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Details on Person UniProt:O43236 SEPTIN4

Class:Id	ReferenceGeneProduct:64320
_chainChangeLog	chain:1-478 added on Fri February 6 2015;chain:1-478 for 64320 removed on Fri Feb 20 2026;chain:1-996 for 64320 added on Fri Feb 20 2026
_displayName	UniProt:O43236 SEPTIN4
_timestamp	2026-05-15 20:00:39
chain	chain:1-996
checksum	8306167C9EF5CFF0
comment	FUNCTION Filament-forming cytoskeletal GTPase (Probable). Pro-apoptotic protein involved in LGR5-positive intestinal stem cell and Paneth cell expansion in the intestines, via its interaction with XIAP (By similarity). May also play a role in the regulation of cell fate in the intestine (By similarity). Positive regulator of apoptosis involved in hematopoietic stem cell homeostasis; via its interaction with XIAP (By similarity). Negative regulator of repair and hair follicle regeneration in response to injury, due to inhibition of hair follicle stem cell proliferation, potentially via its interaction with XIAP (By similarity). Plays an important role in male fertility and sperm motility (PubMed:36135717). During spermiogenesis, essential for the establishment of the annulus (a fibrous ring structure connecting the midpiece and the principal piece of the sperm flagellum) which is a requisite for the structural and mechanical integrity of the sperm (PubMed:36135717). Involved in the migration of cortical neurons and the formation of neuron leading processes during embryonic development (By similarity). Required for dopaminergic metabolism in presynaptic autoreceptors; potentially via activity as a presynaptic scaffold protein (By similarity).FUNCTION Required for the induction of cell death mediated by TGF-beta and possibly by other apoptotic stimuli (PubMed:11146656, PubMed:15837787). Induces apoptosis through binding and inhibition of XIAP resulting in significant reduction in XIAP levels, leading to caspase activation and cell death (PubMed:15029247). Mediates the interaction between BCL2 and XIAP, thereby positively regulating the ubiquitination and degradation of BCL2 and promoting apoptosis (PubMed:29020630).SUBUNIT Septins polymerize into heterooligomeric protein complexes that form filaments, and can associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation. Interacts with SEPTIN8 (PubMed:15116257). In a mesenchymal cell line, interacts with SEPTIN9 isoform 2 variants HNA Trp-106 and Phe-111, but not the wild type SEPTIN9 (PubMed:17546647). Component of a septin core octameric complex consisting of SEPTIN12, SEPTIN7, SEPTIN6 and SEPTIN2 or SEPTIN4 in the order 12-7-6-2-2-6-7-12 or 12-7-6-4-4-6-7-12 (PubMed:25588830). Interacts with SEPTIN14 (via C-terminus) (By similarity). Interacts with DYRK1A (By similarity). Interacts with SLC6A3/DAT and SNCA/alpha-synuclein (By similarity). Interacts with STX1A; in the striatum (By similarity). Interacts with XIAP (via BIR3 domain) following the induction of apoptosis (By similarity). Interacts with AREL1 (via HECT domain); in the cytoplasm following induction of apoptosis (PubMed:23479728).SUBUNIT Part of a complex composed of SEPTIN4 isoform ARTS, XIAP and BCL2, within the complex interacts with both BCL2 (via BH3 domain) and XIAP, ARTS acts as a scaffold protein and stabilizes the complex (PubMed:29020630). Interacts with XIAP (via BIR3 domain) following the induction of apoptosis (PubMed:15029247, PubMed:21695558).INTERACTION In platelets, found in areas surrounding alpha-granules (PubMed:15116257). Found in the sperm annulus, a fibrous ring structure connecting the midpiece and the principal piece of the sperm flagellum (PubMed:25588830, PubMed:36135717). Expressed and colocalized with SLC6A3 and SNCA in axon terminals, especially at the varicosities (By similarity).SUBCELLULAR LOCATION While predominantly localized in the mitochondria under resting conditions, translocates into the nucleus after TGF-beta treatment and apoptosis induction.ALTERNATIVE PRODUCTS Widely expressed in adult and fetal tissues with highest expression in adult brain (at protein level), heart, liver and adrenal gland and fetal heart, kidney, liver and lung. Expressed in presynaptic terminals of dopaminergic neurons projecting from the substantia nigra pars compacta to the striatum (at protein level) (PubMed:17296554). Expressed in axonal varicosities in dopaminergic nerve terminals (at protein level) (PubMed:17296554). Expressed in the putamen and in the adjacent cerebral cortex (at protein level) (PubMed:17296554). Expressed in colonic crypts (at protein level) (PubMed:30389919). Expressed in platelets. Expressed in spermatozoa (at protein level) (PubMed:36135717).TISSUE SPECIFICITY Highly expressed in the brain and heart.PTM Phosphorylated by DYRK1A.PTM Ubiquitinated by AREL1.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Colocalizes with alpha-synuclein in Lewy bodies in the substantia nigra pars compacta of Parkinson disease patients (PubMed:17296554). Shows reduced expression in dopaminergic nerve terminals of the striatum in sporadic Parkinson disease (PubMed:17296554).MISCELLANEOUS May be defective in GTP-binding.SIMILARITY Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.
description	recommendedName: fullName evidence="31"Septin-4 alternativeName: fullName evidence="26"Bradeion beta alternativeName: fullName evidence="1"Brain protein H5 alternativeName: fullName evidence="31"CE5B3 beta alternativeName: fullName evidence="31"Cell division control-related protein 2 shortName evidence="31"hCDCREL-2 alternativeName: fullName evidence="29"Peanut-like protein 2
geneName	SEPTIN4 C17orf47 PNUTL2 SEP4 SEPT4 hucep-7
identifier	O43236
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing Cell cycle Cell division Cell projection Cilium Coiled coil Cytoplasm Cytoplasmic vesicle Differentiation Direct protein sequencing Disease variant Flagellum GTP-binding Mitochondrion Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Spermatogenesis Synapse Ubl conjugation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 [InstanceEdit:9989145] Weiser, Joel, 2026-05-15
name	SEPTIN4
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8990972] ENSEMBL:ENSG00000108387 SEPTIN4 [Homo sapiens]
secondaryIdentifier	SEPT4_HUMAN A0A5F9ZHH3 B2RD42 B3KSX9 B4DXC6 B4DXV5 Q6IAP3 Q8N821 Q8NEP4 Q9H315 Q9UM58
sequenceLength	996
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:153706] UniProt:O43236-2 SEPTIN4 [Homo sapiens] [ReferenceIsoform:401497] UniProt:O43236-1 SEPTIN4 [Homo sapiens] [ReferenceIsoform:6805844] UniProt:O43236-6 SEPTIN4 [Homo sapiens] [ReferenceIsoform:8976758] UniProt:O43236-3 SEPTIN4 [Homo sapiens] [ReferenceIsoform:8976759] UniProt:O43236-4 SEPTIN4 [Homo sapiens] [ReferenceIsoform:8976760] UniProt:O43236-5 SEPTIN4 [Homo sapiens] [ReferenceIsoform:9715503] UniProt:O43236-7 SEPTIN4 [Homo sapiens] [ReferenceIsoform:9715504] UniProt:O43236-8 SEPTIN4 [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:O43236 SEPTIN4 (64320)