SLAF1_CANLF
ID SLAF1_CANLF Reviewed; 342 AA.
AC Q95MM9; Q95L99;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Signaling lymphocytic activation molecule;
DE AltName: CD_antigen=CD150;
DE Flags: Precursor;
GN Name=SLAMF1; Synonyms=SLAM;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH CANINE DISTEMPER VIRUS HN
RP PROTEIN.
RX PubMed=11390585; DOI=10.1128/jvi.75.13.5842-5850.2001;
RA Tatsuo H., Ono N., Yanagi Y.;
RT "Morbilliviruses use signaling lymphocyte activation molecules (CD150) as
RT cellular receptors.";
RL J. Virol. 75:5842-5850(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Richardson C.D.;
RT "CD150 is a cellular receptor for canine distemper virus.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
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.
CC SLAMF1-induced signal-transduction events in T-lymphocytes are
CC different from those in B-cells. Two modes of SLAMF1 signaling seem to
CC exist: one depending on SH2D1A (and perhaps SH2D1B) and another in
CC which protein-tyrosine phosphatase 2C (PTPN11)-dependent signal
CC transduction operates. Initially it has been proposed that association
CC with SH2D1A prevents binding to inhibitory effectors including
CC INPP5D/SHIP1 and PTPN11/SHP-2. However, signaling is also regulated by
CC SH2D1A which can simultaneously interact with and recruit FYN which
CC subsequently phosphorylates and activates SLAMF1. Mediates IL-2-
CC independent proliferation of activated T cells during immune responses
CC and induces IFN-gamma production. Downstreaming signaling involves
CC INPP5D/SHIP1, DOK1 and DOK2 leading to inhibited IFN-gamma production
CC in T-cells, and PRKCQ, BCL10 and NFKB1 leading to increased T-cell
CC activation and Th2 cytokine production. Promotes T-cell receptor-
CC induced IL-4 secretion by CD4(+) cells. Inhibits antigen receptor-
CC mediated production of IFN-gamma, but not IL-2, in CD4(-)/CD8(-) T-
CC cells. Required for IL-4 production by germinal centers T follicular
CC helper (T(Fh))cells. May inhibit CD40-induced signal transduction in
CC monocyte-derived dendritic cells. May play a role in allergic responses
CC and may regulate allergen-induced Th2 cytokine and Th1 cytokine
CC secretion. In conjunction with SLAMF6 controls the transition between
CC positive selection and the subsequent expansion and differentiation of
CC the thymocytic natural killer T (NKT) cell lineage. Involved in the
CC peripheral differentiation of indifferent natural killer T (iNKT) cells
CC toward a regulatory NKT2 type. In macrophages involved in down-
CC regulation of IL-12, TNF-alpha and nitric oxide in response to
CC lipopolysaccharide (LPS). In B-cells activates the ERK signaling
CC pathway independently of SH2D1A but implicating both, SYK and INPP5D,
CC and activates Akt signaling dependent on SYK and SH2D1A. In conjunction
CC with SLAMF5 and SLAMF6 may be a negative regulator of the humoral
CC immune response. {ECO:0000250|UniProtKB:Q13291,
CC ECO:0000250|UniProtKB:Q9QUM4}.
CC -!- SUBUNIT: Interacts (via cytoplasmic domain) with SH2D1A and SH2D1B;
CC SH2D1A mediates association with FYN. Interacts (via cytoplasmic domain
CC phosphorylated on tyrosine residues) with INPP5D and PTPN11; presence
CC of SH2D1A facilitates binding to INPP5D (By similarity). Interacts with
CC MAP4K1. Interacts with PIK3C3, BECN1 and UVRAG; indicative for an
CC association with PI3K complex II (PI3KC3-C2) (By similarity). Interacts
CC with canine distemper virus HN protein; suggesting that it may serve as
CC a receptor. {ECO:0000250|UniProtKB:Q13291,
CC ECO:0000250|UniProtKB:Q9QUM4, ECO:0000269|PubMed:11390585}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q13291};
CC Single-pass type I membrane protein. Note=Present on the surface of B-
CC cells and T-cells. Located at the plasma membrane contacts between
CC neighboring T cells. {ECO:0000250|UniProtKB:Q13291}.
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 'two-out-of-three-pronged'
CC mechanism is proposed involving threonine (position -2), phosphorylated
CC tyrosine (position 0) and valine/isoleucine (position +3). Binding is
CC mediated by either three 'prongs' (for high affinity binding involving
CC ITSM 1) or a combination of any two also including non-phosphorylated
CC Tyr-284 of ITSM 1. ITSM 2 needs to be phosphoryated on Tyr-334 for
CC SH2D1A binding. {ECO:0000250|UniProtKB:Q13291}.
CC -!- PTM: Phosphorylated on tyrosine residues by FYN.
CC {ECO:0000250|UniProtKB:Q13291}.
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DR EMBL; AF325357; AAK61857.1; -; mRNA.
DR EMBL; AF390108; AAK97460.1; -; mRNA.
DR RefSeq; NP_001003084.1; NM_001003084.1.
DR AlphaFoldDB; Q95MM9; -.
DR STRING; 9612.ENSCAFP00000018535; -.
DR PaxDb; Q95MM9; -.
DR Ensembl; ENSCAFT00030032271; ENSCAFP00030028141; ENSCAFG00030017518.
DR Ensembl; ENSCAFT00040028283; ENSCAFP00040024569; ENSCAFG00040015313.
DR Ensembl; ENSCAFT00845053817; ENSCAFP00845042296; ENSCAFG00845030320.
DR GeneID; 403642; -.
DR KEGG; cfa:403642; -.
DR CTD; 6504; -.
DR VEuPathDB; HostDB:ENSCAFG00845030320; -.
DR eggNOG; ENOG502SVMG; Eukaryota.
DR GeneTree; ENSGT01030000234540; -.
DR HOGENOM; CLU_066453_0_0_1; -.
DR InParanoid; Q95MM9; -.
DR OMA; DHVAYNW; -.
DR OrthoDB; 832202at2759; -.
DR TreeFam; TF334964; -.
DR Proteomes; UP000002254; Chromosome 38.
DR Bgee; ENSCAFG00000012579; Expressed in thymus and 23 other tissues.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045335; C:phagocytic vesicle; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0042169; F:SH2 domain binding; IEA:Ensembl.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002232; P:leukocyte chemotaxis involved in inflammatory response; IEA:Ensembl.
DR GO; GO:0002277; P:myeloid dendritic cell activation involved in immune response; IEA:Ensembl.
DR GO; GO:0001779; P:natural killer cell differentiation; IEA:Ensembl.
DR GO; GO:0001787; P:natural killer cell proliferation; IEA:Ensembl.
DR GO; GO:2000349; P:negative regulation of CD40 signaling pathway; IEA:Ensembl.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IEA:Ensembl.
DR GO; GO:0032695; P:negative regulation of interleukin-12 production; IEA:Ensembl.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0002725; P:negative regulation of T cell cytokine production; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IEA:Ensembl.
DR GO; GO:2000510; P:positive regulation of dendritic cell chemotaxis; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IBA:GO_Central.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IEA:Ensembl.
DR GO; GO:2000556; P:positive regulation of T-helper 1 cell cytokine production; IEA:Ensembl.
DR GO; GO:0050790; P:regulation of catalytic activity; IEA:Ensembl.
DR GO; GO:0031338; P:regulation of vesicle fusion; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR010407; Sig_lymph_act_molc_N.
DR Pfam; PF06214; SLAM; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Cell membrane; Disulfide bond; Glycoprotein;
KW Host-virus interaction; Immunity; Immunoglobulin domain; Innate immunity;
KW Membrane; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..342
FT /note="Signaling lymphocytic activation molecule"
FT /id="PRO_0000014958"
FT TOPO_DOM 27..237
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..261
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 262..342
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 29..138
FT /note="Ig-like V-type"
FT DOMAIN 144..223
FT /note="Ig-like C2-type"
FT MOTIF 282..287
FT /note="ITSM 1"
FT /evidence="ECO:0000250|UniProtKB:Q13291"
FT MOTIF 310..315
FT /note="SH2-binding"
FT /evidence="ECO:0000255"
FT MOTIF 332..337
FT /note="ITSM 2"
FT /evidence="ECO:0000250|UniProtKB:Q13291"
FT MOD_RES 284
FT /note="Phosphotyrosine; by FYN"
FT /evidence="ECO:0000250|UniProtKB:Q13291"
FT MOD_RES 310
FT /note="Phosphotyrosine; by FYN"
FT /evidence="ECO:0000250|UniProtKB:Q13291"
FT MOD_RES 334
FT /note="Phosphotyrosine; by FYN"
FT /evidence="ECO:0000250|UniProtKB:Q13291"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 189
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 217
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 158..228
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 164..209
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 72
FT /note="N -> S (in Ref. 2; AAK97460)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 342 AA; 38160 MW; E03E4918A6398AA0 CRC64;
MDSRGFLSLR CLLVLALASK LSCGTGESLM NCPEVPGKLG SSLQLSLASE GISKRMNKSI
HILVTRAESP GNSIKKKIVS LDLPEGGSPR YLENGYKFHL ENLTLRILES RRENEGWYFM
TLEENFSVQH FCLQLKLYEQ VSTPEIKVLN WTQENGNCSM MLACEVEKGD NVVYSWSEKL
GIDPLIPANS SHLLHLSLGP QHVNNVYVCT VSNPVSNRSW SFNPWSKCRP ESSVPRQWRL
YAGLFLGGIV GVILIFEVVL LLLRRRGKTN HYKPTKEEKS LTIYAQVQKS GSTQKKPDPL
PAEDPCTTIY VAATEPVPEP APEPVQEPHS ITVYASVTFP ES
