A1ATR_HUMAN
ID A1ATR_HUMAN Reviewed; 421 AA.
AC P20848; A0A0G2JPK4; S4UD68;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 03-AUG-2022, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Alpha-1-antitrypsin-related protein;
DE AltName: Full=Protease inhibitor 1-like;
DE AltName: Full=Serpin A2;
DE Flags: Precursor;
GN Name=SERPINA2; Synonyms=ARGS, ATR, PIL, SERPINA2P;
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].
RX PubMed=2842251; DOI=10.1016/0888-7543(88)90099-7;
RA Bao J.J., Reed-Fourquet L., Sifers R.N., Kidd V.J., Woo S.L.C.;
RT "Molecular structure and sequence homology of a gene related to alpha 1-
RT antitrypsin in the human genome.";
RL Genomics 2:165-173(1988).
RN [2] {ECO:0000312|EMBL:AGI62067.1}
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS V1 AND V3 PRO-330, VARIANT V1 LYS-342,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, AND INTERACTION
RP WITH CANX AND PDIA3.
RC TISSUE=Testis {ECO:0000312|EMBL:AGI62067.1};
RX PubMed=23826168; DOI=10.1371/journal.pone.0066889;
RA Marques P.I., Ferreira Z., Martins M., Figueiredo J., Silva D.I.,
RA Castro P., Morales-Hojas R., Simoes-Correia J., Seixas S.;
RT "SERPINA2 is a novel gene with a divergent function from SERPINA1.";
RL PLoS ONE 8:E66889-E66889(2013).
RN [3] {ECO:0000312|Proteomes:UP000005640}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP POTENTIAL PSEUDOGENE.
RX PubMed=9383284; DOI=10.1007/s003359900610;
RA Rollini P., Fournier R.E.;
RT "Molecular linkage of the human alpha 1-antitrypsin and corticosteroid-
RT binding globulin genes on chromosome 14q32.1.";
RL Mamm. Genome 8:913-916(1997).
RN [5]
RP IDENTIFICATION, AND TISSUE SPECIFICITY.
RX PubMed=17135331; DOI=10.1093/molbev/msl187;
RA Seixas S., Suriano G., Carvalho F., Seruca R., Rocha J., Di Rienzo A.;
RT "Sequence diversity at the proximal 14q32.1 SERPIN subcluster: evidence for
RT natural selection favoring the pseudogenization of SERPINA2.";
RL Mol. Biol. Evol. 24:587-598(2007).
CC -!- FUNCTION: Putative serine protease inhibitor.
CC -!- SUBUNIT: Interacts with CANX AND PDIA3. {ECO:0000269|PubMed:23826168}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:23826168}.
CC -!- TISSUE SPECIFICITY: Expressed in the liver, leukocytes and testis. Also
CC detected in brain, colon, uterus, esophagus, spleen, trachea, kidney
CC and lung. {ECO:0000269|PubMed:17135331, ECO:0000269|PubMed:23826168}.
CC -!- DOMAIN: The reactive center loop (RCL) extends out from the body of the
CC protein and directs binding to the target protease. The protease
CC cleaves the serpin at the reactive site within the RCL, establishing a
CC covalent linkage between the carboxyl group of the serpin reactive site
CC and the serine hydroxyl of the protease. The resulting inactive serpin-
CC protease complex is highly stable (By similarity). {ECO:0000250}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:23826168}.
CC -!- POLYMORPHISM: Was originally thought to be the product of a pseudogene
CC (PubMed:9383284). Later shown to be a protein-coding gene
CC (PubMed:23826168). Seems to be a polymorphic pseudogene which is
CC protein-coding in some individuals and non-coding in others.
CC {ECO:0000269|PubMed:23826168, ECO:0000269|PubMed:9383284, ECO:0000305}.
CC -!- POLYMORPHISM: The sequence shown is that of the V2 allele. Other
CC alleles are: V1 and V3. {ECO:0000269|PubMed:23826168}.
CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
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DR EMBL; M19684; AAA51544.1; -; Genomic_DNA.
DR EMBL; M19685; AAA51544.1; JOINED; Genomic_DNA.
DR EMBL; JX680599; AGI62067.1; -; mRNA.
DR EMBL; AC235087; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A28882; A28882.
DR RefSeq; NP_006211.2; NM_006220.2.
DR AlphaFoldDB; P20848; -.
DR SMR; P20848; -.
DR MEROPS; I04.952; -.
DR GlyGen; P20848; 4 sites.
DR iPTMnet; P20848; -.
DR PhosphoSitePlus; P20848; -.
DR BioMuta; SERPINA2; -.
DR DMDM; 112891; -.
DR jPOST; P20848; -.
DR MassIVE; P20848; -.
DR MaxQB; P20848; -.
DR PeptideAtlas; P20848; -.
DR PRIDE; P20848; -.
DR ProteomicsDB; 53815; -.
DR DNASU; 390502; -.
DR GeneID; 390502; -.
DR KEGG; hsa:390502; -.
DR CTD; 390502; -.
DR GeneCards; SERPINA2; -.
DR HGNC; HGNC:8985; SERPINA2.
DR MIM; 107410; gene.
DR neXtProt; NX_P20848; -.
DR InParanoid; P20848; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; P20848; -.
DR BioGRID-ORCS; 390502; 2 hits in 31 CRISPR screens.
DR GenomeRNAi; 390502; -.
DR Pharos; P20848; Tdark.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P20848; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 1.
DR InterPro; IPR023795; Serpin_CS.
DR InterPro; IPR023796; Serpin_dom.
DR InterPro; IPR000215; Serpin_fam.
DR InterPro; IPR036186; Serpin_sf.
DR InterPro; IPR042178; Serpin_sf_1.
DR InterPro; IPR042185; Serpin_sf_2.
DR PANTHER; PTHR11461; PTHR11461; 1.
DR Pfam; PF00079; Serpin; 1.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
DR PROSITE; PS00284; SERPIN; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Protease inhibitor;
KW Reference proteome; Serine protease inhibitor; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..421
FT /note="Alpha-1-antitrypsin-related protein"
FT /id="PRO_0000032410"
FT SITE 385..386
FT /note="Reactive bond"
FT /evidence="ECO:0000255"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 330
FT /note="L -> P (in V1 and V3)"
FT /evidence="ECO:0000269|PubMed:23826168"
FT /id="VAR_070190"
FT VARIANT 342
FT /note="E -> K (in V1)"
FT /evidence="ECO:0000269|PubMed:23826168"
FT /id="VAR_070191"
FT CONFLICT 9
FT /note="I -> V (in Ref. 1; AAA51544 and 2; AGI62067)"
FT /evidence="ECO:0000305"
FT CONFLICT 29
FT /note="E -> G (in Ref. 1; AAA51544)"
FT /evidence="ECO:0000305"
FT CONFLICT 67..76
FT /note="ELADLSQTSN -> SWLIYHNQH (in Ref. 1; AAA51544)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="A -> R (in Ref. 1; AAA51544)"
FT /evidence="ECO:0000305"
FT CONFLICT 229
FT /note="H -> R (in Ref. 1; AAA51544 and 2; AGI62067)"
FT /evidence="ECO:0000305"
FT CONFLICT 403..404
FT /note="DD -> EY (in Ref. 1; AAA51544)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 421 AA; 47707 MW; 33A46EF9896FC91D CRC64;
MPFSVSWGIL LLAGLCCLVP SSLVEDPQED AAQKTDTSHH DQGDWEDLAC QKISYNVTDL
AFDLYKELAD LSQTSNVLVT PTSVAMAFAM LSLGTKADTR TEILEGLNVN LTETPEAKIH
ECFQQVLQAL SRPDTRLQLT TGSSLFVNKS MKLVDTFLED TKKLYHSEAS SINFRDTEEA
KEQINNYVEK RTGRKVVDLV KHLKKDTSLA LVDYISFHGK WKDKFKAEHI MVEGFHVDDK
TIIRVPMINH LGRFDIHRDR ELSSWVLAQH YVGNATAFFI LPDPKKMWQL EEKLTYSHLE
NIQRAFDIRS INLHFPKLSI SGTYKLKRVL RNLGITKIFS NEADLSGVSQ EAPLKLSKAV
HVAVLTIDEK GTEATGAPHL EEKAWSKYQT VMFNRPFLVI IKDDITNFPL FIGKVVNPTQ
K
