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CRLD2_HUMAN
ID   CRLD2_HUMAN             Reviewed;         497 AA.
AC   Q9H0B8; D3DUM0; Q6P590; Q6UWH0; Q6UXC6; Q96IB1; Q96K61;
DT   05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   03-AUG-2022, entry version 148.
DE   RecName: Full=Cysteine-rich secretory protein LCCL domain-containing 2;
DE   AltName: Full=Cysteine-rich secretory protein 11;
DE            Short=CRISP-11;
DE   AltName: Full=LCCL domain-containing cysteine-rich secretory protein 2;
DE   Flags: Precursor;
GN   Name=CRISPLD2; Synonyms=CRISP11, LCRISP2; ORFNames=UNQ2914/PRO1156/PRO9783;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Testis;
RX   PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA   Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA   Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA   Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA   Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA   Klein M., Poustka A.;
RT   "Towards a catalog of human genes and proteins: sequencing and analysis of
RT   500 novel complete protein coding human cDNAs.";
RL   Genome Res. 11:422-435(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4), AND VARIANT
RP   SER-322.
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Mammary gland;
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], AND VARIANT GLY-105.
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 5), AND VARIANTS
RP   GLY-105 AND SER-322.
RC   TISSUE=Blood, and Melanoma;
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   VARIANT GLY-137.
RX   PubMed=25691535; DOI=10.1093/hmg/ddv060;
RA   Guipponi M., Chentouf A., Webling K.E., Freimann K., Crespel A., Nobile C.,
RA   Lemke J.R., Hansen J., Dorn T., Lesca G., Ryvlin P., Hirsch E., Rudolf G.,
RA   Rosenberg D.S., Weber Y., Becker F., Helbig I., Muhle H., Salzmann A.,
RA   Chaouch M., Oubaiche M.L., Ziglio S., Gehrig C., Santoni F., Pizzato M.,
RA   Langel U., Antonarakis S.E.;
RT   "Galanin pathogenic mutations in temporal lobe epilepsy.";
RL   Hum. Mol. Genet. 24:3082-3091(2015).
CC   -!- FUNCTION: Promotes matrix assembly. {ECO:0000250}.
CC   -!- SUBUNIT: Binds to heparin, dermatan sulfate and chondroitin sulfate.
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=1;
CC         IsoId=Q9H0B8-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9H0B8-2; Sequence=VSP_020183;
CC       Name=3;
CC         IsoId=Q9H0B8-3; Sequence=VSP_020181, VSP_020182;
CC       Name=4;
CC         IsoId=Q9H0B8-4; Sequence=VSP_020178, VSP_020180;
CC       Name=5;
CC         IsoId=Q9H0B8-5; Sequence=VSP_020179;
CC   -!- SIMILARITY: Belongs to the CRISP family. {ECO:0000305}.
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DR   EMBL; AL136861; CAB66795.1; -; mRNA.
DR   EMBL; AY358413; AAQ88779.1; -; mRNA.
DR   EMBL; AY358790; AAQ89150.1; -; mRNA.
DR   EMBL; AK027395; BAB55081.1; -; mRNA.
DR   EMBL; CH471114; EAW95468.1; -; Genomic_DNA.
DR   EMBL; CH471114; EAW95469.1; -; Genomic_DNA.
DR   EMBL; BC007689; AAH07689.1; -; mRNA.
DR   EMBL; BC063012; AAH63012.1; -; mRNA.
DR   CCDS; CCDS10949.1; -. [Q9H0B8-1]
DR   RefSeq; NP_113664.1; NM_031476.3. [Q9H0B8-1]
DR   RefSeq; XP_005256247.1; XM_005256190.1. [Q9H0B8-1]
DR   AlphaFoldDB; Q9H0B8; -.
DR   SMR; Q9H0B8; -.
DR   BioGRID; 123739; 5.
DR   IntAct; Q9H0B8; 1.
DR   STRING; 9606.ENSP00000262424; -.
DR   GlyGen; Q9H0B8; 5 sites, 2 O-linked glycans (3 sites).
DR   iPTMnet; Q9H0B8; -.
DR   PhosphoSitePlus; Q9H0B8; -.
DR   BioMuta; CRISPLD2; -.
DR   DMDM; 74717972; -.
DR   jPOST; Q9H0B8; -.
DR   MassIVE; Q9H0B8; -.
DR   MaxQB; Q9H0B8; -.
DR   PaxDb; Q9H0B8; -.
DR   PeptideAtlas; Q9H0B8; -.
DR   PRIDE; Q9H0B8; -.
DR   ProteomicsDB; 80245; -. [Q9H0B8-1]
DR   ProteomicsDB; 80246; -. [Q9H0B8-2]
DR   ProteomicsDB; 80247; -. [Q9H0B8-3]
DR   ProteomicsDB; 80248; -. [Q9H0B8-4]
DR   ProteomicsDB; 80249; -. [Q9H0B8-5]
DR   Antibodypedia; 30609; 139 antibodies from 23 providers.
DR   DNASU; 83716; -.
DR   Ensembl; ENST00000262424.10; ENSP00000262424.5; ENSG00000103196.12. [Q9H0B8-1]
DR   Ensembl; ENST00000564567.5; ENSP00000457655.1; ENSG00000103196.12. [Q9H0B8-2]
DR   Ensembl; ENST00000569090.1; ENSP00000454858.1; ENSG00000103196.12. [Q9H0B8-5]
DR   GeneID; 83716; -.
DR   KEGG; hsa:83716; -.
DR   MANE-Select; ENST00000262424.10; ENSP00000262424.5; NM_031476.4; NP_113664.1.
DR   UCSC; uc002fil.3; human. [Q9H0B8-1]
DR   CTD; 83716; -.
DR   DisGeNET; 83716; -.
DR   GeneCards; CRISPLD2; -.
DR   HGNC; HGNC:25248; CRISPLD2.
DR   HPA; ENSG00000103196; Low tissue specificity.
DR   MIM; 612434; gene.
DR   neXtProt; NX_Q9H0B8; -.
DR   OpenTargets; ENSG00000103196; -.
DR   PharmGKB; PA142672077; -.
DR   VEuPathDB; HostDB:ENSG00000103196; -.
DR   eggNOG; KOG3017; Eukaryota.
DR   GeneTree; ENSGT00940000157410; -.
DR   HOGENOM; CLU_138283_0_0_1; -.
DR   InParanoid; Q9H0B8; -.
DR   OMA; VNTCQRM; -.
DR   PhylomeDB; Q9H0B8; -.
DR   TreeFam; TF316148; -.
DR   PathwayCommons; Q9H0B8; -.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   SignaLink; Q9H0B8; -.
DR   BioGRID-ORCS; 83716; 14 hits in 1070 CRISPR screens.
DR   ChiTaRS; CRISPLD2; human.
DR   GeneWiki; CRISPLD2; -.
DR   GenomeRNAi; 83716; -.
DR   Pharos; Q9H0B8; Tbio.
DR   PRO; PR:Q9H0B8; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; Q9H0B8; protein.
DR   Bgee; ENSG00000103196; Expressed in decidua and 199 other tissues.
DR   ExpressionAtlas; Q9H0B8; baseline and differential.
DR   Genevisible; Q9H0B8; HS.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR   GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR   GO; GO:0030133; C:transport vesicle; IDA:LIFEdb.
DR   GO; GO:0005539; F:glycosaminoglycan binding; IBA:GO_Central.
DR   GO; GO:0008201; F:heparin binding; IEA:Ensembl.
DR   GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR   GO; GO:0060325; P:face morphogenesis; IMP:UniProtKB.
DR   GO; GO:0030324; P:lung development; IEA:Ensembl.
DR   Gene3D; 2.170.130.20; -; 2.
DR   Gene3D; 3.40.33.10; -; 1.
DR   InterPro; IPR018244; Allrgn_V5/Tpx1_CS.
DR   InterPro; IPR014044; CAP_domain.
DR   InterPro; IPR035940; CAP_sf.
DR   InterPro; IPR001283; CRISP-related.
DR   InterPro; IPR004043; LCCL.
DR   InterPro; IPR036609; LCCL_sf.
DR   PANTHER; PTHR10334; PTHR10334; 1.
DR   Pfam; PF00188; CAP; 1.
DR   Pfam; PF03815; LCCL; 2.
DR   PRINTS; PR00837; V5TPXLIKE.
DR   SMART; SM00603; LCCL; 2.
DR   SMART; SM00198; SCP; 1.
DR   SUPFAM; SSF55797; SSF55797; 1.
DR   SUPFAM; SSF69848; SSF69848; 2.
DR   PROSITE; PS01010; CRISP_2; 1.
DR   PROSITE; PS50820; LCCL; 2.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Disulfide bond; Glycoprotein; Reference proteome;
KW   Repeat; Secreted; Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..497
FT                   /note="Cysteine-rich secretory protein LCCL domain-
FT                   containing 2"
FT                   /id="PRO_0000248149"
FT   DOMAIN          62..200
FT                   /note="SCP"
FT   DOMAIN          284..379
FT                   /note="LCCL 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00123"
FT   DOMAIN          385..488
FT                   /note="LCCL 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00123"
FT   CARBOHYD        27
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        290..308
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00123"
FT   DISULFID        312..332
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00123"
FT   DISULFID        391..413
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00123"
FT   DISULFID        417..440
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00123"
FT   VAR_SEQ         81..159
FT                   /note="TWDDELEKSAAAWASQCIWEHGPTSLLVSIGQNLGAHWGRYRSPGFHVQSWY
FT                   DEVKDYTYPYPSECNPWCPERCSGPMC -> VSAGSGRRGWHRGWGLGHQPALFPSQLC
FT                   SPASACDGWLRVSSGRGGSRLCSVLFVCFETGSHSATDAGVQWHNRHALKP (in
FT                   isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:12975309"
FT                   /id="VSP_020178"
FT   VAR_SEQ         121..497
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_020179"
FT   VAR_SEQ         160..497
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:12975309"
FT                   /id="VSP_020180"
FT   VAR_SEQ         371
FT                   /note="S -> R (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_020181"
FT   VAR_SEQ         372..497
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_020182"
FT   VAR_SEQ         436..497
FT                   /note="TSSICKTAVHAGVISNESGGDVDVMPVDKKKTYVGSLRNGVQSESLGTPRDG
FT                   KAFRIFAVRQ -> VSRMHFQQLSRKAC (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_020183"
FT   VARIANT         105
FT                   /note="S -> G (in dbSNP:rs12051468)"
FT                   /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4"
FT                   /id="VAR_027256"
FT   VARIANT         137
FT                   /note="D -> G (in dbSNP:rs1297496215)"
FT                   /evidence="ECO:0000269|PubMed:25691535"
FT                   /id="VAR_074672"
FT   VARIANT         322
FT                   /note="T -> S (in dbSNP:rs721005)"
FT                   /evidence="ECO:0000269|PubMed:12975309,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_027257"
SQ   SEQUENCE   497 AA;  55920 MW;  1E7ADDCAB37CA4ED CRC64;
     MSCVLGGVIP LGLLFLVCGS QGYLLPNVTL LEELLSKYQH NESHSRVRRA IPREDKEEIL
     MLHNKLRGQV QPQASNMEYM TWDDELEKSA AAWASQCIWE HGPTSLLVSI GQNLGAHWGR
     YRSPGFHVQS WYDEVKDYTY PYPSECNPWC PERCSGPMCT HYTQIVWATT NKIGCAVNTC
     RKMTVWGEVW ENAVYFVCNY SPKGNWIGEA PYKNGRPCSE CPPSYGGSCR NNLCYREETY
     TPKPETDEMN EVETAPIPEE NHVWLQPRVM RPTKPKKTSA VNYMTQVVRC DTKMKDRCKG
     STCNRYQCPA GCLNHKAKIF GTLFYESSSS ICRAAIHYGI LDDKGGLVDI TRNGKVPFFV
     KSERHGVQSL SKYKPSSSFM VSKVKVQDLD CYTTVAQLCP FEKPATHCPR IHCPAHCKDE
     PSYWAPVFGT NIYADTSSIC KTAVHAGVIS NESGGDVDVM PVDKKKTYVG SLRNGVQSES
     LGTPRDGKAF RIFAVRQ
 
 
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