D3ZUM2

SS
Gene name
Sarm1
Protein name
NAD
Names
+ hydrolase SARM1 , NADase SARM1 , EC 3.2.2.6 , NADP, + hydrolase SARM1 , EC 3.2.2.- , Sterile alpha and TIR motif-containing protein 1
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:287545
EC number
3.2.2.6: Hydrolyzing N-glycosyl compounds
Protein Class

Descriptions

Sterile alpha and Toll/interleukin receptor (TIR) motif-containing protein 1 (SARM1) regulates axon degeneration, functioning as a key player in the cellular processes involved in neurodegenerative diseases and nerve injury. The physical interaction between the autoinhibitory Armadillo/HEAT motif (ARM) and catalytic Toll/interleukin-1 receptor (TIR) domains blocks the NAD hydrolase activity of SARM1. The autoinhibited TIR domain is activated upon axon injury, activating its NAD+ hydrolase activity and enabling TIR-dependent neuronal destruction.

Autoinhibitory domains (AIDs)

50-409 (ARM domain) SS

Target domain

560-703 (TIR domain)

Relief mechanism

Others

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for D3ZUM2

Entry ID Method Resolution Chain Position Source
AF-D3ZUM2-F1 Predicted AlphaFoldDB

3 variants for D3ZUM2

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3321911678 93 A>V No EVA
rs3323670075 172 S>A No EVA
rs3321899533 613 A>V No EVA

No associated diseases with D3ZUM2

3 regional properties for D3ZUM2

Type Name Position InterPro Accession
domain Toll/interleukin-1 receptor homology (TIR) domain 560 - 703 IPR000157
domain Sterile alpha motif domain 409 - 476 IPR001660-1
domain Sterile alpha motif domain 479 - 548 IPR001660-2

Functions

Description
EC Number 3.2.2.6 Hydrolyzing N-glycosyl compounds
Subcellular Localization
  • Cytoplasm
  • Cell projection, axon
  • Cell projection, dendrite
  • Synapse
  • Mitochondrion
  • Associated with microtubules
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

10 GO annotations of cellular component

Name Definition
axon The long process of a neuron that conducts nerve impulses, usually away from the cell body to the terminals and varicosities, which are sites of storage and release of neurotransmitter.
cell surface The external part of the cell wall and/or plasma membrane.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
dendrite A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body.
microtubule Any of the long, generally straight, hollow tubes of internal diameter 12-15 nm and external diameter 24 nm found in a wide variety of eukaryotic cells; each consists (usually) of 13 protofilaments of polymeric tubulin, staggered in such a manner that the tubulin monomers are arranged in a helical pattern on the microtubular surface, and with the alpha/beta axes of the tubulin subunits parallel to the long axis of the tubule; exist in equilibrium with pool of tubulin monomers and can be rapidly assembled or disassembled in response to physiological stimuli; concerned with force generation, e.g. in the spindle.
microtubule cytoskeleton The part of the cytoskeleton (the internal framework of a cell) composed of microtubules and associated proteins.
mitochondrial outer membrane The outer, i.e. cytoplasm-facing, lipid bilayer of the mitochondrial envelope.
mitochondrion A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
protein-containing complex A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.
synapse The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

3 GO annotations of molecular function

Name Definition
NAD+ nucleosidase activity Catalysis of the reaction
NAD+ nucleotidase, cyclic ADP-ribose generating Catalysis of the reaction
signaling adaptor activity The binding activity of a molecule that brings together two or more molecules in a signaling pathway, permitting those molecules to function in a coordinated way. Adaptor molecules themselves do not have catalytic activity.

12 GO annotations of biological process

Name Definition
cell differentiation The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
NAD catabolic process The chemical reactions and pathways resulting in the breakdown of nicotinamide adenine dinucleotide, a coenzyme present in most living cells and derived from the B vitamin nicotinic acid; catabolism may be of either the oxidized form, NAD, or the reduced form, NADH.
negative regulation of MyD88-independent toll-like receptor signaling pathway Any process that stops, prevents, or reduces the frequency, rate, or extent of MyD88-independent toll-like receptor signaling pathway.
nervous system development The process whose specific outcome is the progression of nervous tissue over time, from its formation to its mature state.
nervous system process A organ system process carried out by any of the organs or tissues of neurological system.
protein localization to mitochondrion A process in which a protein is transported to, or maintained in, a location within the mitochondrion.
regulation of dendrite morphogenesis Any process that modulates the frequency, rate or extent of dendrite morphogenesis.
regulation of neuron apoptotic process Any process that modulates the occurrence or rate of cell death by apoptotic process in neurons.
response to axon injury Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an axon injury stimulus.
response to glucose Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a glucose stimulus.
signal transduction The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.

5 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q6IDD9 Sarm NAD Drosophila melanogaster (Fruit fly) SS
Q6SZW1 SARM1 NAD hydrolase SARM1 hydrolase SARM1) Homo sapiens (Human) EV
Q6PDS3 Sarm1 NAD Mus musculus (Mouse) SS
I3L5V6 SARM1 NAD Sus scrofa (Pig) SS
F1QWA8 sarm1 NAD Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MVLTLLFSAY KLCRFFIMSG PRPGADRLTV PGPDRSGGTS PWWAAGGRGS REVSPGVGTE
70 80 90 100 110 120
VQGALERSLP ELQQALSELK QASAAQAVGA GLAEVFQLVE EAWLLPAVGR EVAQGLCDAI
130 140 150 160 170 180
RLDGGLDLLL RLLQAPELET RVQAARLLEQ ILVAENRDRV ARIGLGVILN LSKEREPVEL
190 200 210 220 230 240
ARSVAGILEH MFKHSEETCQ RLVAAGGLDA VLYWCRRTDP ALLRHCALAL ANCALHGGQT
250 260 270 280 290 300
VQRCMVEKRA AEWLFPLAFS KEDELLRLHA CLAVAVLATN KEVEREVEHS GTLALVEPLV
310 320 330 340 350 360
ASLDPGRFAR CLVDASDTSQ GRGPDDLQSL VLLLDSSRLE AQCIGAFYLC AEAAIKSLQG
370 380 390 400 410 420
KTKVFSDIGA IQSLKRLVSY STNGTTSTLA KRALRLLGEE VPRRILPCVA SWKEAEVQTW
430 440 450 460 470 480
LQQIGFSQYC ENFRDQQVDG DLLLRLTDEE LQTDLGMKSS ITRKRFFREL TELKTFASYA
490 500 510 520 530 540
TCDRSNLADW LGSLDPRFRQ YTYGLVSCGL DRSLLHRVSE QQLLEDCGIR LGVHRTRILS
550 560 570 580 590 600
AAREMLHSPL PCTGGKPSGD TPDVFISYRR NSGSQLASLL KVHLQLHGFS VFIDVEKLEA
610 620 630 640 650 660
GKFEDKLIQS VMAARNFVLV LSAGALDKCM QDHECKDWVH KEIVTALSCS KNIVPIIDGF
670 680 690 700 710 720
EWPEPQALPE DMQAVLTFNG IKWSHEYQEA TIEKIIRFLQ GRPSQDSSAG SDTSLEGATS
MGLP