ID   SERC3_HUMAN             Reviewed;         473 AA.
AC   Q13530; B4DUE9; O43717; Q9BR33;
DT   25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   25-NOV-2002, sequence version 2.
DT   27-MAR-2024, entry version 184.
DE   RecName: Full=Serine incorporator 3;
DE   AltName: Full=Tumor differentially expressed protein 1 {ECO:0000303|PubMed:10559794};
GN   Name=SERINC3; Synonyms=DIFF33, TDE1 {ECO:0000303|PubMed:10559794};
GN   ORFNames=SBBI99 {ECO:0000303|Ref.3};
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] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT
RP   ALA-437.
RC   TISSUE=Placenta;
RX   PubMed=10559794;
RX   DOI=10.1002/(sici)1098-2744(199911)26:3<189::aid-mc8>3.3.co;2-k;
RA   Bossolasco M., Lebel M., Lemieux N., Mes-Masson A.-M.;
RT   "The human TDE gene homologue: localization to 20q13.1-13.3 and variable
RT   expression in human tumor cell lines and tissue.";
RL   Mol. Carcinog. 26:189-200(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Placenta;
RA   Dakuor J., Li H., Morrish D.W.;
RL   Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Zhang W., Wan T., Cao X.;
RT   "Hypothetical human protein SBBI99.";
RL   Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Pancreas;
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   [7]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=26416733; DOI=10.1038/nature15400;
RA   Usami Y., Wu Y., Goettlinger H.G.;
RT   "SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by
RT   Nef.";
RL   Nature 526:218-223(2015).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, AND SUBCELLULAR LOCATION (MICROBIAL
RP   INFECTION).
RX   PubMed=26416734; DOI=10.1038/nature15399;
RA   Rosa A., Chande A., Ziglio S., De Sanctis V., Bertorelli R., Goh S.L.,
RA   McCauley S.M., Nowosielska A., Antonarakis S.E., Luban J., Santoni F.A.,
RA   Pizzato M.;
RT   "HIV-1 Nef promotes infection by excluding SERINC5 from virion
RT   incorporation.";
RL   Nature 526:212-217(2015).
CC   -!- FUNCTION: Restriction factor required to restrict infectivity of
CC       lentiviruses, such as HIV-1: acts by inhibiting an early step of viral
CC       infection. Impairs the penetration of the viral particle into the
CC       cytoplasm (PubMed:26416733, PubMed:26416734).
CC       {ECO:0000269|PubMed:26416733, ECO:0000269|PubMed:26416734}.
CC   -!- INTERACTION:
CC       Q13530; P28799: GRN; NbExp=3; IntAct=EBI-1045571, EBI-747754;
CC       Q13530; O43933: PEX1; NbExp=3; IntAct=EBI-1045571, EBI-988601;
CC       Q13530; O76024: WFS1; NbExp=3; IntAct=EBI-1045571, EBI-720609;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q86VE9};
CC       Multi-pass membrane protein {ECO:0000255}. Golgi apparatus membrane
CC       {ECO:0000250|UniProtKB:Q9QZI9}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:Q9QZI9}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC       {ECO:0000305|PubMed:26416734}. Note=(Microbial infection) Upon HIV-1
CC       infection, it is redirected to perinuclear region following interaction
CC       with HIV-1 Nef, excluding it from virions particles, thereby preventing
CC       subsequent antiviral defense activity (Probable).
CC       {ECO:0000305|PubMed:26416734}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q13530-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q13530-2; Sequence=VSP_056833;
CC   -!- TISSUE SPECIFICITY: Ubiquitous. Expression levels were increased
CC       fourfold to tenfold in lung tumor tissues compared with normal
CC       pulmonary tissues. {ECO:0000269|PubMed:10559794}.
CC   -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9QZI9}.
CC   -!- SIMILARITY: Belongs to the TDE1 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB48858.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=AAD34641.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AF112227; AAD22448.1; -; mRNA.
DR   EMBL; U49188; AAB48858.1; ALT_FRAME; mRNA.
DR   EMBL; AF153979; AAD34641.1; ALT_FRAME; mRNA.
DR   EMBL; AK300618; BAG62311.1; -; mRNA.
DR   EMBL; Z97053; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC006088; AAH06088.1; -; mRNA.
DR   CCDS; CCDS13333.1; -. [Q13530-1]
DR   RefSeq; NP_006802.1; NM_006811.3. [Q13530-1]
DR   RefSeq; NP_945179.1; NM_198941.2. [Q13530-1]
DR   RefSeq; XP_016883090.1; XM_017027601.1.
DR   PDB; 7RU6; EM; 4.40 A; A=1-473.
DR   PDB; 7RUG; EM; 4.70 A; A=1-473.
DR   PDBsum; 7RU6; -.
DR   PDBsum; 7RUG; -.
DR   AlphaFoldDB; Q13530; -.
DR   EMDB; EMD-24698; -.
DR   EMDB; EMD-24705; -.
DR   SMR; Q13530; -.
DR   BioGRID; 116155; 19.
DR   IntAct; Q13530; 9.
DR   MINT; Q13530; -.
DR   STRING; 9606.ENSP00000340243; -.
DR   TCDB; 9.A.29.3.4; the lantibiotic immunity protein/serine connector (lip/sip) family.
DR   GlyCosmos; Q13530; 2 sites, 1 glycan.
DR   GlyGen; Q13530; 4 sites, 3 O-linked glycans (3 sites).
DR   iPTMnet; Q13530; -.
DR   PhosphoSitePlus; Q13530; -.
DR   SwissPalm; Q13530; -.
DR   BioMuta; SERINC3; -.
DR   DMDM; 25453293; -.
DR   EPD; Q13530; -.
DR   jPOST; Q13530; -.
DR   MassIVE; Q13530; -.
DR   MaxQB; Q13530; -.
DR   PaxDb; 9606-ENSP00000340243; -.
DR   PeptideAtlas; Q13530; -.
DR   ProteomicsDB; 5183; -.
DR   ProteomicsDB; 59520; -. [Q13530-1]
DR   Pumba; Q13530; -.
DR   Antibodypedia; 43693; 222 antibodies from 27 providers.
DR   DNASU; 10955; -.
DR   Ensembl; ENST00000255175.5; ENSP00000255175.1; ENSG00000132824.14. [Q13530-1]
DR   Ensembl; ENST00000342374.5; ENSP00000340243.4; ENSG00000132824.14. [Q13530-1]
DR   GeneID; 10955; -.
DR   KEGG; hsa:10955; -.
DR   MANE-Select; ENST00000342374.5; ENSP00000340243.4; NM_006811.4; NP_006802.1.
DR   UCSC; uc002xme.4; human. [Q13530-1]
DR   AGR; HGNC:11699; -.
DR   CTD; 10955; -.
DR   DisGeNET; 10955; -.
DR   GeneCards; SERINC3; -.
DR   HGNC; HGNC:11699; SERINC3.
DR   HPA; ENSG00000132824; Low tissue specificity.
DR   MIM; 607165; gene.
DR   neXtProt; NX_Q13530; -.
DR   OpenTargets; ENSG00000132824; -.
DR   PharmGKB; PA36418; -.
DR   VEuPathDB; HostDB:ENSG00000132824; -.
DR   eggNOG; KOG2592; Eukaryota.
DR   GeneTree; ENSGT01030000234623; -.
DR   HOGENOM; CLU_029574_5_0_1; -.
DR   InParanoid; Q13530; -.
DR   OMA; GNPRVWY; -.
DR   OrthoDB; 53161at2759; -.
DR   PhylomeDB; Q13530; -.
DR   TreeFam; TF312881; -.
DR   PathwayCommons; Q13530; -.
DR   Reactome; R-HSA-977347; Serine biosynthesis.
DR   SignaLink; Q13530; -.
DR   SIGNOR; Q13530; -.
DR   BioGRID-ORCS; 10955; 17 hits in 1162 CRISPR screens.
DR   ChiTaRS; SERINC3; human.
DR   GeneWiki; SERINC3; -.
DR   GenomeRNAi; 10955; -.
DR   Pharos; Q13530; Tbio.
DR   PRO; PR:Q13530; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   RNAct; Q13530; Protein.
DR   Bgee; ENSG00000132824; Expressed in endothelial cell and 216 other cell types or tissues.
DR   ExpressionAtlas; Q13530; baseline and differential.
DR   GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0015194; F:L-serine transmembrane transporter activity; TAS:Reactome.
DR   GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR   GO; GO:0009597; P:detection of virus; IDA:UniProtKB.
DR   GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR   GO; GO:0006564; P:L-serine biosynthetic process; TAS:Reactome.
DR   GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR   InterPro; IPR005016; TDE1/TMS.
DR   PANTHER; PTHR10383; SERINE INCORPORATOR; 1.
DR   PANTHER; PTHR10383:SF51; SERINE INCORPORATOR 3; 1.
DR   Pfam; PF03348; Serinc; 1.
DR   Genevisible; Q13530; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Antiviral defense; Cell membrane;
KW   Cytoplasm; Glycoprotein; Golgi apparatus; Host-virus interaction; Immunity;
KW   Innate immunity; Membrane; Phosphoprotein; Reference proteome;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..473
FT                   /note="Serine incorporator 3"
FT                   /id="PRO_0000218970"
FT   TOPO_DOM        1..96
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        97..117
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        118..132
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        133..153
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        154..159
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        160..180
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        181..203
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        204..224
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        225..239
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        240..260
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        261..329
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        330..350
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        351..406
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        407..427
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        428..446
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        447..467
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        468..473
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         371
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9NRX5"
FT   CARBOHYD        34
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..55
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_056833"
FT   VARIANT         437
FT                   /note="T -> A"
FT                   /evidence="ECO:0000269|PubMed:10559794"
FT                   /id="VAR_014315"
SQ   SEQUENCE   473 AA;  52580 MW;  9DCB04B2A0AB1132 CRC64;
     MGAVLGVFSL ASWVPCLCSG ASCLLCSCCP NSKNSTVTRL IYAFILLLST VVSYIMQRKE
     METYLKKIPG FCEGGFKIHE ADINADKDCD VLVGYKAVYR ISFAMAIFFF VFSLLMFKVK
     TSKDLRAAVH NGFWFFKIAA LIGIMVGSFY IPGGYFSSVW FVVGMIGAAL FILIQLVLLV
     DFAHSWNESW VNRMEEGNPR LWYAALLSFT SAFYILSIIC VGLLYTYYTK PDGCTENKFF
     ISINLILCVV ASIISIHPKI QEHQPRSGLL QSSLITLYTM YLTWSAMSNE PDRSCNPNLM
     SFITRITAPT LAPGNSTAVV PTPTPPSKSG SLLDSDNFIG LFVFVLCLLY SSIRTSTNSQ
     VDKLTLSGSD SVILGDTTTS GASDEEDGQP RRAVDNEKEG VQYSYSLFHL MLCLASLYIM
     MTLTSWYSPD AKFQSMTSKW PAVWVKISSS WVCLLLYVWT LVAPLVLTSR DFS
//