SYCP3_HUMAN
ID SYCP3_HUMAN Reviewed; 236 AA.
AC Q8IZU3;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Synaptonemal complex protein 3;
DE Short=SCP-3;
GN Name=SYCP3; Synonyms=SCP3;
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 TISSUE SPECIFICITY.
RX PubMed=12213195; DOI=10.1006/geno.2002.6834;
RA Martinez-Garay I., Jablonka S., Sutajova M., Steuernagel P., Gal A.,
RA Kutsche K.;
RT "A new gene family (FAM9) of low-copy repeats in Xp22.3 expressed
RT exclusively in testis: implications for recombinations in this region.";
RL Genomics 80:259-267(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Adamah D.J.B., Gokhale P.J., Walsh J., Andrews P.W., Martinez Garay I.,
RA Kutsche K.;
RT "A notch-related gene located on the long arm of human chromosome 12.";
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND INVOLVEMENT IN SPGF4.
RX PubMed=14643120; DOI=10.1016/s0140-6736(03)14845-3;
RA Miyamoto T., Hasuike S., Yogev L., Maduro M.R., Ishikawa M., Westphal H.,
RA Lamb D.J.;
RT "Azoospermia in patients heterozygous for a mutation in SYCP3.";
RL Lancet 362:1714-1719(2003).
RN [5]
RP INVOLVEMENT IN RPRGL4.
RX PubMed=19110213; DOI=10.1016/j.ajhg.2008.12.002;
RA Bolor H., Mori T., Nishiyama S., Ito Y., Hosoba E., Inagaki H., Kogo H.,
RA Ohye T., Tsutsumi M., Kato T., Tong M., Nishizawa H., Pryor-Koishi K.,
RA Kitaoka E., Sawada T., Nishiyama Y., Udagawa Y., Kurahashi H.;
RT "Mutations of the SYCP3 gene in women with recurrent pregnancy loss.";
RL Am. J. Hum. Genet. 84:14-20(2009).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 66-230, ELECTRON MICROSCOPY,
RP SUBUNIT, DNA-BINDING, DOMAIN, REGION, AND MUTAGENESIS OF 52-LYS--ARG-57;
RP 69-GLU--LEU-74; 88-LYS--ARG-91 AND 231-LEU--PHE-236.
RX PubMed=24950965; DOI=10.7554/elife.02963;
RA Syrjanen J.L., Pellegrini L., Davies O.R.;
RT "A molecular model for the role of SYCP3 in meiotic chromosome
RT organisation.";
RL Elife 3:0-0(2014).
CC -!- FUNCTION: Component of the synaptonemal complexes (SCS), formed between
CC homologous chromosomes during meiotic prophase. Required for centromere
CC pairing during meiosis in male germ cells (By similarity). Required for
CC normal meiosis during spermatogenesis and male fertility
CC (PubMed:14643120). Plays a lesser role in female fertility. Required
CC for efficient phosphorylation of HORMAD1 and HORMAD2 (By similarity).
CC {ECO:0000250|UniProtKB:P70281, ECO:0000269|PubMed:14643120}.
CC -!- SUBUNIT: Component of the lateral elements of synaptonemal complexes
CC (By similarity). Homotetramer; the tetrameric helix bundles assemble
CC end to end into long homopolimeric fibers that exhibit a transversal
CC striation with a periodicity of about 20 nm (in vitro)
CC (PubMed:24950965). Interacts with SYCP2 (By similarity). Forms a
CC complex with EWSR1, PRDM9, REC8 and SYCP1; complex formation is
CC dependent of phosphorylated form of REC8 and requires PRDM9 bound to
CC hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8
CC (By similarity). {ECO:0000250|UniProtKB:P70281,
CC ECO:0000250|UniProtKB:Q63520, ECO:0000269|PubMed:24950965}.
CC -!- INTERACTION:
CC Q8IZU3; Q9NWQ9: C14orf119; NbExp=3; IntAct=EBI-7574149, EBI-725606;
CC Q8IZU3; Q16543: CDC37; NbExp=3; IntAct=EBI-7574149, EBI-295634;
CC Q8IZU3; Q9UBU9: NXF1; NbExp=3; IntAct=EBI-7574149, EBI-398874;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q60547}.
CC Chromosome {ECO:0000250|UniProtKB:Q60547}. Chromosome, centromere
CC {ECO:0000250|UniProtKB:Q60547}. Note=It is present in early unpaired
CC cores, in the lateral domains of the synaptonemal complex and in the
CC chromosome cores when they separate at diplotene. It is found axial to
CC the metaphase I chromosomes and in association with pairs of sister
CC centromeres. The centromere-associated protein becomes dissociated from
CC the centromeres at anaphase II and is not found in mitotic metaphase
CC centromeres. {ECO:0000250|UniProtKB:Q60547}.
CC -!- TISSUE SPECIFICITY: Testis-specific. {ECO:0000269|PubMed:12213195,
CC ECO:0000269|PubMed:14643120}.
CC -!- DOMAIN: Composed of a long central coiled coil domain. The N-terminal
CC and C-terminal regions interact with DNA.
CC {ECO:0000269|PubMed:24950965}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:P70281}.
CC -!- DISEASE: Spermatogenic failure 4 (SPGF4) [MIM:270960]: An infertility
CC disorder characterized by azoospermia, a condition of having no sperm
CC present in the ejaculate. Testicular histology shows arrest of
CC spermatogenesis at the pachytene stage of primary spermatocytes.
CC {ECO:0000269|PubMed:14643120}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Pregnancy loss, recurrent, 4 (RPRGL4) [MIM:270960]: A common
CC complication of pregnancy, resulting in spontaneous abortion before the
CC fetus has reached viability. The term includes all miscarriages from
CC the time of conception until 24 weeks of gestation. Recurrent pregnancy
CC loss is defined as 3 or more consecutive spontaneous abortions.
CC {ECO:0000269|PubMed:19110213}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the XLR/SYCP3 family. {ECO:0000305}.
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DR EMBL; AF492003; AAN06611.1; -; mRNA.
DR EMBL; AF517774; AAP47204.1; -; mRNA.
DR EMBL; BC062662; AAH62662.1; -; mRNA.
DR CCDS; CCDS9087.1; -.
DR RefSeq; NP_001171419.1; NM_001177948.1.
DR RefSeq; NP_001171420.1; NM_001177949.1.
DR RefSeq; NP_710161.1; NM_153694.4.
DR PDB; 4CPC; X-ray; 2.24 A; A/B/C/D/E/F/G/H=66-230.
DR PDBsum; 4CPC; -.
DR AlphaFoldDB; Q8IZU3; -.
DR SMR; Q8IZU3; -.
DR BioGRID; 119081; 19.
DR DIP; DIP-59536N; -.
DR IntAct; Q8IZU3; 6.
DR MINT; Q8IZU3; -.
DR STRING; 9606.ENSP00000376658; -.
DR iPTMnet; Q8IZU3; -.
DR PhosphoSitePlus; Q8IZU3; -.
DR BioMuta; SYCP3; -.
DR DMDM; 74728444; -.
DR MassIVE; Q8IZU3; -.
DR PaxDb; Q8IZU3; -.
DR PeptideAtlas; Q8IZU3; -.
DR PRIDE; Q8IZU3; -.
DR ProteomicsDB; 71431; -.
DR Antibodypedia; 30441; 468 antibodies from 31 providers.
DR DNASU; 50511; -.
DR Ensembl; ENST00000266743.6; ENSP00000266743.2; ENSG00000139351.15.
DR Ensembl; ENST00000392924.2; ENSP00000376655.1; ENSG00000139351.15.
DR Ensembl; ENST00000392927.7; ENSP00000376658.3; ENSG00000139351.15.
DR GeneID; 50511; -.
DR KEGG; hsa:50511; -.
DR MANE-Select; ENST00000392924.2; ENSP00000376655.1; NM_001177949.2; NP_001171420.1.
DR UCSC; uc001tiq.4; human.
DR CTD; 50511; -.
DR DisGeNET; 50511; -.
DR GeneCards; SYCP3; -.
DR HGNC; HGNC:18130; SYCP3.
DR HPA; ENSG00000139351; Tissue enriched (testis).
DR MalaCards; SYCP3; -.
DR MIM; 270960; phenotype.
DR MIM; 604759; gene.
DR neXtProt; NX_Q8IZU3; -.
DR OpenTargets; ENSG00000139351; -.
DR Orphanet; 399805; Male infertility with azoospermia or oligozoospermia due to single gene mutation.
DR PharmGKB; PA38298; -.
DR VEuPathDB; HostDB:ENSG00000139351; -.
DR eggNOG; ENOG502R883; Eukaryota.
DR GeneTree; ENSGT00390000000062; -.
DR HOGENOM; CLU_101820_2_0_1; -.
DR InParanoid; Q8IZU3; -.
DR OMA; TPVMDKH; -.
DR OrthoDB; 1547468at2759; -.
DR PhylomeDB; Q8IZU3; -.
DR TreeFam; TF328876; -.
DR PathwayCommons; Q8IZU3; -.
DR Reactome; R-HSA-1221632; Meiotic synapsis.
DR SignaLink; Q8IZU3; -.
DR SIGNOR; Q8IZU3; -.
DR BioGRID-ORCS; 50511; 8 hits in 1029 CRISPR screens.
DR GeneWiki; SYCP3; -.
DR GenomeRNAi; 50511; -.
DR Pharos; Q8IZU3; Tbio.
DR PRO; PR:Q8IZU3; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8IZU3; protein.
DR Bgee; ENSG00000139351; Expressed in right testis and 108 other tissues.
DR ExpressionAtlas; Q8IZU3; baseline and differential.
DR Genevisible; Q8IZU3; HS.
DR GO; GO:0000775; C:chromosome, centromeric region; ISS:UniProtKB.
DR GO; GO:0000800; C:lateral element; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000795; C:synaptonemal complex; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007141; P:male meiosis I; NAS:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IBA:GO_Central.
DR GO; GO:0007286; P:spermatid development; IBA:GO_Central.
DR GO; GO:0035093; P:spermatogenesis, exchange of chromosomal proteins; IMP:UniProtKB.
DR InterPro; IPR006888; XLR/SYCP3/FAM9_dom.
DR Pfam; PF04803; Cor1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Cell division; Centromere; Chromosome;
KW Coiled coil; DNA-binding; Meiosis; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..236
FT /note="Synaptonemal complex protein 3"
FT /id="PRO_0000229024"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 52..57
FT /note="Interaction with DNA"
FT /evidence="ECO:0000269|PubMed:24950965"
FT REGION 69..74
FT /note="Important for oligomerization and fiber formation"
FT /evidence="ECO:0000269|PubMed:24950965"
FT REGION 88..91
FT /note="Interaction with DNA"
FT /evidence="ECO:0000269|PubMed:24950965"
FT REGION 231..236
FT /note="Important for oligomerization and fiber formation"
FT /evidence="ECO:0000269|PubMed:24950965"
FT COILED 66..223
FT /evidence="ECO:0000255, ECO:0000269|PubMed:24950965"
FT MOTIF 88..91
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 11..40
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 36
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70281"
FT MOD_RES 38
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63520"
FT MOD_RES 59
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70281"
FT MUTAGEN 52..57
FT /note="KRRKKR->AAAAAA: Impairs DNA binding. Abolishes DNA
FT binding; when associated with 88-A--A-91."
FT /evidence="ECO:0000269|PubMed:24950965"
FT MUTAGEN 69..74
FT /note="EVQNML->AAAAAA: Abolishes fiber formation."
FT /evidence="ECO:0000269|PubMed:24950965"
FT MUTAGEN 88..91
FT /note="KRKR->AAAA: Impairs DNA binding. Abolishes DNA
FT binding; when associated with 52-A--A-57."
FT /evidence="ECO:0000269|PubMed:24950965"
FT MUTAGEN 231..236
FT /note="Missing: Abolishes fiber formation."
FT /evidence="ECO:0000269|PubMed:24950965"
FT HELIX 71..77
FT /evidence="ECO:0007829|PDB:4CPC"
FT HELIX 82..219
FT /evidence="ECO:0007829|PDB:4CPC"
SQ SEQUENCE 236 AA; 27729 MW; D871B6AEA279ABDD CRC64;
MVSSGKKYSR KSGKPSVEDQ FTRAYDFETE DKKDLSGSEE DVIEGKTAVI EKRRKKRSSA
GVVEDMGGEV QNMLEGVGVD INKALLAKRK RLEMYTKASL KTSNQKIEHV WKTQQDQRQK
LNQEYSQQFL TLFQQWDLDM QKAEEQEEKI LNMFRQQQKI LQQSRIVQSQ RLKTIKQLYE
QFIKSMEELE KNHDNLLTGA QNEFKKEMAM LQKKIMMETQ QQEIASVRKS LQSMLF
