SYT8_HUMAN
ID SYT8_HUMAN Reviewed; 401 AA.
AC Q8NBV8; A6NFJ4; Q9NSV9;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 4.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Synaptotagmin-8;
DE AltName: Full=Synaptotagmin VIII;
DE Short=SytVIII;
GN Name=SYT8;
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), AND VARIANT ARG-120.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-120.
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-101 (ISOFORM 1).
RA Zhou G., Cao L., Yu R., Shen C., Li H., Zhong G., Lin L., Yang S.;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
CC -!- FUNCTION: Isoform 4 may play a role in the trafficking and exocytosis
CC of secretory vesicles in non-neuronal tissues. Mediates Ca(2+)-
CC regulation of exocytosis acrosomal reaction in sperm. May mediate
CC Ca(2+)-regulation of exocytosis in insulin secreted cells (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer or homooligomer. Homodimerization and
CC homooligomerization do not depend on Ca(2+). Interacts with SYNCRIP
CC isoform 2 C-terminus. Binds inositol 1,3,4,5-tetrakisphosphate (IP4).
CC Binds to AP2 in a Ca(2+)-independent manner. Interacts with STX1A,
CC STX1B and STX2; the interaction is Ca(2+)-dependent (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type III
CC membrane protein {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle,
CC acrosome {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=4;
CC IsoId=Q8NBV8-4; Sequence=Displayed;
CC Name=1;
CC IsoId=Q8NBV8-1; Sequence=VSP_040846, VSP_040847;
CC -!- DOMAIN: The first C2 domain/C2A does not mediate Ca(2+)-dependent
CC phospholipid binding. {ECO:0000250}.
CC -!- DOMAIN: The second C2 domain/C2B is responsible for SYNCRIP and
CC inositol 1,3,4,5-tetrakisphosphate (IP4)-binding. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the synaptotagmin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ57209.1; Type=Miscellaneous discrepancy; Note=May be due to an intron retention.; Evidence={ECO:0000305};
CC Sequence=CAB70885.2; Type=Miscellaneous discrepancy; Note=The sequence differs from that shown because it is a pre-mRNA.; Evidence={ECO:0000305};
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DR EMBL; AL137708; CAB70885.2; ALT_SEQ; Transcribed_RNA.
DR EMBL; AK075202; BAC11467.1; -; mRNA.
DR EMBL; AY353087; AAQ57209.1; ALT_SEQ; mRNA.
DR EMBL; AC051649; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS7726.2; -. [Q8NBV8-4]
DR PIR; T46410; T46410.
DR RefSeq; NP_612634.3; NM_138567.4. [Q8NBV8-4]
DR AlphaFoldDB; Q8NBV8; -.
DR SMR; Q8NBV8; -.
DR BioGRID; 124654; 1.
DR STRING; 9606.ENSP00000371394; -.
DR iPTMnet; Q8NBV8; -.
DR PhosphoSitePlus; Q8NBV8; -.
DR BioMuta; SYT8; -.
DR DMDM; 327478607; -.
DR EPD; Q8NBV8; -.
DR MassIVE; Q8NBV8; -.
DR PaxDb; Q8NBV8; -.
DR PeptideAtlas; Q8NBV8; -.
DR PRIDE; Q8NBV8; -.
DR ProteomicsDB; 72828; -. [Q8NBV8-4]
DR ProteomicsDB; 72829; -. [Q8NBV8-1]
DR Antibodypedia; 55775; 92 antibodies from 22 providers.
DR DNASU; 90019; -.
DR Ensembl; ENST00000381968.7; ENSP00000371394.3; ENSG00000149043.17. [Q8NBV8-4]
DR Ensembl; ENST00000672195.1; ENSP00000500064.1; ENSG00000288149.1. [Q8NBV8-4]
DR GeneID; 90019; -.
DR KEGG; hsa:90019; -.
DR UCSC; uc001lue.2; human. [Q8NBV8-4]
DR CTD; 90019; -.
DR DisGeNET; 90019; -.
DR GeneCards; SYT8; -.
DR HGNC; HGNC:19264; SYT8.
DR HPA; ENSG00000149043; Tissue enhanced (esophagus, skin, urinary bladder).
DR MIM; 607719; gene.
DR neXtProt; NX_Q8NBV8; -.
DR OpenTargets; ENSG00000149043; -.
DR PharmGKB; PA134993261; -.
DR VEuPathDB; HostDB:ENSG00000149043; -.
DR eggNOG; KOG1028; Eukaryota.
DR GeneTree; ENSGT00940000160892; -.
DR InParanoid; Q8NBV8; -.
DR OrthoDB; 925064at2759; -.
DR PhylomeDB; Q8NBV8; -.
DR TreeFam; TF315600; -.
DR PathwayCommons; Q8NBV8; -.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR SignaLink; Q8NBV8; -.
DR BioGRID-ORCS; 90019; 19 hits in 1065 CRISPR screens.
DR GenomeRNAi; 90019; -.
DR Pharos; Q8NBV8; Tbio.
DR PRO; PR:Q8NBV8; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8NBV8; protein.
DR Bgee; ENSG00000149043; Expressed in skin of leg and 85 other tissues.
DR ExpressionAtlas; Q8NBV8; baseline and differential.
DR Genevisible; Q8NBV8; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0031045; C:dense core granule; IBA:GO_Central.
DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0030672; C:synaptic vesicle membrane; 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:0019905; F:syntaxin binding; IBA:GO_Central.
DR GO; GO:0048791; P:calcium ion-regulated exocytosis of neurotransmitter; IBA:GO_Central.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; IBA:GO_Central.
DR GO; GO:0071277; P:cellular response to calcium ion; IBA:GO_Central.
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:0048488; P:synaptic vesicle endocytosis; 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; IPR030540; SYT8.
DR PANTHER; PTHR10024:SF249; PTHR10024:SF249; 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 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Cytoplasmic vesicle; Membrane;
KW Reference proteome; Repeat; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..401
FT /note="Synaptotagmin-8"
FT /id="PRO_0000183959"
FT TOPO_DOM 1..48
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 49..69
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 70..401
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 117..233
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 245..360
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 83..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 90..104
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 134..172
FT /note="IRVGLRQAADLRPGGTVDPYARVSVSTQAGHRHETKVHR -> VKGPAAQDQ
FT RFCEFPERVTGEGQTPCPGWWGADRAGALG (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005, ECO:0000303|Ref.3"
FT /id="VSP_040846"
FT VAR_SEQ 173..401
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005, ECO:0000303|Ref.3"
FT /id="VSP_040847"
FT VARIANT 17
FT /note="H -> Q (in dbSNP:rs57344881)"
FT /id="VAR_061834"
FT VARIANT 120
FT /note="C -> R (in dbSNP:rs564271)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_046952"
FT VARIANT 129
FT /note="F -> I (in dbSNP:rs34141314)"
FT /id="VAR_046953"
FT CONFLICT 35
FT /note="G -> W (in Ref. 3; AAQ57209)"
FT /evidence="ECO:0000305"
FT CONFLICT 46
FT /note="Missing (in Ref. 1; CAB70885)"
FT /evidence="ECO:0000305"
FT CONFLICT 71
FT /note="C -> R (in Ref. 3; AAQ57209)"
FT /evidence="ECO:0000305"
FT CONFLICT 100
FT /note="L -> LV (in Ref. 1; CAB70885)"
FT /evidence="ECO:0000305"
FT VARIANT Q8NBV8-1:143
FT /note="R -> Q (in dbSNP:rs907608)"
FT /evidence="ECO:0000305"
FT /id="VAR_082921"
FT VARIANT Q8NBV8-1:152
FT /note="T -> M (in dbSNP:rs907609)"
FT /evidence="ECO:0000305"
FT /id="VAR_082922"
SQ SEQUENCE 401 AA; 44138 MW; 1D23C587E2259A5D CRC64;
MLHLHGWQTM QGRKMGHPPV SPSAPAPAGT TAIPGLIPDL VAGTPWPRWA LIAGALAAGV
LLVSCLLCAA CCCCRRHRKK PRDKESVGLG SARGTTTTHL VQPDVDGLES SPGDAQQWGC
LQLSLEFDFG SQEIRVGLRQ AADLRPGGTV DPYARVSVST QAGHRHETKV HRGTLCPVFD
ETCCFHIPQA ELPGATLQVQ LFNFKRFSGH EPLGELRLPL GTVDLQHVLE HWYLLGPPAA
TQPEQVGELC FSLRYVPSSG RLTVVVLEAR GLRPGLAEPY VKVQLMLNQR KWKKRKTATK
KGTAAPYFNE AFTFLVPFSQ VQNVDLVLAV WDRSLPLRTE PVGKVHLGAR ASGQPLQHWA
DMLAHARRPI AQRHPLRPAR EVDRMLALQP RLRLRLPLPH S