KAZD1_HUMAN
ID KAZD1_HUMAN Reviewed; 304 AA.
AC Q96I82; D3DR74; Q6ZMB1; Q9BQ73;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Kazal-type serine protease inhibitor domain-containing protein 1;
DE Flags: Precursor;
GN Name=KAZALD1; ORFNames=FKSG28, FKSG40, UNQ2945/PRO21184;
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 2).
RA Wang Y.-G., Gong L.;
RT "Cloning of FKSG28, a novel gene located on human chromosome 10.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Wang Y.-G., Gong L.;
RT "Identification of FKSG40, a novel gene located on human chromosome 10.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLY-76.
RC TISSUE=Small intestine;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-255.
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 PROTEIN SEQUENCE OF 31-45.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
CC -!- FUNCTION: Involved in the proliferation of osteoblasts during bone
CC formation and bone regeneration. Promotes matrix assembly (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q96I82; P46379-2: BAG6; NbExp=3; IntAct=EBI-25904181, EBI-10988864;
CC Q96I82; O14901: KLF11; NbExp=3; IntAct=EBI-25904181, EBI-948266;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96I82-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96I82-2; Sequence=VSP_014303, VSP_014304;
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DR EMBL; AY014271; AAG50354.1; -; mRNA.
DR EMBL; AF333487; AAG50291.1; -; mRNA.
DR EMBL; AY359087; AAQ89445.1; -; mRNA.
DR EMBL; AK172862; BAD18818.1; -; mRNA.
DR EMBL; AL133215; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49782.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49783.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49784.1; -; Genomic_DNA.
DR EMBL; BC007758; AAH07758.1; -; mRNA.
DR CCDS; CCDS7509.1; -. [Q96I82-1]
DR RefSeq; NP_001306232.1; NM_001319303.1.
DR RefSeq; NP_112191.2; NM_030929.4. [Q96I82-1]
DR RefSeq; XP_016872203.1; XM_017016714.1.
DR RefSeq; XP_016872204.1; XM_017016715.1. [Q96I82-1]
DR AlphaFoldDB; Q96I82; -.
DR BioGRID; 123556; 24.
DR IntAct; Q96I82; 2.
DR STRING; 9606.ENSP00000359219; -.
DR GlyGen; Q96I82; 3 sites.
DR BioMuta; KAZALD1; -.
DR DMDM; 68565605; -.
DR MassIVE; Q96I82; -.
DR PaxDb; Q96I82; -.
DR PeptideAtlas; Q96I82; -.
DR PRIDE; Q96I82; -.
DR ProteomicsDB; 76816; -. [Q96I82-1]
DR ProteomicsDB; 76817; -. [Q96I82-2]
DR Antibodypedia; 1720; 61 antibodies from 17 providers.
DR DNASU; 81621; -.
DR Ensembl; ENST00000370200.6; ENSP00000359219.6; ENSG00000107821.15. [Q96I82-1]
DR GeneID; 81621; -.
DR KEGG; hsa:81621; -.
DR MANE-Select; ENST00000370200.6; ENSP00000359219.6; NM_030929.5; NP_112191.2.
DR UCSC; uc001ksr.4; human. [Q96I82-1]
DR CTD; 81621; -.
DR DisGeNET; 81621; -.
DR GeneCards; KAZALD1; -.
DR HGNC; HGNC:25460; KAZALD1.
DR HPA; ENSG00000107821; Tissue enhanced (lymphoid).
DR MIM; 609208; gene.
DR neXtProt; NX_Q96I82; -.
DR OpenTargets; ENSG00000107821; -.
DR PharmGKB; PA134953983; -.
DR VEuPathDB; HostDB:ENSG00000107821; -.
DR eggNOG; ENOG502QTYU; Eukaryota.
DR GeneTree; ENSGT00530000063555; -.
DR HOGENOM; CLU_075590_1_0_1; -.
DR InParanoid; Q96I82; -.
DR OMA; SPPYDTW; -.
DR OrthoDB; 994901at2759; -.
DR PhylomeDB; Q96I82; -.
DR TreeFam; TF331645; -.
DR PathwayCommons; Q96I82; -.
DR SignaLink; Q96I82; -.
DR BioGRID-ORCS; 81621; 18 hits in 1078 CRISPR screens.
DR ChiTaRS; KAZALD1; human.
DR GeneWiki; KAZALD1; -.
DR GenomeRNAi; 81621; -.
DR Pharos; Q96I82; Tbio.
DR PRO; PR:Q96I82; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q96I82; protein.
DR Bgee; ENSG00000107821; Expressed in spleen and 114 other tissues.
DR Genevisible; Q96I82; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0005614; C:interstitial matrix; IBA:GO_Central.
DR GO; GO:0005520; F:insulin-like growth factor binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW.
DR GO; GO:0001558; P:regulation of cell growth; IEA:InterPro.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR000867; IGFBP-like.
DR InterPro; IPR011390; IGFBP_rP_mac25.
DR InterPro; IPR002350; Kazal_dom.
DR InterPro; IPR036058; Kazal_dom_sf.
DR PANTHER; PTHR14186; PTHR14186; 1.
DR Pfam; PF00219; IGFBP; 1.
DR Pfam; PF07648; Kazal_2; 1.
DR PIRSF; PIRSF018239; IGFBP_rP_mac25; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00280; KAZAL; 1.
DR SUPFAM; SSF100895; SSF100895; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS51323; IGFBP_N_2; 1.
DR PROSITE; PS51465; KAZAL_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Differentiation;
KW Direct protein sequencing; Disulfide bond; Extracellular matrix;
KW Glycoprotein; Immunoglobulin domain; Osteogenesis; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..30
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 31..304
FT /note="Kazal-type serine protease inhibitor domain-
FT containing protein 1"
FT /id="PRO_0000015076"
FT DOMAIN 49..124
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 120..170
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 172..269
FT /note="Ig-like C2-type"
FT CARBOHYD 159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 135..168
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 193..253
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 182..252
FT /note="WNVTGQDVIFGCEVFAYPMASIEWRKDGLDIQLPGDDPHISVQFRGGPQRFE
FT VTGWLQIQAVRPSDEGTYR -> QRGPRLQTLGTEDTLTTLVGAGGMARAVACGEAPGE
FT HLALQVLCLSGKRRHLWQVGSTGSSEGVPSGGSFW (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1, ECO:0000303|Ref.2"
FT /id="VSP_014303"
FT VAR_SEQ 253..304
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1, ECO:0000303|Ref.2"
FT /id="VSP_014304"
FT VARIANT 76
FT /note="C -> G (in dbSNP:rs11547671)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_022739"
FT VARIANT 236
FT /note="G -> D (in dbSNP:rs11190812)"
FT /id="VAR_033628"
FT VARIANT 255
FT /note="G -> A (in dbSNP:rs807037)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_033629"
FT VARIANT 256
FT /note="R -> H (in dbSNP:rs36116329)"
FT /id="VAR_049977"
SQ SEQUENCE 304 AA; 32945 MW; D6259658B62E99CD CRC64;
MLPPPRPAAA LALPVLLLLL VVLTPPPTGA RPSPGPDYLR RGWMRLLAEG EGCAPCRPEE
CAAPRGCLAG RVRDACGCCW ECANLEGQLC DLDPSAHFYG HCGEQLECRL DTGGDLSRGE
VPEPLCACRS QSPLCGSDGH TYSQICRLQE AARARPDANL TVAHPGPCES GPQIVSHPYD
TWNVTGQDVI FGCEVFAYPM ASIEWRKDGL DIQLPGDDPH ISVQFRGGPQ RFEVTGWLQI
QAVRPSDEGT YRCLGRNALG QVEAPASLTV LTPDQLNSTG IPQLRSLNLV PEEEAESEEN
DDYY
