ID DYSF_BOVIN Reviewed; 2107 AA.
AC A6QQP7;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 1.
DT 08-NOV-2023, entry version 81.
DE RecName: Full=Dysferlin;
DE AltName: Full=Dystrophy-associated fer-1-like protein;
DE AltName: Full=Fer-1-like protein 1;
GN Name=DYSF; Synonyms=FER1L1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Key calcium ion sensor involved in the Ca(2+)-triggered
CC synaptic vesicle-plasma membrane fusion. Plays a role in the sarcolemma
CC repair mechanism of both skeletal muscle and cardiomyocytes that
CC permits rapid resealing of membranes disrupted by mechanical stress (By
CC similarity). {ECO:0000250}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with CACNA1S, CAV3 and PARVB. Interacts with ANXA1;
CC the interaction is Ca(2+)- and injury state-dependent. Interacts with
CC ANXA2; the interaction is Ca(2+)- and injury state-dependent. Interacts
CC with AHNAK; the interaction is direct and Ca(2+)-independent. Interacts
CC with AHNAK2; the interaction is direct and Ca(2+)-independent.
CC Interacts with TRIM72/MG53; interaction is required for transport to
CC sites of cell injury during repair patch formation (By similarity).
CC Interacts with RIPOR2; this interaction occurs during early myogenic
CC differentiation (By similarity). {ECO:0000250|UniProtKB:O75923}.
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma; Single-pass type II
CC membrane protein. Cytoplasmic vesicle membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Note=Colocalizes, during muscle differentiation, with
CC BIN1 in the T-tubule system of myotubules and at the site of contact
CC between two myotubes or a myoblast and a myotube. Wounding of myotubes
CC led to its focal enrichment to the site of injury and to its
CC relocalization in a Ca(2+)-dependent manner toward the plasma membrane.
CC Colocalizes with AHNAK, AHNAK2 and PARVB at the sarcolemma of skeletal
CC muscle. Detected on the apical plasma membrane of the
CC syncytiotrophoblast. Reaches the plasmma membrane through a caveolin-
CC independent mechanism. Retained by caveolin at the plasmma membrane (By
CC similarity). Colocalizes, during muscle differentiation, with CACNA1S
CC in the T-tubule system of myotubules (By similarity). Accumulates and
CC colocalizes with fusion vesicles at the sarcolemma disruption sites (By
CC similarity). {ECO:0000250}.
CC -!- DOMAIN: All seven C2 domains associate with lipid membranes in a
CC calcium-dependent manner. Domains C2 1 and 3 have the highest affinity
CC for calcium, the C2 domain 1 seems to be largely unstructured in the
CC absence of bound ligands (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ferlin family. {ECO:0000305}.
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DR EMBL; BC149938; AAI49939.1; -; mRNA.
DR RefSeq; NP_001095960.1; NM_001102490.2.
DR AlphaFoldDB; A6QQP7; -.
DR SMR; A6QQP7; -.
DR STRING; 9913.ENSBTAP00000033077; -.
DR SwissPalm; A6QQP7; -.
DR PaxDb; 9913-ENSBTAP00000033077; -.
DR PeptideAtlas; A6QQP7; -.
DR GeneID; 508157; -.
DR KEGG; bta:508157; -.
DR CTD; 8291; -.
DR eggNOG; KOG1326; Eukaryota.
DR InParanoid; A6QQP7; -.
DR OrthoDB; 991411at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; ISS:UniProtKB.
DR GO; GO:0030315; C:T-tubule; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; ISS:UniProtKB.
DR GO; GO:0002281; P:macrophage activation involved in immune response; IBA:GO_Central.
DR GO; GO:0002280; P:monocyte activation involved in immune response; IBA:GO_Central.
DR GO; GO:0050765; P:negative regulation of phagocytosis; IBA:GO_Central.
DR GO; GO:0001778; P:plasma membrane repair; IBA:GO_Central.
DR GO; GO:0033292; P:T-tubule organization; IBA:GO_Central.
DR GO; GO:0006906; P:vesicle fusion; ISS:UniProtKB.
DR CDD; cd08373; C2A_Ferlin; 1.
DR CDD; cd04011; C2B_Ferlin; 1.
DR CDD; cd04018; C2C_Ferlin; 1.
DR CDD; cd04017; C2D_Ferlin; 1.
DR CDD; cd04037; C2E_Ferlin; 1.
DR CDD; cd08374; C2F_Ferlin; 1.
DR Gene3D; 2.60.40.150; C2 domain; 6.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037726; C2A_Ferlin.
DR InterPro; IPR037720; C2B_Ferlin.
DR InterPro; IPR037722; C2C_Ferlin.
DR InterPro; IPR037723; C2D_Ferlin.
DR InterPro; IPR037724; C2E_Ferlin.
DR InterPro; IPR037725; C2F_Ferlin.
DR InterPro; IPR012968; FerIin_dom.
DR InterPro; IPR037721; Ferlin.
DR InterPro; IPR012560; Ferlin_A-domain.
DR InterPro; IPR012561; Ferlin_B-domain.
DR InterPro; IPR032362; Ferlin_C.
DR InterPro; IPR006614; Peroxin/Ferlin.
DR PANTHER; PTHR12546:SF44; DYSFERLIN; 1.
DR PANTHER; PTHR12546; FER-1-LIKE; 1.
DR Pfam; PF00168; C2; 7.
DR Pfam; PF08165; FerA; 1.
DR Pfam; PF08150; FerB; 1.
DR Pfam; PF08151; FerI; 1.
DR Pfam; PF16165; Ferlin_C; 1.
DR SMART; SM00239; C2; 7.
DR SMART; SM00694; DysFC; 2.
DR SMART; SM00693; DysFN; 2.
DR SMART; SM01200; FerA; 1.
DR SMART; SM01201; FerB; 1.
DR SMART; SM01202; FerI; 1.
DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 7.
DR PROSITE; PS50004; C2; 7.
PE 2: Evidence at transcript level;
KW Calcium; Cell membrane; Cytoplasmic vesicle; Lipid-binding; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..2107
FT /note="Dysferlin"
FT /id="PRO_0000355560"
FT TRANSMEM 2074..2094
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 1..101
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 205..323
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 362..498
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1138..1264
FT /note="C2 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1312..1440
FT /note="C2 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1588..1706
FT /note="C2 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1822..1970
FT /note="C2 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 132..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2021..2044
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..168
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 18
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 19
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 21
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 40
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 411
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 411
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 419
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 467
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 467
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 469
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 469
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 475
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1170
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1176
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1234
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1621
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1627
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1676
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1678
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1941
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1944
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1947
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 166
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O75923"
SQ SEQUENCE 2107 AA; 239314 MW; AE25EADD9780E110 CRC64;
MLRVFILYAE NVHTPDTDIS DAYCSAVFAG VKKRTKVIKN NVNPVWNEGF EWDLKGIPLD
QGSELLVVVK DHETMGRNRF LGEANIPLRE VLATPSLSAS FNAPLLDTKK QPTGASLVLQ
VSYTPLPGAV PTFPPLTPLE PSPTLPDMDT VADTGGEEDT EDQGLTGDEA EPFLDQSGAL
GPGAPSTPKK QPSHPPPYHP GGGRKRSAPA PSKPLSDKPQ DFQIRVQVIK GRQLPGVNIK
PVVKVTAAGQ TKRTRIHKGN SPVFNETLFF NVFDSPAELF NEPIFITVVD SRSLRTDALI
GEFRLDVGSI YREPRHAYLR KWLLLSDPDD FSAGARGYLK ASLCVLGPGD EAPLERKDPS
EDKEDIESNL LRPIGVALRG AHFCLKVFRA EDLPQMDDAV MDNVRQIFGF DSNKKNLVDP
FVEVSFAGKM LCSKILEKTA NPQWNQSITL PAMFPSMCEK MRIRVVDWDR LTHNDIVATT
YLSMSKISAS GGEIEEEPAG VVKPPPATEL DDHLGFLPTF GPCYINLYGS PREFTGFPDP
YAELNTGKGE GVAYRGRLLL SLETKLVERS EQKVEALSAD DILRVEKYLR RRKYSLFAAF
YSATMLQDVD DAVQFEVSIG NYGNKFDTTC LPLASTTQYS RAVFDGCHYY YLPWGNVKPV
VVLSSYWEDI RHRVEAQNQL LRIADQLEAG LEQVHLALKA QCSDEDVDSL VAQLMDELIA
GCSQPLGDVQ EMPSATHLDQ YLYQLRTRHL SQITEAAQAL KLGHSELPAA LEQAEDWLLR
LRALADEPQN SLPDIVIWML QGDKRVAYQR VPAHEVLFSR RGTSYCGKNC GKLQTIFLKY
PMEGVPRARM PVQIRVRLWF GLSVDEKEFN QFAEGKLSVF AETYENQTKL ALVGNWGTTG
LTYPKFSDIT GRIKLPKDSF RPSAGWAWAG DWFVCPEKTL LHDTDAGHLS FVEEVFENQT
RLPGGQWIYM SDNYTDVNGE KVLPKDDIEC PLGWKWEDEE WSTDLNRAVD EQGWEYSITI
PPDRKPRHWV PAEKMYYTHR RRRWVRLRRR DLSQMEALKR HRQAEAEGEG WEYASLFGWK
FHLEYRKTDA FRRRRWRRRM EPLEKTGPAA VFALEGALGG VVDDRSEDSV SVSTLSFGVN
RPTISCIFDY GNRYHLRCYM YQARDLPAMD KDSFSDPYAV VSFLHQSQKT VVAKNTLNPT
WDQTLIFYEI EIFGEPSSIA EQPPSIVVEL YDHDTYGVDE FMGRCICQPS LERTPRLAWF
PLTRGSQPAG ELLASFELIQ REKPAIHHIP GFEVQDTTGI LEESEDTDLP YPPPQREANI
YMVPQNIKPV LQRTAIEILA WGLRNMKSYQ LASVSSPSLV VECGGQSVQS CVIKNLRKNP
NFDICTLFME VMLPREELYC PPIVVKVIDN RQFGRRPVVG QCTIRSLEGF LCDPYSEESP
SPQGGPDDVS LLSPGEDVLI DIDDKEPLIP IQFADGLSGL APTNMASSPS SLHKILLEEE
FIDWWSKFFA SIGESEKCGS YLEKDFDTLK VYDTSLENVK AFEGLSDFCN TFKLYRGKTQ
EETEDPSVIG EFKGLFKIYP LPEDPAIPLP PRQFHQLASQ GPQECLVRVY IIRAFGLQPK
DPNGKCDPYI KISIGKKSVS DQDSYIPCTL EPVFGKMFEL TCTLPLEKDL KVTLYDYDLL
SKDEKIGETV IDLENRLLSK FGARCGLPQT YCVSGPNQWR DQLRPSQLLH LFCQQHRVKA
PVYRTDRVVF QDKEYTVEEI EAGRVPNPHL GPVEERLALH VLQQQGLIPE HVESRPLYSP
LQPDIEQGKL QMWVDLFPKA LGRPGPPFNI TPRRARRFFL RCIIWNTKDV ILDDLSITGE
KMSDIYVKGW MVGFEEHKQK TDVHYRSLGG EGNFNWRFVF PFDYLPAEQV CTVSKKDAFW
RLDKTESKIP ARVVFQIWDN DKFSFDDFLG SLQLDLNHMP KPAKTAEKCS ADQLEDTFHP
ERFVSLFEQK TVKGWWPCVA EEGEKKILAG KLEMTLEIVT ESEHEERPAG HGRDEPNMNP
KLEDPRRPDT SFLWFTSPYK TMKFILWRRF RCAIIFFLIL FIFLLFLGIF VYSFPNYAAM
KLVKPFS
//
