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Q6SZW1

- SARM1_HUMAN

UniProt

Q6SZW1 - SARM1_HUMAN

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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

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 apoptotic process Source: Ensembl
  4. regulation of dendrite morphogenesis Source: UniProtKB
  5. regulation of neuron death Source: UniProtKB
  6. response to glucose Source: Ensembl
  7. toll-like receptor 3 signaling pathway Source: Reactome
  8. toll-like receptor 4 signaling pathway Source: Reactome
  9. toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

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: Chromosome 17

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. cell junction Source: UniProtKB-KW
  2. cytoplasm Source: UniProtKB
  3. cytosol Source: Reactome
  4. dendrite Source: UniProtKB
  5. extrinsic component of mitochondrial outer membrane Source: Ensembl
  6. microtubule Source: UniProtKB
  7. mitochondrion Source: UniProtKB
  8. synapse Source: UniProtKB
Complete GO annotation...

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.
ExpressionAtlasiQ6SZW1. baseline and differential.
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. 21 interactions.
STRINGi9606.ENSP00000368351.

Structurei

3D structure databases

ProteinModelPortaliQ6SZW1.
SMRiQ6SZW1. Positions 113-397, 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.
GeneTreeiENSGT00390000004155.
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

        10         20         30         40         50
MVLTLLLSAY KLCRFFAMSG PRPGAERLAV PGPDGGGGTG PWWAAGGRGP
60 70 80 90 100
REVSPGAGTE VQDALERALP ELQQALSALK QAGGARAVGA GLAEVFQLVE
110 120 130 140 150
EAWLLPAVGR EVAQGLCDAI RLDGGLDLLL RLLQAPELET RVQAARLLEQ
160 170 180 190 200
ILVAENRDRV ARIGLGVILN LAKEREPVEL ARSVAGILEH MFKHSEETCQ
210 220 230 240 250
RLVAAGGLDA VLYWCRRTDP ALLRHCALAL GNCALHGGQA VQRRMVEKRA
260 270 280 290 300
AEWLFPLAFS KEDELLRLHA CLAVAVLATN KEVEREVERS GTLALVEPLV
310 320 330 340 350
ASLDPGRFAR CLVDASDTSQ GRGPDDLQRL VPLLDSNRLE AQCIGAFYLC
360 370 380 390 400
AEAAIKSLQG KTKVFSDIGA IQSLKRLVSY STNGTKSALA KRALRLLGEE
410 420 430 440 450
VPRPILPSVP SWKEAEVQTW LQQIGFSKYC ESFREQQVDG DLLLRLTEEE
460 470 480 490 500
LQTDLGMKSG ITRKRFFREL TELKTFANYS TCDRSNLADW LGSLDPRFRQ
510 520 530 540 550
YTYGLVSCGL DRSLLHRVSE QQLLEDCGIH LGVHRARILT AAREMLHSPL
560 570 580 590 600
PCTGGKPSGD TPDVFISYRR NSGSQLASLL KVHLQLHGFS VFIDVEKLEA
610 620 630 640 650
GKFEDKLIQS VMGARNFVLV LSPGALDKCM QDHDCKDWVH KEIVTALSCG
660 670 680 690 700
KNIVPIIDGF EWPEPQVLPE DMQAVLTFNG IKWSHEYQEA TIEKIIRFLQ
710 720
GRSSRDSSAG SDTSLEGAAP MGPT
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:
EMBLi
GenBanki
DDBJi
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

EnsembliENST00000585482; ENSP00000468032; ENSG00000004139. [Q6SZW1-1]
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:
EMBLi
GenBanki
DDBJi
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 113-397, 412-536.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 116726. 21 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

Ensembli ENST00000585482 ; ENSP00000468032 ; ENSG00000004139 . [Q6SZW1-1 ]
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.
GeneTreei ENSGT00390000004155.
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.
ExpressionAtlasi Q6SZW1. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 94 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