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Protein

SH2 domain-containing protein 1B

Gene

SH2D1B

Organism
Homo sapiens (Human)
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 (PubMed:11689425). 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 without effecting its tyrosine phosphorylation; downstream signaling involves PLCG1 and ERK activation (PubMed:24687958). Activation of SLAMF7-mediated NK cell function does not effect receptor tyrosine phosphorylation but distal signaling (By similarity). 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 procuction dendritic cells downstream of SLAM family receptors probably by inducing activation of the PI3K pathway to inhibit p38 MAPK and JNK activation (By similarity).By similarity1 Publication2 Publications

GO - Molecular functioni

  • protein binding, bridging Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Adaptive immunity, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
SignaLinkiO14796.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:30416. SH2D1B.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • intracellular Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi127 – 1271Y → F: No stimulation of granule polarization during NK-mediated cytoxicity, abolishes activation of CD244/2B4-mediated cytotoxicity, abolishes augmentation of CD244/2B4-triggered PLCG1 phosphorylation and ERK activation. 1 Publication

Organism-specific databases

PharmGKBiPA142670926.

Polymorphism and mutation databases

BioMutaiSH2D1B.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 132132SH2 domain-containing protein 1BPRO_0000097724Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei127 – 1271Phosphotyrosine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO14796.
PRIDEiO14796.

PTM databases

PhosphoSiteiO14796.

Expressioni

Gene expression databases

BgeeiO14796.
CleanExiHS_SH2D1B.
GenevisibleiO14796. HS.

Organism-specific databases

HPAiHPA054791.

Interactioni

Subunit structurei

Binds to the phosphorylated receptors CD84, SLAMF1, LY9 and CD244. Does not bind to non-phosphorylated SLAMF1 (PubMed:11689425). Interacts with SLAMF7 (via ITSM phosphorylated on 'Tyr-304'). Interacts with Src kinases HCK, LYN, FYN, FGR and LCK (via kinase domains) (By similarity). Interacts (phosphorylated at Tyr-127) with PLCG1.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Q53HF23EBI-3923013,EBI-877761
ARP102753EBI-3923013,EBI-608057
CD244Q9BZW85EBI-3923013,EBI-1580565
CD84Q9UIB83EBI-3923013,EBI-6691679
GAB1Q134808EBI-3923013,EBI-517684
KITP107218EBI-3923013,EBI-1379503
METP085816EBI-3923013,EBI-1039152
OLIG1Q8TAK62EBI-3923013,EBI-3867416
PLCG1P191742EBI-3923013,EBI-79387
PLCG2P168852EBI-3923013,EBI-617403
TRIM54Q9BYV23EBI-3923013,EBI-2130429

GO - Molecular functioni

  • protein binding, bridging Source: UniProtKB

Protein-protein interaction databases

BioGridi125563. 11 interactions.
IntActiO14796. 24 interactions.
MINTiMINT-1491557.
STRINGi9606.ENSP00000356906.

Structurei

3D structure databases

ProteinModelPortaliO14796.
SMRiO14796. Positions 1-101.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini5 – 10197SH2PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiKOG0565. Eukaryota.
COG5411. LUCA.
GeneTreeiENSGT00510000046904.
HOGENOMiHOG000231700.
HOVERGENiHBG003702.
InParanoidiO14796.
KOiK07989.
OMAiPYYHGPL.
OrthoDBiEOG7M3J27.
PhylomeDBiO14796.
TreeFamiTF343096.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
[Graphical view]
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 1 (identifier: O14796-1) [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
MDLPYYHGRL TKQDCETLLL KEGVDGNFLL RDSESIPGVL CLCVSFKNIV
60 70 80 90 100
YTYRIFREKH GYYRIQTAEG SPKQVFPSLK ELISKFEKPN QGMVVHLLKP
110 120 130
IKRTSPSLRW RGLKLELETF VNSNSDYVDV LP
Length:132
Mass (Da):15,297
Last modified:September 19, 2002 - v2
Checksum:iBC9FEA398B6B27DE
GO
Isoform 2 (identifier: O14796-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     67-121: Missing.

Show »
Length:77
Mass (Da):9,024
Checksum:i96423A27A9B1FB57
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti36 – 361I → T.
Corresponds to variant rs35688243 [ dbSNP | Ensembl ].
VAR_051347
Natural varianti122 – 1221N → K.1 Publication
Corresponds to variant rs34001279 [ dbSNP | Ensembl ].
VAR_051348

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei67 – 12155Missing in isoform 2. 1 PublicationVSP_010341Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF256653 mRNA. Translation: AAL26000.1.
AF403479 mRNA. Translation: AAL27357.1.
AF484964 mRNA. Translation: AAM28522.1.
AK097162 mRNA. Translation: BAC04968.1.
AK314743 mRNA. Translation: BAG37283.1.
AL512785 Genomic DNA. Translation: CAI15780.1.
CH471067 Genomic DNA. Translation: EAW90703.1.
BC022407 mRNA. Translation: AAH22407.1.
BC066595 mRNA. Translation: AAH66595.1.
AF020264 Genomic DNA. Translation: AAB70927.1.
CCDSiCCDS30928.1. [O14796-1]
RefSeqiNP_444512.2. NM_053282.4. [O14796-1]
UniGeneiHs.350581.

Genome annotation databases

EnsembliENST00000367929; ENSP00000356906; ENSG00000198574. [O14796-1]
GeneIDi117157.
KEGGihsa:117157.
UCSCiuc001gbz.2. human. [O14796-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF256653 mRNA. Translation: AAL26000.1.
AF403479 mRNA. Translation: AAL27357.1.
AF484964 mRNA. Translation: AAM28522.1.
AK097162 mRNA. Translation: BAC04968.1.
AK314743 mRNA. Translation: BAG37283.1.
AL512785 Genomic DNA. Translation: CAI15780.1.
CH471067 Genomic DNA. Translation: EAW90703.1.
BC022407 mRNA. Translation: AAH22407.1.
BC066595 mRNA. Translation: AAH66595.1.
AF020264 Genomic DNA. Translation: AAB70927.1.
CCDSiCCDS30928.1. [O14796-1]
RefSeqiNP_444512.2. NM_053282.4. [O14796-1]
UniGeneiHs.350581.

3D structure databases

ProteinModelPortaliO14796.
SMRiO14796. Positions 1-101.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125563. 11 interactions.
IntActiO14796. 24 interactions.
MINTiMINT-1491557.
STRINGi9606.ENSP00000356906.

PTM databases

PhosphoSiteiO14796.

Polymorphism and mutation databases

BioMutaiSH2D1B.

Proteomic databases

PaxDbiO14796.
PRIDEiO14796.

Protocols and materials databases

DNASUi117157.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000367929; ENSP00000356906; ENSG00000198574. [O14796-1]
GeneIDi117157.
KEGGihsa:117157.
UCSCiuc001gbz.2. human. [O14796-1]

Organism-specific databases

CTDi117157.
GeneCardsiSH2D1B.
HGNCiHGNC:30416. SH2D1B.
HPAiHPA054791.
MIMi608510. gene.
neXtProtiNX_O14796.
PharmGKBiPA142670926.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0565. Eukaryota.
COG5411. LUCA.
GeneTreeiENSGT00510000046904.
HOGENOMiHOG000231700.
HOVERGENiHBG003702.
InParanoidiO14796.
KOiK07989.
OMAiPYYHGPL.
OrthoDBiEOG7M3J27.
PhylomeDBiO14796.
TreeFamiTF343096.

Enzyme and pathway databases

ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
SignaLinkiO14796.

Miscellaneous databases

GeneWikiiSH2D1B.
GenomeRNAii117157.
NextBioi80121.
PROiO14796.
SOURCEiSearch...

Gene expression databases

BgeeiO14796.
CleanExiHS_SH2D1B.
GenevisibleiO14796. HS.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
[Graphical view]
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. "Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells."
    Morra M., Lu J., Poy F., Martin M., Sayos J., Calpe S., Gullo C., Howie D., Rietdijk S., Thompson A., Coyle A.J., Denny C., Yaffe M.B., Engel P., Eck M.J., Terhorst C.
    EMBO J. 20:5840-5852(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION.
  2. Colonna M.
    Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Leukocyte.
  3. "CD84 is up-regulated on a major population of human memory B cells and recruits the SH2 domain containing proteins SAP and EAT-2."
    Tangye S.G., van de Weerdt B.C.M., Avery D.T., Hodgkin P.D.
    Eur. J. Immunol. 32:1640-1649(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH CD84, VARIANT LYS-122.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Spleen.
  5. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Leukocyte and Lung.
  8. "EAT-2 is a novel SH2 domain containing protein that is up regulated by Ewing's sarcoma EWS/FLI1 fusion gene."
    Thompson A.D., Braun B.S., Arvand A., Stewart S.D., May W.A., Chen E., Korenberg J., Denny C.
    Oncogene 13:2649-2658(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-45.
  9. Cited for: REVIEW.
  10. "EAT-2, a SAP-like adaptor, controls NK cell activation through phospholipase Cgamma, Ca++, and Erk, leading to granule polarization."
    Perez-Quintero L.A., Roncagalli R., Guo H., Latour S., Davidson D., Veillette A.
    J. Exp. Med. 211:727-742(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF TYR-127, INTERACTION WITH PLCG1, PHOSPHORYLATION AT TYR-127.

Entry informationi

Entry nameiSH21B_HUMAN
AccessioniPrimary (citable) accession number: O14796
Secondary accession number(s): B2RBN6
, Q5T0L1, Q8NI18, Q969K9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: September 19, 2002
Last modified: April 13, 2016
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.