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TSN4_HUMAN
ID   TSN4_HUMAN              Reviewed;         238 AA.
AC   O14817; Q6IAP6;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   03-AUG-2022, entry version 165.
DE   RecName: Full=Tetraspanin-4;
DE            Short=Tspan-4;
DE   AltName: Full=Novel antigen 2;
DE            Short=NAG-2;
DE   AltName: Full=Transmembrane 4 superfamily member 7;
GN   Name=TSPAN4; Synonyms=NAG2, TM4SF7;
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].
RX   PubMed=9360996; DOI=10.1074/jbc.272.46.29181;
RA   Tachibana I., Bodorova J., Berditchevski F., Zutter M.M., Hemler M.E.;
RT   "NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes
RT   with integrins and other TM4SF proteins.";
RL   J. Biol. Chem. 272:29181-29189(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9714763; DOI=10.1016/s0167-4781(98)00087-6;
RA   Todd S.C., Doctor V.S., Levy S.;
RT   "Sequences and expression of six new members of the tetraspanin/TM4SF
RT   family.";
RL   Biochim. Biophys. Acta 1399:101-104(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Teratocarcinoma;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [6]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=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   [8]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-161.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [9]
RP   VARIANT [LARGE SCALE ANALYSIS] MET-67.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- SUBUNIT: Forms a complex with integrins.
CC   -!- INTERACTION:
CC       O14817; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-8652667, EBI-744545;
CC       O14817; Q9H2X0: CHRD; NbExp=3; IntAct=EBI-8652667, EBI-947551;
CC       O14817; Q9UHP7-3: CLEC2D; NbExp=3; IntAct=EBI-8652667, EBI-11749983;
CC       O14817; Q02930-3: CREB5; NbExp=3; IntAct=EBI-8652667, EBI-10192698;
CC       O14817; A8MQ03: CYSRT1; NbExp=6; IntAct=EBI-8652667, EBI-3867333;
CC       O14817; Q9H8M9: EVA1A; NbExp=3; IntAct=EBI-8652667, EBI-715362;
CC       O14817; A0A0C3SFZ9: FCHO1; NbExp=3; IntAct=EBI-8652667, EBI-11977403;
CC       O14817; O43559: FRS3; NbExp=3; IntAct=EBI-8652667, EBI-725515;
CC       O14817; Q9Y223-2: GNE; NbExp=3; IntAct=EBI-8652667, EBI-11975289;
CC       O14817; P28799: GRN; NbExp=3; IntAct=EBI-8652667, EBI-747754;
CC       O14817; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-8652667, EBI-11978177;
CC       O14817; P49639: HOXA1; NbExp=3; IntAct=EBI-8652667, EBI-740785;
CC       O14817; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-8652667, EBI-10171774;
CC       O14817; Q9BYQ6: KRTAP4-11; NbExp=3; IntAct=EBI-8652667, EBI-10302392;
CC       O14817; Q9BYR2: KRTAP4-5; NbExp=3; IntAct=EBI-8652667, EBI-11993254;
CC       O14817; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-8652667, EBI-11962084;
CC       O14817; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-8652667, EBI-1044640;
CC       O14817; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-8652667, EBI-1043191;
CC       O14817; Q5T7P2: LCE1A; NbExp=3; IntAct=EBI-8652667, EBI-11962058;
CC       O14817; O14633: LCE2B; NbExp=3; IntAct=EBI-8652667, EBI-11478468;
CC       O14817; Q5TA82: LCE2D; NbExp=3; IntAct=EBI-8652667, EBI-10246750;
CC       O14817; Q5TA76: LCE3A; NbExp=3; IntAct=EBI-8652667, EBI-9394625;
CC       O14817; Q5T5A8: LCE3C; NbExp=3; IntAct=EBI-8652667, EBI-10245291;
CC       O14817; Q9BYE3: LCE3D; NbExp=3; IntAct=EBI-8652667, EBI-6658837;
CC       O14817; Q5TA78: LCE4A; NbExp=3; IntAct=EBI-8652667, EBI-10246358;
CC       O14817; Q8N386: LRRC25; NbExp=3; IntAct=EBI-8652667, EBI-11304917;
CC       O14817; Q99750: MDFI; NbExp=3; IntAct=EBI-8652667, EBI-724076;
CC       O14817; Q13064: MKRN3; NbExp=3; IntAct=EBI-8652667, EBI-2340269;
CC       O14817; Q7Z3S9: NOTCH2NLA; NbExp=4; IntAct=EBI-8652667, EBI-945833;
CC       O14817; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-8652667, EBI-22310682;
CC       O14817; Q92570: NR4A3; NbExp=3; IntAct=EBI-8652667, EBI-13644623;
CC       O14817; P32242: OTX1; NbExp=3; IntAct=EBI-8652667, EBI-740446;
CC       O14817; A2BDE7: PHLDA1; NbExp=3; IntAct=EBI-8652667, EBI-14084211;
CC       O14817; Q9NRQ2: PLSCR4; NbExp=3; IntAct=EBI-8652667, EBI-769257;
CC       O14817; O95470: SGPL1; NbExp=3; IntAct=EBI-8652667, EBI-1046170;
CC       O14817; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-8652667, EBI-750487;
CC       O14817; Q96A25: TMEM106A; NbExp=3; IntAct=EBI-8652667, EBI-3915978;
CC       O14817; A8MV65-2: VGLL3; NbExp=3; IntAct=EBI-8652667, EBI-11957216;
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Expressed in multiple tissues but is absent in
CC       brain, lymphoid cells, and platelets.
CC   -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family. {ECO:0000305}.
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DR   EMBL; AF022813; AAC51864.1; -; mRNA.
DR   EMBL; AF054841; AAC69717.1; -; mRNA.
DR   EMBL; AK291089; BAF83778.1; -; mRNA.
DR   EMBL; BT006776; AAP35422.1; -; mRNA.
DR   EMBL; CR457108; CAG33389.1; -; mRNA.
DR   EMBL; CH471158; EAX02409.1; -; Genomic_DNA.
DR   EMBL; BC000389; AAH00389.1; -; mRNA.
DR   EMBL; BC019314; AAH19314.1; -; mRNA.
DR   EMBL; BC093031; AAH93031.1; -; mRNA.
DR   CCDS; CCDS7721.1; -.
DR   PIR; A59265; A59265.
DR   RefSeq; NP_001020405.1; NM_001025234.1.
DR   RefSeq; NP_001020406.1; NM_001025235.1.
DR   RefSeq; NP_001020407.1; NM_001025236.1.
DR   RefSeq; NP_001020408.1; NM_001025237.1.
DR   RefSeq; NP_001020409.1; NM_001025238.1.
DR   RefSeq; NP_001020410.1; NM_001025239.1.
DR   RefSeq; NP_003262.1; NM_003271.4.
DR   RefSeq; XP_005253159.1; XM_005253102.1.
DR   AlphaFoldDB; O14817; -.
DR   SMR; O14817; -.
DR   BioGRID; 112961; 50.
DR   IntAct; O14817; 40.
DR   MINT; O14817; -.
DR   STRING; 9606.ENSP00000380553; -.
DR   GlyGen; O14817; 2 sites.
DR   iPTMnet; O14817; -.
DR   PhosphoSitePlus; O14817; -.
DR   SwissPalm; O14817; -.
DR   BioMuta; TSPAN4; -.
DR   EPD; O14817; -.
DR   jPOST; O14817; -.
DR   MassIVE; O14817; -.
DR   MaxQB; O14817; -.
DR   PaxDb; O14817; -.
DR   PeptideAtlas; O14817; -.
DR   PRIDE; O14817; -.
DR   ProteomicsDB; 48255; -.
DR   Antibodypedia; 10103; 76 antibodies from 18 providers.
DR   DNASU; 7106; -.
DR   Ensembl; ENST00000397397.7; ENSP00000380552.2; ENSG00000214063.12.
DR   Ensembl; ENST00000397404.5; ENSP00000380553.1; ENSG00000214063.12.
DR   Ensembl; ENST00000397406.5; ENSP00000380554.1; ENSG00000214063.12.
DR   Ensembl; ENST00000397408.5; ENSP00000380555.1; ENSG00000214063.12.
DR   Ensembl; ENST00000397411.6; ENSP00000380558.2; ENSG00000214063.12.
DR   Ensembl; ENST00000409543.6; ENSP00000386513.2; ENSG00000214063.12.
DR   GeneID; 7106; -.
DR   KEGG; hsa:7106; -.
DR   MANE-Select; ENST00000397397.7; ENSP00000380552.2; NM_003271.5; NP_003262.1.
DR   UCSC; uc001lsd.2; human.
DR   CTD; 7106; -.
DR   DisGeNET; 7106; -.
DR   GeneCards; TSPAN4; -.
DR   HGNC; HGNC:11859; TSPAN4.
DR   HPA; ENSG00000214063; Low tissue specificity.
DR   MIM; 602644; gene.
DR   neXtProt; NX_O14817; -.
DR   OpenTargets; ENSG00000214063; -.
DR   PharmGKB; PA36560; -.
DR   VEuPathDB; HostDB:ENSG00000214063; -.
DR   eggNOG; KOG3882; Eukaryota.
DR   GeneTree; ENSGT00940000160434; -.
DR   InParanoid; O14817; -.
DR   OMA; KADTYCT; -.
DR   OrthoDB; 1224210at2759; -.
DR   PhylomeDB; O14817; -.
DR   TreeFam; TF352892; -.
DR   PathwayCommons; O14817; -.
DR   SignaLink; O14817; -.
DR   BioGRID-ORCS; 7106; 17 hits in 1073 CRISPR screens.
DR   ChiTaRS; TSPAN4; human.
DR   GeneWiki; TSPAN4; -.
DR   GenomeRNAi; 7106; -.
DR   Pharos; O14817; Tbio.
DR   PRO; PR:O14817; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; O14817; protein.
DR   Bgee; ENSG00000214063; Expressed in stromal cell of endometrium and 197 other tissues.
DR   ExpressionAtlas; O14817; baseline and differential.
DR   Genevisible; O14817; HS.
DR   GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR   GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR   GO; GO:0003823; F:antigen binding; IDA:UniProtKB.
DR   GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR   GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR   Gene3D; 1.10.1450.10; -; 1.
DR   InterPro; IPR018499; Tetraspanin/Peripherin.
DR   InterPro; IPR000301; Tetraspanin_animals.
DR   InterPro; IPR018503; Tetraspanin_CS.
DR   InterPro; IPR008952; Tetraspanin_EC2_sf.
DR   PANTHER; PTHR19282; PTHR19282; 1.
DR   Pfam; PF00335; Tetraspanin; 1.
DR   PIRSF; PIRSF002419; Tetraspanin; 1.
DR   SUPFAM; SSF48652; SSF48652; 1.
DR   PROSITE; PS00421; TM4_1; 1.
PE   1: Evidence at protein level;
KW   Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..238
FT                   /note="Tetraspanin-4"
FT                   /id="PRO_0000219241"
FT   TOPO_DOM        1..13
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        14..34
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        35..55
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        56..76
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        77..85
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        86..106
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        107..201
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        202..222
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        223..238
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        152
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        161
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   VARIANT         67
FT                   /note="I -> M (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036616"
SQ   SEQUENCE   238 AA;  26118 MW;  A6B9A5633065A492 CRC64;
     MARACLQAVK YLMFAFNLLF WLGGCGVLGV GIWLAATQGS FATLSSSFPS LSAANLLIIT
     GAFVMAIGFV GCLGAIKENK CLLLTFFLLL LLVFLLEATI AILFFAYTDK IDRYAQQDLK
     KGLHLYGTQG NVGLTNAWSI IQTDFRCCGV SNYTDWFEVY NATRVPDSCC LEFSESCGLH
     APGTWWKAPC YETVKVWLQE NLLAVGIFGL CTALVQILGL TFAMTMYCQV VKADTYCA
 
 
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