SPAG4_HUMAN
ID SPAG4_HUMAN Reviewed; 437 AA.
AC Q9NPE6; O43648;
DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 155.
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; Synonyms=SUN4;
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 [GENOMIC DNA / MRNA].
RX PubMed=14614621; DOI=10.1007/s00441-003-0821-2;
RA Kennedy C., Sebire K., De Kretser D.M., O'Bryan M.K.;
RT "Human sperm associated antigen 4 (SPAG4) is a potential cancer marker.";
RL Cell Tissue Res. 315:279-283(2004).
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 [GENOMIC DNA] OF 265-303.
RX PubMed=9691178; DOI=10.1159/000014990;
RA Tarnasky H., Gill D., Murthy S., Shao X., Demetrick D.J.,
RA van der Hoorn F.A.;
RT "A novel testis-specific gene, SPAG4, whose product interacts specifically
RT with outer dense fiber protein ODF27, maps to human chromosome 20q11.2.";
RL Cytogenet. Cell Genet. 81:65-67(1998).
RN [4]
RP INTERACTION WITH SEPT12 AND LMNB1, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=25775403; DOI=10.1371/journal.pone.0120722;
RA Yeh C.H., Kuo P.L., Wang Y.Y., Wu Y.Y., Chen M.F., Lin D.Y., Lai T.H.,
RA Chiang H.S., Lin Y.H.;
RT "SEPT12/SPAG4/LAMINB1 complexes are required for maintaining the integrity
RT of the nuclear envelope in postmeiotic male germ cells.";
RL PLoS ONE 10:E0120722-E0120722(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:0000250|UniProtKB:O55034, ECO:0000250|UniProtKB:Q9JJF2}.
CC -!- SUBUNIT: Homodimer. 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 with SUN3 may associate with SYNE1 (By similarity).
CC Interacts with SEPT12 and LMNB1; during spermatogenesis
CC (PubMed:25775403). {ECO:0000250|UniProtKB:O55034,
CC ECO:0000269|PubMed:25775403}.
CC -!- INTERACTION:
CC Q9NPE6; O95870: ABHD16A; NbExp=3; IntAct=EBI-10819434, EBI-348517;
CC Q9NPE6; P07306: ASGR1; NbExp=3; IntAct=EBI-10819434, EBI-1172335;
CC Q9NPE6; O95393: BMP10; NbExp=3; IntAct=EBI-10819434, EBI-3922513;
CC Q9NPE6; Q8TDX6-3: CSGALNACT1; NbExp=3; IntAct=EBI-10819434, EBI-12917736;
CC Q9NPE6; P78329: CYP4F2; NbExp=3; IntAct=EBI-10819434, EBI-1752413;
CC Q9NPE6; Q7Z2K6: ERMP1; NbExp=3; IntAct=EBI-10819434, EBI-10976398;
CC Q9NPE6; O14653: GOSR2; NbExp=3; IntAct=EBI-10819434, EBI-4401517;
CC Q9NPE6; P24593: IGFBP5; NbExp=3; IntAct=EBI-10819434, EBI-720480;
CC Q9NPE6; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-10819434, EBI-12070086;
CC Q9NPE6; Q8IXM6: NRM; NbExp=3; IntAct=EBI-10819434, EBI-10262547;
CC Q9NPE6; P0DJD7: PGA4; NbExp=3; IntAct=EBI-10819434, EBI-12957629;
CC Q9NPE6; P26678: PLN; NbExp=3; IntAct=EBI-10819434, EBI-692836;
CC Q9NPE6; P43378: PTPN9; NbExp=3; IntAct=EBI-10819434, EBI-742898;
CC Q9NPE6; Q96GQ5: RUSF1; NbExp=3; IntAct=EBI-10819434, EBI-8636004;
CC Q9NPE6; Q969E2: SCAMP4; NbExp=3; IntAct=EBI-10819434, EBI-4403649;
CC Q9NPE6; O00767: SCD; NbExp=3; IntAct=EBI-10819434, EBI-2684237;
CC Q9NPE6; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-10819434, EBI-8652744;
CC Q9NPE6; Q8IYM1: SEPTIN12; NbExp=6; IntAct=EBI-10819434, EBI-2585067;
CC Q9NPE6; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-10819434, EBI-10262251;
CC Q9NPE6; Q8TC36: SUN5; NbExp=3; IntAct=EBI-10819434, EBI-13068796;
CC Q9NPE6; Q9BXJ8: TMEM120A; NbExp=3; IntAct=EBI-10819434, EBI-727322;
CC Q9NPE6; Q14656: TMEM187; NbExp=3; IntAct=EBI-10819434, EBI-13046724;
CC Q9NPE6; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-10819434, EBI-2852148;
CC Q9NPE6; Q9H2S6-2: TNMD; NbExp=3; IntAct=EBI-10819434, EBI-12003398;
CC Q9NPE6; Q5TGU0: TSPO2; NbExp=3; IntAct=EBI-10819434, EBI-12195249;
CC Q9NPE6; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-10819434, EBI-11988865;
CC Q9NPE6; Q6UX98: ZDHHC24; NbExp=3; IntAct=EBI-10819434, EBI-10254561;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:O55034}. Cytoplasm, cytoskeleton, flagellum
CC axoneme {ECO:0000250|UniProtKB:O55034}. Nucleus envelope
CC {ECO:0000250|UniProtKB:Q9JJF2}. Nucleus inner membrane
CC {ECO:0000250|UniProtKB:Q9JJF2}. Note=In spermatids, it is localized in
CC the transient manchette and in the axoneme of elongating spermatids and
CC epididymal sperm (By similarity). Colocalized with SEPT12 at the
CC nuclear periphery in round spermatids, at sperm neck in elongated
CC spermatids and at midpiece regions in ejaculated spermatozoa
CC (PubMed:25775403). {ECO:0000250|UniProtKB:O55034,
CC ECO:0000269|PubMed:25775403}.
CC -!- TISSUE SPECIFICITY: Predominantly epressed in testis. Expressed in
CC ejaculated spermatozoa (at protein level).
CC {ECO:0000269|PubMed:25775403}.
CC -!- CAUTION: Although transmembrane domains are strongly predicted, they
CC may rather represent hydrophobic globular domains associated with
CC microtubules. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC32052.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF262992; AAF75267.1; -; mRNA.
DR EMBL; AF262993; AAF75268.1; -; Genomic_DNA.
DR EMBL; AL109827; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF043344; AAC32052.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS13259.1; -.
DR RefSeq; NP_003107.1; NM_003116.2.
DR AlphaFoldDB; Q9NPE6; -.
DR SMR; Q9NPE6; -.
DR BioGRID; 112558; 81.
DR IntAct; Q9NPE6; 27.
DR STRING; 9606.ENSP00000363391; -.
DR iPTMnet; Q9NPE6; -.
DR PhosphoSitePlus; Q9NPE6; -.
DR BioMuta; SPAG4; -.
DR DMDM; 27805726; -.
DR MassIVE; Q9NPE6; -.
DR PaxDb; Q9NPE6; -.
DR PeptideAtlas; Q9NPE6; -.
DR PRIDE; Q9NPE6; -.
DR ProteomicsDB; 81980; -.
DR Antibodypedia; 26200; 101 antibodies from 19 providers.
DR DNASU; 6676; -.
DR Ensembl; ENST00000374273.8; ENSP00000363391.3; ENSG00000061656.11.
DR GeneID; 6676; -.
DR KEGG; hsa:6676; -.
DR MANE-Select; ENST00000374273.8; ENSP00000363391.3; NM_003116.3; NP_003107.1.
DR UCSC; uc002xdb.2; human.
DR CTD; 6676; -.
DR DisGeNET; 6676; -.
DR GeneCards; SPAG4; -.
DR HGNC; HGNC:11214; SPAG4.
DR HPA; ENSG00000061656; Group enriched (pancreas, testis).
DR MIM; 603038; gene.
DR neXtProt; NX_Q9NPE6; -.
DR OpenTargets; ENSG00000061656; -.
DR PharmGKB; PA36050; -.
DR VEuPathDB; HostDB:ENSG00000061656; -.
DR eggNOG; KOG2687; Eukaryota.
DR GeneTree; ENSGT00940000161566; -.
DR HOGENOM; CLU_043737_2_0_1; -.
DR InParanoid; Q9NPE6; -.
DR OMA; TNTAYFW; -.
DR OrthoDB; 1569602at2759; -.
DR PhylomeDB; Q9NPE6; -.
DR TreeFam; TF323915; -.
DR PathwayCommons; Q9NPE6; -.
DR SignaLink; Q9NPE6; -.
DR SIGNOR; Q9NPE6; -.
DR BioGRID-ORCS; 6676; 24 hits in 1081 CRISPR screens.
DR ChiTaRS; SPAG4; human.
DR GenomeRNAi; 6676; -.
DR Pharos; Q9NPE6; Tbio.
DR PRO; PR:Q9NPE6; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9NPE6; protein.
DR Bgee; ENSG00000061656; Expressed in body of pancreas and 110 other tissues.
DR ExpressionAtlas; Q9NPE6; baseline and differential.
DR Genevisible; Q9NPE6; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; 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:0031514; C:motile cilium; IEA:UniProtKB-KW.
DR GO; GO:0005635; C:nuclear envelope; IBA:GO_Central.
DR GO; GO:0043495; F:protein-membrane adaptor activity; IBA:GO_Central.
DR GO; GO:0005198; F:structural molecule activity; TAS:ProtInc.
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; TAS:ProtInc.
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 Cell projection; Cilium; Coiled coil; Cytoplasm; Cytoskeleton;
KW Differentiation; Flagellum; Membrane; Nucleus; Reference proteome;
KW Spermatogenesis; Transmembrane; Transmembrane helix.
FT CHAIN 1..437
FT /note="Sperm-associated antigen 4 protein"
FT /id="PRO_0000218916"
FT TRANSMEM 135..155
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 166..186
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 265..425
FT /note="SUN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00802"
FT REGION 1..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 197..244
FT /evidence="ECO:0000255"
FT COMPBIAS 1..35
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..88
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 437 AA; 48165 MW; 5D1E3BCAEEE8B702 CRC64;
MRRSSRPGSA SSSRKHTPNF FSENSSMSIT SEDSKGLRSA EPGPGEPEGR RARGPSCGEP
ALSAGVPGGT TWAGSSQQKP APRSHNWQTA CGAATVRGGA SEPTGSPVVS EEPLDLLPTL
DLRQEMPPPR VFKSFLSLLF QGLSVLLSLA GDVLVSMYRE VCSIRFLFTA VSLLSLFLSA
FWLGLLYLVS PLENEPKEML TLSEYHERVR SQGQQLQQLQ AELDKLHKEV STVRAANSER
VAKLVFQRLN EDFVRKPDYA LSSVGASIDL QKTSHDYADR NTAYFWNRFS FWNYARPPTV
ILEPHVFPGN CWAFEGDQGQ VVIQLPGRVQ LSDITLQHPP PSVEHTGGAN SAPRDFAVFG
LQVYDETEVS LGKFTFDVEK SEIQTFHLQN DPPAAFPKVK IQILSNWGHP RFTCLYRVRA
HGVRTSEGAE GSAQGPH
