SUN5_HUMAN
ID SUN5_HUMAN Reviewed; 379 AA.
AC Q8TC36; A6NJ82; Q5T9R0;
DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=SUN domain-containing protein 5;
DE AltName: Full=Sad1 and UNC84 domain-containing protein 5;
DE AltName: Full=Sperm-associated antigen 4-like protein;
DE AltName: Full=Testis and spermatogenesis-related gene 4 protein;
GN Name=SUN5; Synonyms=SPAG4L, TSARG4;
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=12621555;
RA Xing X.W., Li L.Y., Fu J.J., Zhu W.B., Liu G., Liu S.F., Lu G.X.;
RT "Cloning of cDNA of TSARG4, a human spermatogenesis related gene.";
RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 35:283-288(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP TISSUE SPECIFICITY.
RX PubMed=21711156; DOI=10.1089/dna.2010.1161;
RA Jiang X.Z., Yang M.G., Huang L.H., Li C.Q., Xing X.W.;
RT "SPAG4L, a novel nuclear envelope protein involved in the meiotic stage of
RT spermatogenesis.";
RL DNA Cell Biol. 30:875-882(2011).
RN [6]
RP VARIANTS SPGF16 ARG-114; LYS-162; MET-261; MET-275; 284-SER--ASP-379 DEL;
RP ILE-348 AND CYS-356, CHARACTERIZATION OF VARIANTS SPGF16 ARG-114; MET-275;
RP 284-SER--ASP-379 DEL AND ILE-348, SUBCELLULAR LOCATION, INVOLVEMENT IN
RP SPGF16, AND TISSUE SPECIFICITY.
RX PubMed=27640305; DOI=10.1016/j.ajhg.2016.08.004;
RA Zhu F., Wang F., Yang X., Zhang J., Wu H., Zhang Z., Zhang Z., He X.,
RA Zhou P., Wei Z., Gecz J., Cao Y.;
RT "Biallelic SUN5 mutations cause autosomal-recessive acephalic spermatozoa
RT syndrome.";
RL Am. J. Hum. Genet. 99:942-949(2016).
RN [7]
RP ERRATUM OF PUBMED:27640305.
RX PubMed=27912045; DOI=10.1016/j.ajhg.2016.11.002;
RA Zhu F., Wang F., Yang X., Zhang J., Wu H., Zhang Z., Zhang Z., He X.,
RA Zhou P., Wei Z., Gecz J., Cao Y.;
RT "Biallelic SUN5 Mutations Cause Autosomal-Recessive Acephalic Spermatozoa
RT Syndrome.";
RL Am. J. Hum. Genet. 99:1405-1405(2016).
RN [8]
RP VARIANTS SPGF16 ARG-114 AND MET-275, AND FUNCTION.
RX PubMed=28945193; DOI=10.7554/elife.28199;
RA Shang Y., Zhu F., Wang L., Ouyang Y.C., Dong M.Z., Liu C., Zhao H., Cui X.,
RA Ma D., Zhang Z., Yang X., Guo Y., Liu F., Yuan L., Gao F., Guo X.,
RA Sun Q.Y., Cao Y., Li W.;
RT "Essential role for SUN5 in anchoring sperm head to the tail.";
RL Elife 6:0-0(2017).
RN [9]
RP INVOLVEMENT IN SPGF16, AND FUNCTION.
RX PubMed=28541472; DOI=10.1093/hmg/ddx200;
RA Elkhatib R.A., Paci M., Longepied G., Saias-Magnan J., Courbiere B.,
RA Guichaoua M.R., Levy N., Metzler-Guillemain C., Mitchell M.J.;
RT "Homozygous deletion of SUN5 in three men with decapitated spermatozoa.";
RL Hum. Mol. Genet. 26:3167-3171(2017).
RN [10]
RP VARIANTS SPGF16 159-ARG--ASP-379 DEL AND LYS-162, AND CHARACTERIZATION OF
RP VARIANTS SPGF16 159-ARG--ASP-379 DEL; LYS-162; MET-261; MET-275;
RP SER-284--ASP-379 DEL; ILE-348 AND CYS-356.
RX PubMed=29298896; DOI=10.1074/jbc.ra117.000861;
RA Shang Y., Yan J., Tang W., Liu C., Xiao S., Guo Y., Yuan L., Chen L.,
RA Jiang H., Guo X., Qiao J., Li W.;
RT "Mechanistic insights into acephalic spermatozoa syndrome-associated
RT mutations in the human SUN5 gene.";
RL J. Biol. Chem. 293:2395-2407(2018).
CC -!- FUNCTION: Plays an essential role in anchoring sperm head to the tail.
CC Is responsible for the attachment of the coupling apparatus to the
CC sperm nuclear envelope. {ECO:0000305|PubMed:28541472,
CC ECO:0000305|PubMed:28945193}.
CC -!- SUBUNIT: Probable homotrimer. Interacts with DNAJB13.
CC {ECO:0000250|UniProtKB:Q9DA32}.
CC -!- INTERACTION:
CC Q8TC36; Q9NPE6: SPAG4; NbExp=3; IntAct=EBI-13068796, EBI-10819434;
CC -!- SUBCELLULAR LOCATION: Nucleus inner membrane
CC {ECO:0000305|PubMed:27640305}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9DA32}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q9DA32}. Note=During spermiogenesis, traffics
CC through the Golgi apparatus before reaching the round spermatid inner
CC membrane of the nuclear envelope and later migrates to the coupling
CC apparatus of the sperm during sperm head elongation and
CC differentiation. In mature spermatozoa, is localized to the coupling
CC apparatus of the sperm head and tail in the implementation fossa.
CC {ECO:0000305|PubMed:27640305}.
CC -!- TISSUE SPECIFICITY: Sperm (at protein level) (PubMed:27640305). Widely
CC expressed (PubMed:12621555). Conflictingly shown to be specifically
CC expressed in testis (PubMed:21711156). {ECO:0000269|PubMed:12621555,
CC ECO:0000269|PubMed:21711156, ECO:0000269|PubMed:27640305}.
CC -!- PTM: Highly glycosylated in the Golgi apparatus during spermiogenesis.
CC {ECO:0000250|UniProtKB:Q9DA32}.
CC -!- DISEASE: Spermatogenic failure 16 (SPGF16) [MIM:617187]: An infertility
CC disorder caused by spermatogenesis defects and characterized by
CC abnormally shaped spermatozoa in the semen of affected individuals.
CC Most spermatozoa are made up of headless tails, while a small
CC proportion has an abnormal head-tail junction. A few spermatozoa are
CC made up of tailless heads. {ECO:0000269|PubMed:27640305,
CC ECO:0000269|PubMed:28541472, ECO:0000269|PubMed:28945193,
CC ECO:0000269|PubMed:29298896}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AF401350; AAM90665.1; -; mRNA.
DR EMBL; AL139826; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121756; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW76343.1; -; Genomic_DNA.
DR EMBL; BC026118; AAH26118.1; -; mRNA.
DR EMBL; BC029528; AAH29528.1; -; mRNA.
DR CCDS; CCDS13209.1; -.
DR RefSeq; NP_542406.2; NM_080675.3.
DR AlphaFoldDB; Q8TC36; -.
DR SMR; Q8TC36; -.
DR BioGRID; 126678; 8.
DR IntAct; Q8TC36; 1.
DR STRING; 9606.ENSP00000348496; -.
DR iPTMnet; Q8TC36; -.
DR PhosphoSitePlus; Q8TC36; -.
DR BioMuta; SUN5; -.
DR DMDM; 27805720; -.
DR MassIVE; Q8TC36; -.
DR PaxDb; Q8TC36; -.
DR PeptideAtlas; Q8TC36; -.
DR PRIDE; Q8TC36; -.
DR ProteomicsDB; 74086; -.
DR Antibodypedia; 25466; 111 antibodies from 24 providers.
DR DNASU; 140732; -.
DR Ensembl; ENST00000356173.8; ENSP00000348496.3; ENSG00000167098.12.
DR GeneID; 140732; -.
DR KEGG; hsa:140732; -.
DR MANE-Select; ENST00000356173.8; ENSP00000348496.3; NM_080675.4; NP_542406.2.
DR UCSC; uc002wyi.4; human.
DR CTD; 140732; -.
DR DisGeNET; 140732; -.
DR GeneCards; SUN5; -.
DR HGNC; HGNC:16252; SUN5.
DR HPA; ENSG00000167098; Tissue enriched (testis).
DR MalaCards; SUN5; -.
DR MIM; 613942; gene.
DR MIM; 617187; phenotype.
DR neXtProt; NX_Q8TC36; -.
DR OpenTargets; ENSG00000167098; -.
DR Orphanet; 529970; Male infertility due to acephalic spermatozoa.
DR PharmGKB; PA38095; -.
DR VEuPathDB; HostDB:ENSG00000167098; -.
DR eggNOG; KOG2687; Eukaryota.
DR GeneTree; ENSGT00940000155225; -.
DR InParanoid; Q8TC36; -.
DR OMA; FWMFSMH; -.
DR OrthoDB; 1569602at2759; -.
DR PhylomeDB; Q8TC36; -.
DR TreeFam; TF323915; -.
DR PathwayCommons; Q8TC36; -.
DR SignaLink; Q8TC36; -.
DR SIGNOR; Q8TC36; -.
DR BioGRID-ORCS; 140732; 16 hits in 1057 CRISPR screens.
DR GeneWiki; SPAG4L; -.
DR GenomeRNAi; 140732; -.
DR Pharos; Q8TC36; Tbio.
DR PRO; PR:Q8TC36; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q8TC36; protein.
DR Bgee; ENSG00000167098; Expressed in right testis and 31 other tissues.
DR ExpressionAtlas; Q8TC36; baseline and differential.
DR Genevisible; Q8TC36; HS.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
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:0005635; C:nuclear envelope; IBA:GO_Central.
DR GO; GO:0005637; C:nuclear inner membrane; IDA:UniProtKB.
DR GO; GO:0097224; C:sperm connecting piece; IDA:UniProtKB.
DR GO; GO:0043495; F:protein-membrane adaptor activity; IBA:GO_Central.
DR GO; GO:0006998; P:nuclear envelope organization; IBA:GO_Central.
DR GO; GO:0007286; P:spermatid development; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IEP:UniProtKB.
DR InterPro; IPR045119; SUN1-5.
DR InterPro; IPR030273; SUN5.
DR InterPro; IPR012919; SUN_dom.
DR PANTHER; PTHR12911; PTHR12911; 1.
DR PANTHER; PTHR12911:SF44; PTHR12911:SF44; 1.
DR Pfam; PF07738; Sad1_UNC; 1.
DR PROSITE; PS51469; SUN; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Differentiation; Disease variant; Glycoprotein;
KW Golgi apparatus; Membrane; Nucleus; Reference proteome; Spermatogenesis;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..379
FT /note="SUN domain-containing protein 5"
FT /id="PRO_0000218919"
FT TOPO_DOM 1..105
FT /note="Nuclear"
FT /evidence="ECO:0000255"
FT TRANSMEM 106..122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 123..379
FT /note="Perinuclear space"
FT /evidence="ECO:0000255"
FT DOMAIN 205..364
FT /note="SUN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00802"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 141..182
FT /evidence="ECO:0000255"
FT VARIANT 16
FT /note="E -> K (in dbSNP:rs3746387)"
FT /id="VAR_015147"
FT VARIANT 39
FT /note="E -> D (in dbSNP:rs1133358)"
FT /id="VAR_026677"
FT VARIANT 114
FT /note="G -> R (in SPGF16; loss of protein expression;
FT impaired localization to nuclear inner membrane)"
FT /evidence="ECO:0000269|PubMed:27640305,
FT ECO:0000269|PubMed:28945193"
FT /id="VAR_077983"
FT VARIANT 120
FT /note="I -> V (in dbSNP:rs35216976)"
FT /id="VAR_052285"
FT VARIANT 159..379
FT /note="Missing (in SPGF16; in mouse model abolishes
FT interaction with DNAJB13)"
FT /evidence="ECO:0000269|PubMed:29298896"
FT /id="VAR_080157"
FT VARIANT 162
FT /note="M -> K (in SPGF16; unknown pathological
FT significance; in mouse model increases interaction with
FT DNAJB13; impaired localization to nuclear inner membrane;
FT dbSNP:rs886041023)"
FT /evidence="ECO:0000269|PubMed:27640305,
FT ECO:0000269|PubMed:29298896"
FT /id="VAR_077984"
FT VARIANT 174
FT /note="A -> T (in dbSNP:rs17123951)"
FT /id="VAR_026678"
FT VARIANT 261
FT /note="V -> M (in SPGF16; unknown pathological
FT significance; in mouse model decreases protein solubility
FT as well as impairs nuclear inner membrane location and
FT decreases interaction with DNAJB13; dbSNP:rs886041024)"
FT /evidence="ECO:0000269|PubMed:27640305,
FT ECO:0000269|PubMed:29298896"
FT /id="VAR_077985"
FT VARIANT 275
FT /note="T -> M (in SPGF16; significant reduction in protein
FT expression; impaired localization to nuclear inner
FT membrane; in mouse model decreases interaction with
FT DNAJB13; dbSNP:rs756459525)"
FT /evidence="ECO:0000269|PubMed:27640305,
FT ECO:0000269|PubMed:28945193, ECO:0000269|PubMed:29298896"
FT /id="VAR_077986"
FT VARIANT 284..379
FT /note="Missing (in SPGF16; significant reduction in protein
FT expression; impaired localization to nuclear inner
FT membrane; in mouse model decreases interaction with
FT DNAJB13)"
FT /evidence="ECO:0000269|PubMed:27640305,
FT ECO:0000269|PubMed:29298896"
FT /id="VAR_080158"
FT VARIANT 348
FT /note="N -> I (in SPGF16; loss of protein expression; in
FT mouse model impairs nuclear inner membrane location and
FT decreases interaction with DNAJB13; dbSNP:rs758335571)"
FT /evidence="ECO:0000269|PubMed:27640305,
FT ECO:0000269|PubMed:29298896"
FT /id="VAR_077987"
FT VARIANT 356
FT /note="R -> C (in SPGF16; unknown pathological
FT significance; in mouse model impairs nuclear inner membrane
FT location and decreases interaction with DNAJB13;
FT dbSNP:rs754130052)"
FT /evidence="ECO:0000269|PubMed:27640305,
FT ECO:0000269|PubMed:29298896"
FT /id="VAR_077988"
SQ SEQUENCE 379 AA; 43081 MW; 0FAE87B1CC1DBCDF CRC64;
MPRSSRSPGD PGALLEDVAH NPRPRRIAQR GRNTSRMAED TSPNMNDNIL LPVRNNDQAL
GLTQCMLGCV SWFTCFACSL RTQAQQVLFN TCRCKLLCQK LMEKTGILLL CAFGFWMFSI
HLPSKMKVWQ DDSINGPLQS LRLYQEKVRH HSGEIQDLRG SMNQLIAKLQ EMEAMSDEQK
MAQKIMKMIH GDYIEKPDFA LKSIGASIDF EHTSVTYNHE KAHSYWNWIQ LWNYAQPPDV
ILEPNVTPGN CWAFEGDRGQ VTIQLAQKVY LSNLTLQHIP KTISLSGSLD TAPKDFVIYG
MEGSPKEEVF LGAFQFQPEN IIQMFPLQNQ PARAFSAVKV KISSNWGNPG FTCLYRVRVH
GSVAPPREQP HQNPYPKRD
