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O88811

- STAM2_MOUSE

UniProt

O88811 - STAM2_MOUSE

Protein

Signal transducing adapter molecule 2

Gene

Stam2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 1 (01 Nov 1998)
      Previous versions | rss
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    Functioni

    Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes By similarity.By similarity

    GO - Molecular functioni

    1. protein binding Source: MGI

    GO - Biological processi

    1. intracellular protein transport Source: InterPro

    Keywords - Biological processi

    Protein transport, Transport

    Enzyme and pathway databases

    ReactomeiREACT_198518. Endosomal Sorting Complex Required For Transport (ESCRT).
    REACT_203917. EGFR downregulation.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Signal transducing adapter molecule 2
    Short name:
    STAM-2
    Alternative name(s):
    Hrs-binding protein
    Gene namesi
    Name:Stam2
    Synonyms:Hbp
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:1929100. Stam2.

    Subcellular locationi

    Cytoplasm 2 Publications. Early endosome membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity

    GO - Cellular componenti

    1. early endosome membrane Source: UniProtKB-SubCell
    2. nucleus Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Endosome, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Adult mice lacking Stam1 and Stam2 due to inducible gene targeting exhibit significant reduction in T-cell development in the thymus and profound reduction in the peripheral mature T-cells.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 523523Signal transducing adapter molecule 2PRO_0000190148Add
    BLAST

    Post-translational modificationi

    Phosphorylated in response to IL-2, GM-CSF, EGF and PDGF.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO88811.
    PaxDbiO88811.
    PRIDEiO88811.

    PTM databases

    PhosphoSiteiO88811.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed, with highest levels in testis.1 Publication

    Gene expression databases

    ArrayExpressiO88811.
    BgeeiO88811.
    GenevestigatoriO88811.

    Interactioni

    Subunit structurei

    Component of the ESCRT-0 complex composed of STAM or STAM2 and HGS. Part of a complex at least composed of HSG, STAM2 and EPS15. Interacts with JAK2 and JAK3. Interacts with ubiquitinated proteins and the deubiquitinating enzyme USP8/UBPY. Interacts (via the via the PxVxL motif) with CBX5; the interaction is direct. Interacts with VPS37C. Interacts with ubiquitin; the interaction is direct By similarity.By similarity

    Protein-protein interaction databases

    BioGridi207904. 8 interactions.
    IntActiO88811. 5 interactions.
    MINTiMINT-144894.

    Structurei

    Secondary structure

    1
    523
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi205 – 2117
    Beta strandi228 – 2336
    Beta strandi236 – 2449
    Beta strandi247 – 2526
    Helixi253 – 2553
    Beta strandi256 – 2583

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1UJ0X-ray1.70A204-261[»]
    ProteinModelPortaliO88811.
    SMRiO88811. Positions 1-150, 204-379.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO88811.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini16 – 144129VHSPROSITE-ProRule annotationAdd
    BLAST
    Repeati165 – 18420UIMAdd
    BLAST
    Domaini202 – 26160SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini360 – 37718ITAMAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni219 – 2202Interaction with USP8
    Regioni334 – 36835Interaction with HGSAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi54 – 6714PxVxL motifAdd
    BLAST

    Domaini

    The VHS and UIM domains mediate the interaction with ubiquitinated proteins.1 Publication
    The SH3 domain mediates the interaction with USP8.1 Publication
    Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain.1 Publication

    Sequence similaritiesi

    Belongs to the STAM family.Curated
    Contains 1 ITAM domain.Curated
    Contains 1 SH3 domain.PROSITE-ProRule annotation
    Contains 1 UIM (ubiquitin-interacting motif) repeat.PROSITE-ProRule annotation
    Contains 1 VHS domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH3 domain

    Phylogenomic databases

    eggNOGiNOG309509.
    GeneTreeiENSGT00700000104139.
    HOGENOMiHOG000231952.
    HOVERGENiHBG053175.
    InParanoidiO88811.
    KOiK04705.
    OMAiHYPPASS.
    OrthoDBiEOG7353WJ.
    PhylomeDBiO88811.
    TreeFamiTF315007.

    Family and domain databases

    Gene3Di1.25.40.90. 1 hit.
    InterProiIPR008942. ENTH_VHS.
    IPR001452. SH3_domain.
    IPR003903. Ubiquitin-int_motif.
    IPR002014. VHS.
    IPR018205. VHS_subgr.
    [Graphical view]
    PfamiPF00018. SH3_1. 1 hit.
    PF02809. UIM. 1 hit.
    PF00790. VHS. 1 hit.
    [Graphical view]
    PRINTSiPR00452. SH3DOMAIN.
    SMARTiSM00326. SH3. 1 hit.
    SM00726. UIM. 1 hit.
    SM00288. VHS. 1 hit.
    [Graphical view]
    SUPFAMiSSF48464. SSF48464. 1 hit.
    SSF50044. SSF50044. 1 hit.
    PROSITEiPS50002. SH3. 1 hit.
    PS50330. UIM. 1 hit.
    PS50179. VHS. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O88811-1) [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

    MPLFTANPFE QDVEKATNEY NTTEDWSLIM DICDRVGSTP SGAKDCLKAI    50
    MKRVNHKVPH VALQALTLLG ACVANCGKIF HLEVCSRDFA TEVRSVIKNK 100
    AHPKVCEKLK SLMVEWSEEF QKDPQFSLIS ATIKSMKEEG VTFPSAGSQT 150
    VAAAAKNGTS LNKNKEDEDI AKAIELSLQE QKQQYTETKA LYPPAESQLN 200
    NKAARRVRAL YDFEAVEDNE LTFKHGELIT VLDDSDANWW QGENHRGTGL 250
    FPSNFVTTDL STEVETATVD KLNVIDDDVE EIKKSEPEPV YIDEGKMDRA 300
    LQILQSIDPK ESKPDSQDLL DLEDVCQQMG PMIDEKLEEI DRKHSELSEL 350
    NVKVLEALDL YNKLVNEAPV YSVYSKLHPA HYPPAAAGVP VQTYPVQSHG 400
    GNYLGHGIHQ VSVAQNYNLG PDPMGSLRSL PPNMNSVTAH TVQPPYLSTG 450
    QDTVSNPSYM NQSSRLQAAA GTAAYTQPVG MSTDVSSFQN TASGLPQLAG 500
    FPVAVPAPVA AQPQASYHQQ PLL 523
    Length:523
    Mass (Da):57,455
    Last modified:November 1, 1998 - v1
    Checksum:iCE00B59F10BA0161
    GO
    Isoform 2 (identifier: O88811-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         68-100: Missing.
         448-448: S → R
         449-523: Missing.

    Show »
    Length:415
    Mass (Da):46,260
    Checksum:i305B94A59C0CA08B
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei68 – 10033Missing in isoform 2. 1 PublicationVSP_014849Add
    BLAST
    Alternative sequencei448 – 4481S → R in isoform 2. 1 PublicationVSP_014850
    Alternative sequencei449 – 52375Missing in isoform 2. 1 PublicationVSP_014851Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB012611 mRNA. Translation: BAA33547.1.
    AK004604 mRNA. Translation: BAB23403.1.
    AK044230 mRNA. Translation: BAC31830.1.
    AL928960 Genomic DNA. Translation: CAM23666.1.
    BC013818 mRNA. Translation: AAH13818.1.
    CCDSiCCDS16037.1. [O88811-1]
    RefSeqiNP_062641.1. NM_019667.2. [O88811-1]
    UniGeneiMm.263639.

    Genome annotation databases

    EnsembliENSMUST00000102759; ENSMUSP00000099820; ENSMUSG00000055371. [O88811-1]
    ENSMUST00000127316; ENSMUSP00000121898; ENSMUSG00000055371. [O88811-2]
    GeneIDi56324.
    KEGGimmu:56324.
    UCSCiuc008jre.1. mouse. [O88811-1]
    uc008jrf.1. mouse. [O88811-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB012611 mRNA. Translation: BAA33547.1 .
    AK004604 mRNA. Translation: BAB23403.1 .
    AK044230 mRNA. Translation: BAC31830.1 .
    AL928960 Genomic DNA. Translation: CAM23666.1 .
    BC013818 mRNA. Translation: AAH13818.1 .
    CCDSi CCDS16037.1. [O88811-1 ]
    RefSeqi NP_062641.1. NM_019667.2. [O88811-1 ]
    UniGenei Mm.263639.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1UJ0 X-ray 1.70 A 204-261 [» ]
    ProteinModelPortali O88811.
    SMRi O88811. Positions 1-150, 204-379.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 207904. 8 interactions.
    IntActi O88811. 5 interactions.
    MINTi MINT-144894.

    PTM databases

    PhosphoSitei O88811.

    Proteomic databases

    MaxQBi O88811.
    PaxDbi O88811.
    PRIDEi O88811.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000102759 ; ENSMUSP00000099820 ; ENSMUSG00000055371 . [O88811-1 ]
    ENSMUST00000127316 ; ENSMUSP00000121898 ; ENSMUSG00000055371 . [O88811-2 ]
    GeneIDi 56324.
    KEGGi mmu:56324.
    UCSCi uc008jre.1. mouse. [O88811-1 ]
    uc008jrf.1. mouse. [O88811-2 ]

    Organism-specific databases

    CTDi 10254.
    MGIi MGI:1929100. Stam2.

    Phylogenomic databases

    eggNOGi NOG309509.
    GeneTreei ENSGT00700000104139.
    HOGENOMi HOG000231952.
    HOVERGENi HBG053175.
    InParanoidi O88811.
    KOi K04705.
    OMAi HYPPASS.
    OrthoDBi EOG7353WJ.
    PhylomeDBi O88811.
    TreeFami TF315007.

    Enzyme and pathway databases

    Reactomei REACT_198518. Endosomal Sorting Complex Required For Transport (ESCRT).
    REACT_203917. EGFR downregulation.

    Miscellaneous databases

    ChiTaRSi STAM2. mouse.
    EvolutionaryTracei O88811.
    NextBioi 312298.
    PROi O88811.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O88811.
    Bgeei O88811.
    Genevestigatori O88811.

    Family and domain databases

    Gene3Di 1.25.40.90. 1 hit.
    InterProi IPR008942. ENTH_VHS.
    IPR001452. SH3_domain.
    IPR003903. Ubiquitin-int_motif.
    IPR002014. VHS.
    IPR018205. VHS_subgr.
    [Graphical view ]
    Pfami PF00018. SH3_1. 1 hit.
    PF02809. UIM. 1 hit.
    PF00790. VHS. 1 hit.
    [Graphical view ]
    PRINTSi PR00452. SH3DOMAIN.
    SMARTi SM00326. SH3. 1 hit.
    SM00726. UIM. 1 hit.
    SM00288. VHS. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48464. SSF48464. 1 hit.
    SSF50044. SSF50044. 1 hit.
    PROSITEi PS50002. SH3. 1 hit.
    PS50330. UIM. 1 hit.
    PS50179. VHS. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A hrs binding protein having a Src homology 3 domain is involved in intracellular degradation of growth factors and their receptors."
      Takata H., Kato M., Denda K., Kitamura N.
      Genes Cells 5:57-69(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH HGS, DOMAIN, SUBCELLULAR LOCATION.
      Tissue: Liver.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
      Strain: C57BL/6J.
      Tissue: Lung.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    4. "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] (ISOFORM 1).
      Strain: FVB/N.
      Tissue: Mammary tumor.
    5. "A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP."
      Kato M., Miyazawa K., Kitamura N.
      J. Biol. Chem. 275:37481-37487(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH USP8.
    6. "Signal-transducing adaptor molecules STAM1 and STAM2 are required for T-cell development and survival."
      Yamada M., Ishii N., Asao H., Murata K., Kanazawa C., Sasaki H., Sugamura K.
      Mol. Cell. Biol. 22:8648-8658(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    7. "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes."
      Bache K.G., Raiborg C., Mehlum A., Stenmark H.
      J. Biol. Chem. 278:12513-12521(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HGS; EPS15 AND UBIQUITIN, SUBCELLULAR LOCATION.
    8. "STAM proteins bind ubiquitinated proteins on the early endosome via the VHS domain and ubiquitin-interacting motif."
      Mizuno E., Kawahata K., Kato M., Kitamura N., Komada M.
      Mol. Biol. Cell 14:3675-3689(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH UBIQUITIN, FUNCTION.
    9. "Structural insight into modest binding of a non-PXXP ligand to the signal transducing adaptor molecule-2 Src homology 3 domain."
      Kaneko T., Kumasaka T., Ganbe T., Sato T., Miyazawa K., Kitamura N., Tanaka N.
      J. Biol. Chem. 278:48162-48168(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 203-260 IN COMPLEX WITH USP8.

    Entry informationi

    Entry nameiSTAM2_MOUSE
    AccessioniPrimary (citable) accession number: O88811
    Secondary accession number(s): A2AU00, Q8C8Y4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2005
    Last sequence update: November 1, 1998
    Last modified: October 1, 2014
    This is version 122 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3