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HIG_DROME
ID   HIG_DROME               Reviewed;         958 AA.
AC   Q09101; Q7KQU0; Q8IH50; Q9I7E3; Q9I7E4; Q9V560;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   08-NOV-2005, sequence version 2.
DT   03-AUG-2022, entry version 176.
DE   RecName: Full=Locomotion-related protein Hikaru genki;
DE   Flags: Precursor;
GN   Name=hig; ORFNames=CG2040;
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), FUNCTION, AND
RP   DISRUPTION PHENOTYPE.
RC   TISSUE=Head;
RX   PubMed=8461133; DOI=10.1016/0896-6273(93)90329-p;
RA   Hoshino M., Matsuzaki F., Nabeshima Y., Hama C.;
RT   "Hikaru genki, a CNS-specific gene identified by abnormal locomotion in
RT   Drosophila, encodes a novel type of protein.";
RL   Neuron 10:395-407(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [3]
RP   GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 429-958 (ISOFORM 1).
RC   STRAIN=Berkeley; TISSUE=Head;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=8625810; DOI=10.1242/dev.122.2.589;
RA   Hoshino M., Suzuki E., Nabeshima Y., Hama C.;
RT   "Hikaru genki protein is secreted into synaptic clefts from an early stage
RT   of synapse formation in Drosophila.";
RL   Development 122:589-597(1996).
RN   [6]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP   STAGE.
RX   PubMed=9914413; DOI=10.1007/s004270050221;
RA   Hoshino M., Suzuki E., Miyake T., Sone M., Komatsu A., Nabeshima Y.,
RA   Hama C.;
RT   "Neural expression of hikaru genki protein during embryonic and larval
RT   development of Drosophila melanogaster.";
RL   Dev. Genes Evol. 209:1-9(1999).
RN   [7]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-376, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=Oregon-R; TISSUE=Head;
RX   PubMed=17893096; DOI=10.1093/glycob/cwm097;
RA   Koles K., Lim J.-M., Aoki K., Porterfield M., Tiemeyer M., Wells L.,
RA   Panin V.;
RT   "Identification of N-glycosylated proteins from the central nervous system
RT   of Drosophila melanogaster.";
RL   Glycobiology 17:1388-1403(2007).
CC   -!- FUNCTION: Plays a role in the formation of functional neural circuits
CC       from the early stages of synapse formation. Has a role in the
CC       development of CNS functions involved in locomotor activity.
CC       {ECO:0000269|PubMed:8461133, ECO:0000269|PubMed:8625810,
CC       ECO:0000269|PubMed:9914413}.
CC   -!- INTERACTION:
CC       Q09101; Q0KI85: side-VI; NbExp=2; IntAct=EBI-172012, EBI-6884983;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8625810,
CC       ECO:0000269|PubMed:9914413}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=3; Synonyms=A;
CC         IsoId=Q09101-1; Sequence=Displayed;
CC       Name=1; Synonyms=D;
CC         IsoId=Q09101-2; Sequence=VSP_002513;
CC       Name=2; Synonyms=C;
CC         IsoId=Q09101-3; Sequence=VSP_002512, VSP_002513;
CC       Name=4; Synonyms=B;
CC         IsoId=Q09101-4; Sequence=VSP_002512;
CC   -!- TISSUE SPECIFICITY: Expressed in PCC neurons and neuroblasts in the
CC       procephalic neurogenic region in the central nervous system. Expressed
CC       in nerves running along the surface of the ventral ganglion and that
CC       extend to the peripheral tissues. Also expressed in motor nerves and
CC       boutons of certain muscles, in particular of muscle 8 in the A2 and
CC       posterior abdominal segments of young adult flies. In the brain,
CC       expressed in both the neuropiles and cortical regions except the
CC       retinular cells and laminar neuropile. {ECO:0000269|PubMed:8625810,
CC       ECO:0000269|PubMed:9914413}.
CC   -!- DEVELOPMENTAL STAGE: Most abundant during and/or after neuronal
CC       differentiation and during cell specification or axogenesis. Required
CC       during pupation for normal motor function development.
CC       {ECO:0000269|PubMed:9914413}.
CC   -!- DISRUPTION PHENOTYPE: Flies are unable to jump or fly and walk slowly
CC       with an unstable gait. Occasionally they exhibit body and wing tremors
CC       while standing or walking. {ECO:0000269|PubMed:8461133}.
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DR   EMBL; D13884; BAA02984.1; -; mRNA.
DR   EMBL; D13885; BAA02985.1; -; mRNA.
DR   EMBL; D13886; BAA02986.1; -; mRNA.
DR   EMBL; D13887; BAA02987.1; -; mRNA.
DR   EMBL; AE013599; AAF58960.1; -; Genomic_DNA.
DR   EMBL; AE013599; AAG22296.1; -; Genomic_DNA.
DR   EMBL; AE013599; AAG22297.1; -; Genomic_DNA.
DR   EMBL; AE013599; AAS64892.2; -; Genomic_DNA.
DR   EMBL; AY069188; AAL39333.1; -; mRNA.
DR   EMBL; BT001427; AAN71182.1; -; mRNA.
DR   RefSeq; NP_001014514.1; NM_001014514.2. [Q09101-2]
DR   RefSeq; NP_525110.2; NM_080371.3. [Q09101-3]
DR   RefSeq; NP_724772.1; NM_165666.2. [Q09101-4]
DR   RefSeq; NP_724773.1; NM_165667.2. [Q09101-1]
DR   AlphaFoldDB; Q09101; -.
DR   SMR; Q09101; -.
DR   BioGRID; 61786; 6.
DR   IntAct; Q09101; 11.
DR   STRING; 7227.FBpp0087688; -.
DR   GlyGen; Q09101; 6 sites.
DR   iPTMnet; Q09101; -.
DR   PaxDb; Q09101; -.
DR   PRIDE; Q09101; -.
DR   DNASU; 35949; -.
DR   EnsemblMetazoa; FBtr0088606; FBpp0087687; FBgn0010114. [Q09101-4]
DR   EnsemblMetazoa; FBtr0088607; FBpp0087688; FBgn0010114. [Q09101-1]
DR   EnsemblMetazoa; FBtr0088608; FBpp0087689; FBgn0010114. [Q09101-3]
DR   EnsemblMetazoa; FBtr0100119; FBpp0100157; FBgn0010114. [Q09101-2]
DR   GeneID; 35949; -.
DR   KEGG; dme:Dmel_CG2040; -.
DR   CTD; 35949; -.
DR   FlyBase; FBgn0010114; hig.
DR   VEuPathDB; VectorBase:FBgn0010114; -.
DR   eggNOG; KOG4297; Eukaryota.
DR   HOGENOM; CLU_348908_0_0_1; -.
DR   InParanoid; Q09101; -.
DR   OMA; RHPSENH; -.
DR   PhylomeDB; Q09101; -.
DR   Reactome; R-DME-114608; Platelet degranulation.
DR   Reactome; R-DME-202733; Cell surface interactions at the vascular wall.
DR   Reactome; R-DME-6798695; Neutrophil degranulation.
DR   Reactome; R-DME-977606; Regulation of Complement cascade.
DR   BioGRID-ORCS; 35949; 0 hits in 3 CRISPR screens.
DR   ChiTaRS; hig; fly.
DR   GenomeRNAi; 35949; -.
DR   PRO; PR:Q09101; -.
DR   Proteomes; UP000000803; Chromosome 2R.
DR   Bgee; FBgn0010114; Expressed in brain and 21 other tissues.
DR   ExpressionAtlas; Q09101; baseline and differential.
DR   Genevisible; Q09101; DM.
DR   GO; GO:0043025; C:neuronal cell body; IDA:FlyBase.
DR   GO; GO:0043083; C:synaptic cleft; IDA:FlyBase.
DR   GO; GO:0008039; P:synaptic target recognition; IMP:FlyBase.
DR   CDD; cd00033; CCP; 4.
DR   Gene3D; 2.60.40.10; -; 1.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR   InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR   Pfam; PF00084; Sushi; 4.
DR   SMART; SM00032; CCP; 5.
DR   SUPFAM; SSF48726; SSF48726; 1.
DR   SUPFAM; SSF57535; SSF57535; 4.
DR   PROSITE; PS50835; IG_LIKE; 1.
DR   PROSITE; PS50923; SUSHI; 5.
PE   1: Evidence at protein level;
KW   Alternative splicing; Developmental protein; Differentiation;
KW   Disulfide bond; Glycoprotein; Immunoglobulin domain; Neurogenesis;
KW   Reference proteome; Repeat; Secreted; Signal; Sushi.
FT   SIGNAL          1..30
FT                   /evidence="ECO:0000255"
FT   CHAIN           31..958
FT                   /note="Locomotion-related protein Hikaru genki"
FT                   /id="PRO_0000014774"
FT   DOMAIN          527..599
FT                   /note="Sushi 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT   DOMAIN          612..708
FT                   /note="Ig-like C2-type"
FT   DOMAIN          712..770
FT                   /note="Sushi 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT   DOMAIN          771..829
FT                   /note="Sushi 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT   DOMAIN          830..892
FT                   /note="Sushi 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT   DOMAIN          892..954
FT                   /note="Sushi 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT   REGION          129..185
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          261..378
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          393..447
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          929..958
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           318..320
FT                   /note="Cell attachment site"
FT   COMPBIAS        266..344
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        412..435
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        376
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:17893096"
FT   CARBOHYD        525
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        605
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        620
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        752
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        789
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        569..597
FT                   /evidence="ECO:0000250"
FT   DISULFID        643..695
FT                   /evidence="ECO:0000250"
FT   DISULFID        714..755
FT                   /evidence="ECO:0000250"
FT   DISULFID        741..768
FT                   /evidence="ECO:0000250"
FT   DISULFID        773..814
FT                   /evidence="ECO:0000250"
FT   DISULFID        800..827
FT                   /evidence="ECO:0000250"
FT   DISULFID        832..877
FT                   /evidence="ECO:0000250"
FT   DISULFID        863..890
FT                   /evidence="ECO:0000250"
FT   DISULFID        894..939
FT                   /evidence="ECO:0000250"
FT   DISULFID        922..952
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         529..553
FT                   /note="Missing (in isoform 2 and isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:12537569,
FT                   ECO:0000303|PubMed:8461133"
FT                   /id="VSP_002512"
FT   VAR_SEQ         892..958
FT                   /note="Missing (in isoform 1 and isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12537569,
FT                   ECO:0000303|PubMed:8461133"
FT                   /id="VSP_002513"
FT   CONFLICT        81
FT                   /note="E -> D (in Ref. 1; BAA02984/BAA02985/BAA02986/
FT                   BAA02987)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        292
FT                   /note="P -> L (in Ref. 1; BAA02984/BAA02985/BAA02986/
FT                   BAA02987)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        367
FT                   /note="D -> N (in Ref. 1; BAA02984/BAA02985/BAA02986/
FT                   BAA02987)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        396
FT                   /note="K -> R (in Ref. 1)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        398
FT                   /note="T -> A (in Ref. 1)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        716
FT                   /note="Q -> R (in Ref. 1; BAA02984/BAA02985/BAA02986/
FT                   BAA02987)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        760
FT                   /note="N -> S (in Ref. 1; BAA02984/BAA02985/BAA02986/
FT                   BAA02987)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   958 AA;  107028 MW;  7B2A08477672E674 CRC64;
     MWSRQRMRHK PLWALISLTV LLLVLDKSNA NTEPVETSTT SEPDASPGCR APDVRFTIVK
     PEATTEQPLA KFETTQIYLP EDFTTADVEF VDSVPRHPNE NHAAVINPYS LDLGDDHLHV
     GDAAASLVGD DDLGDEDEDH HGDPEDKRLN ANRKQGKRRR AGSGRRRRIE NENGQTGRGR
     GSRYKRHAIL HDTEASPETD RWAGSKLAAE GDVYYVHIAD ILKSREPNRE LKSKLHKLKM
     KARLNKCLAE GGKEKCTRLL KKKPKKKVVE KEQTLKKEKK FPKEEQSKEK VPENGQTPKE
     DELELDHPET AAAHHRRRGD SHAAELDQRD RSPRWRRRRS TEFKGDLGQL PPESGIGPEP
     EPLADQDLKD LQQYGNQSSS ARVALLWQRV KRKSGKTTGA LSRPKGGGDS SSKTTSRKDK
     GIYDEEAGYT PIHPDDPEFD EEEEEDEEVD ILQQFTEVSE IRFPGEIGPM GDRRLCKIRC
     VKGKWVGPLC ATNEEDDNGN VKFQPLYKSC HVNRIPSHLL LSYRNISVTP IPPNRGWRKT
     RLSKSTLLSN TEINVGWDLP HGHSLQARCQ ELGIYKLLGE SRVLCSNGLW APRMPSCVPT
     TVLTNYSEDS APSIRIKIFN GSHSFEPSGV MAVPPHSTVL MDCMYPRVRG TPEWSWTSWY
     MQYSTGWSPA QEEKAVRYRL SIKNIENNDS GTFTCTSPRG LTNSIAVVVA TSTCPQLTEP
     LAPLKLRLEG NKLGQRAHYE CPEGFRLDGA WNATCLASGN WSSPTPTCHA IQCPRLELDD
     PHLSLIELNT SAWGRAVFKC QWGFKLTGPA QLDCEPSGVW SGPVPRCKVI QCVMPVAPLN
     GRIGGTSLSQ RRLTVGALVT FSCNDGHSLV GESSIICTEN GQWSHSPPFC KSQCPYPGDP
     PNGLIAPLKF NYDAGDYLSV QCRPGFVQSY EGPPERPKCQ PDGRWSGPMP KCKSYEEV
 
 
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