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Protein

Sterile alpha and TIR motif-containing protein 1

Gene

SARM1

Organism
Homo sapiens (Human)
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/p38.4 Publications

Caution

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

GO - Biological processi

Keywordsi

Biological processDifferentiation, Immunity, Innate immunity, Neurogenesis

Enzyme and pathway databases

ReactomeiR-HSA-166166 MyD88-independent TLR4 cascade
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade
R-HSA-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-HSA-937041 IKK complex recruitment mediated by RIP1
R-HSA-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex
SIGNORiQ6SZW1

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
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000004139.13
HGNCiHGNC:17074 SARM1
MIMi607732 gene
neXtProtiNX_Q6SZW1

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi11K → A: No effect on mitochondrial localization. 1 Publication1
Mutagenesisi14R → A: Loss in ability to localize to mitochondria and reduction in apoptotic activity. 1 Publication1
Mutagenesisi22R → A: No effect on mitochondrial localization. 1 Publication1
Mutagenesisi27R → A: No effect on mitochondrial localization. 1 Publication1

Organism-specific databases

DisGeNETi23098
OpenTargetsiENSG00000004139
PharmGKBiPA134971180

Polymorphism and mutation databases

BioMutaiSARM1
DMDMi83288284

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 27MitochondrionAdd BLAST27
ChainiPRO_000009758928 – 724Sterile alpha and TIR motif-containing protein 1Add BLAST697

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei548PhosphoserineBy similarity1
Modified residuei558PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6SZW1
MaxQBiQ6SZW1
PaxDbiQ6SZW1
PeptideAtlasiQ6SZW1
PRIDEiQ6SZW1
ProteomicsDBi67362
67363 [Q6SZW1-2]

PTM databases

iPTMnetiQ6SZW1
PhosphoSitePlusiQ6SZW1

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

BgeeiENSG00000004139
CleanExiHS_SARM1
ExpressionAtlasiQ6SZW1 baseline and differential
GenevisibleiQ6SZW1 HS

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

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi116726, 27 interactors
IntActiQ6SZW1, 5 interactors
STRINGi9606.ENSP00000406738

Structurei

3D structure databases

ProteinModelPortaliQ6SZW1
SMRiQ6SZW1
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

eggNOGiKOG3678 Eukaryota
ENOG410XQ4A LUCA
GeneTreeiENSGT00390000004155
HOGENOMiHOG000008460
HOVERGENiHBG079166
InParanoidiQ6SZW1
OMAiCEVQTWL
OrthoDBiEOG091G01TX
PhylomeDBiQ6SZW1

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
IPR039184 SARM1
IPR000157 TIR_dom
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR22998 PTHR22998, 1 hit
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 (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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_06170223P → R. Corresponds to variant dbSNP:rs7212814Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0136031 – 106MVLTL…AWLLP → MGAVARAHGGLRVARARESV AGGRHRGAGRPGARAAGAAA GLVRAEAGGRRAGRGRRPGR GLPTGGGGLAAA in isoform 2. 1 PublicationAdd BLAST106

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
CCDSiCCDS11230.2 [Q6SZW1-1]
RefSeqiNP_055892.2, NM_015077.3 [Q6SZW1-1]
UniGeneiHs.743510

Genome annotation databases

EnsembliENST00000585482; ENSP00000468032; ENSG00000004139 [Q6SZW1-1]
GeneIDi23098
KEGGihsa:23098
UCSCiuc032ezg.2 human [Q6SZW1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSARM1_HUMAN
AccessioniPrimary (citable) accession number: Q6SZW1
Secondary accession number(s): O60277, Q7LGG3, Q9NXY5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: July 5, 2004
Last modified: July 18, 2018
This is version 123 of the entry and version 1 of the sequence. See 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

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

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