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Database: UniProt
Entry: Q6SZW1
LinkDB: Q6SZW1
Original site: Q6SZW1 
ID   SARM1_HUMAN             Reviewed;         724 AA.
AC   Q6SZW1; O60277; Q7LGG3; Q9NXY5;
DT   10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   03-SEP-2014, entry version 91.
DE   RecName: Full=Sterile alpha and TIR motif-containing protein 1;
DE   AltName: Full=Sterile alpha and Armadillo repeat protein;
DE   AltName: Full=Sterile alpha motif domain-containing protein 2;
DE            Short=MyD88-5;
DE            Short=SAM domain-containing protein 2;
DE   AltName: Full=Tir-1 homolog;
DE   Flags: Precursor;
GN   Name=SARM1; Synonyms=KIAA0524, SAMD2, SARM;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=11386760; DOI=10.1006/geno.2001.6548;
RA   Mink M., Fogelgren B., Olszewski K., Maroy P., Csiszar K.;
RT   "A novel human gene (SARM) at chromosome 17q11 encodes a protein with
RT   a SAM motif and structural similarity to Armadillo/beta-catenin that
RT   is conserved in mouse, Drosophila, and Caenorhabditis elegans.";
RL   Genomics 74:234-244(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Bousson J.-C., Casteran C., Tiraby G.;
RT   "SARM1 isoforms nucleotide sequence.";
RL   Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 127-724.
RC   TISSUE=Brain;
RX   PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA   Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA   Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. IX.
RT   The complete sequences of 100 new cDNA clones from brain which can
RT   code for large proteins in vitro.";
RL   DNA Res. 5:31-39(1998).
RN   [4]
RP   FUNCTION.
RX   PubMed=15123841; DOI=10.1073/pnas.0308625101;
RA   Liberati N.T., Fitzgerald K.A., Kim D.H., Feinbaum R., Golenbock D.T.,
RA   Ausubel F.M.;
RT   "Requirement for a conserved Toll/interleukin-1 resistance domain
RT   protein in the Caenorhabditis elegans immune response.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:6593-6598(2004).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH TICAM1.
RX   PubMed=16964262; DOI=10.1038/ni1382;
RA   Carty M., Goodbody R., Schroeder M., Stack J., Moynagh P.N.,
RA   Bowie A.G.;
RT   "The human adaptor SARM negatively regulates adaptor protein TRIF-
RT   dependent Toll-like receptor signaling.";
RL   Nat. Immunol. 7:1074-1081(2006).
RN   [6]
RP   FUNCTION.
RX   PubMed=16985498; DOI=10.1038/ni1006-1023;
RA   O'Neill L.A.J.;
RT   "DisSARMing Toll-like receptor signaling.";
RL   Nat. Immunol. 7:1023-1025(2006).
RN   [7]
RP   TISSUE SPECIFICITY.
RX   PubMed=17724133; DOI=10.1084/jem.20070868;
RA   Kim Y., Zhou P., Qian L., Chuang J.Z., Lee J., Li C., Iadecola C.,
RA   Nathan C., Ding A.;
RT   "MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and
RT   regulates neuronal survival.";
RL   J. Exp. Med. 204:2063-2074(2007).
RN   [8]
RP   REVIEW.
RX   PubMed=18089857; DOI=10.1126/stke.4172007pe73;
RA   Dalod M.;
RT   "Studies of SARM1 uncover similarities between immune and neuronal
RT   responses to danger.";
RL   Sci. STKE 2007:PE73-PE73(2007).
RN   [9]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX   PubMed=20306472; DOI=10.1002/eji.200940034;
RA   Peng J., Yuan Q., Lin B., Panneerselvam P., Wang X., Luan X.L.,
RA   Lim S.K., Leung B.P., Ho B., Ding J.L.;
RT   "SARM inhibits both TRIF- and MyD88-mediated AP-1 activation.";
RL   Eur. J. Immunol. 40:1738-1747(2010).
RN   [10]
RP   SUBCELLULAR LOCATION, MITOCHONDRIAL TRANSIT PEPTIDE CLEAVAGE SITE, AND
RP   MUTAGENESIS OF LYS-11; ARG-14; ARG-22 AND ARG-27.
RX   PubMed=22145856; DOI=10.1042/BJ20111653;
RA   Panneerselvam P., Singh L.P., Ho B., Chen J., Ding J.L.;
RT   "Targeting of pro-apoptotic TLR adaptor SARM to mitochondria:
RT   definition of the critical region and residues in the signal
RT   sequence.";
RL   Biochem. J. 442:263-271(2012).
CC   -!- FUNCTION: Negative regulator of MYD88- and TRIF-dependent toll-
CC       like receptor signaling pathway which plays a pivotal role in
CC       activating axonal degeneration following injury. Promotes
CC       Wallerian degeneration an injury-induced axonal death pathway
CC       which involves degeneration of an axon distal to the injury site.
CC       Can activate neuronal death in response to stress. Regulates
CC       dendritic arborization through the MAPK4-JNK pathway. Involved in
CC       innate immune response. Inhibits both TICAM1/TRIF- and MYD88-
CC       dependent activation of JUN/AP-1, TRIF-dependent activation of NF-
CC       kappa-B and IRF3, and the phosphorylation of MAPK14/p38.
CC   -!- SUBUNIT: Interacts with TICAM1/TRIF and thereby interferes with
CC       TICAM1/TRIF function. Interacts with MAPK10/JNK3 and SDC2 (via
CC       cytoplasmic domain) (By similarity).
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Cell projection, axon (By
CC       similarity). Cell projection, dendrite (By similarity). Cell
CC       junction, synapse (By similarity). Mitochondrion. Note=Associated
CC       with microtubules (By similarity).
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q6SZW1-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q6SZW1-2; Sequence=VSP_013603;
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in brain, kidney and
CC       liver. Expressed at lower level in placenta.
CC   -!- INDUCTION: Up-regulated by lipopolysaccharides (LPS).
CC   -!- SIMILARITY: Contains 2 SAM (sterile alpha motif) domains.
CC   -!- SIMILARITY: Contains 1 TIR domain.
CC   -!- CAUTION: Was initially (PubMed:11386760) reported to contain ARM
CC       repeats. Such repeats are however not predicted by any detection
CC       method.
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DR   EMBL; AJ290445; CAB90355.1; -; mRNA.
DR   EMBL; AY444166; AAR17520.1; -; mRNA.
DR   EMBL; AB011096; BAA25450.1; -; mRNA.
DR   RefSeq; NP_055892.2; NM_015077.3. [Q6SZW1-1]
DR   UniGene; Hs.743510; -.
DR   ProteinModelPortal; Q6SZW1; -.
DR   SMR; Q6SZW1; 412-536.
DR   BioGrid; 116726; 20.
DR   STRING; 9606.ENSP00000368351; -.
DR   PhosphoSite; Q6SZW1; -.
DR   DMDM; 83288284; -.
DR   MaxQB; Q6SZW1; -.
DR   PaxDb; Q6SZW1; -.
DR   PRIDE; Q6SZW1; -.
DR   GeneID; 23098; -.
DR   KEGG; hsa:23098; -.
DR   UCSC; uc010crl.1; human. [Q6SZW1-1]
DR   CTD; 23098; -.
DR   GeneCards; GC17P026698; -.
DR   H-InvDB; HIX0013645; -.
DR   HGNC; HGNC:17074; SARM1.
DR   HPA; HPA024359; -.
DR   HPA; HPA024759; -.
DR   MIM; 607732; gene.
DR   neXtProt; NX_Q6SZW1; -.
DR   PharmGKB; PA134971180; -.
DR   eggNOG; NOG329244; -.
DR   HOGENOM; HOG000008460; -.
DR   HOVERGEN; HBG079166; -.
DR   InParanoid; Q6SZW1; -.
DR   PhylomeDB; Q6SZW1; -.
DR   Reactome; REACT_25148; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR   Reactome; REACT_25351; TRAF6 mediated induction of TAK1 complex.
DR   Reactome; REACT_25374; IKK complex recruitment mediated by RIP1.
DR   ChiTaRS; SARM1; human.
DR   GenomeRNAi; 23098; -.
DR   NextBio; 44273; -.
DR   PRO; PR:Q6SZW1; -.
DR   CleanEx; HS_SARM1; -.
DR   Genevestigator; Q6SZW1; -.
DR   GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR   GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR   GO; GO:0005874; C:microtubule; ISS:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0045202; C:synapse; ISS:UniProtKB.
DR   GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR   GO; GO:0002756; P:MyD88-independent toll-like receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0048814; P:regulation of dendrite morphogenesis; ISS:UniProtKB.
DR   GO; GO:1901214; P:regulation of neuron death; ISS:UniProtKB.
DR   GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
DR   GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR   GO; GO:0002224; P:toll-like receptor signaling pathway; TAS:Reactome.
DR   Gene3D; 1.10.150.50; -; 2.
DR   Gene3D; 1.25.10.10; -; 1.
DR   Gene3D; 3.40.50.10140; -; 1.
DR   InterPro; IPR011989; ARM-like.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR001660; SAM.
DR   InterPro; IPR013761; SAM/pointed.
DR   InterPro; IPR011510; SAM_2.
DR   InterPro; IPR000157; TIR_dom.
DR   Pfam; PF07647; SAM_2; 2.
DR   Pfam; PF13676; TIR_2; 1.
DR   SMART; SM00454; SAM; 2.
DR   SMART; SM00255; TIR; 1.
DR   SUPFAM; SSF47769; SSF47769; 2.
DR   SUPFAM; SSF48371; SSF48371; 1.
DR   SUPFAM; SSF52200; SSF52200; 1.
DR   PROSITE; PS50105; SAM_DOMAIN; 2.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell junction; Cell projection;
KW   Complete proteome; Cytoplasm; Differentiation; Immunity;
KW   Innate immunity; Mitochondrion; Neurogenesis; Polymorphism;
KW   Reference proteome; Repeat; Synapse; Transit peptide.
FT   TRANSIT       1     27       Mitochondrion.
FT   CHAIN        28    724       Sterile alpha and TIR motif-containing
FT                                protein 1.
FT                                /FTId=PRO_0000097589.
FT   DOMAIN      412    476       SAM 1.
FT   DOMAIN      486    548       SAM 2.
FT   DOMAIN      559    657       TIR.
FT   VAR_SEQ       1    106       MVLTLLLSAYKLCRFFAMSGPRPGAERLAVPGPDGGGGTGP
FT                                WWAAGGRGPREVSPGAGTEVQDALERALPELQQALSALKQA
FT                                GGARAVGAGLAEVFQLVEEAWLLP -> MGAVARAHGGLRV
FT                                ARARESVAGGRHRGAGRPGARAAGAAAGLVRAEAGGRRAGR
FT                                GRRPGRGLPTGGGGLAAA (in isoform 2).
FT                                /FTId=VSP_013603.
FT   VARIANT      23     23       P -> R (in dbSNP:rs7212814).
FT                                /FTId=VAR_061702.
FT   MUTAGEN      11     11       K->A: No effect on mitochondrial
FT                                localization.
FT   MUTAGEN      14     14       R->A: Loss in ability to localize to
FT                                mitochondria and reduction in apoptotic
FT                                activity.
FT   MUTAGEN      22     22       R->A: No effect on mitochondrial
FT                                localization.
FT   MUTAGEN      27     27       R->A: No effect on mitochondrial
FT                                localization.
SQ   SEQUENCE   724 AA;  79388 MW;  6391EA4C31EF6604 CRC64;
     MVLTLLLSAY KLCRFFAMSG PRPGAERLAV PGPDGGGGTG PWWAAGGRGP REVSPGAGTE
     VQDALERALP ELQQALSALK QAGGARAVGA GLAEVFQLVE EAWLLPAVGR EVAQGLCDAI
     RLDGGLDLLL RLLQAPELET RVQAARLLEQ ILVAENRDRV ARIGLGVILN LAKEREPVEL
     ARSVAGILEH MFKHSEETCQ RLVAAGGLDA VLYWCRRTDP ALLRHCALAL GNCALHGGQA
     VQRRMVEKRA AEWLFPLAFS KEDELLRLHA CLAVAVLATN KEVEREVERS GTLALVEPLV
     ASLDPGRFAR CLVDASDTSQ GRGPDDLQRL VPLLDSNRLE AQCIGAFYLC AEAAIKSLQG
     KTKVFSDIGA IQSLKRLVSY STNGTKSALA KRALRLLGEE VPRPILPSVP SWKEAEVQTW
     LQQIGFSKYC ESFREQQVDG DLLLRLTEEE LQTDLGMKSG ITRKRFFREL TELKTFANYS
     TCDRSNLADW LGSLDPRFRQ YTYGLVSCGL DRSLLHRVSE QQLLEDCGIH LGVHRARILT
     AAREMLHSPL PCTGGKPSGD TPDVFISYRR NSGSQLASLL KVHLQLHGFS VFIDVEKLEA
     GKFEDKLIQS VMGARNFVLV LSPGALDKCM QDHDCKDWVH KEIVTALSCG KNIVPIIDGF
     EWPEPQVLPE DMQAVLTFNG IKWSHEYQEA TIEKIIRFLQ GRSSRDSSAG SDTSLEGAAP
     MGPT
//
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