SYT1_HUMAN » Synaptotagmin-1

SYT1_HUMAN » Synaptotagmin-1
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Topology in Vesicle membrane
Topologyvesicle lumenal side
cytoplasmic side
SYT1_HUMAN » Synaptotagmin-1 » Synaptotagmin I;SytI; p65;
Hydrophobic Thickness 30.8 ± 3.8 Å
Tilt Angle 44 ± 0°
ΔGtransfer -25.2 kcal/mol
ΔGfold -20.2 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome, HMDB
Topology Out
TM Segments 58-82 (58-88)
Pathways

Neuronal System (Reactome)

Synaptic vesicle cycle (KEGG)

PDB 3f00 (141-266), 3f05 (141-266), 3f04 (141-266), 3f01 (141-266), 2k45 (141-268), 2lha (272-422), 2r83 (A/B=141-422), 2k8m (A/D=141-268), 2ki6 (A/F=141-268), 2k4a (A=141-268), 4v11 (A=273-422), 4isq (D/E/F=33-53)
OPM 1byn (RAT), 1rsy (RAT), 1uov (RAT), 2r83, 3f00, 4v11
Complexes none
Interactions

GOLM1, Complex: SYT1:GOLM1, PubMed

STX1A, Complex: STX1A:CPLX1:SYT1:SNAA, PubMed

STX1A, Complex: STX1A:SYT1, PubMed

STX2, Complex: SYT1:STX2, PubMed

STX3, Complex: STX3:SYT1, PubMed

STX4, Complex: STX4:SYT1, PubMed

SYT4, Complex: SYT4:SYT1, PubMed

VAMP2, Complex: SYT1:SNP25:UN13B:VAMP2, PubMed

VAMP2, Complex: SYT1:VAMP2, PubMed

Domains

AA: 157-263, PDBID: 1BYN, Subunit A, Seq Identity:100%, C2 domain

AA: 288-394, PDBID: 1K5W, Subunit A, Seq Identity:100%, C2 domain

UniProt annotation for SYT1_HUMAN » Synaptotagmin-1
FUNCTION: May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca(2+)-dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca(2+)-independent manner; these are neurexins, syntaxin and AP2.

SUBUNIT: Homotetramer (Probable). Interacts with SCAMP5, STON2, SV2A, SV2B, SV2C and RIMS1. Forms a complex with SV2B, syntaxin 1 and SNAP25 (By similarity).

DOMAIN: The first C2 domain mediates Ca(2+)-dependent phospholipid binding.

DOMAIN: The second C2 domain mediates interaction with SV2A and STN2.

DISEASE: Note=A SYT1 rare mutation has been found in a child with a severe neuro-developmental disorder. The individual harboring this variant shows early onset dyskinetic movement disorder, severe motor delay and profound cognitive impairment, suggesting that SYT1 may play a role in the pathogenesis of this neuro- developmental disorder.

UniProt features for SYT1_HUMAN » Synaptotagmin-1
CHAIN 1 422 Synaptotagmin-1.
DOMAIN 157 245 C2 1.
DOMAIN 287 378 C2 2.
REGION 136 382 Phospholipid binding (Probable).
Amino Acid Sequence for SYT1_HUMAN » Synaptotagmin-1
MVSESHHEAL AAPPVTTVAT VLPSNATEPA SPGEGKEDAF SKLKEKFMNE LHKIPLPPWA LIAIAIVAVL LVLTCCFCIC KKCLFKKKNK KKGKEKGGKN AINMKDVKDL GKTMKDQALK DDDAETGLTD GEEKEEPKEE EKLGKLQYSL DYDFQNNQLL VGIIQAAELP ALDMGGTSDP YVKVFLLPDK KKKFETKVHR KTLNPVFNEQ FTFKVPYSEL GGKTLVMAVY DFDRFSKHDI IGEFKVPMNT VDFGHVTEEW RDLQSAEKEE QEKLGDICFS LRYVPTAGKL TVVILEAKNL KKMDVGGLSD PYVKIHLMQN GKRLKKKKTT IKKNTLNPYY NESFSFEVPF EQIQKVQVVV TVLDYDKIGK NDAIGKVFVG YNSTGAELRH WSDMLANPRR PIAQWHTLQV EEEVDAMLAV KK