.1.
UniGeneiMm.57009.

Similar proteinsi

Entry informationi

Entry nameiSH21B_MOUSE
AccessioniPrimary (citable) accession number: O35324
Secondary accession number(s): Q8C268
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: January 1, 1998
Last modified: August 30, 2017
This is version 113 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references