ID CD70_HUMAN Reviewed; 193 AA. AC P32970; B4DPR8; Q53XX4; Q96J57; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 06-JUN-2002, sequence version 2. DT 27-MAR-2024, entry version 190. DE RecName: Full=CD70 antigen; DE AltName: Full=CD27 ligand; DE Short=CD27-L; DE AltName: Full=Tumor necrosis factor ligand superfamily member 7; DE AltName: CD_antigen=CD70; GN Name=CD70; Synonyms=CD27L, CD27LG, TNFSF7; 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=B-cell; RX PubMed=8387892; DOI=10.1016/0092-8674(93)90133-b; RA Goodwin R.G., Alderson M.R., Smith C.A., Armitage R.J., Vandenbos T., RA Jerzy R., Tough T.W., Schoenborn M.A., David-Smith T., Hennen K., Falk B., RA Cosman D., Baker E., Sutherland G.R., Grabstein K.H., Farrah T., Giri J.G., RA Beckmann M.P.; RT "Molecular and biological characterization of a ligand for CD27 defines a RT new family of cytokines with homology to tumor necrosis factor."; RL Cell 73:447-456(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND RP INTERACTION WITH CD27. RX PubMed=8120384; RA Bowman M.R., Crimmins M.A., Yetz-Aldape J., Kriz R., Kelleher K., RA Herrmann S.; RT "The cloning of CD70 and its identification as the ligand for CD27."; RL J. Immunol. 152:1756-1761(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [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 [GENOMIC DNA]. RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., RA Nickerson D.A.; RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Kidney; 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 [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [10] RP VARIANT LPFS3 179-ARG--PRO-193 DEL, CHARACTERIZATION OF VARIANT LPFS3 RP 179-ARG--PRO-193 DEL, INVOLVEMENT IN LPFS3, AND FUNCTION. RX PubMed=28011863; DOI=10.1084/jem.20160784; RA Izawa K., Martin E., Soudais C., Bruneau J., Boutboul D., Rodriguez R., RA Lenoir C., Hislop A.D., Besson C., Touzot F., Picard C., Callebaut I., RA de Villartay J.P., Moshous D., Fischer A., Latour S.; RT "Inherited CD70 deficiency in humans reveals a critical role for the CD70- RT CD27 pathway in immunity to Epstein-Barr virus infection."; RL J. Exp. Med. 214:73-89(2017). RN [11] RP VARIANT LPFS3 186-PHE--PRO-193 DEL, CHARACTERIZATION OF VARIANT LPFS3 RP 186-PHE--PRO-193 DEL, INVOLVEMENT IN LPFS3, AND FUNCTION. RX PubMed=28011864; DOI=10.1084/jem.20160849; RA Abolhassani H., Edwards E.S., Ikinciogullari A., Jing H., Borte S., RA Buggert M., Du L., Matsuda-Lennikov M., Romano R., Caridha R., Bade S., RA Zhang Y., Frederiksen J., Fang M., Bal S.K., Haskologlu S., Dogu F., RA Tacyildiz N., Matthews H.F., McElwee J.J., Gostick E., Price D.A., RA Palendira U., Aghamohammadi A., Boisson B., Rezaei N., Karlsson A.C., RA Lenardo M.J., Casanova J.L., Hammarstroem L., Tangye S.G., Su H.C., RA Pan-Hammarstroem Q.; RT "Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy RT in humans with inherited CD70 deficiency."; RL J. Exp. Med. 214:91-106(2017). CC -!- FUNCTION: Cytokine which is the ligand for CD27. The CD70-CD27 pathway CC plays an important role in the generation and maintenance of T cell CC immunity, in particular during antiviral responses. Upon CD27 binding, CC induces the proliferation of costimulated T-cells and enhances the CC generation of cytolytic T-cells. {ECO:0000269|PubMed:28011863, CC ECO:0000269|PubMed:28011864, ECO:0000269|PubMed:8120384}. CC -!- SUBUNIT: Homotrimer. {ECO:0000305}. CC -!- INTERACTION: CC P32970; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-18539709, EBI-18535450; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:8120384}; Single- CC pass type II membrane protein {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P32970-1; Sequence=Displayed; CC Name=2; CC IsoId=P32970-2; Sequence=VSP_056416; CC -!- DISEASE: Lymphoproliferative syndrome 3 (LPFS3) [MIM:618261]: An CC autosomal recessive, early-onset immunologic disorder characterized by CC increased susceptibility to Epstein-Barr virus infection in B cells, CC abnormal B-cell proliferation and increased susceptibility to B-cell CC malignancies, including Hodgkin lymphoma. Patients usually have CC lymphadenopathy and hypogammaglobulinemia, and may suffer from CC recurrent infections. {ECO:0000269|PubMed:28011863, CC ECO:0000269|PubMed:28011864}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the tumor necrosis factor family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L08096; AAA36175.1; -; mRNA. DR EMBL; S69339; AAB30121.1; -; mRNA. DR EMBL; BT007211; AAP35875.1; -; mRNA. DR EMBL; AK298467; BAG60680.1; -; mRNA. DR EMBL; EF064709; ABK41892.1; -; Genomic_DNA. DR EMBL; AC008760; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471139; EAW69074.1; -; Genomic_DNA. DR EMBL; BC000725; AAH00725.1; -; mRNA. DR CCDS; CCDS12170.1; -. [P32970-1] DR CCDS; CCDS82283.1; -. [P32970-2] DR PIR; I56214; A40738. DR RefSeq; NP_001243.1; NM_001252.4. [P32970-1] DR RefSeq; NP_001317261.1; NM_001330332.1. [P32970-2] DR PDB; 7KX0; X-ray; 2.69 A; A/B/C=39-193. DR PDBsum; 7KX0; -. DR AlphaFoldDB; P32970; -. DR SMR; P32970; -. DR BioGRID; 107408; 187. DR IntAct; P32970; 83. DR STRING; 9606.ENSP00000395294; -. DR ChEMBL; CHEMBL3712913; -. DR DrugBank; DB15100; Cusatuzumab. DR GlyCosmos; P32970; 2 sites, No reported glycans. DR GlyGen; P32970; 4 sites, 2 O-linked glycans (1 site). DR iPTMnet; P32970; -. DR PhosphoSitePlus; P32970; -. DR SwissPalm; P32970; -. DR BioMuta; CD70; -. DR DMDM; 21431837; -. DR CPTAC; CPTAC-5959; -. DR EPD; P32970; -. DR MassIVE; P32970; -. DR MaxQB; P32970; -. DR PaxDb; 9606-ENSP00000245903; -. DR PeptideAtlas; P32970; -. DR ProteomicsDB; 4807; -. DR ProteomicsDB; 54894; -. [P32970-1] DR Pumba; P32970; -. DR ABCD; P32970; 41 sequenced antibodies. DR Antibodypedia; 24212; 1066 antibodies from 41 providers. DR CPTC; P32970; 3 antibodies. DR DNASU; 970; -. DR Ensembl; ENST00000245903.4; ENSP00000245903.2; ENSG00000125726.11. [P32970-1] DR Ensembl; ENST00000423145.7; ENSP00000395294.2; ENSG00000125726.11. [P32970-2] DR GeneID; 970; -. DR KEGG; hsa:970; -. DR MANE-Select; ENST00000245903.4; ENSP00000245903.2; NM_001252.5; NP_001243.1. DR UCSC; uc002mfi.3; human. [P32970-1] DR AGR; HGNC:11937; -. DR CTD; 970; -. DR DisGeNET; 970; -. DR GeneCards; CD70; -. DR HGNC; HGNC:11937; CD70. DR HPA; ENSG00000125726; Tissue enhanced (lymphoid). DR MalaCards; CD70; -. DR MIM; 602840; gene. DR MIM; 618261; phenotype. DR neXtProt; NX_P32970; -. DR OpenTargets; ENSG00000125726; -. DR Orphanet; 538958; Combined immunodeficiency due to CD70 deficiency. DR PharmGKB; PA36627; -. DR VEuPathDB; HostDB:ENSG00000125726; -. DR eggNOG; ENOG502TEKD; Eukaryota. DR GeneTree; ENSGT00390000006744; -. DR HOGENOM; CLU_114585_0_0_1; -. DR InParanoid; P32970; -. DR OMA; FGIQWVH; -. DR OrthoDB; 5255922at2759; -. DR PhylomeDB; P32970; -. DR TreeFam; TF338269; -. DR PathwayCommons; P32970; -. DR Reactome; R-HSA-5669034; TNFs bind their physiological receptors. DR SignaLink; P32970; -. DR SIGNOR; P32970; -. DR BioGRID-ORCS; 970; 11 hits in 1152 CRISPR screens. DR ChiTaRS; CD70; human. DR GenomeRNAi; 970; -. DR Pharos; P32970; Tbio. DR PRO; PR:P32970; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P32970; Protein. DR Bgee; ENSG00000125726; Expressed in cartilage tissue and 130 other cell types or tissues. DR ExpressionAtlas; P32970; baseline and differential. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HGNC-UCL. DR GO; GO:0005125; F:cytokine activity; IMP:UniProtKB. DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL. DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc. DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro. DR GO; GO:0019724; P:B cell mediated immunity; IMP:UniProtKB. DR GO; GO:0042100; P:B cell proliferation; IMP:UniProtKB. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:BHF-UCL. DR GO; GO:0042102; P:positive regulation of T cell proliferation; TAS:GO_Central. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0002456; P:T cell mediated immunity; IMP:UniProtKB. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:InterPro. DR CDD; cd00184; TNF; 1. DR Gene3D; 2.60.120.40; -; 1. DR InterPro; IPR042374; CD70. DR InterPro; IPR021184; TNF_CS. DR InterPro; IPR006052; TNF_dom. DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom. DR PANTHER; PTHR15152; CD70 ANTIGEN; 1. DR PANTHER; PTHR15152:SF0; CD70 ANTIGEN; 1. DR Pfam; PF00229; TNF; 1. DR SMART; SM00207; TNF; 1. DR SUPFAM; SSF49842; TNF-like; 1. DR PROSITE; PS00251; TNF_1; 1. DR PROSITE; PS50049; TNF_2; 1. DR Genevisible; P32970; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytokine; Disease variant; KW Disulfide bond; Glycoprotein; Membrane; Reference proteome; Signal-anchor; KW Transmembrane; Transmembrane helix. FT CHAIN 1..193 FT /note="CD70 antigen" FT /id="PRO_0000185497" FT TOPO_DOM 1..17 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 18..38 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 39..193 FT /note="Extracellular" FT /evidence="ECO:0000255" FT CARBOHYD 63 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 170 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 133..151 FT /evidence="ECO:0000255" FT VAR_SEQ 151..193 FT /note="CTIASQRLTPLARGDTLCTNLTGTLLPSRNTDETFFGVQWVRP -> LFGFW FT NWGLKVKCFLRHLIWTAHCFIPLTQLVFMQALQSWRNHHCSHFTDEENRGVNR (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056416" FT VARIANT 179..193 FT /note="Missing (in LPFS3; loss of interaction with CD27)" FT /evidence="ECO:0000269|PubMed:28011863" FT /id="VAR_081988" FT VARIANT 186..193 FT /note="Missing (in LPFS3; loss of interaction with CD27)" FT /evidence="ECO:0000269|PubMed:28011864" FT /id="VAR_081989" FT CONFLICT 154 FT /note="A -> V (in Ref. 1; AAA36175)" FT /evidence="ECO:0000305" FT STRAND 57..65 FT /evidence="ECO:0007829|PDB:7KX0" FT STRAND 72..76 FT /evidence="ECO:0007829|PDB:7KX0" FT TURN 79..81 FT /evidence="ECO:0007829|PDB:7KX0" FT STRAND 85..88 FT /evidence="ECO:0007829|PDB:7KX0" FT STRAND 90..92 FT /evidence="ECO:0007829|PDB:7KX0" FT STRAND 95..97 FT /evidence="ECO:0007829|PDB:7KX0" FT STRAND 102..112 FT /evidence="ECO:0007829|PDB:7KX0" FT HELIX 117..122 FT /evidence="ECO:0007829|PDB:7KX0" FT STRAND 127..132 FT /evidence="ECO:0007829|PDB:7KX0" FT STRAND 134..136 FT /evidence="ECO:0007829|PDB:7KX0" FT STRAND 141..146 FT /evidence="ECO:0007829|PDB:7KX0" FT STRAND 151..161 FT /evidence="ECO:0007829|PDB:7KX0" FT STRAND 166..174 FT /evidence="ECO:0007829|PDB:7KX0" FT TURN 181..183 FT /evidence="ECO:0007829|PDB:7KX0" FT STRAND 185..192 FT /evidence="ECO:0007829|PDB:7KX0" SQ SEQUENCE 193 AA; 21118 MW; 9265856E33BE4D50 CRC64; MPEEGSGCSV RRRPYGCVLR AALVPLVAGL VICLVVCIQR FAQAQQQLPL ESLGWDVAEL QLNHTGPQQD PRLYWQGGPA LGRSFLHGPE LDKGQLRIHR DGIYMVHIQV TLAICSSTTA SRHHPTTLAV GICSPASRSI SLLRLSFHQG CTIASQRLTP LARGDTLCTN LTGTLLPSRN TDETFFGVQW VRP //