STB5L_HUMAN
ID STB5L_HUMAN Reviewed; 1186 AA.
AC Q9Y2K9; Q4G1B4; Q6PIC3;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2005, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Syntaxin-binding protein 5-like;
DE AltName: Full=Lethal(2) giant larvae protein homolog 4;
DE AltName: Full=Tomosyn-2;
GN Name=STXBP5L; Synonyms=KIAA1006, LLGL4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 434-1186 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=14767561;
RA Katoh M., Katoh M.;
RT "Identification and characterization of human LLGL4 gene and mouse Llgl4
RT gene in silico.";
RL Int. J. Oncol. 24:737-742(2004).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [5]
RP FUNCTION, VARIANT ILE-1043, AND CHARACTERIZATION OF VARIANT ILE-1043.
RX PubMed=25504045; DOI=10.1093/hmg/ddu614;
RA Kumar R., Corbett M.A., Smith N.J., Jolly L.A., Tan C., Keating D.J.,
RA Duffield M.D., Utsumi T., Moriya K., Smith K.R., Hoischen A., Abbott K.,
RA Harbord M.G., Compton A.G., Woenig J.A., Arts P., Kwint M., Wieskamp N.,
RA Gijsen S., Veltman J.A., Bahlo M., Gleeson J.G., Haan E., Gecz J.;
RT "Homozygous mutation of STXBP5L explains an autosomal recessive infantile-
RT onset neurodegenerative disorder.";
RL Hum. Mol. Genet. 24:2000-2010(2015).
CC -!- FUNCTION: Plays a role in vesicle trafficking and exocytosis
CC inhibition. In pancreatic beta-cells, inhibits insulin secretion
CC probably by interacting with and regulating STX1A and STX4, key t-SNARE
CC proteins involved in the fusion of insulin granules to the plasma
CC membrane. Also plays a role in neurotransmitter release by inhibiting
CC basal acetylcholine release from axon terminals and by preventing
CC synaptic fatigue upon repetitive stimulation (By similarity). Promotes
CC as well axonal outgrowth (PubMed:25504045).
CC {ECO:0000250|UniProtKB:Q5DQR4, ECO:0000269|PubMed:25504045}.
CC -!- SUBUNIT: Interacts with STX1A and STX4. {ECO:0000250|UniProtKB:Q5DQR4}.
CC -!- INTERACTION:
CC Q9Y2K9; Q9Y4H4: GPSM3; NbExp=3; IntAct=EBI-11294039, EBI-347538;
CC Q9Y2K9; Q86Y82: STX12; NbExp=3; IntAct=EBI-11294039, EBI-2691717;
CC Q9Y2K9; P32856-2: STX2; NbExp=3; IntAct=EBI-11294039, EBI-11956649;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Cell membrane
CC {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Membrane
CC {ECO:0000305}; Peripheral membrane protein {ECO:0000305}.
CC Note=Cytoplasmic, and associated with vesicular membranes and the
CC plasma membrane. {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y2K9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y2K9-2; Sequence=VSP_016293, VSP_016294;
CC -!- TISSUE SPECIFICITY: Detected in kidney, hippocampus and lung carcinoma.
CC {ECO:0000269|PubMed:14767561}.
CC -!- PTM: Phosphorylated, leading to STXBP5L increased turnover and
CC subsequent de-repression of insulin secretion (By similarity).
CC Phosphorylated on serine residues in response to glucose or phorbol
CC esters (By similarity). {ECO:0000250|UniProtKB:Q5DQR4}.
CC -!- PTM: Ubiquitinated by the E3 ligase SYVN1, leading to STXBP5L
CC proteasomal degradation. {ECO:0000250|UniProtKB:Q5DQR4}.
CC -!- SIMILARITY: Belongs to the WD repeat L(2)GL family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA76850.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB023223; BAA76850.1; ALT_INIT; mRNA.
DR EMBL; BC022029; AAH22029.1; -; mRNA.
DR EMBL; BC037531; AAH37531.1; -; mRNA.
DR CCDS; CCDS43137.1; -. [Q9Y2K9-1]
DR RefSeq; NP_001335272.1; NM_001348343.1. [Q9Y2K9-1]
DR RefSeq; NP_055795.1; NM_014980.2. [Q9Y2K9-1]
DR RefSeq; XP_006713888.1; XM_006713825.3. [Q9Y2K9-1]
DR AlphaFoldDB; Q9Y2K9; -.
DR SMR; Q9Y2K9; -.
DR BioGRID; 114892; 251.
DR IntAct; Q9Y2K9; 5.
DR STRING; 9606.ENSP00000273666; -.
DR iPTMnet; Q9Y2K9; -.
DR PhosphoSitePlus; Q9Y2K9; -.
DR BioMuta; STXBP5L; -.
DR DMDM; 82582271; -.
DR jPOST; Q9Y2K9; -.
DR MassIVE; Q9Y2K9; -.
DR MaxQB; Q9Y2K9; -.
DR PaxDb; Q9Y2K9; -.
DR PeptideAtlas; Q9Y2K9; -.
DR PRIDE; Q9Y2K9; -.
DR ProteomicsDB; 85830; -. [Q9Y2K9-1]
DR ProteomicsDB; 85831; -. [Q9Y2K9-2]
DR Antibodypedia; 32817; 5 antibodies from 4 providers.
DR DNASU; 9515; -.
DR Ensembl; ENST00000273666.10; ENSP00000273666.6; ENSG00000145087.13. [Q9Y2K9-1]
DR Ensembl; ENST00000461772.5; ENSP00000420642.1; ENSG00000145087.13. [Q9Y2K9-2]
DR GeneID; 9515; -.
DR KEGG; hsa:9515; -.
DR UCSC; uc003eec.5; human. [Q9Y2K9-1]
DR CTD; 9515; -.
DR DisGeNET; 9515; -.
DR GeneCards; STXBP5L; -.
DR HGNC; HGNC:30757; STXBP5L.
DR HPA; ENSG00000145087; Tissue enriched (brain).
DR MIM; 609381; gene.
DR neXtProt; NX_Q9Y2K9; -.
DR OpenTargets; ENSG00000145087; -.
DR PharmGKB; PA134976391; -.
DR VEuPathDB; HostDB:ENSG00000145087; -.
DR eggNOG; KOG1983; Eukaryota.
DR GeneTree; ENSGT00950000182906; -.
DR HOGENOM; CLU_2891755_0_0_1; -.
DR InParanoid; Q9Y2K9; -.
DR OrthoDB; 84844at2759; -.
DR PhylomeDB; Q9Y2K9; -.
DR TreeFam; TF314585; -.
DR PathwayCommons; Q9Y2K9; -.
DR SignaLink; Q9Y2K9; -.
DR BioGRID-ORCS; 9515; 12 hits in 1066 CRISPR screens.
DR ChiTaRS; STXBP5L; human.
DR GenomeRNAi; 9515; -.
DR Pharos; Q9Y2K9; Tbio.
DR PRO; PR:Q9Y2K9; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9Y2K9; protein.
DR Bgee; ENSG00000145087; Expressed in Brodmann (1909) area 23 and 103 other tissues.
DR ExpressionAtlas; Q9Y2K9; baseline and differential.
DR Genevisible; Q9Y2K9; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0031201; C:SNARE complex; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0045159; F:myosin II binding; IBA:GO_Central.
DR GO; GO:0019905; F:syntaxin binding; IBA:GO_Central.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0017157; P:regulation of exocytosis; IBA:GO_Central.
DR GO; GO:0050708; P:regulation of protein secretion; IBA:GO_Central.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR000664; Lethal2_giant.
DR InterPro; IPR013905; Lgl_C_dom.
DR InterPro; IPR013577; LLGL2.
DR InterPro; IPR042855; V_SNARE_CC.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF08596; Lgl_C; 1.
DR Pfam; PF08366; LLGL; 1.
DR Pfam; PF00400; WD40; 1.
DR PRINTS; PR00962; LETHAL2GIANT.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 2.
DR PROSITE; PS50892; V_SNARE; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 3.
DR PROSITE; PS50082; WD_REPEATS_2; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell membrane; Coiled coil; Cytoplasm;
KW Disease variant; Exocytosis; Membrane; Methylation; Phosphoprotein;
KW Protein transport; Reference proteome; Repeat; Transport; Ubl conjugation;
KW WD repeat.
FT CHAIN 1..1186
FT /note="Syntaxin-binding protein 5-like"
FT /id="PRO_0000051247"
FT REPEAT 74..107
FT /note="WD 1"
FT REPEAT 114..153
FT /note="WD 2"
FT REPEAT 158..194
FT /note="WD 3"
FT REPEAT 213..247
FT /note="WD 4"
FT REPEAT 253..285
FT /note="WD 5"
FT REPEAT 307..349
FT /note="WD 6"
FT REPEAT 357..391
FT /note="WD 7"
FT REPEAT 413..490
FT /note="WD 8"
FT REPEAT 518..629
FT /note="WD 9"
FT REPEAT 643..705
FT /note="WD 10"
FT REPEAT 832..889
FT /note="WD 11"
FT REPEAT 898..969
FT /note="WD 12"
FT REPEAT 974..1018
FT /note="WD 13"
FT REPEAT 1032..1055
FT /note="WD 14"
FT DOMAIN 1121..1181
FT /note="v-SNARE coiled-coil homology"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00290"
FT REGION 15..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 748..771
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 15..33
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 750..771
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 568
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 574
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 589
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 593
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 596
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 599
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 709
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 763
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 765
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 766
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 771
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 772
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 793
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 800
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 812
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 820
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 822
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 823
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT MOD_RES 1093
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5DQR4"
FT VAR_SEQ 64..74
FT /note="TVRHGFPHQPT -> FGMVFLISPQH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016293"
FT VAR_SEQ 75..1186
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016294"
FT VARIANT 568
FT /note="T -> S (in dbSNP:rs17249244)"
FT /id="VAR_050076"
FT VARIANT 855
FT /note="V -> I (in dbSNP:rs17740066)"
FT /id="VAR_050077"
FT VARIANT 1043
FT /note="V -> I (found in a family with autosomal recessive
FT infantile-onset neurodegenerative disease; unknown
FT pathological significance; loss of axonal outgrowth;
FT dbSNP:rs767675000)"
FT /evidence="ECO:0000269|PubMed:25504045"
FT /id="VAR_081642"
FT CONFLICT 819
FT /note="S -> Y (in Ref. 2; AAH37531)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1186 AA; 131887 MW; 8CBDB5FAB4B777DA CRC64;
MKKFNFRKVL DGLTASSPGS GSSSGSNSGG GAGSGSVHPA GTAGVLREEI QETLTSEYFQ
ICKTVRHGFP HQPTALAFDP VQKILAIGTR TGAIRILGRP GVDCYCQHES GAAVLQLQFL
INEGALVSAS SDDTLHLWNL RQKRPAILHS LKFNRERITY CHLPFQSKWL YVGTERGNTH
IVNIESFILS GYVIMWNKAI ELSTKTHPGP VVHLSDSPRD EGKLLIGYEN GTVVFWDLKS
KRAELRVYYD EAIHSIDWHH EGKQFMCSHS DGSLTLWNLK SPSRPFQTTI PHGKSQREGR
KSESCKPILK VEYKTCKNSE PFIIFSGGLS YDKACRRPSL TIMHGKAITV LEMDHPIVEF
LTLCETPYPN EFQEPYAVVV LLEKDLIVVD LTQSNFPIFE NPYPMDIHES PVTCTAYFAD
CPPDLILVLY SIGVKHKKQG YSNKEWPISG GAWNLGAQTY PEIIITGHAD GSIKFWDASA
ITLQMLYKLK TSKVFEKQKV GEGKQTCEIV EEDPFAIQMI YWCPESRIFC VSGVSAYVII
YKFSRHEITT EIVSLEVRLQ YDVEDIITPE PETSPPFPDL SAQLPSSRSL SGSTNTVASE
GVTKDSIPCL NVKTRPVRMP PGYQAELVIQ LVWVDGEPPQ QITSLAVSSA YGIVAFGNCN
GLAVVDFIQK TVLLSMGTID LYRSSDLYQR QPRSPRKNKQ FIADNFCMRG LSNFYPDLTK
RIRTSYQSLT ELNDSPVPLE LERCKSPTSD HVNGHCTSPT SQSCSSGKRL SSADVSKVNR
WGPGRPPFRK AQSAACMEIS LPVTTEENRE NSYNRSRSSS ISSIDKDSKE AITALYFMDS
FARKNDSTIS PCLFVGTSLG MVLIISLNLP LADEQRFTEP VMVLPSGTFL SLKGAVLTFS
CMDRMGGLMQ PPYEVWRDPN NIDENEKSWR RKVVMNSSSA SQEIGDHQYT IICSEKQAKV
FSLPSQTCLY VHNITETSFI LQANVVVMCS SACLACFCAN GHIMIMSLPS LRPMLDVNYL
PLTDMRIART FCFTNEGQAL YLVSPTEIQR LTYSQEMCDN LQDMLGDLFT PIETPEAQNR
GFLKGLFGGS GQTFDREELF GEASAGKASR SLAQHIPGPG SIEGMKGAAG GVMGELTRAR
IALDERGQRL GELEEKTAGM MTSAEAFSKH AHELMLKYKD KKWYQF
