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Q6SZW1

- SARM1_HUMAN

UniProt

Q6SZW1 - SARM1_HUMAN

Protein

Sterile alpha and TIR motif-containing protein 1

Gene

SARM1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 92 (01 Oct 2014)
      Sequence version 1 (05 Jul 2004)
      Previous versions | rss
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    Functioni

    Negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway which plays a pivotal role in activating axonal degeneration following injury. Promotes Wallerian degeneration an injury-induced axonal death pathway which involves degeneration of an axon distal to the injury site. Can activate neuronal death in response to stress. Regulates dendritic arborization through the MAPK4-JNK pathway. Involved in innate immune response. Inhibits both TICAM1/TRIF- and MYD88-dependent activation of JUN/AP-1, TRIF-dependent activation of NF-kappa-B and IRF3, and the phosphorylation of MAPK14/p38.4 Publications

    GO - Biological processi

    1. innate immune response Source: Reactome
    2. MyD88-independent toll-like receptor signaling pathway Source: Reactome
    3. regulation of dendrite morphogenesis Source: UniProtKB
    4. regulation of neuron death Source: UniProtKB
    5. toll-like receptor 3 signaling pathway Source: Reactome
    6. toll-like receptor 4 signaling pathway Source: Reactome
    7. toll-like receptor signaling pathway Source: Reactome

    Keywords - Biological processi

    Differentiation, Immunity, Innate immunity, Neurogenesis

    Enzyme and pathway databases

    ReactomeiREACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
    REACT_25351. TRAF6 mediated induction of TAK1 complex.
    REACT_25374. IKK complex recruitment mediated by RIP1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sterile alpha and TIR motif-containing protein 1
    Alternative name(s):
    Sterile alpha and Armadillo repeat protein
    Sterile alpha motif domain-containing protein 2
    Short name:
    MyD88-5
    Short name:
    SAM domain-containing protein 2
    Tir-1 homolog
    Gene namesi
    Name:SARM1
    Synonyms:KIAA0524, SAMD2, SARM
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Unplaced

    Organism-specific databases

    HGNCiHGNC:17074. SARM1.

    Subcellular locationi

    Cytoplasm. Cell projectionaxon By similarity. Cell projectiondendrite By similarity. Cell junctionsynapse By similarity. Mitochondrion
    Note: Associated with microtubules.By similarity

    GO - Cellular componenti

    1. axon Source: UniProtKB-SubCell
    2. cell junction Source: UniProtKB-KW
    3. cytoplasm Source: UniProtKB
    4. cytosol Source: Reactome
    5. dendrite Source: UniProtKB
    6. microtubule Source: UniProtKB
    7. mitochondrion Source: UniProtKB
    8. synapse Source: UniProtKB

    Keywords - Cellular componenti

    Cell junction, Cell projection, Cytoplasm, Mitochondrion, Synapse

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi11 – 111K → A: No effect on mitochondrial localization. 1 Publication
    Mutagenesisi14 – 141R → A: Loss in ability to localize to mitochondria and reduction in apoptotic activity. 1 Publication
    Mutagenesisi22 – 221R → A: No effect on mitochondrial localization. 1 Publication
    Mutagenesisi27 – 271R → A: No effect on mitochondrial localization. 1 Publication

    Organism-specific databases

    PharmGKBiPA134971180.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 2727MitochondrionAdd
    BLAST
    Chaini28 – 724697Sterile alpha and TIR motif-containing protein 1PRO_0000097589Add
    BLAST

    Proteomic databases

    MaxQBiQ6SZW1.
    PaxDbiQ6SZW1.
    PRIDEiQ6SZW1.

    PTM databases

    PhosphoSiteiQ6SZW1.

    Expressioni

    Tissue specificityi

    Predominantly expressed in brain, kidney and liver. Expressed at lower level in placenta.2 Publications

    Inductioni

    Up-regulated by lipopolysaccharides (LPS).1 Publication

    Gene expression databases

    CleanExiHS_SARM1.
    GenevestigatoriQ6SZW1.

    Organism-specific databases

    HPAiHPA024359.
    HPA024759.

    Interactioni

    Subunit structurei

    Interacts with TICAM1/TRIF and thereby interferes with TICAM1/TRIF function. Interacts with MAPK10/JNK3 and SDC2 (via cytoplasmic domain) By similarity.By similarity

    Protein-protein interaction databases

    BioGridi116726. 20 interactions.
    STRINGi9606.ENSP00000368351.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6SZW1.
    SMRiQ6SZW1. Positions 412-536.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini412 – 47665SAM 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini486 – 54863SAM 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini559 – 65799TIRAdd
    BLAST

    Sequence similaritiesi

    Contains 2 SAM (sterile alpha motif) domains.PROSITE-ProRule annotation
    Contains 1 TIR domain.Curated

    Keywords - Domaini

    Repeat, Transit peptide

    Phylogenomic databases

    eggNOGiNOG329244.
    HOGENOMiHOG000008460.
    HOVERGENiHBG079166.
    InParanoidiQ6SZW1.
    PhylomeDBiQ6SZW1.

    Family and domain databases

    Gene3Di1.10.150.50. 2 hits.
    1.25.10.10. 1 hit.
    3.40.50.10140. 1 hit.
    InterProiIPR011989. ARM-like.
    IPR016024. ARM-type_fold.
    IPR001660. SAM.
    IPR013761. SAM/pointed.
    IPR011510. SAM_2.
    IPR000157. TIR_dom.
    [Graphical view]
    PfamiPF07647. SAM_2. 2 hits.
    PF13676. TIR_2. 1 hit.
    [Graphical view]
    SMARTiSM00454. SAM. 2 hits.
    SM00255. TIR. 1 hit.
    [Graphical view]
    SUPFAMiSSF47769. SSF47769. 2 hits.
    SSF48371. SSF48371. 1 hit.
    SSF52200. SSF52200. 1 hit.
    PROSITEiPS50105. SAM_DOMAIN. 2 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q6SZW1-1) [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

    MVLTLLLSAY KLCRFFAMSG PRPGAERLAV PGPDGGGGTG PWWAAGGRGP    50
    REVSPGAGTE VQDALERALP ELQQALSALK QAGGARAVGA GLAEVFQLVE 100
    EAWLLPAVGR EVAQGLCDAI RLDGGLDLLL RLLQAPELET RVQAARLLEQ 150
    ILVAENRDRV ARIGLGVILN LAKEREPVEL ARSVAGILEH MFKHSEETCQ 200
    RLVAAGGLDA VLYWCRRTDP ALLRHCALAL GNCALHGGQA VQRRMVEKRA 250
    AEWLFPLAFS KEDELLRLHA CLAVAVLATN KEVEREVERS GTLALVEPLV 300
    ASLDPGRFAR CLVDASDTSQ GRGPDDLQRL VPLLDSNRLE AQCIGAFYLC 350
    AEAAIKSLQG KTKVFSDIGA IQSLKRLVSY STNGTKSALA KRALRLLGEE 400
    VPRPILPSVP SWKEAEVQTW LQQIGFSKYC ESFREQQVDG DLLLRLTEEE 450
    LQTDLGMKSG ITRKRFFREL TELKTFANYS TCDRSNLADW LGSLDPRFRQ 500
    YTYGLVSCGL DRSLLHRVSE QQLLEDCGIH LGVHRARILT AAREMLHSPL 550
    PCTGGKPSGD TPDVFISYRR NSGSQLASLL KVHLQLHGFS VFIDVEKLEA 600
    GKFEDKLIQS VMGARNFVLV LSPGALDKCM QDHDCKDWVH KEIVTALSCG 650
    KNIVPIIDGF EWPEPQVLPE DMQAVLTFNG IKWSHEYQEA TIEKIIRFLQ 700
    GRSSRDSSAG SDTSLEGAAP MGPT 724
    Length:724
    Mass (Da):79,388
    Last modified:July 5, 2004 - v1
    Checksum:i6391EA4C31EF6604
    GO
    Isoform 2 (identifier: Q6SZW1-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-106: MVLTLLLSAY...QLVEEAWLLP → MGAVARAHGG...PTGGGGLAAA

    Show »
    Length:690
    Mass (Da):75,337
    Checksum:i18E0005AF7A7B1C5
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti23 – 231P → R.
    Corresponds to variant rs7212814 [ dbSNP | Ensembl ].
    VAR_061702

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 106106MVLTL…AWLLP → MGAVARAHGGLRVARARESV AGGRHRGAGRPGARAAGAAA GLVRAEAGGRRAGRGRRPGR GLPTGGGGLAAA in isoform 2. 1 PublicationVSP_013603Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ290445 mRNA. Translation: CAB90355.1.
    AY444166 mRNA. Translation: AAR17520.1.
    AB011096 mRNA. Translation: BAA25450.1.
    RefSeqiNP_055892.2. NM_015077.3. [Q6SZW1-1]
    UniGeneiHs.743510.

    Genome annotation databases

    GeneIDi23098.
    KEGGihsa:23098.
    UCSCiuc010crl.1. human. [Q6SZW1-1]

    Polymorphism databases

    DMDMi83288284.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ290445 mRNA. Translation: CAB90355.1 .
    AY444166 mRNA. Translation: AAR17520.1 .
    AB011096 mRNA. Translation: BAA25450.1 .
    RefSeqi NP_055892.2. NM_015077.3. [Q6SZW1-1 ]
    UniGenei Hs.743510.

    3D structure databases

    ProteinModelPortali Q6SZW1.
    SMRi Q6SZW1. Positions 412-536.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116726. 20 interactions.
    STRINGi 9606.ENSP00000368351.

    PTM databases

    PhosphoSitei Q6SZW1.

    Polymorphism databases

    DMDMi 83288284.

    Proteomic databases

    MaxQBi Q6SZW1.
    PaxDbi Q6SZW1.
    PRIDEi Q6SZW1.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 23098.
    KEGGi hsa:23098.
    UCSCi uc010crl.1. human. [Q6SZW1-1 ]

    Organism-specific databases

    CTDi 23098.
    GeneCardsi GC17P026698.
    H-InvDB HIX0013645.
    HGNCi HGNC:17074. SARM1.
    HPAi HPA024359.
    HPA024759.
    MIMi 607732. gene.
    neXtProti NX_Q6SZW1.
    PharmGKBi PA134971180.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG329244.
    HOGENOMi HOG000008460.
    HOVERGENi HBG079166.
    InParanoidi Q6SZW1.
    PhylomeDBi Q6SZW1.

    Enzyme and pathway databases

    Reactomei REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
    REACT_25351. TRAF6 mediated induction of TAK1 complex.
    REACT_25374. IKK complex recruitment mediated by RIP1.

    Miscellaneous databases

    ChiTaRSi SARM1. human.
    GenomeRNAii 23098.
    NextBioi 44273.
    PROi Q6SZW1.
    SOURCEi Search...

    Gene expression databases

    CleanExi HS_SARM1.
    Genevestigatori Q6SZW1.

    Family and domain databases

    Gene3Di 1.10.150.50. 2 hits.
    1.25.10.10. 1 hit.
    3.40.50.10140. 1 hit.
    InterProi IPR011989. ARM-like.
    IPR016024. ARM-type_fold.
    IPR001660. SAM.
    IPR013761. SAM/pointed.
    IPR011510. SAM_2.
    IPR000157. TIR_dom.
    [Graphical view ]
    Pfami PF07647. SAM_2. 2 hits.
    PF13676. TIR_2. 1 hit.
    [Graphical view ]
    SMARTi SM00454. SAM. 2 hits.
    SM00255. TIR. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47769. SSF47769. 2 hits.
    SSF48371. SSF48371. 1 hit.
    SSF52200. SSF52200. 1 hit.
    PROSITEi PS50105. SAM_DOMAIN. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A novel human gene (SARM) at chromosome 17q11 encodes a protein with a SAM motif and structural similarity to Armadillo/beta-catenin that is conserved in mouse, Drosophila, and Caenorhabditis elegans."
      Mink M., Fogelgren B., Olszewski K., Maroy P., Csiszar K.
      Genomics 74:234-244(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
      Tissue: Brain.
    2. "SARM1 isoforms nucleotide sequence."
      Bousson J.-C., Casteran C., Tiraby G.
      Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
      Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
      DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 127-724.
      Tissue: Brain.
    4. "Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response."
      Liberati N.T., Fitzgerald K.A., Kim D.H., Feinbaum R., Golenbock D.T., Ausubel F.M.
      Proc. Natl. Acad. Sci. U.S.A. 101:6593-6598(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling."
      Carty M., Goodbody R., Schroeder M., Stack J., Moynagh P.N., Bowie A.G.
      Nat. Immunol. 7:1074-1081(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH TICAM1.
    6. "DisSARMing Toll-like receptor signaling."
      O'Neill L.A.J.
      Nat. Immunol. 7:1023-1025(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival."
      Kim Y., Zhou P., Qian L., Chuang J.Z., Lee J., Li C., Iadecola C., Nathan C., Ding A.
      J. Exp. Med. 204:2063-2074(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    8. "Studies of SARM1 uncover similarities between immune and neuronal responses to danger."
      Dalod M.
      Sci. STKE 2007:PE73-PE73(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    9. Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION.
    10. "Targeting of pro-apoptotic TLR adaptor SARM to mitochondria: definition of the critical region and residues in the signal sequence."
      Panneerselvam P., Singh L.P., Ho B., Chen J., Ding J.L.
      Biochem. J. 442:263-271(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, MITOCHONDRIAL TRANSIT PEPTIDE CLEAVAGE SITE, MUTAGENESIS OF LYS-11; ARG-14; ARG-22 AND ARG-27.

    Entry informationi

    Entry nameiSARM1_HUMAN
    AccessioniPrimary (citable) accession number: Q6SZW1
    Secondary accession number(s): O60277, Q7LGG3, Q9NXY5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 10, 2005
    Last sequence update: July 5, 2004
    Last modified: October 1, 2014
    This is version 92 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Caution

    Was initially (PubMed:11386760) reported to contain ARM repeats. Such repeats are however not predicted by any detection method.1 Publication

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3