STAM2_MOUSE
ID STAM2_MOUSE Reviewed; 523 AA.
AC O88811; A2AU00; Q8C8Y4;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Signal transducing adapter molecule 2;
DE Short=STAM-2;
DE AltName: Full=Hrs-binding protein;
GN Name=Stam2; Synonyms=Hbp;
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] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION
RP WITH HGS, DOMAIN, AND SUBCELLULAR LOCATION.
RC TISSUE=Liver;
RX PubMed=10651905; DOI=10.1046/j.1365-2443.2000.00303.x;
RA Takata H., Kato M., Denda K., Kitamura N.;
RT "A hrs binding protein having a Src homology 3 domain is involved in
RT intracellular degradation of growth factors and their receptors.";
RL Genes Cells 5:57-69(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=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 [5]
RP INTERACTION WITH USP8.
RX PubMed=10982817; DOI=10.1074/jbc.m007251200;
RA Kato M., Miyazawa K., Kitamura N.;
RT "A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of
RT Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP.";
RL J. Biol. Chem. 275:37481-37487(2000).
RN [6]
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 [7]
RP INTERACTION WITH HGS; EPS15 AND UBIQUITIN, AND SUBCELLULAR LOCATION.
RX PubMed=12551915; DOI=10.1074/jbc.m210843200;
RA Bache K.G., Raiborg C., Mehlum A., Stenmark H.;
RT "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on
RT early endosomes.";
RL J. Biol. Chem. 278:12513-12521(2003).
RN [8]
RP INTERACTION WITH UBIQUITIN, AND FUNCTION.
RX PubMed=12972556; DOI=10.1091/mbc.e02-12-0823;
RA Mizuno E., Kawahata K., Kato M., Kitamura N., Komada M.;
RT "STAM proteins bind ubiquitinated proteins on the early endosome via the
RT VHS domain and ubiquitin-interacting motif.";
RL Mol. Biol. Cell 14:3675-3689(2003).
RN [9]
RP INTERACTION WITH UBQLN1, AND MUTAGENESIS OF LEU-176 AND SER-177.
RX PubMed=16159959; DOI=10.1242/jcs.02571;
RA Regan-Klapisz E., Sorokina I., Voortman J., de Keizer P., Roovers R.C.,
RA Verheesen P., Urbe S., Fallon L., Fon E.A., Verkleij A., Benmerah A.,
RA van Bergen en Henegouwen P.M.;
RT "Ubiquilin recruits Eps15 into ubiquitin-rich cytoplasmic aggregates via a
RT UIM-UBL interaction.";
RL J. Cell Sci. 118:4437-4450(2005).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, Spleen, and Testis;
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).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 203-260 IN COMPLEX WITH USP8.
RX PubMed=13129930; DOI=10.1074/jbc.m306677200;
RA Kaneko T., Kumasaka T., Ganbe T., Sato T., Miyazawa K., Kitamura N.,
RA Tanaka N.;
RT "Structural insight into modest binding of a non-PXXP ligand to the signal
RT transducing adaptor molecule-2 Src homology 3 domain.";
RL J. Biol. Chem. 278:48162-48168(2003).
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 ECO:0000269|PubMed:12972556}.
CC -!- SUBUNIT: Component of the ESCRT-0 complex composed of STAM or STAM2 and
CC HGS. Part of a complex at least composed of HSG, STAM2 and EPS15.
CC Interacts with JAK2 and JAK3. Interacts with ubiquitinated proteins and
CC the deubiquitinating enzyme USP8/UBPY. Interacts (via the via the PxVxL
CC motif) with CBX5; the interaction is direct. Interacts with VPS37C.
CC Interacts with ubiquitin; the interaction is direct (By similarity).
CC Interacts (via UIM domain) with UBQLN1 (via ubiquitin-like domain).
CC {ECO:0000250|UniProtKB:O75886, ECO:0000269|PubMed:16159959}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10651905,
CC ECO:0000269|PubMed:12551915}. Early endosome membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}; Cytoplasmic side
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O88811-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O88811-2; Sequence=VSP_014849, VSP_014850, VSP_014851;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in
CC testis. {ECO:0000269|PubMed:10651905}.
CC -!- DOMAIN: The VHS and UIM domains mediate the interaction with
CC ubiquitinated proteins. {ECO:0000269|PubMed:10651905}.
CC -!- DOMAIN: The SH3 domain mediates the interaction with USP8.
CC {ECO:0000269|PubMed:10651905}.
CC -!- DOMAIN: Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is
CC required for interaction with chromoshadow domains. This motif requires
CC additional residues -7, -6, +4 and +5 of the central Val which contact
CC the chromoshadow domain. {ECO:0000269|PubMed:10651905}.
CC -!- PTM: Phosphorylated in response to IL-2, GM-CSF, EGF and PDGF.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Adult mice lacking Stam and Stam2 due to
CC inducible gene targeting exhibit significant reduction in T-cell
CC development in the thymus and profound reduction in the peripheral
CC mature T-cells. {ECO:0000269|PubMed:12446783}.
CC -!- SIMILARITY: Belongs to the STAM family. {ECO:0000305}.
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DR EMBL; AB012611; BAA33547.1; -; mRNA.
DR EMBL; AK004604; BAB23403.1; -; mRNA.
DR EMBL; AK044230; BAC31830.1; -; mRNA.
DR EMBL; AL928960; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013818; AAH13818.1; -; mRNA.
DR CCDS; CCDS16037.1; -. [O88811-1]
DR RefSeq; NP_062641.1; NM_019667.2. [O88811-1]
DR PDB; 1UJ0; X-ray; 1.70 A; A=204-261.
DR PDBsum; 1UJ0; -.
DR AlphaFoldDB; O88811; -.
DR SMR; O88811; -.
DR BioGRID; 207904; 18.
DR CORUM; O88811; -.
DR IntAct; O88811; 5.
DR MINT; O88811; -.
DR STRING; 10090.ENSMUSP00000099820; -.
DR iPTMnet; O88811; -.
DR PhosphoSitePlus; O88811; -.
DR EPD; O88811; -.
DR jPOST; O88811; -.
DR MaxQB; O88811; -.
DR PaxDb; O88811; -.
DR PeptideAtlas; O88811; -.
DR PRIDE; O88811; -.
DR ProteomicsDB; 258656; -. [O88811-1]
DR ProteomicsDB; 258657; -. [O88811-2]
DR Antibodypedia; 33682; 369 antibodies from 36 providers.
DR DNASU; 56324; -.
DR Ensembl; ENSMUST00000102759; ENSMUSP00000099820; ENSMUSG00000055371. [O88811-1]
DR Ensembl; ENSMUST00000127316; ENSMUSP00000121898; ENSMUSG00000055371. [O88811-2]
DR GeneID; 56324; -.
DR KEGG; mmu:56324; -.
DR UCSC; uc008jre.1; mouse. [O88811-1]
DR UCSC; uc008jrf.1; mouse. [O88811-2]
DR CTD; 10254; -.
DR MGI; MGI:1929100; Stam2.
DR VEuPathDB; HostDB:ENSMUSG00000055371; -.
DR eggNOG; KOG2199; Eukaryota.
DR GeneTree; ENSGT00940000157055; -.
DR HOGENOM; CLU_010104_0_2_1; -.
DR InParanoid; O88811; -.
DR OMA; FASEVRV; -.
DR PhylomeDB; O88811; -.
DR TreeFam; TF315007; -.
DR Reactome; R-MMU-182971; EGFR downregulation.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
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; 56324; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Stam2; mouse.
DR EvolutionaryTrace; O88811; -.
DR PRO; PR:O88811; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; O88811; protein.
DR Bgee; ENSMUSG00000055371; Expressed in spermatid and 260 other tissues.
DR ExpressionAtlas; O88811; baseline and differential.
DR Genevisible; O88811; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030139; C:endocytic vesicle; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0043130; F:ubiquitin binding; IEA:InterPro.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd11963; SH3_STAM2; 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; IPR035675; STAM2_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; SM00726; UIM; 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 3D-structure; Alternative splicing; Cytoplasm; Endosome; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; SH3 domain;
KW Transport.
FT CHAIN 1..523
FT /note="Signal transducing adapter molecule 2"
FT /id="PRO_0000190148"
FT DOMAIN 16..144
FT /note="VHS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00218"
FT DOMAIN 165..184
FT /note="UIM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 202..261
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 360..377
FT /note="ITAM"
FT REGION 219..220
FT /note="Interaction with USP8"
FT /evidence="ECO:0000269|PubMed:10982817"
FT REGION 334..368
FT /note="Interaction with HGS"
FT MOTIF 54..67
FT /note="PxVxL motif"
FT VAR_SEQ 68..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_014849"
FT VAR_SEQ 448
FT /note="S -> R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_014850"
FT VAR_SEQ 449..523
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_014851"
FT MUTAGEN 176
FT /note="L->A: Loss of interaction with UBQLN1; when
FT associated with A-177."
FT /evidence="ECO:0000269|PubMed:16159959"
FT MUTAGEN 177
FT /note="S->A: Loss of interaction with UBQLN1; when
FT associated with A-176."
FT /evidence="ECO:0000269|PubMed:16159959"
FT STRAND 205..211
FT /evidence="ECO:0007829|PDB:1UJ0"
FT STRAND 228..233
FT /evidence="ECO:0007829|PDB:1UJ0"
FT STRAND 236..244
FT /evidence="ECO:0007829|PDB:1UJ0"
FT STRAND 247..252
FT /evidence="ECO:0007829|PDB:1UJ0"
FT HELIX 253..255
FT /evidence="ECO:0007829|PDB:1UJ0"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:1UJ0"
SQ SEQUENCE 523 AA; 57455 MW; CE00B59F10BA0161 CRC64;
MPLFTANPFE QDVEKATNEY NTTEDWSLIM DICDRVGSTP SGAKDCLKAI MKRVNHKVPH
VALQALTLLG ACVANCGKIF HLEVCSRDFA TEVRSVIKNK AHPKVCEKLK SLMVEWSEEF
QKDPQFSLIS ATIKSMKEEG VTFPSAGSQT VAAAAKNGTS LNKNKEDEDI AKAIELSLQE
QKQQYTETKA LYPPAESQLN NKAARRVRAL YDFEAVEDNE LTFKHGELIT VLDDSDANWW
QGENHRGTGL FPSNFVTTDL STEVETATVD KLNVIDDDVE EIKKSEPEPV YIDEGKMDRA
LQILQSIDPK ESKPDSQDLL DLEDVCQQMG PMIDEKLEEI DRKHSELSEL NVKVLEALDL
YNKLVNEAPV YSVYSKLHPA HYPPAAAGVP VQTYPVQSHG GNYLGHGIHQ VSVAQNYNLG
PDPMGSLRSL PPNMNSVTAH TVQPPYLSTG QDTVSNPSYM NQSSRLQAAA GTAAYTQPVG
MSTDVSSFQN TASGLPQLAG FPVAVPAPVA AQPQASYHQQ PLL
