SPR2A_HUMAN
ID SPR2A_HUMAN Reviewed; 72 AA.
AC P35326; B2R4T3; D3DV35; Q5T529;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Small proline-rich protein 2A {ECO:0000305};
DE Short=SPR-2A {ECO:0000303|PubMed:2388825};
DE AltName: Full=2-1 {ECO:0000303|PubMed:2388825};
GN Name=SPRR2A {ECO:0000303|PubMed:34735226, ECO:0000312|HGNC:HGNC:11261};
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 [GENOMIC DNA], AND INDUCTION.
RC TISSUE=Blood;
RX PubMed=2388825; DOI=10.1093/nar/18.15.4401;
RA Gibbs S., Lohman F., Teubel W., van de Putte P., Backendorf C.;
RT "Characterization of the human spr2 promoter: induction after UV
RT irradiation or TPA treatment and regulation during differentiation of
RT cultured primary keratinocytes.";
RL Nucleic Acids Res. 18:4401-4407(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=8325635; DOI=10.1006/geno.1993.1240;
RA Gibbs S., Fijneman R., Wiegant J., Geurts van Kessel A., van de Putte P.,
RA Backendorf C.;
RT "Molecular characterization and evolution of the SPRR family of
RT keratinocyte differentiation markers encoding small proline-rich
RT proteins.";
RL Genomics 16:630-637(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
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 GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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, SUBCELLULAR LOCATION, DISULFIDE BONDS, AND TISSUE SPECIFICITY.
RX PubMed=34735226; DOI=10.1126/science.abe6723;
RA Hu Z., Zhang C., Sifuentes-Dominguez L., Zarek C.M., Propheter D.C.,
RA Kuang Z., Wang Y., Pendse M., Ruhn K.A., Hassell B., Behrendt C.L.,
RA Zhang B., Raj P., Harris-Tryon T.A., Reese T.A., Hooper L.V.;
RT "Small proline-rich protein 2A is a gut bactericidal protein deployed
RT during helminth infection.";
RL Science 374:eabe6723-eabe6723(2021).
CC -!- FUNCTION: Gut bactericidal protein that selectively kills Gram-positive
CC bacteria by binding to negatively charged lipids on bacterial
CC membranes, leading to bacterial membrane permeabilization and
CC disruption (PubMed:34735226). Specifically binds lipids bearing
CC negatively charged headgroups, such as phosphatidic acid,
CC phosphatidylserine (PS), cardiolipin (CL), and phosphatidylinositol
CC phosphates, but not to zwitterionic or neutral lipids
CC (PubMed:34735226). Induced by type-2 cytokines in response to helminth
CC infection and is required to protect against helminth-induced bacterial
CC invasion of intestinal tissue (By similarity). May also be involved in
CC the development of the cornified envelope of squamous epithelia;
CC however, additional evidences are required to confirm this result in
CC vivo (PubMed:8325635). {ECO:0000250|UniProtKB:P0DV37,
CC ECO:0000269|PubMed:34735226, ECO:0000269|PubMed:8325635}.
CC -!- INTERACTION:
CC P35326; P12931: SRC; NbExp=3; IntAct=EBI-1047940, EBI-621482;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:34735226}. Secreted,
CC extracellular space {ECO:0000269|PubMed:34735226}. Cytoplasmic vesicle,
CC secretory vesicle {ECO:0000269|PubMed:34735226}. Note=Present in
CC intestinal secretory epithelial cells and is secreted into the
CC intestinal lumen. {ECO:0000269|PubMed:34735226}.
CC -!- TISSUE SPECIFICITY: Expressed in intestine; selectively expressed in
CC goblet cells. {ECO:0000269|PubMed:34735226}.
CC -!- INDUCTION: During squamous differentiation of epidermal keratinocytes.
CC {ECO:0000269|PubMed:2388825}.
CC -!- PTM: Forms five pairs of intrachain disulfide bonds.
CC {ECO:0000269|PubMed:34735226}.
CC -!- SIMILARITY: Belongs to the cornifin (SPRR) family. {ECO:0000305}.
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DR EMBL; X53064; CAA37239.1; -; Genomic_DNA.
DR EMBL; AL356867; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK311939; BAG34880.1; -; mRNA.
DR EMBL; CH471121; EAW53346.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53347.1; -; Genomic_DNA.
DR EMBL; BC096108; AAH96108.1; -; mRNA.
DR EMBL; BC096109; AAH96109.1; -; mRNA.
DR EMBL; BC096110; AAH96110.1; -; mRNA.
DR EMBL; BC096111; AAH96111.1; -; mRNA.
DR EMBL; BC128049; AAI28050.1; -; mRNA.
DR CCDS; CCDS1034.1; -.
DR PIR; S12712; S12712.
DR RefSeq; NP_005979.1; NM_005988.2.
DR AlphaFoldDB; P35326; -.
DR BioGRID; 112578; 15.
DR IntAct; P35326; 15.
DR MINT; P35326; -.
DR STRING; 9606.ENSP00000357744; -.
DR iPTMnet; P35326; -.
DR PhosphoSitePlus; P35326; -.
DR BioMuta; SPRR2A; -.
DR EPD; P35326; -.
DR MassIVE; P35326; -.
DR MaxQB; P35326; -.
DR PaxDb; P35326; -.
DR PeptideAtlas; P35326; -.
DR PRIDE; P35326; -.
DR ProteomicsDB; 55024; -.
DR Antibodypedia; 54240; 131 antibodies from 19 providers.
DR DNASU; 6700; -.
DR Ensembl; ENST00000392653.3; ENSP00000376423.2; ENSG00000241794.2.
DR GeneID; 6700; -.
DR KEGG; hsa:6700; -.
DR MANE-Select; ENST00000392653.3; ENSP00000376423.2; NM_005988.3; NP_005979.1.
DR UCSC; uc001fbd.4; human.
DR CTD; 6700; -.
DR DisGeNET; 6700; -.
DR GeneCards; SPRR2A; -.
DR HGNC; HGNC:11261; SPRR2A.
DR HPA; ENSG00000241794; Tissue enriched (esophagus).
DR MIM; 182267; gene.
DR neXtProt; NX_P35326; -.
DR OpenTargets; ENSG00000241794; -.
DR PharmGKB; PA36090; -.
DR VEuPathDB; HostDB:ENSG00000241794; -.
DR eggNOG; ENOG502TEHF; Eukaryota.
DR GeneTree; ENSGT01050000245156; -.
DR HOGENOM; CLU_192372_0_0_1; -.
DR InParanoid; P35326; -.
DR OMA; PSKEPKC; -.
DR PathwayCommons; P35326; -.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; P35326; -.
DR SIGNOR; P35326; -.
DR BioGRID-ORCS; 6700; 14 hits in 259 CRISPR screens.
DR ChiTaRS; SPRR2A; human.
DR GeneWiki; SPRR2A; -.
DR GenomeRNAi; 6700; -.
DR Pharos; P35326; Tbio.
DR PRO; PR:P35326; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P35326; protein.
DR Bgee; ENSG00000241794; Expressed in buccal mucosa cell and 94 other tissues.
DR Genevisible; P35326; HS.
DR GO; GO:0001533; C:cornified envelope; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0030141; C:secretory granule; IDA:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0008289; F:lipid binding; IDA:UniProtKB.
DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0048874; P:host-mediated regulation of intestinal microbiota composition; ISS:UniProtKB.
DR InterPro; IPR029142; SPRR2.
DR Pfam; PF14820; SPRR2; 1.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Cytoplasmic vesicle; Disulfide bond;
KW Lipid-binding; Reference proteome; Repeat; Secreted.
FT CHAIN 1..72
FT /note="Small proline-rich protein 2A"
FT /id="PRO_0000150008"
FT REPEAT 21..29
FT /note="1"
FT /evidence="ECO:0000255"
FT REPEAT 30..38
FT /note="2"
FT /evidence="ECO:0000255"
FT REPEAT 39..47
FT /note="3"
FT /evidence="ECO:0000255"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 21..47
FT /note="3 X 9 AA tandem repeats of P-K-C-P-[EQ]-P-C-P-P"
FT /evidence="ECO:0000255"
FT REGION 42..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 72 AA; 7965 MW; 28B452D0F8B6344A CRC64;
MSYQQQQCKQ PCQPPPVCPT PKCPEPCPPP KCPEPCPPPK CPQPCPPQQC QQKYPPVTPS
PPCQSKYPPK SK
