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Sperm-associated antigen 4 protein (Outer dense fiber-associated protein SPAG4) (SUN domain-containing protein 4)

 SPAG4_HUMAN             Reviewed;         437 AA.
Q9NPE6; O43648;
17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
01-OCT-2000, sequence version 1.
02-JUN-2021, entry version 151.
RecName: Full=Sperm-associated antigen 4 protein;
AltName: Full=Outer dense fiber-associated protein SPAG4;
AltName: Full=SUN domain-containing protein 4;
Name=SPAG4; Synonyms=SUN4;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
PubMed=14614621; DOI=10.1007/s00441-003-0821-2;
Kennedy C., Sebire K., De Kretser D.M., O'Bryan M.K.;
"Human sperm associated antigen 4 (SPAG4) is a potential cancer marker.";
Cell Tissue Res. 315:279-283(2004).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=11780052; DOI=10.1038/414865a;
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
"The DNA sequence and comparative analysis of human chromosome 20.";
Nature 414:865-871(2001).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 265-303.
PubMed=9691178; DOI=10.1159/000014990;
Tarnasky H., Gill D., Murthy S., Shao X., Demetrick D.J.,
van der Hoorn F.A.;
"A novel testis-specific gene, SPAG4, whose product interacts specifically
with outer dense fiber protein ODF27, maps to human chromosome 20q11.2.";
Cytogenet. Cell Genet. 81:65-67(1998).
[4]
INTERACTION WITH SEPT12 AND LMNB1, TISSUE SPECIFICITY, AND SUBCELLULAR
LOCATION.
PubMed=25775403; DOI=10.1371/journal.pone.0120722;
Yeh C.H., Kuo P.L., Wang Y.Y., Wu Y.Y., Chen M.F., Lin D.Y., Lai T.H.,
Chiang H.S., Lin Y.H.;
"SEPT12/SPAG4/LAMINB1 complexes are required for maintaining the integrity
of the nuclear envelope in postmeiotic male germ cells.";
PLoS ONE 10:E0120722-E0120722(2015).
-!- FUNCTION: Involved in spermatogenesis. Required for sperm head
formation but not required to establish and maintain general polarity
of the sperm head. Required for anchoring and organization of the
manchette. Required for targeting of SUN3 and probably SYNE1 through a
probable SUN1:SYNE3 LINC complex to the nuclear envelope and involved
in accurate posterior sperm head localization of the complex. May
anchor SUN3 the nuclear envelope. Involved in maintenance of the
nuclear envelope integrity. May assist the organization and assembly of
outer dense fibers (ODFs), a specific structure of the sperm tail.
{ECO:0000250|UniProtKB:O55034, ECO:0000250|UniProtKB:Q9JJF2}.
-!- SUBUNIT: Homodimer. Interacts with ODF1. May associate with
microtubules (By similarity). Interacts with SUN3 and SYNE1; suggesting
the formation of a spermatogenesis-specific LINC complex; a SUN domain-
based heterotrimer with SUN3 may associate with SYNE1 (By similarity).
Interacts with SEPT12 and LMNB1; during spermatogenesis
(PubMed:25775403). {ECO:0000250|UniProtKB:O55034,
ECO:0000269|PubMed:25775403}.
-!- INTERACTION:
Q9NPE6; O95870: ABHD16A; NbExp=3; IntAct=EBI-10819434, EBI-348517;
Q9NPE6; P07306: ASGR1; NbExp=3; IntAct=EBI-10819434, EBI-1172335;
Q9NPE6; O95393: BMP10; NbExp=3; IntAct=EBI-10819434, EBI-3922513;
Q9NPE6; Q8TDX6-3: CSGALNACT1; NbExp=3; IntAct=EBI-10819434, EBI-12917736;
Q9NPE6; P78329: CYP4F2; NbExp=3; IntAct=EBI-10819434, EBI-1752413;
Q9NPE6; Q7Z2K6: ERMP1; NbExp=3; IntAct=EBI-10819434, EBI-10976398;
Q9NPE6; O14653: GOSR2; NbExp=3; IntAct=EBI-10819434, EBI-4401517;
Q9NPE6; P24593: IGFBP5; NbExp=3; IntAct=EBI-10819434, EBI-720480;
Q9NPE6; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-10819434, EBI-12070086;
Q9NPE6; Q8IXM6: NRM; NbExp=3; IntAct=EBI-10819434, EBI-10262547;
Q9NPE6; P0DJD7: PGA4; NbExp=3; IntAct=EBI-10819434, EBI-12957629;
Q9NPE6; P26678: PLN; NbExp=3; IntAct=EBI-10819434, EBI-692836;
Q9NPE6; P43378: PTPN9; NbExp=3; IntAct=EBI-10819434, EBI-742898;
Q9NPE6; Q96GQ5: RUSF1; NbExp=3; IntAct=EBI-10819434, EBI-8636004;
Q9NPE6; Q969E2: SCAMP4; NbExp=3; IntAct=EBI-10819434, EBI-4403649;
Q9NPE6; O00767: SCD; NbExp=3; IntAct=EBI-10819434, EBI-2684237;
Q9NPE6; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-10819434, EBI-8652744;
Q9NPE6; Q8IYM1: SEPTIN12; NbExp=6; IntAct=EBI-10819434, EBI-2585067;
Q9NPE6; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-10819434, EBI-10262251;
Q9NPE6; Q8TC36: SUN5; NbExp=3; IntAct=EBI-10819434, EBI-13068796;
Q9NPE6; Q9BXJ8: TMEM120A; NbExp=3; IntAct=EBI-10819434, EBI-727322;
Q9NPE6; Q14656: TMEM187; NbExp=3; IntAct=EBI-10819434, EBI-13046724;
Q9NPE6; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-10819434, EBI-2852148;
Q9NPE6; Q9H2S6-2: TNMD; NbExp=3; IntAct=EBI-10819434, EBI-12003398;
Q9NPE6; Q5TGU0: TSPO2; NbExp=3; IntAct=EBI-10819434, EBI-12195249;
Q9NPE6; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-10819434, EBI-11988865;
Q9NPE6; Q6UX98: ZDHHC24; NbExp=3; IntAct=EBI-10819434, EBI-10254561;
-!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
protein {ECO:0000305}. Cytoplasm, cytoskeleton
{ECO:0000250|UniProtKB:O55034}. Cytoplasm, cytoskeleton, flagellum
axoneme {ECO:0000250|UniProtKB:O55034}. Nucleus envelope
{ECO:0000250|UniProtKB:Q9JJF2}. Nucleus inner membrane
{ECO:0000250|UniProtKB:Q9JJF2}. Note=In spermatids, it is localized in
the transient manchette and in the axoneme of elongating spermatids and
epididymal sperm (By similarity). Colocalized with SEPT12 at the
nuclear periphery in round spermatids, at sperm neck in elongated
spermatids and at midpiece regions in ejaculated spermatozoa
(PubMed:25775403). {ECO:0000250|UniProtKB:O55034,
ECO:0000269|PubMed:25775403}.
-!- TISSUE SPECIFICITY: Predominantly epressed in testis. Expressed in
ejaculated spermatozoa (at protein level).
{ECO:0000269|PubMed:25775403}.
-!- CAUTION: Although transmembrane domains are strongly predicted, they
may rather represent hydrophobic globular domains associated with
microtubules. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=AAC32052.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
---------------------------------------------------------------------------
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EMBL; AF262992; AAF75267.1; -; mRNA.
EMBL; AF262993; AAF75268.1; -; Genomic_DNA.
EMBL; AL109827; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AF043344; AAC32052.1; ALT_SEQ; Genomic_DNA.
CCDS; CCDS13259.1; -.
RefSeq; NP_003107.1; NM_003116.2.
SMR; Q9NPE6; -.
BioGRID; 112558; 25.
IntAct; Q9NPE6; 27.
STRING; 9606.ENSP00000363391; -.
iPTMnet; Q9NPE6; -.
PhosphoSitePlus; Q9NPE6; -.
BioMuta; SPAG4; -.
DMDM; 27805726; -.
MassIVE; Q9NPE6; -.
PaxDb; Q9NPE6; -.
PeptideAtlas; Q9NPE6; -.
PRIDE; Q9NPE6; -.
ProteomicsDB; 81980; -.
Antibodypedia; 26200; 91 antibodies.
DNASU; 6676; -.
Ensembl; ENST00000374273; ENSP00000363391; ENSG00000061656.
GeneID; 6676; -.
KEGG; hsa:6676; -.
UCSC; uc002xdb.2; human.
CTD; 6676; -.
DisGeNET; 6676; -.
GeneCards; SPAG4; -.
HGNC; HGNC:11214; SPAG4.
HPA; ENSG00000061656; Tissue enhanced (pancreas).
MIM; 603038; gene.
neXtProt; NX_Q9NPE6; -.
OpenTargets; ENSG00000061656; -.
PharmGKB; PA36050; -.
VEuPathDB; HostDB:ENSG00000061656.9; -.
eggNOG; KOG2687; Eukaryota.
GeneTree; ENSGT00940000161566; -.
HOGENOM; CLU_043737_2_0_1; -.
InParanoid; Q9NPE6; -.
OMA; TNTAYFW; -.
OrthoDB; 1569602at2759; -.
PhylomeDB; Q9NPE6; -.
TreeFam; TF323915; -.
PathwayCommons; Q9NPE6; -.
SIGNOR; Q9NPE6; -.
BioGRID-ORCS; 6676; 15 hits in 996 CRISPR screens.
ChiTaRS; SPAG4; human.
GenomeRNAi; 6676; -.
Pharos; Q9NPE6; Tdark.
PRO; PR:Q9NPE6; -.
Proteomes; UP000005640; Chromosome 20.
RNAct; Q9NPE6; protein.
Bgee; ENSG00000061656; Expressed in pancreas and 147 other tissues.
ExpressionAtlas; Q9NPE6; baseline and differential.
Genevisible; Q9NPE6; HS.
GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0034993; C:meiotic nuclear membrane microtubule tethering complex; IBA:GO_Central.
GO; GO:0031514; C:motile cilium; IEA:UniProtKB-KW.
GO; GO:0005635; C:nuclear envelope; IBA:GO_Central.
GO; GO:0005637; C:nuclear inner membrane; IEA:UniProtKB-SubCell.
GO; GO:0043495; F:protein-membrane adaptor activity; IBA:GO_Central.
GO; GO:0005198; F:structural molecule activity; TAS:ProtInc.
GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
GO; GO:0006998; P:nuclear envelope organization; IBA:GO_Central.
GO; GO:0007283; P:spermatogenesis; TAS:ProtInc.
Gene3D; 2.60.120.260; -; 1.
InterPro; IPR008979; Galactose-bd-like_sf.
InterPro; IPR027776; SPAG4/SUN4.
InterPro; IPR012919; SUN_dom.
PANTHER; PTHR12911:SF16; PTHR12911:SF16; 1.
Pfam; PF07738; Sad1_UNC; 1.
PROSITE; PS51469; SUN; 1.
1: Evidence at protein level;
Cell projection; Cilium; Coiled coil; Cytoplasm; Cytoskeleton;
Differentiation; Flagellum; Membrane; Nucleus; Reference proteome;
Spermatogenesis; Transmembrane; Transmembrane helix.
CHAIN 1..437
/note="Sperm-associated antigen 4 protein"
/id="PRO_0000218916"
TRANSMEM 135..155
/note="Helical"
/evidence="ECO:0000255"
TRANSMEM 166..186
/note="Helical"
/evidence="ECO:0000255"
DOMAIN 265..425
/note="SUN"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00802"
REGION 1..88
/note="Disordered"
/evidence="ECO:0000256|SAM:MobiDB-lite"
COILED 197..244
/evidence="ECO:0000255"
COMPBIAS 1..35
/note="Polar residues"
/evidence="ECO:0000256|SAM:MobiDB-lite"
COMPBIAS 69..88
/note="Polar residues"
/evidence="ECO:0000256|SAM:MobiDB-lite"
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


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WP1690: Propanoate metabolism
WP1694: Pyrimidine metabolism
WP1654: gamma-Hexachlorocyclohexane degradation
WP232: G Protein Signaling Pathways
WP1661: Glyoxylate and dicarboxylate metabolism
WP2371: Parkinsons Disease Pathway
WP1371: G Protein Signaling Pathways

Related Genes :
[Odf2 Odf84 KKT4] Outer dense fiber protein 2 (84 kDa outer dense fiber protein) (Cenexin) (Outer dense fiber of sperm tails protein 2)
[ODF2] Outer dense fiber protein 2 (Cenexin) (Outer dense fiber of sperm tails protein 2)
[Odf2 Odf84] Outer dense fiber protein 2 (84 kDa outer dense fiber protein) (Cenexin) (Outer dense fiber of sperm tails protein 2)
[ODF2] Outer dense fiber protein 2 (84 kDa outer dense fiber protein) (Cenexin) (Outer dense fiber of sperm tails protein 2) (Fragment)
[ODF2 QtsA-12846 QtsA-13326] Outer dense fiber protein 2 (Cenexin) (Outer dense fiber of sperm tails protein 2)
[Syne1] Nesprin-1 (Enaptin) (KASH domain-containing protein 1) (KASH1) (Myocyte nuclear envelope protein 1) (Myne-1) (Nuclear envelope spectrin repeat protein 1) (Synaptic nuclear envelope protein 1) (Syne-1)
[ABHD16A BAT5 G5 NG26 PP199] Phosphatidylserine lipase ABHD16A (EC 3.1.-.-) (Alpha/beta hydrolase domain-containing protein 16A) (Abhydrolase domain-containing protein 16A) (HLA-B-associated transcript 5) (hBAT5) (Monoacylglycerol lipase ABHD16A) (EC 3.1.1.23) (Protein G5)
[SYNE1 C6orf98 KIAA0796 KIAA1262 KIAA1756 MYNE1] Nesprin-1 (Enaptin) (KASH domain-containing protein 1) (KASH1) (Myocyte nuclear envelope protein 1) (Myne-1) (Nuclear envelope spectrin repeat protein 1) (Synaptic nuclear envelope protein 1) (Syne-1)
[SPAG1] Sperm-associated antigen 1 (HSD-3.8) (Infertility-related sperm protein Spag-1)
[CRYAB CRYA2 HSPB5] Alpha-crystallin B chain (Alpha(B)-crystallin) (Heat shock protein beta-5) (HspB5) (Renal carcinoma antigen NY-REN-27) (Rosenthal fiber component)
[ODF2] Outer dense fiber protein 2 (Cenexin) (Outer dense fiber of sperm tails protein 2)
[ODF2] Outer dense fiber protein 2 (Cenexin) (Outer dense fiber of sperm tails protein 2)
[CYP4F2] Cytochrome P450 4F2 (EC 1.14.14.1) (20-hydroxyeicosatetraenoic acid synthase) (20-HETE synthase) (Arachidonic acid omega-hydroxylase) (CYPIVF2) (Cytochrome P450-LTB-omega) (Docosahexaenoic acid omega-hydroxylase) (EC 1.14.14.79) (Leukotriene-B(4) 20-monooxygenase 1) (Leukotriene-B(4) omega-hydroxylase 1) (EC 1.14.14.94) (Phylloquinone omega-hydroxylase CYP4F2) (EC 1.14.14.78)
[ARID4B BRCAA1 RBBP1L1 RBP1L1 SAP180] AT-rich interactive domain-containing protein 4B (ARID domain-containing protein 4B) (180 kDa Sin3-associated polypeptide) (Sin3-associated polypeptide p180) (Breast cancer-associated antigen BRCAA1) (Histone deacetylase complex subunit SAP180) (Retinoblastoma-binding protein 1-like 1)
[SEPTIN12 SEPT12] Septin-12
[Spag16 Pf20] Sperm-associated antigen 16 protein (Pf20 protein homolog)
[Pre C,C C core E PC pre-C pre-C/C PreC preC PreC/C preC/C precore-core HBVgp4] Capsid protein (Core antigen) (Core protein) (HBcAg) (p21.5)
[Sun1 Unc84a] SUN domain-containing protein 1 (Protein unc-84 homolog A) (Sad1/unc-84 protein-like 1)
[GPI] Glucose-6-phosphate isomerase (GPI) (EC 5.3.1.9) (Autocrine motility factor) (AMF) (Neuroleukin) (NLK) (Phosphoglucose isomerase) (PGI) (Phosphohexose isomerase) (PHI) (Sperm antigen 36) (SA-36)
[SPAG16 PF20] Sperm-associated antigen 16 protein (Pf20 protein homolog)
[Hsp90aa1 Hsp86 Hsp86-1 Hspca] Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Tumor-specific transplantation 86 kDa antigen) (TSTA)
[SLC25A31 AAC4 ANT4 SFEC] ADP/ATP translocase 4 (ADP,ATP carrier protein 4) (Adenine nucleotide translocator 4) (ANT 4) (Solute carrier family 25 member 31) (Sperm flagellar energy carrier protein)
[GCC2 KIAA0336 RANBP2L4] GRIP and coiled-coil domain-containing protein 2 (185 kDa Golgi coiled-coil protein) (GCC185) (CLL-associated antigen KW-11) (CTCL tumor antigen se1-1) (Ran-binding protein 2-like 4) (RanBP2L4) (Renal carcinoma antigen NY-REN-53)
[CD46 MCP MIC10] Membrane cofactor protein (TLX) (Trophoblast leukocyte common antigen) (CD antigen CD46)
[SUN1 KIAA0810 UNC84A] SUN domain-containing protein 1 (Protein unc-84 homolog A) (Sad1/unc-84 protein-like 1)
[] Outer capsid protein VP4 (Hemagglutinin) [Cleaved into: Outer capsid protein VP8*; Outer capsid protein VP5*]
[Txndc2 Sptrx Sptrx1 Trx4] Thioredoxin domain-containing protein 2 (Spermatid-specific thioredoxin-1) (Sptrx-1) (Thioredoxin-4)
[KDM5B JARID1B PLU1 RBBP2H1] Lysine-specific demethylase 5B (EC 1.14.11.67) (Cancer/testis antigen 31) (CT31) (Histone demethylase JARID1B) (Jumonji/ARID domain-containing protein 1B) (PLU-1) (Retinoblastoma-binding protein 2 homolog 1) (RBP2-H1) ([histone H3]-trimethyl-L-lysine(4) demethylase 5B)
[MKI67] Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67)
[Elavl4 Hud] ELAV-like protein 4 (Hu-antigen D) (HuD) (Paraneoplastic encephalomyelitis antigen HuD)

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