ID   SYTL4_RAT               Reviewed;         672 AA.
AC   Q8VHQ7; Q8VHQ6;
DT   25-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   08-NOV-2023, entry version 148.
DE   RecName: Full=Synaptotagmin-like protein 4;
DE   AltName: Full=Exophilin-2;
DE   AltName: Full=Granuphilin;
GN   Name=Sytl4;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), MUTAGENESIS OF VAL-21 AND
RP   LEU-43, INTERACTION WITH RAB3A AND STXBP1, AND SUBCELLULAR LOCATION.
RC   TISSUE=Insulinoma;
RX   PubMed=12058058; DOI=10.1091/mbc.02-02-0025;
RA   Coppola T., Frantz C., Perret-Menoud V., Gattesco S., Hirling H.,
RA   Regazzi R.;
RT   "Pancreatic beta-cell protein granuphilin binds Rab3 and Munc-18 and
RT   controls exocytosis.";
RL   Mol. Biol. Cell 13:1906-1915(2002).
RN   [2]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-217 AND SER-274, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
CC   -!- FUNCTION: Modulates exocytosis of dense-core granules and secretion of
CC       hormones in the pancreas and the pituitary. Interacts with vesicles
CC       containing negatively charged phospholipids in a Ca(2+)-independent
CC       manner (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Part of a ternary complex containing STX1A and RAB27A. Can
CC       bind both dominant negative and dominant active mutants of RAB27A.
CC       Binds STXBP1, RAB3A, RAB8A and RAB27B. Interacts with MYO5A (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:12058058};
CC       Peripheral membrane protein {ECO:0000269|PubMed:12058058}. Cytoplasmic
CC       vesicle, secretory vesicle membrane {ECO:0000269|PubMed:12058058};
CC       Peripheral membrane protein {ECO:0000269|PubMed:12058058}.
CC       Note=Detected close to the plasma membrane and on secretory granules.
CC       In pancreas, interacts with insulin-containing vesicles.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=Granuphilin-a;
CC         IsoId=Q8VHQ7-1; Sequence=Displayed;
CC       Name=2; Synonyms=Granuphilin-b;
CC         IsoId=Q8VHQ7-2; Sequence=VSP_007903, VSP_007904;
CC   -!- TISSUE SPECIFICITY: Detected in insulin-secreting cell lines.
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DR   EMBL; AF419341; AAL38513.1; -; mRNA.
DR   EMBL; AF419342; AAL38514.1; -; mRNA.
DR   RefSeq; NP_536335.1; NM_080410.1.
DR   AlphaFoldDB; Q8VHQ7; -.
DR   SMR; Q8VHQ7; -.
DR   BioGRID; 250808; 2.
DR   IntAct; Q8VHQ7; 1.
DR   STRING; 10116.ENSRNOP00000004909; -.
DR   CarbonylDB; Q8VHQ7; -.
DR   iPTMnet; Q8VHQ7; -.
DR   PhosphoSitePlus; Q8VHQ7; -.
DR   jPOST; Q8VHQ7; -.
DR   PaxDb; 10116-ENSRNOP00000004909; -.
DR   GeneID; 140594; -.
DR   KEGG; rno:140594; -.
DR   UCSC; RGD:620204; rat. [Q8VHQ7-1]
DR   AGR; RGD:620204; -.
DR   CTD; 94121; -.
DR   RGD; 620204; Sytl4.
DR   eggNOG; KOG1028; Eukaryota.
DR   InParanoid; Q8VHQ7; -.
DR   OrthoDB; 590187at2759; -.
DR   PhylomeDB; Q8VHQ7; -.
DR   Reactome; R-RNO-114608; Platelet degranulation.
DR   PRO; PR:Q8VHQ7; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR   GO; GO:0005768; C:endosome; ISO:RGD.
DR   GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0030141; C:secretory granule; ISO:RGD.
DR   GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0042043; F:neurexin family protein binding; ISS:UniProtKB.
DR   GO; GO:0005543; F:phospholipid binding; ISS:UniProtKB.
DR   GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR   GO; GO:0006887; P:exocytosis; ISS:UniProtKB.
DR   GO; GO:0030073; P:insulin secretion; ISO:RGD.
DR   GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR   GO; GO:0032418; P:lysosome localization; ISO:RGD.
DR   GO; GO:0071985; P:multivesicular body sorting pathway; ISO:RGD.
DR   GO; GO:0046676; P:negative regulation of insulin secretion; ISO:RGD.
DR   GO; GO:0001778; P:plasma membrane repair; ISO:RGD.
DR   GO; GO:0045921; P:positive regulation of exocytosis; ISO:RGD.
DR   GO; GO:0050714; P:positive regulation of protein secretion; ISO:RGD.
DR   GO; GO:1905684; P:regulation of plasma membrane repair; ISO:RGD.
DR   CDD; cd04029; C2A_SLP-4_5; 1.
DR   CDD; cd04020; C2B_SLP_1-2-3-4; 1.
DR   CDD; cd15764; FYVE_Slp4; 1.
DR   Gene3D; 2.60.40.150; C2 domain; 2.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR   InterPro; IPR000008; C2_dom.
DR   InterPro; IPR035892; C2_domain_sf.
DR   InterPro; IPR041282; FYVE_2.
DR   InterPro; IPR044134; FYVE_Slp4.
DR   InterPro; IPR010911; Rab_BD.
DR   InterPro; IPR037303; SLP-4/5_C2A.
DR   InterPro; IPR043567; SYTL1-5_C2B.
DR   InterPro; IPR011011; Znf_FYVE_PHD.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   PANTHER; PTHR45716; BITESIZE, ISOFORM I; 1.
DR   PANTHER; PTHR45716:SF4; SYNAPTOTAGMIN-LIKE PROTEIN 4; 1.
DR   Pfam; PF00168; C2; 2.
DR   Pfam; PF02318; FYVE_2; 1.
DR   SMART; SM00239; C2; 2.
DR   SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 2.
DR   SUPFAM; SSF57903; FYVE/PHD zinc finger; 1.
DR   PROSITE; PS50004; C2; 2.
DR   PROSITE; PS50916; RABBD; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasmic vesicle; Membrane; Metal-binding;
KW   Phosphoprotein; Reference proteome; Repeat; Zinc; Zinc-finger.
FT   CHAIN           1..672
FT                   /note="Synaptotagmin-like protein 4"
FT                   /id="PRO_0000190218"
FT   DOMAIN          4..122
FT                   /note="RabBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00234"
FT   DOMAIN          357..479
FT                   /note="C2 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   DOMAIN          508..634
FT                   /note="C2 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   ZN_FING         63..105
FT                   /note="FYVE-type"
FT   REGION          199..222
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         201
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9R0Q1"
FT   MOD_RES         204
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96C24"
FT   MOD_RES         217
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         221
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96C24"
FT   MOD_RES         274
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         489
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96C24"
FT   VAR_SEQ         485..501
FT                   /note="ISTESSPGLPAHKGELV -> GSVVAKWWTGWIRLVKK (in isoform
FT                   2)"
FT                   /evidence="ECO:0000303|PubMed:12058058"
FT                   /id="VSP_007903"
FT   VAR_SEQ         502..672
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12058058"
FT                   /id="VSP_007904"
FT   MUTAGEN         21
FT                   /note="V->A: Strongly reduces interaction with RAB3A and
FT                   modulation of exocytosis."
FT                   /evidence="ECO:0000269|PubMed:12058058"
FT   MUTAGEN         43
FT                   /note="L->A: Strongly reduces interaction with RAB3A and
FT                   modulation of exocytosis."
FT                   /evidence="ECO:0000269|PubMed:12058058"
SQ   SEQUENCE   672 AA;  75900 MW;  0F994F4D85202400 CRC64;
     MSEILDLSFL SEMERDLILS VLQRDEELRK ADEKRIRRLK NELLEIKRKG AKRGSQHYSD
     RTCARCQEGL GRLISKSNTC VGCNHLVCRE CRVLESNGSW RCKVCSKEIE LKKATGDWFY
     DQKVNRFAYR TGSDIIRMSL RRKPAVNKRE TVGQSLLQQT QMGDIWPGRR IIQEQQKEQS
     VLFEVPKLKS GKSALEAESE SLDSYTADSD STSRRDSLDK SGLFPEWKKM SAPKSQVEKE
     IAPGNQNAVC GDEGDMIFKK NTRKVLRPSE YTKSVIDLRP EDVAQESGIL GDRSKSVPGL
     SVDMEDEEEE EEDIDHLVKL HRQKLARGSM QSGSSMSTIG SMMSLYSEAG DFGNVSVTGK
     IAFSLKFEQK TQTLVIHVKE CHQLAYADEA KKRSNPYVKT YLLPDKSRQG KRKTSIKRDT
     INPLYDETFR YEISESLLAQ RTLQFSVWHH GRFGRNTFLG EAEVHMDSWK LDKKLDHCLP
     LHGKISTESS PGLPAHKGEL VVSLKYIPAS KLPVGGDRKK SKGGEGGELQ VWIKEAKNLT
     AAKSGGTSDS FVKGYLLPMR NKASKRKTPV MKKTLNPHYN HTFVYNGVRL EDLQHMCLEL
     TVWDREPLAS NDFLGGVRLG VGTGISSGEV VDWMDSTGEE VSLWQKMRQY PGSWAEGTLQ
     LRSSMVKQKL GV
//