SPAG4_MOUSE
ID SPAG4_MOUSE Reviewed; 443 AA.
AC Q9JJF2; A3KGK4;
DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Sperm-associated antigen 4 protein;
DE AltName: Full=Outer dense fiber-associated protein SPAG4;
DE AltName: Full=SUN domain-containing protein 4;
GN Name=Spag4; ORFNames=MNCb-0953, Sun4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Osada N., Kusuda J., Tanuma R., Ito A., Hirata M., Sugano S., Hashimoto K.;
RT "Isolation of full-length cDNA clones from mouse brain cDNA library made by
RT oligo-capping method.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-274 (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=11042159; DOI=10.1101/gr.145100;
RA Carninci P., Shibata Y., Hayatsu N., Sugahara Y., Shibata K., Itoh M.,
RA Konno H., Okazaki Y., Muramatsu M., Hayashizaki Y.;
RT "Normalization and subtraction of cap-trapper-selected cDNAs to prepare
RT full-length cDNA libraries for rapid discovery of new genes.";
RL Genome Res. 10:1617-1630(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-443 (ISOFORM 1).
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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=10373309; DOI=10.1006/dbio.1999.9297;
RA Shao X., Tarnasky H.A., Lee J.P., Oko R., van der Hoorn F.A.;
RT "Spag4, a novel sperm protein, binds outer dense-fiber protein Odf1 and
RT localizes to microtubules of manchette and axoneme.";
RL Dev. Biol. 211:109-123(1999).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, FUNCTION,
RP INTERACTION WITH SUN3 AND SYNE1; SELF-ASSOCIATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=26621829; DOI=10.1242/bio.015768;
RA Pasch E., Link J., Beck C., Scheuerle S., Alsheimer M.;
RT "The LINC complex component Sun4 plays a crucial role in sperm head
RT formation and fertility.";
RL Biol. Open 4:1792-1802(2015).
CC -!- FUNCTION: Involved in spermatogenesis. Required for sperm head
CC formation but not required to establish and maintain general polarity
CC of the sperm head. Required for anchoring and organization of the
CC manchette. Required for targeting of SUN3 and probably SYNE1 through a
CC probable SUN1:SYNE3 LINC complex to the nuclear envelope and involved
CC in accurate posterior sperm head localization of the complex. May
CC anchor SUN3 the nuclear envelope. Involved in maintenance of the
CC nuclear envelope integrity. May assist the organization and assembly of
CC outer dense fibers (ODFs), a specific structure of the sperm tail.
CC {ECO:0000269|PubMed:26621829}.
CC -!- SUBUNIT: Self-associates. Interacts with ODF1. May associate with
CC microtubules (By similarity). Interacts with SUN3 and SYNE1; suggesting
CC the formation of a spermatogenesis-specific LINC complex; a SUN domain-
CC based heterotrimer of SPAG4 and SUN3 may associate with SYNE1
CC (PubMed:26621829). Interacts with SEPT12 and LMNB1; during
CC spermatogenesis (By similarity). {ECO:0000250|UniProtKB:O55034,
CC ECO:0000250|UniProtKB:Q9NPE6, ECO:0000269|PubMed:26621829}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Cytoplasm, cytoskeleton {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Membrane {ECO:0000305}; Multi-pass
CC membrane protein {ECO:0000305}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:O55034}. Nucleus envelope
CC {ECO:0000269|PubMed:26621829}. Nucleus inner membrane {ECO:0000305}.
CC Cytoplasm, cytoskeleton, flagellum axoneme
CC {ECO:0000250|UniProtKB:O55034}. Note=In spermatids, isoform 1 is
CC localized in the transient manchette and in the axoneme of elongating
CC spermatids and epididymal sperm (By similarity). Conflictingly is not
CC found in axoneme but only associated with the manchette where
CC cytoplasmic microtubules contact the nuclear envelope. Localizes at the
CC posterior lateral side of round and elongating spermatids
CC (PubMed:26621829). {ECO:0000250|UniProtKB:O55034,
CC ECO:0000269|PubMed:26621829}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9JJF2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JJF2-2; Sequence=VSP_005958, VSP_005959;
CC -!- TISSUE SPECIFICITY: Isoform 1 is testis specific and is exclusively
CC expressed in spermatids. {ECO:0000269|PubMed:10373309,
CC ECO:0000269|PubMed:26621829}.
CC -!- DEVELOPMENTAL STAGE: Weakly expressed at day 18 p.p. and increased
CC expression at day 21-25 p.p. with increasing spermatid numbers.
CC {ECO:0000269|PubMed:26621829}.
CC -!- DISRUPTION PHENOTYPE: Male infertility with severe defects in sperm
CC head formation and globozoospermia-like phenotype.
CC {ECO:0000269|PubMed:26621829}.
CC -!- CAUTION: Although transmembrane domains are strongly predicted, they
CC may rather represent hydrophobic globular domains associated with
CC microtubules. {ECO:0000305}.
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DR EMBL; AB041554; BAA95039.1; -; mRNA.
DR EMBL; AL833786; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466551; EDL06167.1; -; Genomic_DNA.
DR EMBL; BB610287; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BU937622; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CA466584; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS50777.1; -. [Q9JJF2-1]
DR RefSeq; NP_631890.3; NM_139151.4. [Q9JJF2-1]
DR AlphaFoldDB; Q9JJF2; -.
DR SMR; Q9JJF2; -.
DR BioGRID; 232842; 1.
DR IntAct; Q9JJF2; 2.
DR STRING; 10090.ENSMUSP00000036484; -.
DR PhosphoSitePlus; Q9JJF2; -.
DR PaxDb; Q9JJF2; -.
DR PRIDE; Q9JJF2; -.
DR ProteomicsDB; 257301; -. [Q9JJF2-1]
DR ProteomicsDB; 257302; -. [Q9JJF2-2]
DR Antibodypedia; 26200; 101 antibodies from 19 providers.
DR DNASU; 245865; -.
DR Ensembl; ENSMUST00000038860; ENSMUSP00000036484; ENSMUSG00000038180. [Q9JJF2-1]
DR GeneID; 245865; -.
DR KEGG; mmu:245865; -.
DR UCSC; uc008nmc.1; mouse. [Q9JJF2-1]
DR CTD; 6676; -.
DR MGI; MGI:2444120; Spag4.
DR VEuPathDB; HostDB:ENSMUSG00000038180; -.
DR eggNOG; KOG2687; Eukaryota.
DR GeneTree; ENSGT00940000161566; -.
DR HOGENOM; CLU_043737_2_0_1; -.
DR InParanoid; Q9JJF2; -.
DR OMA; TNTAYFW; -.
DR PhylomeDB; Q9JJF2; -.
DR TreeFam; TF323915; -.
DR BioGRID-ORCS; 245865; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Spag4; mouse.
DR PRO; PR:Q9JJF2; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9JJF2; protein.
DR Bgee; ENSMUSG00000038180; Expressed in spermatid and 64 other tissues.
DR ExpressionAtlas; Q9JJF2; baseline and differential.
DR Genevisible; Q9JJF2; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005639; C:integral component of nuclear inner membrane; IEA:InterPro.
DR GO; GO:0034993; C:meiotic nuclear membrane microtubule tethering complex; IBA:GO_Central.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-KW.
DR GO; GO:0005635; C:nuclear envelope; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0043495; F:protein-membrane adaptor activity; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0006998; P:nuclear envelope organization; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR InterPro; IPR027776; SPAG4/SUN4.
DR InterPro; IPR045119; SUN1-5.
DR InterPro; IPR012919; SUN_dom.
DR PANTHER; PTHR12911; PTHR12911; 1.
DR PANTHER; PTHR12911:SF16; PTHR12911:SF16; 1.
DR Pfam; PF07738; Sad1_UNC; 1.
DR PROSITE; PS51469; SUN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Cilium; Coiled coil; Cytoplasm;
KW Cytoskeleton; Differentiation; Flagellum; Membrane; Nucleus;
KW Reference proteome; Spermatogenesis; Transmembrane; Transmembrane helix.
FT CHAIN 1..443
FT /note="Sperm-associated antigen 4 protein"
FT /id="PRO_0000218917"
FT TRANSMEM 137..157
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 267..427
FT /note="SUN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00802"
FT REGION 1..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 203..244
FT /evidence="ECO:0000255"
FT COMPBIAS 1..39
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 98..103
FT /note="VRGGAS -> NRLDLL (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_005958"
FT VAR_SEQ 104..443
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_005959"
FT CONFLICT 81
FT /note="K -> E (in Ref. 1; BAA95039)"
FT /evidence="ECO:0000305"
FT CONFLICT 259
FT /note="P -> T (in Ref. 1; BAA95039)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 443 AA; 48582 MW; F5B8BD2F57E5F200 CRC64;
MRRSPRSGSA ASSHNHTPNF YSENSNSSHS ATSGDSNGRR SAGPELGEPE GRRARGSSCG
EPALSPGMPG GDTWAGSSRP KLAPRSHNGQ TACGAATVRG GASEPSGSSV VLEEQLNLLP
ILDLRQEMPT PRVSKSFLSL LFQVLSMVLS LAVDGLVCVC REICSIRFLF TAVSLLSIFL
AALWWGLLYL IPPLENEPTE MLTLSQYHHR VHSQGQQLQQ LQAELNKLHK EVSSVRAAHS
ERVAKLVFQR LNEDFVRKPD YALSSVGASI DLEKTSSDYE DQNTAYFWNR LSFWNYARPP
SVILEPDVFP GNCWAFEGDK GQVVIRLPGH VQLSDITLQH PPPTVAHTGG ASSAPRDFAV
YGLQADDETE VFLGKFIFDV QKSEIQTFHL QNDPPSAFPK VKIQILSNWG HPRFTCLYRV
RAHGVRTSEW ADDNATGVTG GPH
