ID ITIH6_HUMAN Reviewed; 1313 AA. AC Q6UXX5; A6NN03; DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 02-OCT-2024, entry version 145. DE RecName: Full=Inter-alpha-trypsin inhibitor heavy chain H6; DE AltName: Full=Inter-alpha-trypsin inhibitor heavy chain H5-like protein; DE Short=Inter-alpha inhibitor H5-like protein; DE Flags: Precursor; GN Name=ITIH6; Synonyms=ITIH5L; ORFNames=UNQ6369/PRO21074; 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]. 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [3] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. CC -!- INTERACTION: CC Q6UXX5; Q49AR9: ANKS1A; NbExp=3; IntAct=EBI-11028396, EBI-11954519; CC Q6UXX5; Q03828: EVX2; NbExp=3; IntAct=EBI-11028396, EBI-17280301; CC Q6UXX5; Q5T749: KPRP; NbExp=3; IntAct=EBI-11028396, EBI-10981970; CC Q6UXX5; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-11028396, EBI-12111050; CC Q6UXX5; A0A2U3TZT1: SMIM29; NbExp=3; IntAct=EBI-11028396, EBI-50432835; CC Q6UXX5; O43711: TLX3; NbExp=3; IntAct=EBI-11028396, EBI-3939165; CC Q6UXX5; O95231: VENTX; NbExp=3; IntAct=EBI-11028396, EBI-10191303; CC Q6UXX5; Q96IQ9: ZNF414; NbExp=3; IntAct=EBI-11028396, EBI-744257; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. CC -!- SIMILARITY: Belongs to the ITIH 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; AY358170; AAQ88537.1; -; mRNA. DR EMBL; Z98046; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL022575; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471154; EAW93186.1; -; Genomic_DNA. DR CCDS; CCDS14361.1; -. DR RefSeq; NP_940912.1; NM_198510.2. DR AlphaFoldDB; Q6UXX5; -. DR SMR; Q6UXX5; -. DR BioGRID; 131428; 12. DR IntAct; Q6UXX5; 12. DR STRING; 9606.ENSP00000218436; -. DR GlyCosmos; Q6UXX5; 6 sites, No reported glycans. DR GlyGen; Q6UXX5; 7 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q6UXX5; -. DR PhosphoSitePlus; Q6UXX5; -. DR BioMuta; ITIH6; -. DR DMDM; 74762375; -. DR MassIVE; Q6UXX5; -. DR PaxDb; 9606-ENSP00000218436; -. DR PeptideAtlas; Q6UXX5; -. DR ProteomicsDB; 67671; -. DR Antibodypedia; 62222; 13 antibodies from 9 providers. DR DNASU; 347365; -. DR Ensembl; ENST00000218436.7; ENSP00000218436.6; ENSG00000102313.9. DR GeneID; 347365; -. DR KEGG; hsa:347365; -. DR MANE-Select; ENST00000218436.7; ENSP00000218436.6; NM_198510.3; NP_940912.1. DR UCSC; uc004dtj.2; human. DR AGR; HGNC:28907; -. DR CTD; 347365; -. DR DisGeNET; 347365; -. DR GeneCards; ITIH6; -. DR HGNC; HGNC:28907; ITIH6. DR HPA; ENSG00000102313; Tissue enhanced (skeletal). DR neXtProt; NX_Q6UXX5; -. DR OpenTargets; ENSG00000102313; -. DR PharmGKB; PA134930661; -. DR VEuPathDB; HostDB:ENSG00000102313; -. DR eggNOG; ENOG502QPS2; Eukaryota. DR GeneTree; ENSGT00940000162980; -. DR HOGENOM; CLU_008101_1_0_1; -. DR InParanoid; Q6UXX5; -. DR OMA; LPRWASC; -. DR OrthoDB; 608326at2759; -. DR PhylomeDB; Q6UXX5; -. DR TreeFam; TF328982; -. DR PathwayCommons; Q6UXX5; -. DR SignaLink; Q6UXX5; -. DR BioGRID-ORCS; 347365; 4 hits in 771 CRISPR screens. DR GenomeRNAi; 347365; -. DR Pharos; Q6UXX5; Tdark. DR PRO; PR:Q6UXX5; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q6UXX5; protein. DR Bgee; ENSG00000102313; Expressed in cartilage tissue and 13 other cell types or tissues. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0030212; P:hyaluronan metabolic process; IEA:InterPro. DR CDD; cd01461; vWA_interalpha_trypsin_inhibitor; 1. DR Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 1. DR InterPro; IPR010600; ITI_HC_C. DR InterPro; IPR050934; ITIH. DR InterPro; IPR013694; VIT. DR InterPro; IPR002035; VWF_A. DR InterPro; IPR036465; vWFA_dom_sf. DR PANTHER; PTHR10338; INTER-ALPHA-TRYPSIN INHIBITOR HEAVY CHAIN FAMILY MEMBER; 1. DR PANTHER; PTHR10338:SF155; INTER-ALPHA-TRYPSIN INHIBITOR HEAVY CHAIN H6; 1. DR Pfam; PF06668; ITI_HC_C; 1. DR Pfam; PF08487; VIT; 1. DR Pfam; PF00092; VWA; 1. DR SMART; SM00609; VIT; 1. DR SMART; SM00327; VWA; 1. DR SUPFAM; SSF53300; vWA-like; 1. DR PROSITE; PS51468; VIT; 1. DR PROSITE; PS50234; VWFA; 1. PE 1: Evidence at protein level; KW Glycoprotein; Protease inhibitor; Proteomics identification; KW Reference proteome; Secreted; Serine protease inhibitor; Signal. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT CHAIN 24..1313 FT /note="Inter-alpha-trypsin inhibitor heavy chain H6" FT /id="PRO_0000285680" FT DOMAIN 24..150 FT /note="VIT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00801" FT DOMAIN 283..469 FT /note="VWFA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219" FT REGION 612..644 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 783..817 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 856..928 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 959..983 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 793..814 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 860..877 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 878..900 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 901..925 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 83 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 374 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 540 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 594 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 971 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1231 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VARIANT 387 FT /note="G -> R (in dbSNP:rs34188213)" FT /id="VAR_032042" FT VARIANT 561 FT /note="R -> C (in dbSNP:rs34004499)" FT /id="VAR_032043" FT VARIANT 1041 FT /note="W -> S (in dbSNP:rs17316491)" FT /id="VAR_032044" FT VARIANT 1170 FT /note="G -> A (in dbSNP:rs35355718)" FT /id="VAR_032045" SQ SEQUENCE 1313 AA; 143187 MW; 4C63CF26AF187734 CRC64; MSGWRYLICV SFLLTILLEL TYQGPPVPAS SSTKLLMTSY SMRSTVVSRY AHTLVTSVLF NPHAEAHEAI FDLDLPHLAF ISNFTMTINN KVYIAEVKEK HQAKKIYEEA HQQGKTAAHV GIRDRESEKF RISTSLAAGT EVTFSLAYEE LLQRHQGQYQ LVVSLRPGQL VKRLSIEVTV SERTGISYVH IPPLRTGRLR TNAHASEVDS PPSTRIERGE TCVRITYCPT LQDQSSISGS GIMADFLVQY DVVMEDIIGD VQIYDDYFIH YFAPRGLPPM EKNVVFVIDV SSSMFGTKME QTKTAMNVIL SDLQANDYFN IISFSDTVNV WKAGGSIQAT IQNVHSAKDY LHCMEADGWT DVNSALLAAA SVLNHSNQEP GRGPSVGRIP LIIFLTDGEP TAGVTTPSVI LSNVRQALGH RVSLFSLAFG DDADFTLLRR LSLENRGIAR RIYEDTDAAL QLKGLYEEIS MPLLADVRLN YLGGLVGASP WAVFPNYFGG SELVVAGQVQ PGKQELGIHL AARGPKDQLL VAHHSEGATN NSQKAFGCPG EPAPNVAHFI RRLWAYVTIG ELLDAHFQAR DTTTRHLLAA KVLNLSLEYN FVTPLTSLVM VQPKQASEET RRQTSTSAGP DTIMPSSSSR HGLGVSTAQP ALVPKVISPK SRPVKPKFYL SSTTTASTKK MLSSKELEPL GESPHTLSMP TYPKAKIPAQ QDSGTLAQPT LRTKPTILVP SNSGTLLPLK PGSLSHQNPD ILPTNSRTQV PPVKPGIPAS PKADTVKCVT PLHSKPGAPS HPQLGALTSQ APKGLPQSRP GVSTLQVPKY PLHTRPRVPA PKTRNNMPHL GPGILLSKTP KILLSLKPSA PPHQISTSIS LSKPETPNPH MPQTPLPPRP DRPRPPLPES LSTFPNTISS STGPSSTTTT SVLGEPLPMP FTPTLPPGRF WHQYDLLPGP QRTRQVLGPS RPGVPTMSLL NSSRPTPEGS PPNLPILLPS SILPEAISLL LLPEELELLS ESMVESKFVE SLNPPAFYTF LTPDEDGSPN WDGNSEEILG GAGGSMESQG SSVGLAKGTL PSIFTFSSSV DGDPHFVIQI PHSEEKICFT LNGHPGDLLQ LIEDPKAGLH VSGKLLGAPP RPGHKDQTRT YFQIITVTTD KPRAYTITIS RSSISLRGEG TLRLSWDQPA LLKRPQLELY VAAAARLTLR LGPYLEFLVL RHRYRHPSTL QLPHLGFYVA NGSGLSPSAR GLIGQFQHAD IRLVTGPMGP CLRRHHGPDV PVILGKRLLK DSPRLLPRWA SCWLVKRSHV ELLLGHPYLS YVL //