SLAF5_HUMAN
ID SLAF5_HUMAN Reviewed; 345 AA.
AC Q9UIB8; B2R8T1; B7Z3R8; O15430; O95266; O95660; Q5H9R1; Q6FHA8; Q8WLP1;
AC Q8WWI8; Q9UF04; Q9UIB6; Q9UIB7; Q9UIT7;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=SLAM family member 5;
DE AltName: Full=Cell surface antigen MAX.3;
DE AltName: Full=Hly9-beta;
DE AltName: Full=Leukocyte differentiation antigen CD84;
DE AltName: Full=Signaling lymphocytic activation molecule 5;
DE AltName: CD_antigen=CD84;
DE Flags: Precursor;
GN Name=CD84; Synonyms=SLAMF5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), GLYCOSYLATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=9310491;
RA de la Fuente M.A., Pizcueta P., Nadal M., Bosch J., Engel P.;
RT "CD84 leukocyte antigen is a new member of the Ig superfamily.";
RL Blood 90:2398-2405(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PROTEIN SEQUENCE OF 22-35,
RP GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX PubMed=10698700; DOI=10.1042/bj3460729;
RA Krause S.W., Rehli M., Heinz S., Ebner R., Andreesen R.;
RT "Characterization of MAX.3 antigen, a glycoprotein expressed on mature
RT macrophages, dendritic cells and blood platelets: identity with CD84.";
RL Biochem. J. 346:729-736(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2; 3; 4; 5 AND 6).
RX PubMed=10746783; DOI=10.1034/j.1399-0039.2000.550203.x;
RA Palou E., Pirotto F., Sole J., Freed J.H., Peral B., Vilardell C.,
RA Vilella R., Vives J., Gaya A.;
RT "Genomic characterization of CD84 reveals the existence of five isoforms
RT differing in their cytoplasmic domains.";
RL Tissue Antigens 55:118-127(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 7).
RC TISSUE=Thalamus, and Umbilical cord blood;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
RC TISSUE=Semen;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PHOSPHORYLATION, SUBCELLULAR LOCATION, AND INTERACTION WITH SH2D1A AND
RP PTPN11.
RX PubMed=11389028; DOI=10.1182/blood.v97.12.3867;
RA Sayos J., Martin M., Chen A., Simarro M., Howie D., Morra M., Engel P.,
RA Terhorst C.;
RT "Cell surface receptors Ly-9 and CD84 recruit the X-linked
RT lymphoproliferative disease gene product SAP.";
RL Blood 97:3867-3874(2001).
RN [11]
RP INTERACTION WITH PTPN6 AND PTPN11.
RX PubMed=11414741; DOI=10.1006/clim.2001.5035;
RA Lewis J., Eiben L.J., Nelson D.L., Cohen J.I., Nichols K.E., Ochs H.D.,
RA Notarangelo L.D., Duckett C.S.;
RT "Distinct interactions of the X-linked lymphoproliferative syndrome gene
RT product SAP with cytoplasmic domains of members of the CD2 receptor
RT family.";
RL Clin. Immunol. 100:15-23(2001).
RN [12]
RP DOMAIN ITSM MOTIF.
RX PubMed=11313386; DOI=10.4049/jimmunol.166.9.5480;
RA Shlapatska L.M., Mikhalap S.V., Berdova A.G., Zelensky O.M., Yun T.J.,
RA Nichols K.E., Clark E.A., Sidorenko S.P.;
RT "CD150 association with either the SH2-containing inositol phosphatase or
RT the SH2-containing protein tyrosine phosphatase is regulated by the adaptor
RT protein SH2D1A.";
RL J. Immunol. 166:5480-5487(2001).
RN [13]
RP TISSUE SPECIFICITY, HOMODIMERIZATION, AND FUNCTION.
RX PubMed=11564780; DOI=10.4049/jimmunol.167.7.3668;
RA Martin M., Romero X., de la Fuente M.A., Tovar V., Zapater N.,
RA Esplugues E., Pizcueta P., Bosch J., Engel P.;
RT "CD84 functions as a homophilic adhesion molecule and enhances IFN-gamma
RT secretion: adhesion is mediated by Ig-like domain 1.";
RL J. Immunol. 167:3668-3676(2001).
RN [14]
RP FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION, DEVELOPMENTAL STAGE, AND
RP INTERACTION WITH SH2D1A AND SH2D1B.
RX PubMed=12115647;
RX DOI=10.1002/1521-4141(200206)32:6<1640::aid-immu1640>3.0.co;2-s;
RA Tangye S.G., van de Weerdt B.C.M., Avery D.T., Hodgkin P.D.;
RT "CD84 is up-regulated on a major population of human memory B cells and
RT recruits the SH2 domain containing proteins SAP and EAT-2.";
RL Eur. J. Immunol. 32:1640-1649(2002).
RN [15]
RP INTERACTION WITH SH2D1A; SH2D1B; INPP5D AND PTPN11, AND PHOSPHORYLATION AT
RP TYR-279 AND TYR-316.
RX PubMed=12458214; DOI=10.1074/jbc.m206649200;
RA Li C., Iosef C., Jia C.Y., Han V.K., Li S.S.;
RT "Dual functional roles for the X-linked lymphoproliferative syndrome gene
RT product SAP/SH2D1A in signaling through the signaling lymphocyte activation
RT molecule (SLAM) family of immune receptors.";
RL J. Biol. Chem. 278:3852-3859(2003).
RN [16]
RP FUNCTION, PHOSPHORYLATION, AND MUTAGENESIS OF TYR-279 AND TYR-316.
RX PubMed=12928397; DOI=10.4049/jimmunol.171.5.2485;
RA Tangye S.G., Nichols K.E., Hare N.J., van de Weerdt B.C.M.;
RT "Functional requirements for interactions between CD84 and Src homology 2
RT domain-containing proteins and their contribution to human T cell
RT activation.";
RL J. Immunol. 171:2485-2495(2003).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12962726; DOI=10.1016/s0301-472x(03)00187-5;
RA Zaiss M., Hirtreiter C., Rehli M., Rehm A., Kunz-Schughart L.A.,
RA Andreesen R., Hennemann B.;
RT "CD84 expression on human hematopoietic progenitor cells.";
RL Exp. Hematol. 31:798-805(2003).
RN [18]
RP TISSUE SPECIFICITY.
RX PubMed=15245368; DOI=10.1111/j.1399-0039.2004.00247.x;
RA Romero X., Benitez D., March S., Vilella R., Miralpeix M., Engel P.;
RT "Differential expression of SAP and EAT-2-binding leukocyte cell-surface
RT molecules CD84, CD150 (SLAM), CD229 (Ly9) and CD244 (2B4).";
RL Tissue Antigens 64:132-144(2004).
RN [19]
RP FUNCTION, PHOSPHORYLATION AT TYR-296 AND TYR-316, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=16037392; DOI=10.1182/blood-2005-01-0333;
RA Nanda N., Andre P., Bao M., Clauser K., Deguzman F., Howie D., Conley P.B.,
RA Terhorst C., Phillips D.R.;
RT "Platelet aggregation induces platelet aggregate stability via SLAM family
RT receptor signaling.";
RL Blood 106:3028-3034(2005).
RN [20]
RP FUNCTION, PHOSPHORYLATION AT TYR-296 AND TYR-341, AND TISSUE SPECIFICITY.
RX PubMed=22068234; DOI=10.4049/jimmunol.1101626;
RA Alvarez-Errico D., Oliver-Vila I., Ainsua-Enrich E., Gilfillan A.M.,
RA Picado C., Sayos J., Martin M.;
RT "CD84 negatively regulates IgE high-affinity receptor signaling in human
RT mast cells.";
RL J. Immunol. 187:5577-5586(2011).
RN [21]
RP FUNCTION.
RX PubMed=29434592; DOI=10.3389/fimmu.2018.00062;
RA Agod Z., Pazmandi K., Bencze D., Vereb G., Biro T., Szabo A.,
RA Rajnavolgyi E., Bacsi A., Engel P., Lanyi A.;
RT "Signaling lymphocyte activation molecule family 5 enhances autophagy and
RT fine-tunes cytokine response in monocyte-derived dendritic cells via
RT stabilization of interferon regulatory factor 8.";
RL Front. Immunol. 9:62-62(2018).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.04 ANGSTROMS) OF 22-131, SUBUNIT, AND MUTAGENESIS
RP OF THR-55; TYR-62; THR-77; HIS-78; ASP-110; ASN-112 AND THR-119.
RX PubMed=17563375; DOI=10.1073/pnas.0703893104;
RA Yan Q., Malashkevich V.N., Fedorov A., Fedorov E., Cao E., Lary J.W.,
RA Cole J.L., Nathenson S.G., Almo S.C.;
RT "Structure of CD84 provides insight into SLAM family function.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:10583-10588(2007).
CC -!- FUNCTION: Self-ligand receptor of the signaling lymphocytic activation
CC molecule (SLAM) family. SLAM receptors triggered by homo- or
CC heterotypic cell-cell interactions are modulating the activation and
CC differentiation of a wide variety of immune cells and thus are involved
CC in the regulation and interconnection of both innate and adaptive
CC immune response. Activities are controlled by presence or absence of
CC small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Can
CC mediate natural killer (NK) cell cytotoxicity dependent on SH2D1A and
CC SH2D1B (By similarity). Increases proliferative responses of activated
CC T-cells and SH2D1A/SAP does not seem be required for this process.
CC Homophilic interactions enhance interferon gamma/IFNG secretion in
CC lymphocytes and induce platelet stimulation via a SH2D1A-dependent
CC pathway. May serve as a marker for hematopoietic progenitor cells
CC (PubMed:11564780, PubMed:12115647. PubMed:12928397, PubMed:12962726,
CC PubMed:16037392) Required for a prolonged T-cell:B-cell contact,
CC optimal T follicular helper function, and germinal center formation. In
CC germinal centers involved in maintaining B-cell tolerance and in
CC preventing autoimmunity (By similarity). In mast cells negatively
CC regulates high affinity immunoglobulin epsilon receptor signaling;
CC independent of SH2D1A and SH2D1B but implicating FES and PTPN6/SHP-1
CC (PubMed:22068234). In macrophages enhances LPS-induced MAPK
CC phosphorylation and NF-kappaB activation and modulates LPS-induced
CC cytokine secretion; involving ITSM 2 (By similarity). Positively
CC regulates macroautophagy in primary dendritic cells via stabilization
CC of IRF8; inhibits TRIM21-mediated proteasomal degradation of IRF8
CC (PubMed:29434592). {ECO:0000250|UniProtKB:Q18PI6,
CC ECO:0000269|PubMed:11564780, ECO:0000269|PubMed:12115647,
CC ECO:0000269|PubMed:12928397, ECO:0000269|PubMed:12962726,
CC ECO:0000269|PubMed:16037392, ECO:0000269|PubMed:22068234,
CC ECO:0000269|PubMed:29434592, ECO:0000305}.
CC -!- SUBUNIT: Homodimer; via its extracellular domain. Forms a head to tail
CC dimer with a CD48 molecule from another cell. Interacts with SH2
CC domain-containing proteins SH2D1A/SAP and SH2D1B/EAT-2. Interacts with
CC tyrosine-protein phosphatases PTPN6/SHP-1 and PTPN11//SHP-2 via its
CC phosphorylated cytoplasmic domain, and this interaction is blocked by
CC SH2D1A. Interacts (via phosphorylated ITSM 1 and 2) with INPP5D/SHIP1.
CC {ECO:0000269|PubMed:11389028, ECO:0000269|PubMed:11414741,
CC ECO:0000269|PubMed:12115647, ECO:0000269|PubMed:12458214,
CC ECO:0000269|PubMed:17563375}.
CC -!- INTERACTION:
CC Q9UIB8; Q9UIB8: CD84; NbExp=3; IntAct=EBI-6691679, EBI-6691679;
CC Q9UIB8; O14796: SH2D1B; NbExp=3; IntAct=EBI-6691679, EBI-3923013;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11389028,
CC ECO:0000269|PubMed:12962726}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:11389028, ECO:0000269|PubMed:12962726}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1; Synonyms=CD84a;
CC IsoId=Q9UIB8-1; Sequence=Displayed;
CC Name=2; Synonyms=CD84b;
CC IsoId=Q9UIB8-2; Sequence=VSP_020852;
CC Name=3; Synonyms=CD84c;
CC IsoId=Q9UIB8-3; Sequence=VSP_020851;
CC Name=4; Synonyms=CD84e;
CC IsoId=Q9UIB8-4; Sequence=VSP_020854, VSP_020856;
CC Name=5; Synonyms=CD84d;
CC IsoId=Q9UIB8-5; Sequence=VSP_020853, VSP_020855;
CC Name=6; Synonyms=CD84s;
CC IsoId=Q9UIB8-6; Sequence=VSP_020849, VSP_020850;
CC Name=7;
CC IsoId=Q9UIB8-7; Sequence=VSP_020848, VSP_020851;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in hematopoietic tissues,
CC such as lymph node, spleen and peripheral leukocytes. Expressed in
CC macrophages, B-cells, monocytes, platelets, thymocytes, T-cells and
CC dendritic cells. Highly expressed in memory T-cells. Expressed in mast
CC cells. {ECO:0000269|PubMed:10698700, ECO:0000269|PubMed:11564780,
CC ECO:0000269|PubMed:12115647, ECO:0000269|PubMed:12962726,
CC ECO:0000269|PubMed:15245368, ECO:0000269|PubMed:22068234,
CC ECO:0000269|PubMed:9310491}.
CC -!- DEVELOPMENTAL STAGE: Expression is slightly increased in naive B-cells
CC after the first dividion. By contrast, expression on memory B-cells
CC decreased with each successive division. {ECO:0000269|PubMed:12115647}.
CC -!- DOMAIN: The ITSMs (immunoreceptor tyrosine-based switch motifs) with
CC the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors
CC have overlapping specificity for activating and inhibitory SH2 domain-
CC containingbinding partners. Especially they mediate the interaction
CC with the SH2 domain of SH2D1A and SH2D1B. A 'three-pronged' mechanism
CC is proposed involving threonine (position -2), phosphorylated tyrosine
CC (position 0) and valine/isoleucine (position +3).
CC {ECO:0000250|UniProtKB:Q13291, ECO:0000305|PubMed:11313386}.
CC -!- PTM: Phosphorylated by tyrosine-protein kinase LCK on tyrosine residues
CC following ligation induced by agonist monoclonal antibody. The
CC association with SH2D1A is dependent of tyrosine phosphorylation of its
CC cytoplasmic domain. Phosphorylated on Tyr-296 and Tyr-316 following
CC platelet aggregation. Phosphorylated on tyrosine residues upon high
CC affinity immunoglobulin epsilon receptor aggregation in mast cells.
CC {ECO:0000269|PubMed:11389028, ECO:0000269|PubMed:12115647,
CC ECO:0000269|PubMed:12928397, ECO:0000269|PubMed:16037392,
CC ECO:0000269|PubMed:22068234}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10698700,
CC ECO:0000269|PubMed:9310491}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U82988; AAB84364.1; -; mRNA.
DR EMBL; AJ223324; CAA11264.1; -; mRNA.
DR EMBL; AF054815; AAF21721.1; -; mRNA.
DR EMBL; AF054816; AAF21722.1; -; mRNA.
DR EMBL; AF054817; AAF21723.1; -; mRNA.
DR EMBL; AF054818; AAF21724.1; -; mRNA.
DR EMBL; AF081189; AAD13155.1; -; Genomic_DNA.
DR EMBL; AH008972; AAF21784.1; -; Genomic_DNA.
DR EMBL; AH008376; AAF06840.1; -; Genomic_DNA.
DR EMBL; U96627; AAD04232.1; -; mRNA.
DR EMBL; Y12632; CAA73181.1; -; mRNA.
DR EMBL; AK296290; BAH12304.1; -; mRNA.
DR EMBL; AK313496; BAG36278.1; -; mRNA.
DR EMBL; CR541847; CAG46645.1; -; mRNA.
DR EMBL; CR933666; CAI45963.1; -; mRNA.
DR EMBL; AL138930; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW52707.1; -; Genomic_DNA.
DR EMBL; BC020063; AAH20063.1; -; mRNA.
DR CCDS; CCDS1206.1; -. [Q9UIB8-3]
DR CCDS; CCDS53395.1; -. [Q9UIB8-7]
DR CCDS; CCDS53396.1; -. [Q9UIB8-1]
DR CCDS; CCDS53397.1; -. [Q9UIB8-5]
DR CCDS; CCDS81388.1; -. [Q9UIB8-2]
DR RefSeq; NP_001171808.1; NM_001184879.1. [Q9UIB8-1]
DR RefSeq; NP_001171810.1; NM_001184881.1. [Q9UIB8-5]
DR RefSeq; NP_001171811.1; NM_001184882.1. [Q9UIB8-7]
DR RefSeq; NP_001317671.1; NM_001330742.1. [Q9UIB8-2]
DR RefSeq; NP_003865.1; NM_003874.3. [Q9UIB8-3]
DR PDB; 2PKD; X-ray; 2.04 A; A/B/C/D/E/F=22-131.
DR PDBsum; 2PKD; -.
DR AlphaFoldDB; Q9UIB8; -.
DR SMR; Q9UIB8; -.
DR BioGRID; 114359; 6.
DR DIP; DIP-60957N; -.
DR ELM; Q9UIB8; -.
DR IntAct; Q9UIB8; 4.
DR MINT; Q9UIB8; -.
DR STRING; 9606.ENSP00000312367; -.
DR GlyGen; Q9UIB8; 1 site.
DR iPTMnet; Q9UIB8; -.
DR PhosphoSitePlus; Q9UIB8; -.
DR BioMuta; CD84; -.
DR DMDM; 74762772; -.
DR EPD; Q9UIB8; -.
DR jPOST; Q9UIB8; -.
DR MassIVE; Q9UIB8; -.
DR MaxQB; Q9UIB8; -.
DR PaxDb; Q9UIB8; -.
DR PeptideAtlas; Q9UIB8; -.
DR PRIDE; Q9UIB8; -.
DR ProteomicsDB; 84484; -. [Q9UIB8-1]
DR ProteomicsDB; 84485; -. [Q9UIB8-2]
DR ProteomicsDB; 84486; -. [Q9UIB8-3]
DR ProteomicsDB; 84487; -. [Q9UIB8-4]
DR ProteomicsDB; 84488; -. [Q9UIB8-5]
DR ProteomicsDB; 84489; -. [Q9UIB8-6]
DR ProteomicsDB; 84490; -. [Q9UIB8-7]
DR Antibodypedia; 20494; 745 antibodies from 41 providers.
DR DNASU; 8832; -.
DR Ensembl; ENST00000311224.8; ENSP00000312367.4; ENSG00000066294.15. [Q9UIB8-1]
DR Ensembl; ENST00000368048.7; ENSP00000357027.3; ENSG00000066294.15. [Q9UIB8-2]
DR Ensembl; ENST00000368051.3; ENSP00000357030.3; ENSG00000066294.15. [Q9UIB8-5]
DR Ensembl; ENST00000368054.8; ENSP00000357033.4; ENSG00000066294.15. [Q9UIB8-3]
DR Ensembl; ENST00000534968.5; ENSP00000442845.1; ENSG00000066294.15. [Q9UIB8-7]
DR GeneID; 8832; -.
DR KEGG; hsa:8832; -.
DR MANE-Select; ENST00000368054.8; ENSP00000357033.4; NM_003874.4; NP_003865.1. [Q9UIB8-3]
DR UCSC; uc001fwf.5; human. [Q9UIB8-1]
DR CTD; 8832; -.
DR DisGeNET; 8832; -.
DR GeneCards; CD84; -.
DR HGNC; HGNC:1704; CD84.
DR HPA; ENSG00000066294; Tissue enhanced (lymphoid).
DR MIM; 604513; gene.
DR neXtProt; NX_Q9UIB8; -.
DR OpenTargets; ENSG00000066294; -.
DR PharmGKB; PA26242; -.
DR VEuPathDB; HostDB:ENSG00000066294; -.
DR eggNOG; ENOG502SB7W; Eukaryota.
DR GeneTree; ENSGT01030000234540; -.
DR HOGENOM; CLU_069386_1_1_1; -.
DR InParanoid; Q9UIB8; -.
DR OMA; YVMVTRD; -.
DR OrthoDB; 990343at2759; -.
DR PhylomeDB; Q9UIB8; -.
DR TreeFam; TF334964; -.
DR PathwayCommons; Q9UIB8; -.
DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR SignaLink; Q9UIB8; -.
DR BioGRID-ORCS; 8832; 10 hits in 1069 CRISPR screens.
DR EvolutionaryTrace; Q9UIB8; -.
DR GeneWiki; CD84; -.
DR GenomeRNAi; 8832; -.
DR Pharos; Q9UIB8; Tbio.
DR PRO; PR:Q9UIB8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UIB8; protein.
DR Bgee; ENSG00000066294; Expressed in tibia and 168 other tissues.
DR Genevisible; Q9UIB8; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0006952; P:defense response; TAS:ProtInc.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0032685; P:negative regulation of granulocyte macrophage colony-stimulating factor production; IDA:UniProtKB.
DR GO; GO:0032701; P:negative regulation of interleukin-18 production; IDA:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IBA:GO_Central.
DR GO; GO:0033004; P:negative regulation of mast cell activation; IDA:UniProtKB.
DR GO; GO:0043305; P:negative regulation of mast cell degranulation; IDA:UniProtKB.
DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; IBA:GO_Central.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IBA:GO_Central.
DR GO; GO:0043030; P:regulation of macrophage activation; IBA:GO_Central.
DR GO; GO:2001256; P:regulation of store-operated calcium entry; IDA:UniProtKB.
DR GO; GO:0042110; P:T cell activation; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR SMART; SM00409; IG; 2.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Autophagy;
KW Cell adhesion; Cell membrane; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Innate immunity; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:10698700"
FT CHAIN 22..345
FT /note="SLAM family member 5"
FT /id="PRO_0000252029"
FT TOPO_DOM 22..225
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 226..246
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 247..345
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 26..129
FT /note="Ig-like V-type"
FT DOMAIN 135..207
FT /note="Ig-like C2-type"
FT REGION 326..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 277..282
FT /note="ITSM 1"
FT /evidence="ECO:0000250|UniProtKB:Q13291"
FT MOTIF 314..319
FT /note="ITSM 2"
FT /evidence="ECO:0000250|UniProtKB:Q13291"
FT MOD_RES 279
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:12458214"
FT MOD_RES 296
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000269|PubMed:16037392,
FT ECO:0000269|PubMed:22068234"
FT MOD_RES 316
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:16037392,
FT ECO:0000305|PubMed:12458214"
FT MOD_RES 341
FT /note="Phosphotyrosine; by FES"
FT /evidence="ECO:0000269|PubMed:22068234"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 155..193
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 16..130
FT /note="WPEAAGKDSEIFTVNGILGESVTFPVNIQEPRQVKIIAWTSKTSVAYVTPGD
FT SETAPVVTVTHRNYYERIHALGPNYNLVISDLRMEDAGDYKADINTQADPYTTTKRYNL
FT QIYR -> C (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_020848"
FT VAR_SEQ 214..241
FT /note="DIAMGFRTHHTGLLSVLAMFFLLVLILS -> GNQLCPSLLVSLRDHSEELQ
FT GLNVGHIL (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:10746783"
FT /id="VSP_020849"
FT VAR_SEQ 242..345
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:10746783"
FT /id="VSP_020850"
FT VAR_SEQ 254..271
FT /note="GRIFPEGSCLNTFTKNPY -> D (in isoform 3 and isoform
FT 7)"
FT /evidence="ECO:0000303|PubMed:10698700,
FT ECO:0000303|PubMed:10746783, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005,
FT ECO:0000303|PubMed:9310491, ECO:0000303|Ref.4"
FT /id="VSP_020851"
FT VAR_SEQ 254..259
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10746783"
FT /id="VSP_020852"
FT VAR_SEQ 255..272
FT /note="RIFPEGSCLNTFTKNPYA -> ASLQGRASEHSLFRSAVC (in isoform
FT 5)"
FT /evidence="ECO:0000303|PubMed:10746783"
FT /id="VSP_020853"
FT VAR_SEQ 261..280
FT /note="SCLNTFTKNPYAASKKTIYT -> KMWKLTFSPPGTEAIYPRFS (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:10746783"
FT /id="VSP_020854"
FT VAR_SEQ 273..345
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:10746783"
FT /id="VSP_020855"
FT VAR_SEQ 281..345
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10746783"
FT /id="VSP_020856"
FT MUTAGEN 55
FT /note="T->A: Loss of dimerization."
FT /evidence="ECO:0000269|PubMed:17563375"
FT MUTAGEN 62
FT /note="Y->A: No effect."
FT /evidence="ECO:0000269|PubMed:17563375"
FT MUTAGEN 62
FT /note="Y->D: Loss of dimerization."
FT /evidence="ECO:0000269|PubMed:17563375"
FT MUTAGEN 77
FT /note="T->A: Loss of dimerization."
FT /evidence="ECO:0000269|PubMed:17563375"
FT MUTAGEN 78
FT /note="H->A: Loss of dimerization."
FT /evidence="ECO:0000269|PubMed:17563375"
FT MUTAGEN 110
FT /note="D->A: Loss of dimerization."
FT /evidence="ECO:0000269|PubMed:17563375"
FT MUTAGEN 112
FT /note="N->A: Loss of dimerization."
FT /evidence="ECO:0000269|PubMed:17563375"
FT MUTAGEN 119
FT /note="T->A: Loss of dimerization."
FT /evidence="ECO:0000269|PubMed:17563375"
FT MUTAGEN 279
FT /note="Y->F: Reduced tyrosine phosphorylation, reduced
FT binding of SH2D1B and loss of binding of SH2D1A."
FT /evidence="ECO:0000269|PubMed:12928397"
FT MUTAGEN 316
FT /note="Y->F: Reduced tyrosine phosphorylation and reduced
FT binding of SH2D1B. Loss of phosphorylation and loss of
FT binding of SH2D1A and SH2D1B; when associated with F-279."
FT /evidence="ECO:0000269|PubMed:12928397"
FT CONFLICT 311
FT /note="P -> S (in Ref. 4; CAG46645)"
FT /evidence="ECO:0000305"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:2PKD"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:2PKD"
FT STRAND 49..64
FT /evidence="ECO:0007829|PDB:2PKD"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:2PKD"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:2PKD"
FT HELIX 79..81
FT /evidence="ECO:0007829|PDB:2PKD"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:2PKD"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:2PKD"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:2PKD"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:2PKD"
FT STRAND 105..115
FT /evidence="ECO:0007829|PDB:2PKD"
FT STRAND 118..129
FT /evidence="ECO:0007829|PDB:2PKD"
SQ SEQUENCE 345 AA; 38782 MW; DA06BC5A682E62DE CRC64;
MAQHHLWILL LCLQTWPEAA GKDSEIFTVN GILGESVTFP VNIQEPRQVK IIAWTSKTSV
AYVTPGDSET APVVTVTHRN YYERIHALGP NYNLVISDLR MEDAGDYKAD INTQADPYTT
TKRYNLQIYR RLGKPKITQS LMASVNSTCN VTLTCSVEKE EKNVTYNWSP LGEEGNVLQI
FQTPEDQELT YTCTAQNPVS NNSDSISARQ LCADIAMGFR THHTGLLSVL AMFFLLVLIL
SSVFLFRLFK RRQGRIFPEG SCLNTFTKNP YAASKKTIYT YIMASRNTQP AESRIYDEIL
QSKVLPSKEE PVNTVYSEVQ FADKMGKAST QDSKPPGTSS YEIVI
