SYT4_HUMAN
ID SYT4_HUMAN Reviewed; 425 AA.
AC Q9H2B2; B4DEU3; Q9P2K4;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Synaptotagmin-4;
DE AltName: Full=Synaptotagmin IV;
DE Short=SytIV;
GN Name=SYT4; Synonyms=KIAA1342;
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 [MRNA] (ISOFORM 1).
RX PubMed=10938284; DOI=10.1074/jbc.m005801200;
RA Ferguson G.D., Chen X.-N., Korenberg J.R., Herschman H.R.;
RT "The human synaptotagmin IV gene defines an evolutionary break point
RT between syntenic mouse and human chromosome regions but retains ligand
RT inducibility and tissue specificity.";
RL J. Biol. Chem. 275:36920-36926(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (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 [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23999003; DOI=10.1016/j.jdermsci.2013.07.010;
RA Yoo J.C., Lim T.Y., Park J.S., Hah Y.S., Park N., Hong S.G., Park J.Y.,
RA Yoon T.J.;
RT "SYT14L, especially its C2 domain, is involved in regulating melanocyte
RT differentiation.";
RL J. Dermatol. Sci. 72:246-251(2013).
RN [7]
RP STRUCTURE BY NMR OF 154-278.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first C2 domain of synaptotagmin IV from human
RT fetal brain (KIAA1342).";
RL Submitted (DEC-2003) to the PDB data bank.
CC -!- FUNCTION: Synaptotagmin family member which does not bind Ca(2+)
CC (PubMed:23999003) (By similarity). Involved in neuronal dense core
CC vesicles (DCVs) mobility through its interaction with KIF1A. Upon
CC increased neuronal activity, phosphorylation by MAPK8/JNK1 destabilizes
CC the interaction with KIF1A and captures DCVs to synapses (By
CC similarity). Plays a role in dendrite formation by melanocytes
CC (PubMed:23999003). {ECO:0000250|UniProtKB:P50232,
CC ECO:0000269|PubMed:23999003}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with KIF1A; the interaction increases in presence of
CC calcium and decreases when SYT4 is phosphorylated at Ser-135.
CC {ECO:0000250|UniProtKB:P50232}.
CC -!- INTERACTION:
CC Q9H2B2; Q14596: NBR1; NbExp=3; IntAct=EBI-751132, EBI-742698;
CC Q9H2B2; Q14596-2: NBR1; NbExp=3; IntAct=EBI-751132, EBI-11081753;
CC Q9H2B2; Q9UI09: NDUFA12; NbExp=3; IntAct=EBI-751132, EBI-1246332;
CC Q9H2B2; O43765: SGTA; NbExp=7; IntAct=EBI-751132, EBI-347996;
CC Q9H2B2; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-751132, EBI-744081;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, neuronal
CC dense core vesicle membrane {ECO:0000250|UniProtKB:P50232}; Single-pass
CC membrane protein {ECO:0000250|UniProtKB:P50232}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H2B2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H2B2-2; Sequence=VSP_056643;
CC -!- TISSUE SPECIFICITY: Expressed in melanocytes (PubMed:23999003).
CC Expressed in brain. Within brain, expression is highest in hippocampus,
CC with substantial levels also detected in amygdala and thalamus
CC (PubMed:23999003). {ECO:0000269|PubMed:23999003}.
CC -!- DOMAIN: Unlike in other synaptotagmin family members, the first C2
CC domain/C2A does not bind Ca(2+) neither mediates Ca(2+)-dependent
CC phospholipid binding. An aspartate-to-serine substitution in this
CC domain inactivates Ca(2+)/phospho-lipid binding.
CC {ECO:0000250|UniProtKB:P50232}.
CC -!- PTM: Phosphorylation at Ser-135 by MAPK8/JNK1 reduces interaction with
CC KIF1A and neuronal dense core vesicles mobility.
CC {ECO:0000250|UniProtKB:P50232}.
CC -!- SIMILARITY: Belongs to the synaptotagmin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92580.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF299075; AAG37229.1; -; mRNA.
DR EMBL; AB037763; BAA92580.1; ALT_INIT; mRNA.
DR EMBL; AK293791; BAG57204.1; -; mRNA.
DR EMBL; AC091039; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036538; AAH36538.1; -; mRNA.
DR CCDS; CCDS11922.1; -. [Q9H2B2-1]
DR RefSeq; NP_065834.1; NM_020783.3. [Q9H2B2-1]
DR PDB; 1UGK; NMR; -; A=154-278.
DR PDBsum; 1UGK; -.
DR AlphaFoldDB; Q9H2B2; -.
DR SMR; Q9H2B2; -.
DR BioGRID; 112724; 8.
DR ELM; Q9H2B2; -.
DR IntAct; Q9H2B2; 6.
DR MINT; Q9H2B2; -.
DR STRING; 9606.ENSP00000255224; -.
DR GlyConnect; 2930; 1 O-Linked glycan (1 site).
DR iPTMnet; Q9H2B2; -.
DR PhosphoSitePlus; Q9H2B2; -.
DR BioMuta; SYT4; -.
DR DMDM; 18202937; -.
DR MassIVE; Q9H2B2; -.
DR PaxDb; Q9H2B2; -.
DR PeptideAtlas; Q9H2B2; -.
DR PRIDE; Q9H2B2; -.
DR ProteomicsDB; 80522; -. [Q9H2B2-1]
DR Antibodypedia; 22400; 390 antibodies from 30 providers.
DR DNASU; 6860; -.
DR Ensembl; ENST00000255224.8; ENSP00000255224.2; ENSG00000132872.12. [Q9H2B2-1]
DR Ensembl; ENST00000590752.5; ENSP00000466930.1; ENSG00000132872.12. [Q9H2B2-2]
DR GeneID; 6860; -.
DR KEGG; hsa:6860; -.
DR MANE-Select; ENST00000255224.8; ENSP00000255224.2; NM_020783.4; NP_065834.1.
DR UCSC; uc002law.4; human. [Q9H2B2-1]
DR CTD; 6860; -.
DR DisGeNET; 6860; -.
DR GeneCards; SYT4; -.
DR HGNC; HGNC:11512; SYT4.
DR HPA; ENSG00000132872; Tissue enhanced (brain, pituitary gland, retina).
DR MIM; 600103; gene.
DR neXtProt; NX_Q9H2B2; -.
DR OpenTargets; ENSG00000132872; -.
DR PharmGKB; PA36293; -.
DR VEuPathDB; HostDB:ENSG00000132872; -.
DR eggNOG; KOG1028; Eukaryota.
DR GeneTree; ENSGT00940000159026; -.
DR HOGENOM; CLU_023008_7_3_1; -.
DR InParanoid; Q9H2B2; -.
DR OMA; DFPRRQI; -.
DR OrthoDB; 925064at2759; -.
DR PhylomeDB; Q9H2B2; -.
DR TreeFam; TF315600; -.
DR PathwayCommons; Q9H2B2; -.
DR SignaLink; Q9H2B2; -.
DR BioGRID-ORCS; 6860; 14 hits in 1068 CRISPR screens.
DR ChiTaRS; SYT4; human.
DR EvolutionaryTrace; Q9H2B2; -.
DR GeneWiki; SYT4; -.
DR GenomeRNAi; 6860; -.
DR Pharos; Q9H2B2; Tbio.
DR PRO; PR:Q9H2B2; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q9H2B2; protein.
DR Bgee; ENSG00000132872; Expressed in cerebellar vermis and 128 other tissues.
DR ExpressionAtlas; Q9H2B2; baseline and differential.
DR Genevisible; Q9H2B2; HS.
DR GO; GO:0097449; C:astrocyte projection; IEA:Ensembl.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0032127; C:dense core granule membrane; NAS:ParkinsonsUK-UCL.
DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0030173; C:integral component of Golgi membrane; NAS:ParkinsonsUK-UCL.
DR GO; GO:0099066; C:integral component of neuronal dense core vesicle membrane; IEA:Ensembl.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; NAS:ParkinsonsUK-UCL.
DR GO; GO:1990742; C:microvesicle; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0098992; C:neuronal dense core vesicle; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IBA:GO_Central.
DR GO; GO:0030276; F:clathrin binding; IBA:GO_Central.
DR GO; GO:0001786; F:phosphatidylserine binding; IBA:GO_Central.
DR GO; GO:0000149; F:SNARE binding; IBA:GO_Central.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0071277; P:cellular response to calcium ion; IBA:GO_Central.
DR GO; GO:0099519; P:dense core granule cytoskeletal transport; ISS:UniProtKB.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; NAS:ParkinsonsUK-UCL.
DR GO; GO:0033604; P:negative regulation of catecholamine secretion; IGI:ParkinsonsUK-UCL.
DR GO; GO:0050709; P:negative regulation of protein secretion; IEA:Ensembl.
DR GO; GO:1905433; P:negative regulation of retrograde trans-synaptic signaling by neuropeptide; IEA:Ensembl.
DR GO; GO:0048174; P:negative regulation of short-term neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:2000301; P:negative regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR GO; GO:0007269; P:neurotransmitter secretion; IEA:Ensembl.
DR GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; NAS:ParkinsonsUK-UCL.
DR GO; GO:1903861; P:positive regulation of dendrite extension; IDA:UniProtKB.
DR GO; GO:1905415; P:positive regulation of dense core granule exocytosis; IEA:Ensembl.
DR GO; GO:0014049; P:positive regulation of glutamate secretion; IEA:Ensembl.
DR GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; IBA:GO_Central.
DR GO; GO:0014059; P:regulation of dopamine secretion; IBA:GO_Central.
DR GO; GO:0030100; P:regulation of endocytosis; IEA:Ensembl.
DR GO; GO:0099161; P:regulation of presynaptic dense core granule exocytosis; IEA:Ensembl.
DR GO; GO:0031338; P:regulation of vesicle fusion; IEA:Ensembl.
DR GO; GO:0099183; P:trans-synaptic signaling by BDNF, modulating synaptic transmission; IEA:Ensembl.
DR GO; GO:0006906; P:vesicle fusion; IBA:GO_Central.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR Gene3D; 2.60.40.150; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR001565; Synaptotagmin.
DR InterPro; IPR028683; SYT4.
DR PANTHER; PTHR10024:SF114; PTHR10024:SF114; 1.
DR Pfam; PF00168; C2; 2.
DR PRINTS; PR00399; SYNAPTOTAGMN.
DR SMART; SM00239; C2; 2.
DR SUPFAM; SSF49562; SSF49562; 2.
DR PROSITE; PS50004; C2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cytoplasmic vesicle;
KW Differentiation; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix.
FT CHAIN 1..425
FT /note="Synaptotagmin-4"
FT /id="PRO_0000183948"
FT TOPO_DOM 1..16
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..425
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 153..274
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 287..420
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 73..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 127..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 249
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 135
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:P40749"
FT VAR_SEQ 12..29
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056643"
FT VARIANT 142
FT /note="S -> N (in dbSNP:rs16977447)"
FT /id="VAR_052239"
FT STRAND 156..164
FT /evidence="ECO:0007829|PDB:1UGK"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:1UGK"
FT STRAND 169..179
FT /evidence="ECO:0007829|PDB:1UGK"
FT TURN 185..188
FT /evidence="ECO:0007829|PDB:1UGK"
FT STRAND 191..199
FT /evidence="ECO:0007829|PDB:1UGK"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:1UGK"
FT STRAND 204..207
FT /evidence="ECO:0007829|PDB:1UGK"
FT STRAND 218..226
FT /evidence="ECO:0007829|PDB:1UGK"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:1UGK"
FT STRAND 237..245
FT /evidence="ECO:0007829|PDB:1UGK"
FT STRAND 255..260
FT /evidence="ECO:0007829|PDB:1UGK"
FT STRAND 271..276
FT /evidence="ECO:0007829|PDB:1UGK"
SQ SEQUENCE 425 AA; 47958 MW; DA3D4CB175CB528D CRC64;
MAPITTSREE FDEIPTVVGI FSAFGLVFTV SLFAWICCQR KSSKSNKTPP YKFVHVLKGV
DIYPENLNSK KKFGADDKNE VKNKPAVPKN SLHLDLEKRD LNGNFPKTNL KPGSPSDLEN
ATPKLFLEGE KESVSPESLK SSTSLTSEEK QEKLGTLFFS LEYNFERKAF VVNIKEARGL
PAMDEQSMTS DPYIKMTILP EKKHKVKTRV LRKTLDPAFD ETFTFYGIPY TQIQELALHF
TILSFDRFSR DDIIGEVLIP LSGIELSEGK MLMNREIIKR NVRKSSGRGE LLISLCYQST
TNTLTVVVLK ARHLPKSDVS GLSDPYVKVN LYHAKKRISK KKTHVKKCTP NAVFNELFVF
DIPCEGLEDI SVEFLVLDSE RGSRNEVIGQ LVLGAAAEGT GGEHWKEICD YPRRQIAKWH
VLCDG
