ZIC2_HUMAN
ID ZIC2_HUMAN Reviewed; 532 AA.
AC O95409; Q5VYA9; Q9H309;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2002, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Zinc finger protein ZIC 2;
DE AltName: Full=Zinc finger protein of the cerebellum 2;
GN Name=ZIC2;
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 [MRNA], AND CHARACTERIZATION OF VARIANT HPE5 POLY-ALA
RP INS.
RX PubMed=9771712; DOI=10.1038/2484;
RA Brown S.A., Warburton D., Brown L.Y., Yu C.Y., Roeder E.R.,
RA Stengel-Rutkowski S., Hennekam R.C.M., Muenke M.;
RT "Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-
RT paired.";
RL Nat. Genet. 20:180-183(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=10984499; DOI=10.1074/jbc.m007906200;
RA Yang Y., Hwang C.K., Junn E., Lee G., Mouradian M.M.;
RT "ZIC2 and Sp3 repress Sp1-induced activation of the human D1A dopamine
RT receptor gene.";
RL J. Biol. Chem. 275:38863-38869(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [4]
RP INTERACTION WITH DHX9.
RX PubMed=17251188; DOI=10.1074/jbc.m610821200;
RA Ishiguro A., Ideta M., Mikoshiba K., Chen D.J., Aruga J.;
RT "ZIC2-dependent transcriptional regulation is mediated by DNA-dependent
RT protein kinase, poly(ADP-ribose) polymerase, and RNA helicase A.";
RL J. Biol. Chem. 282:9983-9995(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [6]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-253, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [7]
RP VARIANTS HPE5 POLY-ALA INS AND PHE-152, AND POLYMORPHISM OF POLY-HIS
RP REGION.
RX PubMed=11285244; DOI=10.1093/hmg/10.8.791;
RA Brown L.Y., Odent S., David V., Blayau M., Dubourg C., Apacik C.,
RA Delgado M.A., Hall B.D., Reynolds J.F., Sommer A., Wieczorek D.,
RA Brown S.A., Muenke M.;
RT "Holoprosencephaly due to mutations in ZIC2: alanine tract expansion
RT mutations may be caused by parental somatic recombination.";
RL Hum. Mol. Genet. 10:791-796(2001).
RN [8]
RP VARIANTS HPE5 PRO-36 AND PHE-152, AND VARIANTS HIS-239 INS AND HIS-239 DEL.
RX PubMed=15221788; DOI=10.1002/humu.20056;
RA Dubourg C., Lazaro L., Pasquier L., Bendavid C., Blayau M., Le Duff F.,
RA Durou M.-R., Odent S., David V.;
RT "Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with
RT features of holoprosencephaly spectrum: mutation review and genotype-
RT phenotype correlations.";
RL Hum. Mutat. 24:43-51(2004).
RN [9]
RP CHARACTERIZATION OF VARIANTS HPE5 PRO-36; PHE-152 AND POLY-ALA INS.
RX PubMed=15590697; DOI=10.1093/hmg/ddi037;
RA Brown L., Paraso M., Arkell R., Brown S.;
RT "In vitro analysis of partial loss-of-function ZIC2 mutations in
RT holoprosencephaly: alanine tract expansion modulates DNA binding and
RT transactivation.";
RL Hum. Mol. Genet. 14:411-420(2005).
RN [10]
RP VARIANTS HPE5 ASN-37; ASN-128; ASN-272; LEU-286; GLN-286; TYR-286; TYR-291;
RP ARG-304; CYS-314; SER-325; LEU-325; TYR-327; PHE-335; PRO-373; ASN-402;
RP LYS-403; ARG-404; TRP-409 AND GLN-415.
RX PubMed=19177455; DOI=10.1002/humu.20982;
RA Roessler E., Lacbawan F., Dubourg C., Paulussen A., Herbergs J., Hehr U.,
RA Bendavid C., Zhou N., Ouspenskaia M., Bale S., Odent S., David V.,
RA Muenke M.;
RT "The full spectrum of holoprosencephaly-associated mutations within the
RT ZIC2 gene in humans predicts loss-of-function as the predominant disease
RT mechanism.";
RL Hum. Mutat. 30:E541-E554(2009).
CC -!- FUNCTION: Acts as a transcriptional activator or repressor. Plays
CC important roles in the early stage of organogenesis of the CNS.
CC Activates the transcription of the serotonin transporter SERT in
CC uncrossed ipsilateral retinal ganglion cells (iRGCs) to refine eye-
CC specific projections in primary visual targets. Its transcriptional
CC activity is repressed by MDFIC. Involved in the formation of the
CC ipsilateral retinal projection at the optic chiasm midline. Drives the
CC expression of EPHB1 on ipsilaterally projecting growth cones. Binds to
CC the minimal GLI-consensus sequence 5'-TGGGTGGTC-3'. Associates to the
CC basal SERT promoter region from ventrotemporal retinal segments of
CC retinal embryos.
CC -!- SUBUNIT: Interacts with RNF180. Interacts (via the C2H2-type domains 3,
CC 4 and 5) with MDFIC (via the C2H2-type domains 3, 4 and 5); the
CC interaction reduces its transcriptional activity. Interacts with GLI1
CC and GLI2 (By similarity). Interacts (via C2H2-type domain 3) with DHX9
CC (PubMed:17251188). {ECO:0000250|UniProtKB:Q62520,
CC ECO:0000269|PubMed:17251188}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm {ECO:0000250}. Note=Localizes
CC in the cytoplasm in presence of MDFIC overexpression. Both
CC phosphorylated and unphosphorylated forms are localized in the nucleus
CC (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The C2H2-type 3, 4 and 5 zinc finger domains are necessary for
CC transcription activation. {ECO:0000250}.
CC -!- PTM: Phosphorylated.
CC -!- PTM: Ubiquitinated by RNF180, leading to its degradation.
CC -!- POLYMORPHISM: The poly-His region between amino acids 231-239 of ZIC2
CC is polymorphic and the number of His can vary from 8 to 12.
CC {ECO:0000269|PubMed:11285244}.
CC -!- DISEASE: Holoprosencephaly 5 (HPE5) [MIM:609637]: A structural anomaly
CC of the brain, in which the developing forebrain fails to correctly
CC separate into right and left hemispheres. Holoprosencephaly is
CC genetically heterogeneous and associated with several distinct facies
CC and phenotypic variability. {ECO:0000269|PubMed:11285244,
CC ECO:0000269|PubMed:15221788, ECO:0000269|PubMed:15590697,
CC ECO:0000269|PubMed:19177455, ECO:0000269|PubMed:9771712}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
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DR EMBL; AF104902; AAC96325.1; -; mRNA.
DR EMBL; AF193855; AAG28409.1; -; mRNA.
DR EMBL; AL355338; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS9495.1; -.
DR RefSeq; NP_009060.2; NM_007129.3.
DR AlphaFoldDB; O95409; -.
DR SMR; O95409; -.
DR BioGRID; 113378; 41.
DR IntAct; O95409; 5.
DR MINT; O95409; -.
DR STRING; 9606.ENSP00000365514; -.
DR iPTMnet; O95409; -.
DR PhosphoSitePlus; O95409; -.
DR BioMuta; ZIC2; -.
DR EPD; O95409; -.
DR jPOST; O95409; -.
DR MassIVE; O95409; -.
DR MaxQB; O95409; -.
DR PaxDb; O95409; -.
DR PeptideAtlas; O95409; -.
DR PRIDE; O95409; -.
DR ProteomicsDB; 50861; -.
DR Antibodypedia; 10980; 186 antibodies from 31 providers.
DR DNASU; 7546; -.
DR Ensembl; ENST00000376335.8; ENSP00000365514.3; ENSG00000043355.12.
DR GeneID; 7546; -.
DR KEGG; hsa:7546; -.
DR MANE-Select; ENST00000376335.8; ENSP00000365514.3; NM_007129.5; NP_009060.2.
DR UCSC; uc001von.4; human.
DR CTD; 7546; -.
DR DisGeNET; 7546; -.
DR GeneCards; ZIC2; -.
DR GeneReviews; ZIC2; -.
DR HGNC; HGNC:12873; ZIC2.
DR HPA; ENSG00000043355; Group enriched (brain, choroid plexus).
DR MalaCards; ZIC2; -.
DR MIM; 603073; gene.
DR MIM; 609637; phenotype.
DR neXtProt; NX_O95409; -.
DR OpenTargets; ENSG00000043355; -.
DR Orphanet; 93925; Alobar holoprosencephaly.
DR Orphanet; 93924; Lobar holoprosencephaly.
DR Orphanet; 280200; Microform holoprosencephaly.
DR Orphanet; 93926; Midline interhemispheric variant of holoprosencephaly.
DR Orphanet; 220386; Semilobar holoprosencephaly.
DR Orphanet; 280195; Septopreoptic holoprosencephaly.
DR PharmGKB; PA37462; -.
DR VEuPathDB; HostDB:ENSG00000043355; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000160645; -.
DR HOGENOM; CLU_002678_37_1_1; -.
DR InParanoid; O95409; -.
DR OMA; GRSDQYR; -.
DR OrthoDB; 768287at2759; -.
DR PhylomeDB; O95409; -.
DR TreeFam; TF351425; -.
DR PathwayCommons; O95409; -.
DR SignaLink; O95409; -.
DR SIGNOR; O95409; -.
DR BioGRID-ORCS; 7546; 29 hits in 1108 CRISPR screens.
DR ChiTaRS; ZIC2; human.
DR GeneWiki; ZIC2; -.
DR GenomeRNAi; 7546; -.
DR Pharos; O95409; Tbio.
DR PRO; PR:O95409; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; O95409; protein.
DR Bgee; ENSG00000043355; Expressed in cerebellar cortex and 114 other tissues.
DR ExpressionAtlas; O95409; baseline and differential.
DR Genevisible; O95409; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; TAS:ProtInc.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; ISS:UniProtKB.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR InterPro; IPR041643; Znf_ZIC.
DR Pfam; PF00096; zf-C2H2; 3.
DR Pfam; PF18366; zf_ZIC; 1.
DR SMART; SM00355; ZnF_C2H2; 5.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 1: Evidence at protein level;
KW Activator; Cytoplasm; Developmental protein; Differentiation;
KW Disease variant; DNA-binding; Holoprosencephaly; Isopeptide bond;
KW Metal-binding; Neurogenesis; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Repressor; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..532
FT /note="Zinc finger protein ZIC 2"
FT /id="PRO_0000047247"
FT ZN_FING 256..291
FT /note="C2H2-type 1; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 300..327
FT /note="C2H2-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 333..357
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 363..387
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 393..415
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 100..255
FT /note="Necessary for interaction with MDFIC and
FT transcriptional activation or repression"
FT /evidence="ECO:0000250"
FT REGION 406..452
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 475..532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 418..452
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 514..532
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 191
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62520"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62520"
FT CROSSLNK 253
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 36
FT /note="Q -> P (in HPE5; 2-fold increase in luciferase
FT activity; dbSNP:rs1185333947)"
FT /evidence="ECO:0000269|PubMed:15221788,
FT ECO:0000269|PubMed:15590697"
FT /id="VAR_023793"
FT VARIANT 37
FT /note="D -> N (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058592"
FT VARIANT 128
FT /note="D -> N (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058593"
FT VARIANT 152
FT /note="D -> F (in HPE5; requires 2 nucleotide
FT substitutions; 50% reduction of luciferase activity)"
FT /evidence="ECO:0000269|PubMed:11285244,
FT ECO:0000269|PubMed:15221788, ECO:0000269|PubMed:15590697"
FT /id="VAR_023794"
FT VARIANT 239
FT /note="H -> HH"
FT /evidence="ECO:0000269|PubMed:15221788"
FT /id="VAR_023795"
FT VARIANT 239
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:15221788"
FT /id="VAR_023796"
FT VARIANT 272
FT /note="S -> N (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058594"
FT VARIANT 286
FT /note="H -> L (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058595"
FT VARIANT 286
FT /note="H -> Q (in HPE5; dbSNP:rs1325393230)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058596"
FT VARIANT 286
FT /note="H -> Y (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058597"
FT VARIANT 291
FT /note="H -> Y (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058598"
FT VARIANT 304
FT /note="W -> R (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058599"
FT VARIANT 314
FT /note="F -> C (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058600"
FT VARIANT 325
FT /note="R -> L (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058601"
FT VARIANT 325
FT /note="R -> S (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058602"
FT VARIANT 327
FT /note="H -> Y (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058603"
FT VARIANT 335
FT /note="C -> F (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058604"
FT VARIANT 373
FT /note="R -> P (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058605"
FT VARIANT 402
FT /note="Y -> N (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058606"
FT VARIANT 403
FT /note="T -> K (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058607"
FT VARIANT 404
FT /note="H -> R (in HPE5)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058608"
FT VARIANT 409
FT /note="R -> W (in HPE5; dbSNP:rs1594291868)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058609"
FT VARIANT 415
FT /note="H -> Q (in HPE5; dbSNP:rs794729641)"
FT /evidence="ECO:0000269|PubMed:19177455"
FT /id="VAR_058610"
FT VARIANT 470
FT /note="A -> AAAAAAAAAAA (in HPE5; near-complete loss of
FT luciferase activity)"
FT /id="VAR_008856"
FT CONFLICT 124..128
FT /note="RGFGD -> ARLPGT (in Ref. 1; AAC96325)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 532 AA; 55006 MW; BA3E6455DAF97EAC CRC64;
MLLDAGPQFP AIGVGSFARH HHHSAAAAAA AAAEMQDREL SLAAAQNGFV DSAAAHMGAF
KLNPGAHELS PGQSSAFTSQ GPGAYPGSAA AAAAAAALGP HAAHVGSYSG PPFNSTRDFL
FRSRGFGDSA PGGGQHGLFG PGAGGLHHAH SDAQGHLLFP GLPEQHGPHG SQNVLNGQMR
LGLPGEVFGR SEQYRQVASP RTDPYSAAQL HNQYGPMNMN MGMNMAAAAA HHHHHHHHHP
GAFFRYMRQQ CIKQELICKW IDPEQLSNPK KSCNKTFSTM HELVTHVSVE HVGGPEQSNH
VCFWEECPRE GKPFKAKYKL VNHIRVHTGE KPFPCPFPGC GKVFARSENL KIHKRTHTGE
KPFQCEFEGC DRRFANSSDR KKHMHVHTSD KPYLCKMCDK SYTHPSSLRK HMKVHESSPQ
GSESSPAASS GYESSTPPGL VSPSAEPQSS SNLSPAAAAA AAAAAAAAAA VSAVHRGGGS
GSGGAGGGSG GGSGSGGGGG GAGGGGGGSS GGGSGTAGGH SGLSSNFNEW YV
