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   27-MAR-2024, entry version 142.
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; A0A024RCZ4: C6orf1; NbExp=3; IntAct=EBI-11028396, EBI-23226736;
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; 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}.
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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; 9.
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   EPD; Q6UXX5; -.
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; 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.
DR   Genevisible; Q6UXX5; HS.
PE   1: Evidence at protein level;
KW   Glycoprotein; Protease inhibitor; Reference proteome; Secreted;
KW   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
//