HAP2_PLABA
ID HAP2_PLABA Reviewed; 828 AA.
AC Q4YCF6; A0A509AQL1;
DT 10-MAY-2017, integrated into UniProtKB/Swiss-Prot.
DT 07-APR-2021, sequence version 2.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Hapless 2;
DE AltName: Full=Generative cell specific-1 {ECO:0000303|PubMed:18403203};
DE Flags: Precursor;
GN Name=HAP2 {ECO:0000303|PubMed:18367645};
GN Synonyms=GCS1 {ECO:0000303|PubMed:18403203, ECO:0000303|PubMed:21209845};
GN ORFNames=PBANKA_1212600 {ECO:0000312|EMBL:VUC57025.1};
OS Plasmodium berghei (strain Anka).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Vinckeia).
OX NCBI_TaxID=5823;
RN [1] {ECO:0000312|Proteomes:UP000074855}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ANKA {ECO:0000312|Proteomes:UP000074855};
RX PubMed=25359557; DOI=10.1186/s12915-014-0086-0;
RA Otto T.D., Bohme U., Jackson A.P., Hunt M., Franke-Fayard B.,
RA Hoeijmakers W.A., Religa A.A., Robertson L., Sanders M., Ogun S.A.,
RA Cunningham D., Erhart A., Billker O., Khan S.M., Stunnenberg H.G.,
RA Langhorne J., Holder A.A., Waters A.P., Newbold C.I., Pain A., Berriman M.,
RA Janse C.J.;
RT "A comprehensive evaluation of rodent malaria parasite genomes and gene
RT expression.";
RL BMC Biol. 12:86-86(2014).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=18403203; DOI=10.1016/j.cub.2008.03.045;
RA Hirai M., Arai M., Mori T., Miyagishima S.Y., Kawai S., Kita K.,
RA Kuroiwa T., Terenius O., Matsuoka H.;
RT "Male fertility of malaria parasites is determined by GCS1, a plant-type
RT reproduction factor.";
RL Curr. Biol. 18:607-613(2008).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18367645; DOI=10.1101/gad.1656508;
RA Liu Y., Tewari R., Ning J., Blagborough A.M., Garbom S., Pei J.,
RA Grishin N.V., Steele R.E., Sinden R.E., Snell W.J., Billker O.;
RT "The conserved plant sterility gene HAP2 functions after attachment of
RT fusogenic membranes in Chlamydomonas and Plasmodium gametes.";
RL Genes Dev. 22:1051-1068(2008).
RN [4]
RP FUNCTION, DOMAIN, AND SUBCELLULAR LOCATION.
RX PubMed=21209845; DOI=10.1371/journal.pone.0015957;
RA Mori T., Hirai M., Kuroiwa T., Miyagishima S.Y.;
RT "The functional domain of GCS1-based gamete fusion resides in the amino
RT terminus in plant and parasite species.";
RL PLoS ONE 5:E15957-E15957(2010).
RN [5]
RP REVIEW.
RX PubMed=20080406; DOI=10.1016/j.tcb.2009.12.007;
RA Wong J.L., Johnson M.A.;
RT "Is HAP2-GCS1 an ancestral gamete fusogen?";
RL Trends Cell Biol. 20:134-141(2010).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND BIOTECHNOLOGY.
RX PubMed=29212032; DOI=10.1016/j.celrep.2017.11.024;
RA Angrisano F., Sala K.A., Da D.F., Liu Y., Pei J., Grishin N.V., Snell W.J.,
RA Blagborough A.M.;
RT "Targeting the Conserved Fusion Loop of HAP2 Inhibits the Transmission of
RT Plasmodium berghei and falciparum.";
RL Cell Rep. 21:2868-2878(2017).
CC -!- FUNCTION: During fertilization, required on male gametes for their
CC fusion with female gametes, and for subsequent ookinete formation in
CC the host (PubMed:18403203, PubMed:18367645, PubMed:21209845,
CC PubMed:29212032). Thereby, required for mosquito-mediated transmission
CC to other animals (PubMed:18403203, PubMed:18367645, PubMed:29212032).
CC Probably initiates the fusion of gamete cell membranes by inserting
CC part of its extracellular domain into the cell membrane of a female
CC gamete (PubMed:20080406). {ECO:0000269|PubMed:18367645,
CC ECO:0000269|PubMed:18403203, ECO:0000269|PubMed:21209845,
CC ECO:0000269|PubMed:29212032, ECO:0000303|PubMed:20080406}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:29212032,
CC ECO:0000305|PubMed:18367645, ECO:0000305|PubMed:21209845}; Single-pass
CC type I membrane protein {ECO:0000269|PubMed:29212032,
CC ECO:0000305|PubMed:18367645, ECO:0000305|PubMed:21209845}.
CC -!- DEVELOPMENTAL STAGE: Detected in male gametocytes and gametes, but not
CC in female gametes, nor in the asexual stages present in host
CC erythrocytes (at protein level). {ECO:0000269|PubMed:18367645,
CC ECO:0000269|PubMed:18403203, ECO:0000269|PubMed:29212032}.
CC -!- DOMAIN: The N-terminal extracellular domain is important for gamete
CC fusion. {ECO:0000269|PubMed:21209845}.
CC -!- DISRUPTION PHENOTYPE: No effect on gametogenesis, but abolishes the
CC ability of male gametes to merge with female gates. As a consequence,
CC fertilization cannot occur, the normal life cycle is disrupted and
CC mosquito-mediated transmission is abolished.
CC {ECO:0000269|PubMed:18367645, ECO:0000269|PubMed:18403203}.
CC -!- BIOTECHNOLOGY: Potential candidate for the development of parasite
CC sexual stage vaccines. In vitro and in vivo, neutralizing antibodies
CC against the cd loop prevent gamete fertilization and thus transmission.
CC {ECO:0000269|PubMed:29212032}.
CC -!- MISCELLANEOUS: HAP2/GCS1 family members mediate membrane fusion between
CC gametes in a broad range of eukaryotes, ranging from algae and higher
CC plants to protozoans and cnidaria, suggesting they are derived from an
CC ancestral gamete fusogen. They function similar to viral fusogens, by
CC inserting part of their extracellular domain into the lipid bilayer of
CC an adjoining cell. {ECO:0000303|PubMed:20080406}.
CC -!- SIMILARITY: Belongs to the HAP2/GCS1 family. {ECO:0000305}.
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DR EMBL; LK023127; VUC57025.1; -; Genomic_DNA.
DR RefSeq; XP_676900.1; XM_671808.1.
DR PDB; 7LR3; X-ray; 2.80 A; C/D=502-618.
DR PDB; 7LR4; X-ray; 2.10 A; C/D=502-618.
DR PDBsum; 7LR3; -.
DR PDBsum; 7LR4; -.
DR AlphaFoldDB; Q4YCF6; -.
DR SMR; Q4YCF6; -.
DR STRING; 5821.PBANKA_121260; -.
DR TCDB; 1.N.3.1.7; the hapless2 male gamete fusion factor (fusexin) family.
DR VEuPathDB; PlasmoDB:PBANKA_1212600; -.
DR eggNOG; ENOG502SE1K; Eukaryota.
DR InParanoid; Q4YCF6; -.
DR OMA; EVYEIRP; -.
DR Proteomes; UP000074855; Chromosome 12.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IMP:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0009566; P:fertilization; IMP:UniProtKB.
DR GO; GO:0007342; P:fusion of sperm to egg plasma membrane involved in single fertilization; IMP:UniProtKB.
DR InterPro; IPR040326; HAP2/GCS1.
DR PANTHER; PTHR31764; PTHR31764; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; Fertilization; Glycoprotein;
KW Lipid-binding; Membrane; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..828
FT /note="Hapless 2"
FT /evidence="ECO:0000255"
FT /id="PRO_0000439930"
FT TOPO_DOM 33..680
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:29212032"
FT TRANSMEM 681..701
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 702..828
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 174..191
FT /note="cd loop; involved in gamete fusion"
FT /evidence="ECO:0000269|PubMed:29212032"
FT REGION 773..828
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 775..798
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 233
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 250
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 293
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 479
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 516
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 531
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 539
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 53..62
FT /evidence="ECO:0000250|UniProtKB:A4GRC6"
FT DISULFID 142..209
FT /evidence="ECO:0000250|UniProtKB:A4GRC6"
FT DISULFID 170..381
FT /evidence="ECO:0000250|UniProtKB:A4GRC6"
FT DISULFID 172..191
FT /evidence="ECO:0000250|UniProtKB:A4GRC6"
FT DISULFID 363..388
FT /evidence="ECO:0000250|UniProtKB:A4GRC6"
FT DISULFID 546..592
FT /evidence="ECO:0000250|UniProtKB:A4GRC6"
FT STRAND 503..508
FT /evidence="ECO:0007829|PDB:7LR4"
FT STRAND 522..530
FT /evidence="ECO:0007829|PDB:7LR4"
FT STRAND 538..547
FT /evidence="ECO:0007829|PDB:7LR4"
FT STRAND 551..553
FT /evidence="ECO:0007829|PDB:7LR3"
FT STRAND 556..558
FT /evidence="ECO:0007829|PDB:7LR3"
FT STRAND 564..568
FT /evidence="ECO:0007829|PDB:7LR4"
FT STRAND 573..581
FT /evidence="ECO:0007829|PDB:7LR4"
FT STRAND 590..597
FT /evidence="ECO:0007829|PDB:7LR4"
FT STRAND 603..611
FT /evidence="ECO:0007829|PDB:7LR4"
SQ SEQUENCE 828 AA; 95824 MW; 17D7255CDE8D7D27 CRC64;
MKNKLINLRS KHIYKLIIII FFCIILKYYK WCDFKNKVFF IQLVYSFAKK SVCTSSLDDS
TCHTVTFGEL DVSNNSVVRL KVMRKGGKGY FLTIRRDYVT VSYYLKYVKD IPLEFREIID
IFNNHKFEQY TQEQINKYTY TCNVRKIEDI DKYDEKNPTK FHEYTRGEAC RCQTYNYFKD
DEFIKRAKLK CIYYNMLFTE SATVYSRHCP IIDLMHFAVY DIEYPPIFNT IVNITIEEYY
YNDVSSVLNN KSDLVTKEKK YQLNDTITEI RDDYFDLWLF LKGETHGKRT LVNLSNDYIV
IPSSPINNRD VIASDITRNC GLSQNSPLLK GCNYSSICNI MHPCLRKAMM LPKYMFDLSG
KTCGKLGVSL NTWRKSEGNF CGSEAGYCIS NNLKKYYDIH NSASIKDGIS LSKYKIKNIY
NSEPQTKIYE SYKLPDYLKD KIKNNNHAEM DENDLDNKIF YKPNVAAHSQ FIDYKYNGNH
SVEIKFETDA IEVYEIRPVS IATITHVTIP NDCASNNSNS NECVLIIHVW NNSKFVGSNF
SCSIACTNKE TDQLASHINP IAPVRAFIGP NKNYAFYFII KFLINKEITT LCKAIVKDSN
GKECSIEEFE LQSKESVHIV ESEVDETTDQ VVVEHHTQSP DIKNPDEYVC KCTINLLCYV
INFKTCSNYY INTVKTLIGK FAIIAILIIL APALIPLLPF FLNFFFLFIS TILKLYQSII
STIGQIRIRN NDKPIIYKKK IHDMKTNYLS VSSYSSLSDS SSIYSTDSVS SMRKNKKKFN
KNNISSNIKH KKGGKKVKQK EPNRNSNHTS HEYADTSPSG KSKIPPLR
