STAM1_MOUSE
ID STAM1_MOUSE Reviewed; 548 AA.
AC P70297;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Signal transducing adapter molecule 1;
DE Short=STAM-1;
GN Name=Stam; Synonyms=Stam1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=T-cell;
RX PubMed=8780729; DOI=10.1006/bbrc.1996.1290;
RA Takeshita T., Arita T., Asao H., Tanaka N., Higuchi M., Kuroda H.,
RA Kaneko K., Munakata H., Endo Y., Fujita T., Sugamura K.;
RT "Cloning of a novel signal-transducing adaptor molecule containing an SH3
RT domain and ITAM.";
RL Biochem. Biophys. Res. Commun. 225:1035-1039(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Mammary tumor;
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 [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=11340172; DOI=10.1128/mcb.21.11.3807-3819.2001;
RA Yamada M., Takeshita T., Miura S., Murata K., Kimura Y., Ishii N., Nose M.,
RA Sakagami H., Kondo H., Tashiro F., Miyazaki J., Sasaki H., Sugamura K.;
RT "Loss of hippocampal CA3 pyramidal neurons in mice lacking STAM1.";
RL Mol. Cell. Biol. 21:3807-3819(2001).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=12446783; DOI=10.1128/mcb.22.24.8648-8658.2002;
RA Yamada M., Ishii N., Asao H., Murata K., Kanazawa C., Sasaki H.,
RA Sugamura K.;
RT "Signal-transducing adaptor molecules STAM1 and STAM2 are required for T-
RT cell development and survival.";
RL Mol. Cell. Biol. 22:8648-8658(2002).
RN [5]
RP INTERACTION WITH HGS.
RX PubMed=19278655; DOI=10.1016/j.str.2009.01.012;
RA Ren X., Kloer D.P., Kim Y.C., Ghirlando R., Saidi L.F., Hummer G.,
RA Hurley J.H.;
RT "Hybrid structural model of the complete human ESCRT-0 complex.";
RL Structure 17:406-416(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Involved in intracellular signal transduction mediated by
CC cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it
CC plays a role in signaling leading to DNA synthesis and MYC induction.
CC May also play a role in T-cell development. Involved in down-regulation
CC of receptor tyrosine kinase via multivesicular body (MVBs) when
CC complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds
CC ubiquitin and acts as sorting machinery that recognizes ubiquitinated
CC receptors and transfers them to further sequential lysosomal
CC sorting/trafficking processes (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Component of the ESCRT-0 complex composed of STAM or STAM2 and
CC HGS (PubMed:19278655). Probably part of a complex at least composed of
CC HSG, STAM and EPS15 (By similarity). Found in a complex with HGS and E3
CC ligase ITCH and DTX3L (By similarity). Interacts with E3 ligase DTX3L;
CC the interaction brings together STAM and HSG, promotes their
CC recruitment to early endosomes and decreases STAM and HGS
CC ubiquitination by ITCH (By similarity). Interacts with STAMBP/AMSH (By
CC similarity). Interacts with PDGFRB (By similarity). Interacts with
CC LITAF; the interaction is direct (By similarity). Identified in a
CC complex with HGS and LITAF (By similarity). Interacts with HAVCR1 (By
CC similarity). {ECO:0000250|UniProtKB:Q92783,
CC ECO:0000269|PubMed:19278655}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q92783}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q92783}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q92783}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Enriched expression in
CC synaptic vesicles. {ECO:0000269|PubMed:8780729}.
CC -!- DEVELOPMENTAL STAGE: No change during brain development.
CC -!- DOMAIN: The VHS domain mediates high-avidity binding to Lys63-linked
CC and Lys48-linked polyubiquitinated cargos.
CC {ECO:0000250|UniProtKB:Q92783}.
CC -!- PTM: Phosphorylated on Tyr-198. Phosphorylated in response to IL2, IL3,
CC IL4, IL7, CSF2/GM-CSF, EGF and PDGFB. Phosphorylated by activated
CC PDGFRB (By similarity). {ECO:0000250|UniProtKB:Q92783}.
CC -!- PTM: Ubiquitinated by ITCH. {ECO:0000250|UniProtKB:Q92783}.
CC -!- DISRUPTION PHENOTYPE: Mice display disappearance of hippocampal CA3
CC pyramidal neurons as well as growth retardation in the third week after
CC birth. Adult mice lacking Stam and Stam2 due to inducible gene
CC targeting exhibit significant reduction in T-cell development in the
CC thymus and profound reduction in the peripheral mature T-cells.
CC {ECO:0000269|PubMed:11340172, ECO:0000269|PubMed:12446783}.
CC -!- SIMILARITY: Belongs to the STAM family. {ECO:0000305}.
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DR EMBL; U43900; AAC52840.1; -; mRNA.
DR EMBL; BC044666; AAH44666.1; -; mRNA.
DR EMBL; BC055326; AAH55326.1; -; mRNA.
DR CCDS; CCDS15698.1; -.
DR PIR; JC4917; JC4917.
DR RefSeq; NP_035614.1; NM_011484.2.
DR AlphaFoldDB; P70297; -.
DR BMRB; P70297; -.
DR SMR; P70297; -.
DR BioGRID; 203519; 13.
DR IntAct; P70297; 1.
DR MINT; P70297; -.
DR STRING; 10090.ENSMUSP00000100025; -.
DR iPTMnet; P70297; -.
DR PhosphoSitePlus; P70297; -.
DR EPD; P70297; -.
DR jPOST; P70297; -.
DR PaxDb; P70297; -.
DR PeptideAtlas; P70297; -.
DR PRIDE; P70297; -.
DR ProteomicsDB; 258637; -.
DR Antibodypedia; 25306; 349 antibodies from 33 providers.
DR DNASU; 20844; -.
DR Ensembl; ENSMUST00000102960; ENSMUSP00000100025; ENSMUSG00000026718.
DR GeneID; 20844; -.
DR KEGG; mmu:20844; -.
DR UCSC; uc008ikh.1; mouse.
DR CTD; 8027; -.
DR MGI; MGI:1329014; Stam.
DR VEuPathDB; HostDB:ENSMUSG00000026718; -.
DR eggNOG; KOG2199; Eukaryota.
DR GeneTree; ENSGT00940000157171; -.
DR HOGENOM; CLU_010104_0_2_1; -.
DR InParanoid; P70297; -.
DR OMA; AHALCQN; -.
DR OrthoDB; 906159at2759; -.
DR PhylomeDB; P70297; -.
DR TreeFam; TF315007; -.
DR Reactome; R-MMU-182971; EGFR downregulation.
DR Reactome; R-MMU-5689901; Metalloprotease DUBs.
DR Reactome; R-MMU-6807004; Negative regulation of MET activity.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-MMU-9013420; RHOU GTPase cycle.
DR Reactome; R-MMU-917729; Endosomal Sorting Complex Required For Transport (ESCRT).
DR BioGRID-ORCS; 20844; 5 hits in 70 CRISPR screens.
DR ChiTaRS; Stam; mouse.
DR PRO; PR:P70297; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P70297; protein.
DR Bgee; ENSMUSG00000026718; Expressed in embryonic brain and 266 other tissues.
DR ExpressionAtlas; P70297; baseline and differential.
DR Genevisible; P70297; MM.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033565; C:ESCRT-0 complex; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0043130; F:ubiquitin binding; IEA:InterPro.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; ISO:MGI.
DR GO; GO:1903543; P:positive regulation of exosomal secretion; ISO:MGI.
DR GO; GO:0043328; P:protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IBA:GO_Central.
DR GO; GO:1903551; P:regulation of extracellular exosome assembly; ISO:MGI.
DR CDD; cd11964; SH3_STAM1; 1.
DR Gene3D; 1.25.40.90; -; 1.
DR InterPro; IPR008942; ENTH_VHS.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR035657; STAM1_SH3.
DR InterPro; IPR003903; UIM_dom.
DR InterPro; IPR002014; VHS_dom.
DR Pfam; PF00018; SH3_1; 1.
DR Pfam; PF02809; UIM; 1.
DR Pfam; PF00790; VHS; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00288; VHS; 1.
DR SUPFAM; SSF48464; SSF48464; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50002; SH3; 1.
DR PROSITE; PS50330; UIM; 1.
DR PROSITE; PS50179; VHS; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Endosome; Isopeptide bond; Membrane; Phosphoprotein;
KW Protein transport; Reference proteome; SH3 domain; Transport;
KW Ubl conjugation.
FT CHAIN 1..548
FT /note="Signal transducing adapter molecule 1"
FT /id="PRO_0000190146"
FT DOMAIN 16..143
FT /note="VHS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00218"
FT DOMAIN 171..190
FT /note="UIM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 210..269
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 369..386
FT /note="ITAM"
FT REGION 436..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 517..548
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92783"
FT MOD_RES 198
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q92783"
FT MOD_RES 381
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q92783"
FT MOD_RES 384
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q92783"
FT CROSSLNK 276
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q92783"
SQ SEQUENCE 548 AA; 59771 MW; 1149D4F9F540C8B8 CRC64;
MPLFATNPFD QDVEKATSEL NTAEDWGLIL DICDKVGQSR TGPKDCLRSI MRRVNHKDPH
VAMQALTLLG ACVSNCGKIF HLEVCSRDFA SEVSNVLNKG HPKVCEKLKA LMVEWTDEFK
NDPQLSLISA MIKNLKEQGV TFPAIGSQAA EQAKASPALV AKDPGTVATK KEEEDLAKAI
ELSLKEQRQQ SAPVSTLYPS TSNLLTNHQH EGRKVRAVYD FEAAEDNELT FKAGEIITVL
DDSDPNWWKG ETHQGVGLFP SNFVTADLTA EPEMIKTEKK TVQFNDDVQI ETIEPEPEPA
FIDEDKMDQL LQMLQSTDPS DNQPDLPELL HLEAMCHQMG PLIDEKLEDI DRKHSELSEL
NVKVMEALSL YTKLMNEDPM YSMYAKLQSQ QYYLQSSAVS ASQVYPGPAQ SGTYLVAGSA
QMTHLQSYSL PPEQLSSISQ GAVPSSANQA LPSQQTQASY PNAMVSSVQG NSYPSQASIY
SPPAAAAAAA AAAVVPVPVP ADVTIYQNAG PTMSQVPNYT LTSSTLPQTG GSQQPPQPQQ
AYSQKALL
