ID   MS4A3_HUMAN             Reviewed;         214 AA.
AC   Q96HJ5; A8MTP8; Q8NHW2;
DT   04-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   24-JAN-2024, entry version 166.
DE   RecName: Full=Membrane-spanning 4-domains subfamily A member 3;
DE   AltName: Full=CD20 antigen-like protein;
DE   AltName: Full=Hematopoietic-specific transmembrane protein 4;
DE            Short=HTm4;
GN   Name=MS4A3; Synonyms=CD20L, HTM4;
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).
RC   TISSUE=Hematopoietic;
RX   PubMed=7524084; DOI=10.1073/pnas.91.21.10178;
RA   Adra C.N., Lelias J.-M., Kobayashi H., Kaghad M., Morrison P., Rowley J.D.,
RA   Lim B.;
RT   "Cloning of the cDNA for a hematopoietic cell-specific protein related to
RT   CD20 and the beta subunit of the high-affinity IgE receptor: evidence for a
RT   family of proteins with four membrane-spanning regions.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:10178-10182(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   TISSUE=Bone marrow;
RA   Xie C., Yuan H.F., Xie X.Y., Li Y.H., Shi W., Wang D.M., Li H.M., Yue W.,
RA   Bai C.X., Zhang R., Pei X.T.;
RT   "Cloning and function analysis of the transcript variant of human
RT   hematopoietic cell-specific protein HTm4.";
RL   Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Shirakawa T., Yang X., Lyengar A., Sayegh M., Scadden D., Adra C.;
RL   Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC   TISSUE=Epidermal carcinoma, and Lung;
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   FUNCTION, AND INTERACTION WITH CDKN3.
RX   PubMed=11781350; DOI=10.1172/jci14025;
RA   Donato J.-L., Ko J., Kutok J.L., Cheng T., Shirakawa T., Mao X.-Q.,
RA   Beach D., Scadden D.T., Sayegh M.H., Adra C.N.;
RT   "Human HTm4 is a hematopoietic cell cycle regulator.";
RL   J. Clin. Invest. 109:51-58(2002).
RN   [7]
RP   INTERACTION WITH CDKN3.
RX   PubMed=15671017; DOI=10.1074/jbc.m413437200;
RA   Chinami M., Yano Y., Yang X., Salahuddin S., Moriyama K., Shiroishi M.,
RA   Turner H., Shirakawa T., Adra C.N.;
RT   "Binding of HTm4 to cyclin-dependent kinase (Cdk)-associated phosphatase
RT   (KAP).Cdk2.cyclin A complex enhances the phosphatase activity of KAP,
RT   dissociates cyclin A, and facilitates KAP dephosphorylation of Cdk2.";
RL   J. Biol. Chem. 280:17235-17242(2005).
CC   -!- FUNCTION: Hematopoietic modulator for the G1-S cell cycle transition.
CC       Modulates the level of phosphorylation of cyclin-dependent kinase 2
CC       (CDK2) through its direct binding to cyclin-dependent kinase inhibitor
CC       3 (CDKN3/KAP). {ECO:0000269|PubMed:11781350}.
CC   -!- SUBUNIT: Interacts with CDKN3. Interacts with CDKN3-CDK2 complexes
CC       through its binding to CDKN3; this interaction facilitates dissociation
CC       of cyclin A from CDKN3-CDK2 complexes. {ECO:0000269|PubMed:11781350,
CC       ECO:0000269|PubMed:15671017}.
CC   -!- INTERACTION:
CC       Q96HJ5; Q15848: ADIPOQ; NbExp=3; IntAct=EBI-12806656, EBI-10827839;
CC       Q96HJ5; Q99437: ATP6V0B; NbExp=5; IntAct=EBI-12806656, EBI-3904417;
CC       Q96HJ5; O95393: BMP10; NbExp=3; IntAct=EBI-12806656, EBI-3922513;
CC       Q96HJ5; Q12983: BNIP3; NbExp=3; IntAct=EBI-12806656, EBI-749464;
CC       Q96HJ5; Q8WVX3-2: C4orf3; NbExp=3; IntAct=EBI-12806656, EBI-12003442;
CC       Q96HJ5; Q9P0B6: CCDC167; NbExp=3; IntAct=EBI-12806656, EBI-9083477;
CC       Q96HJ5; P19397: CD53; NbExp=3; IntAct=EBI-12806656, EBI-6657396;
CC       Q96HJ5; P21854: CD72; NbExp=3; IntAct=EBI-12806656, EBI-307924;
CC       Q96HJ5; O95832: CLDN1; NbExp=3; IntAct=EBI-12806656, EBI-723889;
CC       Q96HJ5; P56747: CLDN6; NbExp=5; IntAct=EBI-12806656, EBI-12955011;
CC       Q96HJ5; P52803: EFNA5; NbExp=3; IntAct=EBI-12806656, EBI-1753674;
CC       Q96HJ5; P54852: EMP3; NbExp=3; IntAct=EBI-12806656, EBI-3907816;
CC       Q96HJ5; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-12806656, EBI-711490;
CC       Q96HJ5; Q01628: IFITM3; NbExp=3; IntAct=EBI-12806656, EBI-7932862;
CC       Q96HJ5; P24593: IGFBP5; NbExp=3; IntAct=EBI-12806656, EBI-720480;
CC       Q96HJ5; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-12806656, EBI-12070086;
CC       Q96HJ5; Q16617: NKG7; NbExp=3; IntAct=EBI-12806656, EBI-3919611;
CC       Q96HJ5; P60201-2: PLP1; NbExp=3; IntAct=EBI-12806656, EBI-12188331;
CC       Q96HJ5; Q8IY26: PLPP6; NbExp=3; IntAct=EBI-12806656, EBI-11721828;
CC       Q96HJ5; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-12806656, EBI-8652744;
CC       Q96HJ5; O43765: SGTA; NbExp=3; IntAct=EBI-12806656, EBI-347996;
CC       Q96HJ5; Q9Y267: SLC22A14; NbExp=4; IntAct=EBI-12806656, EBI-12824155;
CC       Q96HJ5; Q9NY91: SLC5A4; NbExp=3; IntAct=EBI-12806656, EBI-12409133;
CC       Q96HJ5; Q9NRQ5: SMCO4; NbExp=3; IntAct=EBI-12806656, EBI-8640191;
CC       Q96HJ5; Q9BZL3: SMIM3; NbExp=3; IntAct=EBI-12806656, EBI-741850;
CC       Q96HJ5; Q9UNK0: STX8; NbExp=3; IntAct=EBI-12806656, EBI-727240;
CC       Q96HJ5; Q9Y6I9: TEX264; NbExp=4; IntAct=EBI-12806656, EBI-10329860;
CC       Q96HJ5; Q96CE8: TM4SF18; NbExp=3; IntAct=EBI-12806656, EBI-13351685;
CC       Q96HJ5; P55061: TMBIM6; NbExp=3; IntAct=EBI-12806656, EBI-1045825;
CC       Q96HJ5; Q6UX40: TMEM107; NbExp=3; IntAct=EBI-12806656, EBI-12845616;
CC       Q96HJ5; Q9NV12: TMEM140; NbExp=3; IntAct=EBI-12806656, EBI-2844246;
CC       Q96HJ5; Q6ZP80: TMEM182; NbExp=5; IntAct=EBI-12806656, EBI-10255122;
CC       Q96HJ5; A2RU14: TMEM218; NbExp=5; IntAct=EBI-12806656, EBI-10173151;
CC       Q96HJ5; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-12806656, EBI-11528917;
CC       Q96HJ5; Q8N0U8: VKORC1L1; NbExp=3; IntAct=EBI-12806656, EBI-11337915;
CC       Q96HJ5; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-12806656, EBI-751210;
CC       Q96HJ5; O95159: ZFPL1; NbExp=3; IntAct=EBI-12806656, EBI-718439;
CC   -!- SUBCELLULAR LOCATION: Endomembrane system {ECO:0000250}; Multi-pass
CC       membrane protein {ECO:0000250}. Cytoplasm, perinuclear region
CC       {ECO:0000250}. Note=Located in the perinuclear area.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q96HJ5-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q96HJ5-2; Sequence=VSP_007109;
CC       Name=3;
CC         IsoId=Q96HJ5-3; Sequence=VSP_045798;
CC   -!- TISSUE SPECIFICITY: Expressed specifically in hematopoietic cells and
CC       tissues.
CC   -!- DOMAIN: The C-terminal region is required for binding to CDKN3-CDK2
CC       complexes and the modulation of CDKN3 activity.
CC   -!- SIMILARITY: Belongs to the MS4A family. {ECO:0000305}.
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DR   EMBL; L35848; AAA62319.1; -; mRNA.
DR   EMBL; AY095480; AAM23312.1; -; mRNA.
DR   EMBL; AY258289; AAP14648.1; -; Genomic_DNA.
DR   EMBL; AP000790; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC008487; AAH08487.1; -; mRNA.
DR   EMBL; BG494288; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS31567.1; -. [Q96HJ5-1]
DR   CCDS; CCDS31568.1; -. [Q96HJ5-2]
DR   CCDS; CCDS41651.1; -. [Q96HJ5-3]
DR   PIR; I59258; I59258.
DR   RefSeq; NP_001026836.1; NM_001031666.1. [Q96HJ5-3]
DR   RefSeq; NP_001026979.1; NM_001031809.1. [Q96HJ5-2]
DR   RefSeq; NP_006129.4; NM_006138.4. [Q96HJ5-1]
DR   AlphaFoldDB; Q96HJ5; -.
DR   SMR; Q96HJ5; -.
DR   BioGRID; 107370; 39.
DR   IntAct; Q96HJ5; 37.
DR   STRING; 9606.ENSP00000278865; -.
DR   iPTMnet; Q96HJ5; -.
DR   PhosphoSitePlus; Q96HJ5; -.
DR   BioMuta; MS4A3; -.
DR   DMDM; 29611825; -.
DR   EPD; Q96HJ5; -.
DR   MassIVE; Q96HJ5; -.
DR   PaxDb; 9606-ENSP00000278865; -.
DR   PeptideAtlas; Q96HJ5; -.
DR   Antibodypedia; 14413; 187 antibodies from 24 providers.
DR   DNASU; 932; -.
DR   Ensembl; ENST00000278865.8; ENSP00000278865.3; ENSG00000149516.14. [Q96HJ5-1]
DR   Ensembl; ENST00000358152.6; ENSP00000350872.2; ENSG00000149516.14. [Q96HJ5-2]
DR   Ensembl; ENST00000395032.6; ENSP00000378473.2; ENSG00000149516.14. [Q96HJ5-3]
DR   Ensembl; ENST00000534744.1; ENSP00000434117.1; ENSG00000149516.14. [Q96HJ5-2]
DR   Ensembl; ENST00000644768.2; ENSP00000495201.1; ENSG00000284903.2. [Q96HJ5-1]
DR   Ensembl; ENST00000645286.2; ENSP00000493798.1; ENSG00000284903.2. [Q96HJ5-1]
DR   GeneID; 932; -.
DR   KEGG; hsa:932; -.
DR   MANE-Select; ENST00000278865.8; ENSP00000278865.3; NM_006138.5; NP_006129.4.
DR   UCSC; uc001nom.4; human. [Q96HJ5-1]
DR   AGR; HGNC:7317; -.
DR   CTD; 932; -.
DR   DisGeNET; 932; -.
DR   GeneCards; MS4A3; -.
DR   HGNC; HGNC:7317; MS4A3.
DR   HPA; ENSG00000149516; Tissue enriched (bone).
DR   MIM; 606498; gene.
DR   neXtProt; NX_Q96HJ5; -.
DR   OpenTargets; ENSG00000149516; -.
DR   PharmGKB; PA31112; -.
DR   VEuPathDB; HostDB:ENSG00000149516; -.
DR   eggNOG; ENOG502T41X; Eukaryota.
DR   GeneTree; ENSGT00940000162383; -.
DR   HOGENOM; CLU_091032_6_2_1; -.
DR   InParanoid; Q96HJ5; -.
DR   OMA; TFHTGYP; -.
DR   OrthoDB; 4641703at2759; -.
DR   PhylomeDB; Q96HJ5; -.
DR   TreeFam; TF335157; -.
DR   PathwayCommons; Q96HJ5; -.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   SignaLink; Q96HJ5; -.
DR   BioGRID-ORCS; 932; 9 hits in 1153 CRISPR screens.
DR   GeneWiki; MS4A3; -.
DR   GenomeRNAi; 932; -.
DR   Pharos; Q96HJ5; Tbio.
DR   PRO; PR:Q96HJ5; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q96HJ5; Protein.
DR   Bgee; ENSG00000149516; Expressed in bone marrow and 85 other cell types or tissues.
DR   ExpressionAtlas; Q96HJ5; baseline and differential.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR   InterPro; IPR007237; CD20-like.
DR   InterPro; IPR030417; MS4A.
DR   PANTHER; PTHR23320:SF74; MEMBRANE-SPANNING 4-DOMAINS SUBFAMILY A MEMBER 3; 1.
DR   PANTHER; PTHR23320; MEMBRANE-SPANNING 4-DOMAINS SUBFAMILY A MS4A -RELATED; 1.
DR   Pfam; PF04103; CD20; 1.
DR   Genevisible; Q96HJ5; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; Membrane; Receptor; Reference proteome;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..214
FT                   /note="Membrane-spanning 4-domains subfamily A member 3"
FT                   /id="PRO_0000158632"
FT   TOPO_DOM        1..49
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        50..70
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        71..81
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        82..102
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        103..124
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        125..145
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        146..175
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        176..196
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        197..214
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..31
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..123
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_045798"
FT   VAR_SEQ         53..98
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_007109"
FT   CONFLICT        24
FT                   /note="A -> T (in Ref. 1; AAA62319)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        35
FT                   /note="Q -> H (in Ref. 1; AAA62319)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        38
FT                   /note="D -> N (in Ref. 1; AAA62319)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   214 AA;  22933 MW;  D30C276213DB8F3D CRC64;
     MASHEVDNAE LGSASAHGTP GSEAGPEELN TSVYQPIDGS PDYQKAKLQV LGAIQILNAA
     MILALGVFLG SLQYPYHFQK HFFFFTFYTG YPIWGAVFFC SSGTLSVVAG IKPTRTWIQN
     SFGMNIASAT IALVGTAFLS LNIAVNIQSL RSCHSSSESP DLCNYMGSIS NGMVSLLLIL
     TLLELCVTIS TIAMWCNANC CNSREEISSP PNSV
//