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 01-MAY-2013, entry version 79.
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, AND MUTAGENESIS
RP 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 IPI; IPI00007919; -.
DR IPI; IPI00448630; -.
DR RefSeq; NP_055892.2; NM_015077.2.
DR UniGene; Hs.446689; -.
DR ProteinModelPortal; Q6SZW1; -.
DR STRING; 9606.ENSP00000368351; -.
DR PhosphoSite; Q6SZW1; -.
DR DMDM; 83288284; -.
DR PaxDb; Q6SZW1; -.
DR PRIDE; Q6SZW1; -.
DR GeneID; 23098; -.
DR KEGG; hsa:23098; -.
DR UCSC; uc010crl.1; human.
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 OrthoDB; EOG46WZ7W; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; SARM1; human.
DR GenomeRNAi; 23098; -.
DR NextBio; 44273; -.
DR CleanEx; HS_SARM1; -.
DR Genevestigator; Q6SZW1; -.
DR GermOnline; ENSG00000004139; Homo sapiens.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
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; IEA:UniProtKB-KW.
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:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.10.150.50; -; 2.
DR Gene3D; 1.25.10.10; -; 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; SSF48371; ARM-type_fold; 1.
DR SUPFAM; SSF47769; SAM_homology; 1.
DR SUPFAM; SSF52200; TIR; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 2.
DR PROSITE; PS50104; TIR; FALSE_NEG.
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
//
