Q6SZW1 (SARM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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=SAM domain-containing protein 2
Tir-1 homolog

Gene names

Name:	SARM1
Synonyms:	KIAA0524, SAMD2, SARM

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	724 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in innate immnune response. Acts as a negative regulator of TICAM1/TRIF-dependent Toll-like receptor signaling by inhibiting induction of TLR3- and TLR4-dependent genes. Specifically blocks TICAM1/TRIF-dependent transcription-factor activation and gene induction, without affecting the MYD88-dependent pathway or non-TLR signaling. Negative regulator of NF-kappa-B and IRF activation. Ref.4 Ref.5 Ref.6
Subunit structure	Interacts with TICAM1/TRIF and thereby interferes with TICAM1/TRIF function. Ref.5
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Predominantly expressed in kidney and liver. Expressed at lower level in placenta. Ref.1
Sequence similarities	Contains 2 SAM (sterile alpha motif) domains. Contains 1 TIR domain.
Caution	Was initially (Ref.1) reported to contain ARM repeats. Such repeats are however not predicted by any detection method.

Ontologies

Keywords
Biological process	Immunity Innate immunity
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	innate immune response Inferred from electronic annotation. Source: UniProtKB-KW signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6SZW1-1)

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.

Isoform 2 (identifier: Q6SZW1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-106: MVLTLLLSAY...QLVEEAWLLP → MGAVARAHGG...PTGGGGLAAA

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 724	724	Sterile alpha and TIR motif-containing protein 1		PRO_0000097589
Regions
	Domain	412 – 476	65	SAM 1
	Domain	486 – 548	63	SAM 2
	Domain	559 – 657	99	TIR
Natural variations
	Alternative sequence	1 – 106	106	MVLTL…AWLLP → MGAVARAHGGLRVARARESV AGGRHRGAGRPGARAAGAAA GLVRAEAGGRRAGRGRRPGR GLPTGGGGLAAA in isoform 2.		VSP_013603
	Natural variant	23	1	P → R. Corresponds to variant rs7212814 [ dbSNP | Ensembl ].		VAR_061702

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 6391EA4C31EF6604	FASTA	724	79,388
	10 20 30 40 50 60 MVLTLLLSAY KLCRFFAMSG PRPGAERLAV PGPDGGGGTG PWWAAGGRGP REVSPGAGTE 70 80 90 100 110 120 VQDALERALP ELQQALSALK QAGGARAVGA GLAEVFQLVE EAWLLPAVGR EVAQGLCDAI 130 140 150 160 170 180 RLDGGLDLLL RLLQAPELET RVQAARLLEQ ILVAENRDRV ARIGLGVILN LAKEREPVEL 190 200 210 220 230 240 ARSVAGILEH MFKHSEETCQ RLVAAGGLDA VLYWCRRTDP ALLRHCALAL GNCALHGGQA 250 260 270 280 290 300 VQRRMVEKRA AEWLFPLAFS KEDELLRLHA CLAVAVLATN KEVEREVERS GTLALVEPLV 310 320 330 340 350 360 ASLDPGRFAR CLVDASDTSQ GRGPDDLQRL VPLLDSNRLE AQCIGAFYLC AEAAIKSLQG 370 380 390 400 410 420 KTKVFSDIGA IQSLKRLVSY STNGTKSALA KRALRLLGEE VPRPILPSVP SWKEAEVQTW 430 440 450 460 470 480 LQQIGFSKYC ESFREQQVDG DLLLRLTEEE LQTDLGMKSG ITRKRFFREL TELKTFANYS 490 500 510 520 530 540 TCDRSNLADW LGSLDPRFRQ YTYGLVSCGL DRSLLHRVSE QQLLEDCGIH LGVHRARILT 550 560 570 580 590 600 AAREMLHSPL PCTGGKPSGD TPDVFISYRR NSGSQLASLL KVHLQLHGFS VFIDVEKLEA 610 620 630 640 650 660 GKFEDKLIQS VMGARNFVLV LSPGALDKCM QDHDCKDWVH KEIVTALSCG KNIVPIIDGF 670 680 690 700 710 720 EWPEPQVLPE DMQAVLTFNG IKWSHEYQEA TIEKIIRFLQ GRSSRDSSAG SDTSLEGAAP MGPT
	Isoform 2 [UniParc]. Checksum: 18E0005AF7A7B1C5	FASTA	690	75,337
	10 20 30 40 50 60 MGAVARAHGG LRVARARESV AGGRHRGAGR PGARAAGAAA GLVRAEAGGR RAGRGRRPGR 70 80 90 100 110 120 GLPTGGGGLA AAAVGREVAQ GLCDAIRLDG GLDLLLRLLQ APELETRVQA ARLLEQILVA 130 140 150 160 170 180 ENRDRVARIG LGVILNLAKE REPVELARSV AGILEHMFKH SEETCQRLVA AGGLDAVLYW 190 200 210 220 230 240 CRRTDPALLR HCALALGNCA LHGGQAVQRR MVEKRAAEWL FPLAFSKEDE LLRLHACLAV 250 260 270 280 290 300 AVLATNKEVE REVERSGTLA LVEPLVASLD PGRFARCLVD ASDTSQGRGP DDLQRLVPLL 310 320 330 340 350 360 DSNRLEAQCI GAFYLCAEAA IKSLQGKTKV FSDIGAIQSL KRLVSYSTNG TKSALAKRAL 370 380 390 400 410 420 RLLGEEVPRP ILPSVPSWKE AEVQTWLQQI GFSKYCESFR EQQVDGDLLL RLTEEELQTD 430 440 450 460 470 480 LGMKSGITRK RFFRELTELK TFANYSTCDR SNLADWLGSL DPRFRQYTYG LVSCGLDRSL 490 500 510 520 530 540 LHRVSEQQLL EDCGIHLGVH RARILTAARE MLHSPLPCTG GKPSGDTPDV FISYRRNSGS 550 560 570 580 590 600 QLASLLKVHL QLHGFSVFID VEKLEAGKFE DKLIQSVMGA RNFVLVLSPG ALDKCMQDHD 610 620 630 640 650 660 CKDWVHKEIV TALSCGKNIV PIIDGFEWPE PQVLPEDMQA VLTFNGIKWS HEYQEATIEK 670 680 690 IIRFLQGRSS RDSSAGSDTS LEGAAPMGPT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 11386760] [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: 9628581] [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: 15123841] [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: 16964262] [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: 16985498] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ290445 mRNA. Translation: CAB90355.1. AY444166 mRNA. Translation: AAR17520.1. AB011096 mRNA. Translation: BAA25450.1.
IPI	IPI00007919. IPI00448630.
RefSeq	NP_055892.2. NM_015077.2.
UniGene	Hs.446689. Hs.728332.
3D structure databases
ProteinModelPortal	Q6SZW1.
SMR	Q6SZW1. Positions 323-399, 405-547, 560-700.
ModBase	Search...
Protein-protein interaction databases
STRING	Q6SZW1.
PTM databases
PhosphoSite	Q6SZW1.
Polymorphism databases
DMDM	83288284.
Proteomic databases
PRIDE	Q6SZW1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000379061; ENSP00000368351; ENSG00000004139.
GeneID	23098.
KEGG	hsa:23098.
UCSC	uc010crl.1. human.
Organism-specific databases
CTD	23098.
GeneCards	GC17P026698.
HGNC	HGNC:17074. SARM1.
HPA	HPA024359. HPA024759.
MIM	607732. gene.
neXtProt	NX_Q6SZW1.
PharmGKB	PA134971180.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17300.
GeneTree	ENSGT00390000004155.
HOGENOM	HBG444316.
HOVERGEN	HBG079166.
InParanoid	Q6SZW1.
OrthoDB	EOG46WZ7W.
Gene expression databases
ArrayExpress	Q6SZW1.
Bgee	Q6SZW1.
CleanEx	HS_SARM1.
Genevestigator	Q6SZW1.
GermOnline	ENSG00000004139. Homo sapiens.
Family and domain databases
InterPro	IPR011989. ARM-like. IPR016024. ARM-type_fold. IPR001660. SAM. IPR013761. SAM/pointed. IPR011510. SAM_2. IPR000157. TIR_dom. [Graphical view]
Gene3D	G3DSA:1.25.10.10. ARM-like. 1 hit. G3DSA:1.10.150.50. SAM_type. 2 hits.
Pfam	PF07647. SAM_2. 2 hits. [Graphical view]
SMART	SM00454. SAM. 2 hits. SM00255. TIR. 1 hit. [Graphical view]
SUPFAM	SSF48371. ARM-type_fold. 1 hit. SSF47769. SAM_homology. 1 hit. SSF52200. TIR. 1 hit.
PROSITE	PS50105. SAM_DOMAIN. 2 hits. PS50104. TIR. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	44273.
SOURCE	Search...

Entry information

Entry name

SARM1_HUMAN

Accession

Primary (citable) accession number: Q6SZW1
Secondary accession number(s): O60277, Q7LGG3, Q9NXY5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2005
Last sequence update:	July 5, 2004
Last modified:	January 25, 2012
This is version 67 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.