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Protein

Sterile alpha and TIR motif-containing protein 1

Gene

Sarm1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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. Can restrict West Nile virus (WNV) pathogenesis.4 Publications

GO - Biological processi

  • innate immune response Source: UniProtKB-KW
  • regulation of apoptotic process Source: MGI
  • regulation of dendrite morphogenesis Source: UniProtKB
  • regulation of neuron death Source: UniProtKB
  • response to glucose Source: MGI
  • signal transduction Source: GO_Central

Keywordsi

Biological processDifferentiation, Immunity, Innate immunity, Neurogenesis

Enzyme and pathway databases

ReactomeiR-MMU-166166 MyD88-independent TLR4 cascade
R-MMU-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-MMU-937041 IKK complex recruitment mediated by RIP1
R-MMU-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex

Names & Taxonomyi

Protein namesi
Recommended name:
Sterile alpha and TIR motif-containing protein 1
Alternative name(s):
Tir-1 homolog
Short name:
MyD88-5
Gene namesi
Name:Sarm1
Synonyms:Kiaa0524
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:2136419 Sarm1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell projection, Cytoplasm, Mitochondrion, Synapse

Pathology & Biotechi

Disruption phenotypei

Severed Sarm1 null axons are able to persist up to 72 hrs after axotomy, whereas wild-type axons degenerate within 8 hrs. Similarly, axons appear to be protected from degeneration in a sciatic nerve lesion model, lasting up to 14 days compared with 3 days for wild type.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 27MitochondrionBy similarityAdd BLAST27
ChainiPRO_000009759028 – 724Sterile alpha and TIR motif-containing protein 1Add BLAST697

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei548PhosphoserineCombined sources1
Modified residuei558PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PeptideAtlasiQ6PDS3
PRIDEiQ6PDS3

PTM databases

iPTMnetiQ6PDS3
PhosphoSitePlusiQ6PDS3

Expressioni

Tissue specificityi

Widely expressed in the brain and neurons (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000050132
GenevisibleiQ6PDS3 MM

Interactioni

Subunit structurei

Interacts with TICAM1/TRIF and thereby interferes with TICAM1/TRIF function (By similarity). Interacts with SDC2 (via cytoplasmic domain) and MAPK10/JNK3.By similarity2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi231917, 1 interactor
IntActiQ6PDS3, 11 interactors

Structurei

3D structure databases

ProteinModelPortaliQ6PDS3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini412 – 476SAM 1PROSITE-ProRule annotationAdd BLAST65
Domaini486 – 548SAM 2PROSITE-ProRule annotationAdd BLAST63
Domaini559 – 657TIRAdd BLAST99

Keywords - Domaini

Repeat, Transit peptide

Phylogenomic databases

GeneTreeiENSGT00390000004155
HOGENOMiHOG000008460
HOVERGENiHBG079166
InParanoidiQ6PDS3
OMAiCEVQTWL
OrthoDBiEOG091G01TX
PhylomeDBiQ6PDS3
TreeFamiTF315263

Family and domain databases

Gene3Di1.25.10.10, 1 hit
3.40.50.10140, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR001660 SAM
IPR013761 SAM/pointed_sf
IPR000157 TIR_dom
IPR035897 Toll_tir_struct_dom_sf
PfamiView protein in Pfam
PF07647 SAM_2, 2 hits
PF13676 TIR_2, 1 hit
SMARTiView protein in SMART
SM00454 SAM, 2 hits
SM00255 TIR, 1 hit
SUPFAMiSSF47769 SSF47769, 2 hits
SSF48371 SSF48371, 1 hit
SSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS50105 SAM_DOMAIN, 2 hits

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6PDS3-1) [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
MVLTLLFSAY KLCRFFTMSG PRPGADRLTV PGPDRSGGAS PWWAAGGRGS
60 70 80 90 100
REVSPGVGTE VQGALERSLP ELQQALSELK QASAARAVGA 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 ANCALHGGQT VQRCMVEKRA
260 270 280 290 300
AEWLFPLAFS KEDELLRLHA CLAVAVLATN KEVEREVEHS GTLALVEPLV
310 320 330 340 350
ASLDPGRFAR CLVDASDTSQ GRGPDDLQSL VLLLDSSRLE AQCIGAFYLC
360 370 380 390 400
AEAAIKSLQG KTKVFSDIGA IQSLKRLVSY STNGTTSALA KRALRLLGEE
410 420 430 440 450
VPRRILPCVA SWKEAEVQTW LQQIGFSQYC ENFREQQVDG DLLLRLTDEE
460 470 480 490 500
LQTDLGMKSS ITRKRFFREL TELKTFASYA TCDRSNLADW LGSLDPRFRQ
510 520 530 540 550
YTYGLVSCGL DRSLLHRVSE QQLLEDCGIR LGVHRTRILS AAREMLHSPL
560 570 580 590 600
PCTGGKLSGD TPDVFISYRR NSGSQLASLL KVHLQLHGFS VFIDVEKLEA
610 620 630 640 650
GKFEDKLIQS VIAARNFVLV LSAGALDKCM QDHDCKDWVH KEIVTALSCG
660 670 680 690 700
KNIVPIIDGF EWPEPQALPE DMQAVLTFNG IKWSHEYQEA TIEKIIRFLQ
710 720
GRPSQDSSAG SDTSLEGATP MGLP
Length:724
Mass (Da):79,606
Last modified:July 5, 2004 - v1
Checksum:i9A5BF03ED22E6102
GO
Isoform 2 (identifier: Q6PDS3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     435-439: Missing.

Note: No experimental confirmation available.
Show »
Length:719
Mass (Da):79,007
Checksum:i08843BA13C0DD69F
GO
Isoform 3 (identifier: Q6PDS3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     543-543: R → RGHFAQTGLRSLRRPSLHDDGPRDKQWGRATLTSMSLSLAP

Show »
Length:764
Mass (Da):84,006
Checksum:iD76542F538604CF8
GO
Isoform 4 (identifier: Q6PDS3-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-536: Missing.
     537-543: RILSAAR → MSLSLAP

Note: No experimental confirmation available.
Show »
Length:188
Mass (Da):20,594
Checksum:i35C1A626B521791D
GO

Sequence cautioni

The sequence BAD32242 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAI25546 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti61V → A in AAR17521 (Ref. 1) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0136061 – 536Missing in isoform 4. CuratedAdd BLAST536
Alternative sequenceiVSP_013604435 – 439Missing in isoform 2. 1 Publication5
Alternative sequenceiVSP_013607537 – 543RILSAAR → MSLSLAP in isoform 4. Curated7
Alternative sequenceiVSP_013605543R → RGHFAQTGLRSLRRPSLHDD GPRDKQWGRATLTSMSLSLA P in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY444167 mRNA Translation: AAR17521.1
AK172964 Transcribed RNA Translation: BAD32242.1 Different initiation.
AK044113 mRNA Translation: BAC31784.1
AL591177 Genomic DNA Translation: CAI25544.1
AL591177 Genomic DNA Translation: CAI25545.1
AL591177 Genomic DNA Translation: CAI25546.1 Sequence problems.
BC058534 mRNA Translation: AAH58534.1
BC080850 mRNA Translation: AAH80850.1
CCDSiCCDS25105.1 [Q6PDS3-1]
CCDS48857.1 [Q6PDS3-3]
RefSeqiNP_001161993.1, NM_001168521.1 [Q6PDS3-3]
NP_766383.2, NM_172795.3 [Q6PDS3-1]
UniGeneiMm.210332

Genome annotation databases

EnsembliENSMUST00000061174; ENSMUSP00000051059; ENSMUSG00000050132 [Q6PDS3-1]
ENSMUST00000108287; ENSMUSP00000103922; ENSMUSG00000050132 [Q6PDS3-3]
GeneIDi237868
KEGGimmu:237868
UCSCiuc007kjh.2 mouse [Q6PDS3-4]
uc007kji.2 mouse [Q6PDS3-1]
uc007kjj.2 mouse [Q6PDS3-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSARM1_MOUSE
AccessioniPrimary (citable) accession number: Q6PDS3
Secondary accession number(s): Q5SYG5
, Q5SYG6, Q6A054, Q6SZW0, Q8BRI9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: July 5, 2004
Last modified: March 28, 2018
This is version 125 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health