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Protein

Cell migration-inducing and hyaluronan-binding protein

Gene

CEMIP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Mediates depolymerization of hyaluronic acid (HA) via the cell membrane-associated clathrin-coated pit endocytic pathway. Binds to hyaluronic acid. Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product, a process that may occur through rapid vesicle endocytosis and recycling without intracytoplasmic accumulation or digestion in lysosomes. Involved in hyaluronan catabolism in the dermis of the skin and arthritic synovium. Positively regulates epithelial-mesenchymal transition (EMT), and hence tumor cell growth, invasion and cancer dissemination. In collaboration with HSPA5/BIP, promotes cancer cell migration in a calcium and PKC-dependent manner. May be involved in hearing.3 Publications

Catalytic activityi

Random hydrolysis of (1->4)-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate.2 Publications

Activity regulationi

Activity is up-regulated by histamine.1 Publication

GO - Molecular functioni

  • clathrin heavy chain binding Source: UniProtKB
  • ER retention sequence binding Source: UniProtKB
  • hyaluronic acid binding Source: UniProtKB
  • hyalurononglucosaminidase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionGlycosidase, Hydrolase
LigandHyaluronic acid

Enzyme and pathway databases

ReactomeiR-HSA-2142850 Hyaluronan biosynthesis and export

Names & Taxonomyi

Protein namesi
Recommended name:
Cell migration-inducing and hyaluronan-binding protein (EC:3.2.1.352 Publications)
Gene namesi
Name:CEMIP
Synonyms:KIAA1199
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000103888.15
HGNCiHGNC:29213 CEMIP
MIMi608366 gene
neXtProtiNX_Q8WUJ3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Coated pit, Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi57214
OpenTargetsiENSG00000103888
PharmGKBiPA134967531

Polymorphism and mutation databases

BioMutaiKIAA1199
DMDMi46396475

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 301 PublicationAdd BLAST30
ChainiPRO_000002153831 – 1361Cell migration-inducing and hyaluronan-binding proteinAdd BLAST1331

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi119N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi165N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi312N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi370N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi420N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi889N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi921N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated; glycosylation is not necessary for HA-binding.2 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8WUJ3
PeptideAtlasiQ8WUJ3
PRIDEiQ8WUJ3
ProteomicsDBi74690
74691 [Q8WUJ3-2]

PTM databases

CarbonylDBiQ8WUJ3
iPTMnetiQ8WUJ3
PhosphoSitePlusiQ8WUJ3

Expressioni

Tissue specificityi

Expressed in dermal and in synovial fibroblasts. Strongly expressed in gastric cancers compared with the paired normal tissues. Strongly expressed in both ductal carcinoma and invasive breast cancer cells compared with benign epithelial cells (at protein level). Strongly expressed in brain, placenta, prostate, breast, lung and testis. Expressed in fibroblasts, epithelial cells and cancer cells. In ear, it is specifically expressed in inner ear. Expressed in cochlea and vestibule tissues. Strongly expressed in gastric cancers compared with the paired normal tissues. Strongly expressed in colon adenocarcinomas compared with normal colonic mucosas. Strongly expressed in breast cancer as compared to normal breast tissue.8 Publications

Inductioni

Up-regulated by histamine. Up-regulated by the adapter protein complex 1 (AP-1) and NF-kappaB/RELA. Down-regulated by transforming growth factor TGFB1.2 Publications

Gene expression databases

BgeeiENSG00000103888 Expressed in 153 organ(s), highest expression level in trigeminal ganglion
CleanExiHS_KIAA1199
ExpressionAtlasiQ8WUJ3 baseline and differential
GenevisibleiQ8WUJ3 HS

Interactioni

Subunit structurei

Interacts with EPHA2 and ITPR3. Interacts with HSPA5/BIP; the interaction induces calcium leakage from the endoplasmic reticulum and cell migration. Interacts with clathrin heavy chain/CLTC.3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121452, 2 interactors
IntActiQ8WUJ3, 1 interactor
STRINGi9606.ENSP00000220244

Structurei

3D structure databases

ProteinModelPortaliQ8WUJ3
SMRiQ8WUJ3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 166G8PROSITE-ProRule annotationAdd BLAST123
Repeati572 – 594PbH1 1Add BLAST23
Repeati595 – 617PbH1 2Add BLAST23
Repeati719 – 741PbH1 3Add BLAST23
Repeati798 – 819PbH1 4Add BLAST22

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni295 – 591Necessary for its endoplasmic reticulum (ER) retention and interaction with HSPA51 PublicationAdd BLAST297

Domaini

The signal sequence is essential in mediating its proper translocation, hyaluronic acid (HA) degradation activity and secretion.

Sequence similaritiesi

Belongs to the CEMIP family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IFCM Eukaryota
ENOG410XQ01 LUCA
GeneTreeiENSGT00780000121902
HOGENOMiHOG000290723
HOVERGENiHBG052198
InParanoidiQ8WUJ3
KOiK19031
OMAiHFTAYKN
OrthoDBiEOG091G00JT
PhylomeDBiQ8WUJ3
TreeFamiTF316575

Family and domain databases

CDDicd13938 PANDER_like_TMEM2, 1 hit
InterProiView protein in InterPro
IPR019316 G8_domain
IPR039477 ILEI/PANDER_dom
IPR011050 Pectin_lyase_fold/virulence
IPR039473 TMEM2_PANDER-like
IPR025155 WxxW_domain
PfamiView protein in Pfam
PF10162 G8, 1 hit
PF15711 ILEI, 2 hits
PF13330 Mucin2_WxxW, 1 hit
SMARTiView protein in SMART
SM01225 G8, 1 hit
SUPFAMiSSF51126 SSF51126, 1 hit
PROSITEiView protein in PROSITE
PS51484 G8, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8WUJ3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGAAGRQDFL FKAMLTISWL TLTCFPGATS TVAAGCPDQS PELQPWNPGH
60 70 80 90 100
DQDHHVHIGQ GKTLLLTSSA TVYSIHISEG GKLVIKDHDE PIVLRTRHIL
110 120 130 140 150
IDNGGELHAG SALCPFQGNF TIILYGRADE GIQPDPYYGL KYIGVGKGGA
160 170 180 190 200
LELHGQKKLS WTFLNKTLHP GGMAEGGYFF ERSWGHRGVI VHVIDPKSGT
210 220 230 240 250
VIHSDRFDTY RSKKESERLV QYLNAVPDGR ILSVAVNDEG SRNLDDMARK
260 270 280 290 300
AMTKLGSKHF LHLGFRHPWS FLTVKGNPSS SVEDHIEYHG HRGSAAARVF
310 320 330 340 350
KLFQTEHGEY FNVSLSSEWV QDVEWTEWFD HDKVSQTKGG EKISDLWKAH
360 370 380 390 400
PGKICNRPID IQATTMDGVN LSTEVVYKKG QDYRFACYDR GRACRSYRVR
410 420 430 440 450
FLCGKPVRPK LTVTIDTNVN STILNLEDNV QSWKPGDTLV IASTDYSMYQ
460 470 480 490 500
AEEFQVLPCR SCAPNQVKVA GKPMYLHIGE EIDGVDMRAE VGLLSRNIIV
510 520 530 540 550
MGEMEDKCYP YRNHICNFFD FDTFGGHIKF ALGFKAAHLE GTELKHMGQQ
560 570 580 590 600
LVGQYPIHFH LAGDVDERGG YDPPTYIRDL SIHHTFSRCV TVHGSNGLLI
610 620 630 640 650
KDVVGYNSLG HCFFTEDGPE ERNTFDHCLG LLVKSGTLLP SDRDSKMCKM
660 670 680 690 700
ITEDSYPGYI PKPRQDCNAV STFWMANPNN NLINCAAAGS EETGFWFIFH
710 720 730 740 750
HVPTGPSVGM YSPGYSEHIP LGKFYNNRAH SNYRAGMIID NGVKTTEASA
760 770 780 790 800
KDKRPFLSII SARYSPHQDA DPLKPREPAI IRHFIAYKNQ DHGAWLRGGD
810 820 830 840 850
VWLDSCRFAD NGIGLTLASG GTFPYDDGSK QEIKNSLFVG ESGNVGTEMM
860 870 880 890 900
DNRIWGPGGL DHSGRTLPIG QNFPIRGIQL YDGPINIQNC TFRKFVALEG
910 920 930 940 950
RHTSALAFRL NNAWQSCPHN NVTGIAFEDV PITSRVFFGE PGPWFNQLDM
960 970 980 990 1000
DGDKTSVFHD VDGSVSEYPG SYLTKNDNWL VRHPDCINVP DWRGAICSGC
1010 1020 1030 1040 1050
YAQMYIQAYK TSNLRMKIIK NDFPSHPLYL EGALTRSTHY QQYQPVVTLQ
1060 1070 1080 1090 1100
KGYTIHWDQT APAELAIWLI NFNKGDWIRV GLCYPRGTTF SILSDVHNRL
1110 1120 1130 1140 1150
LKQTSKTGVF VRTLQMDKVE QSYPGRSHYY WDEDSGLLFL KLKAQNEREK
1160 1170 1180 1190 1200
FAFCSMKGCE RIKIKALIPK NAGVSDCTAT AYPKFTERAV VDVPMPKKLF
1210 1220 1230 1240 1250
GSQLKTKDHF LEVKMESSKQ HFFHLWNDFA YIEVDGKKYP SSEDGIQVVV
1260 1270 1280 1290 1300
IDGNQGRVVS HTSFRNSILQ GIPWQLFNYV ATIPDNSIVL MASKGRYVSR
1310 1320 1330 1340 1350
GPWTRVLEKL GADRGLKLKE QMAFVGFKGS FRPIWVTLDT EDHKAKIFQV
1360
VPIPVVKKKK L
Length:1,361
Mass (Da):152,998
Last modified:April 13, 2004 - v2
Checksum:i40CDFFB84F99516C
GO
Isoform 2 (identifier: Q8WUJ3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     978-992: NWLVRHPDCINVPDW → KWHSLASKAASGPSG
     993-1361: Missing.

Note: No experimental confirmation available.
Show »
Length:992
Mass (Da):110,357
Checksum:iAF371C2A8633012D
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YCE1H0YCE1_HUMAN
Cell migration-inducing and hyaluro...
CEMIP
76Annotation score:
H0YL56H0YL56_HUMAN
Cell migration-inducing and hyaluro...
CEMIP
145Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti558 – 564HFHLAGD → TRPPTRP in CAB94391 (Ref. 6) Curated7
Sequence conflicti862H → T in AAG41059 (PubMed:11247670).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_018165187R → C in a family with non-syndromic hearing loss; reduces hyaluronic acid degradation activity. 2 PublicationsCorresponds to variant dbSNP:rs368854657Ensembl.1
Natural variantiVAR_018166187R → H in two unrelated families with non-syndromic hearing loss; reduces hyaluronic acid (HA) degradation activity. 2 PublicationsCorresponds to variant dbSNP:rs144446375Ensembl.1
Natural variantiVAR_018167783H → R Does not inhibit hyaluronic acid degradation activity. 2 PublicationsCorresponds to variant dbSNP:rs12441101Ensembl.1
Natural variantiVAR_018168783H → Y in a sporadic case of non-syndromic hearing loss. 1 PublicationCorresponds to variant dbSNP:rs996035812Ensembl.1
Natural variantiVAR_0181691109V → I Does not inhibit hyaluronic acid degradation activity. 2 PublicationsCorresponds to variant dbSNP:rs751807711Ensembl.1
Natural variantiVAR_0181701169P → A Common polymorphism. 1 PublicationCorresponds to variant dbSNP:rs16972583Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_009814978 – 992NWLVR…NVPDW → KWHSLASKAASGPSG in isoform 2. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_009815993 – 1361Missing in isoform 2. 1 PublicationAdd BLAST369

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB103330 mRNA Translation: BAD02451.1
CH471136 Genomic DNA Translation: EAW99111.1
BC020256 mRNA Translation: AAH20256.1
AB033025 mRNA Translation: BAA86513.1
AL359061 mRNA Translation: CAB94391.1
AY007811 mRNA Translation: AAG41059.1
CCDSiCCDS10315.1 [Q8WUJ3-1]
RefSeqiNP_001280227.1, NM_001293298.1 [Q8WUJ3-1]
NP_001280233.1, NM_001293304.1 [Q8WUJ3-1]
NP_061159.1, NM_018689.2 [Q8WUJ3-1]
UniGeneiHs.459088

Genome annotation databases

EnsembliENST00000220244; ENSP00000220244; ENSG00000103888 [Q8WUJ3-1]
ENST00000356249; ENSP00000348583; ENSG00000103888 [Q8WUJ3-1]
ENST00000394685; ENSP00000378177; ENSG00000103888 [Q8WUJ3-1]
GeneIDi57214
KEGGihsa:57214
UCSCiuc002bfw.2 human [Q8WUJ3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB103330 mRNA Translation: BAD02451.1
CH471136 Genomic DNA Translation: EAW99111.1
BC020256 mRNA Translation: AAH20256.1
AB033025 mRNA Translation: BAA86513.1
AL359061 mRNA Translation: CAB94391.1
AY007811 mRNA Translation: AAG41059.1
CCDSiCCDS10315.1 [Q8WUJ3-1]
RefSeqiNP_001280227.1, NM_001293298.1 [Q8WUJ3-1]
NP_001280233.1, NM_001293304.1 [Q8WUJ3-1]
NP_061159.1, NM_018689.2 [Q8WUJ3-1]
UniGeneiHs.459088

3D structure databases

ProteinModelPortaliQ8WUJ3
SMRiQ8WUJ3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121452, 2 interactors
IntActiQ8WUJ3, 1 interactor
STRINGi9606.ENSP00000220244

PTM databases

CarbonylDBiQ8WUJ3
iPTMnetiQ8WUJ3
PhosphoSitePlusiQ8WUJ3

Polymorphism and mutation databases

BioMutaiKIAA1199
DMDMi46396475

Proteomic databases

PaxDbiQ8WUJ3
PeptideAtlasiQ8WUJ3
PRIDEiQ8WUJ3
ProteomicsDBi74690
74691 [Q8WUJ3-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000220244; ENSP00000220244; ENSG00000103888 [Q8WUJ3-1]
ENST00000356249; ENSP00000348583; ENSG00000103888 [Q8WUJ3-1]
ENST00000394685; ENSP00000378177; ENSG00000103888 [Q8WUJ3-1]
GeneIDi57214
KEGGihsa:57214
UCSCiuc002bfw.2 human [Q8WUJ3-1]

Organism-specific databases

CTDi57214
DisGeNETi57214
EuPathDBiHostDB:ENSG00000103888.15
GeneCardsiCEMIP
HGNCiHGNC:29213 CEMIP
MIMi608366 gene
neXtProtiNX_Q8WUJ3
OpenTargetsiENSG00000103888
PharmGKBiPA134967531
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFCM Eukaryota
ENOG410XQ01 LUCA
GeneTreeiENSGT00780000121902
HOGENOMiHOG000290723
HOVERGENiHBG052198
InParanoidiQ8WUJ3
KOiK19031
OMAiHFTAYKN
OrthoDBiEOG091G00JT
PhylomeDBiQ8WUJ3
TreeFamiTF316575

Enzyme and pathway databases

ReactomeiR-HSA-2142850 Hyaluronan biosynthesis and export

Miscellaneous databases

ChiTaRSiCEMIP human
GeneWikiiKIAA1199
GenomeRNAii57214
PROiPR:Q8WUJ3
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000103888 Expressed in 153 organ(s), highest expression level in trigeminal ganglion
CleanExiHS_KIAA1199
ExpressionAtlasiQ8WUJ3 baseline and differential
GenevisibleiQ8WUJ3 HS

Family and domain databases

CDDicd13938 PANDER_like_TMEM2, 1 hit
InterProiView protein in InterPro
IPR019316 G8_domain
IPR039477 ILEI/PANDER_dom
IPR011050 Pectin_lyase_fold/virulence
IPR039473 TMEM2_PANDER-like
IPR025155 WxxW_domain
PfamiView protein in Pfam
PF10162 G8, 1 hit
PF15711 ILEI, 2 hits
PF13330 Mucin2_WxxW, 1 hit
SMARTiView protein in SMART
SM01225 G8, 1 hit
SUPFAMiSSF51126 SSF51126, 1 hit
PROSITEiView protein in PROSITE
PS51484 G8, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCEMIP_HUMAN
AccessioniPrimary (citable) accession number: Q8WUJ3
Secondary accession number(s): Q6L9J5
, Q9H1K5, Q9NPN9, Q9ULM1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: April 13, 2004
Last modified: November 7, 2018
This is version 130 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  6. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
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